PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34668283-5 2021 With increasing concentrations of tacrolimus, there was a trend to reduction in the release of IL-2 (p = 0.0137), and IFN-gamma (p = 0.0147) in response to peptide stimulation. Tacrolimus 34-44 interleukin 2 Homo sapiens 95-99 2465593-4 1989 FK506 inhibited in a dose-dependent manner both interleukin 2 and gamma-interferon secretion of PBMC stimulated with PHA. Tacrolimus 0-5 interleukin 2 Homo sapiens 48-61 2472451-1 1989 FK506, a neutral macrolide with immunosuppressive properties, was shown to selectively and rapidly inhibit the accumulation of IL-2 mRNA, as well as the mRNAs of other early (E) phase T cell activation genes such as IL-3, IL-4, GM-CSF, TNF alpha, IFN-gamma, and c-myc in activated human peripheral blood T cells. Tacrolimus 0-5 interleukin 2 Homo sapiens 127-131 2472451-2 1989 The activity of FK506, when compared to Cyclosporin A, another immunosuppressant, was 10 to 100x more potent in its ability to inhibit IL-2 mRNA synthesis. Tacrolimus 16-21 interleukin 2 Homo sapiens 135-139 2472451-3 1989 FK506 inhibited IL-2 mRNA accumulation in Con A, Con A plus PMA, Ionomycin plus PMA, anti-CD3, and anti-CD3 plus PMA activated T cells. Tacrolimus 0-5 interleukin 2 Homo sapiens 16-20 2472451-8 1989 Nuclear run-off transcription studies indicate that FK506 inhibits transcription of the IL-2 gene. Tacrolimus 52-57 interleukin 2 Homo sapiens 88-92 34607938-9 2021 In vitro treatment of healthy CD4+ and CD8+ T cells with tacrolimus abrogated the proliferation and cytokine (INF-gamma, IL-2, and TNF-alpha) secretion associated with the type 1 inflammatory phenotype observed in pre- and post-PTx rejectors. Tacrolimus 57-67 interleukin 2 Homo sapiens 121-125 2465593-5 1989 Complete inhibition was obtained at the concentration of 0.25 nM of FK506 for IL-2 and 1 nM of FK506 for gamma-IFN production. Tacrolimus 68-73 interleukin 2 Homo sapiens 78-82 32749395-5 2020 Furthermore, T cell infiltration, and secretion of IL-2 and IFN-gamma were dramatically reduced in the GM-FK506 group. Tacrolimus 106-111 interleukin 2 Homo sapiens 51-55 32932253-7 2020 The immunological impact of tacrolimus was revealed by reduced percentages of Tfh, Breg, CD19+BAFF-R+ B cells, and increased percentages of Treg cells as well as down-regulated expression of IL-2, IL-4, IL-10, and IL-13 mRNA levels in PBMCs during the treatment. Tacrolimus 28-38 interleukin 2 Homo sapiens 191-195 32268334-1 2020 BACKGROUND: This study aims to assess outcomes of interleukin-2 (IL-2) receptor blocker induction therapy on allograft and patients" outcomes in standard risk recipients in the tacrolimus era, analysing data form the British Renal Transplant Registry. Tacrolimus 177-187 interleukin 2 Homo sapiens 50-63 32268334-1 2020 BACKGROUND: This study aims to assess outcomes of interleukin-2 (IL-2) receptor blocker induction therapy on allograft and patients" outcomes in standard risk recipients in the tacrolimus era, analysing data form the British Renal Transplant Registry. Tacrolimus 177-187 interleukin 2 Homo sapiens 65-69 31321978-8 2019 Inactivation of CaN by forming the FKBP12-FK506-CaN ternary complex prevents the activation of nuclear factor of activated T cells (NF-AT), inhibiting the production of interleukin-2 and subsequent T-cell proliferation. Tacrolimus 42-47 interleukin 2 Homo sapiens 169-182 30472069-3 2019 Tacrolimus, an immunosuppressant used in AChR-MG and transplantation patients, inhibits T cell responses through interference with IL-2 transcription. Tacrolimus 0-10 interleukin 2 Homo sapiens 131-135 30883749-1 2019 Tacrolimus (TAC) acts as an inhibitor of calcineurin, which inhibits the production of interleukin-2. Tacrolimus 0-10 interleukin 2 Homo sapiens 87-100 30883749-1 2019 Tacrolimus (TAC) acts as an inhibitor of calcineurin, which inhibits the production of interleukin-2. Tacrolimus 12-15 interleukin 2 Homo sapiens 87-100 30729267-0 2019 IL-2 gene polymorphisms affect tacrolimus response in myasthenia gravis. Tacrolimus 31-41 interleukin 2 Homo sapiens 0-4 30729267-2 2019 However, there are no published studies examining the influence of the IL-2 gene polymorphisms on the response of myasthenia gravis (MG) patients to tacrolimus (Tac). Tacrolimus 149-159 interleukin 2 Homo sapiens 71-75 30729267-3 2019 The goal of this study was to investigate the relationship between the polymorphisms of IL-2 and Tac response in MG patients. Tacrolimus 97-100 interleukin 2 Homo sapiens 88-92 30729267-10 2019 CONCLUSION: Myasthenia gravis patients with the rs2069762 variant, rs2069762 G/T and G/G genotype, and TAGG haplotype for IL-2 tended to respond poorly to Tac treatment. Tacrolimus 155-158 interleukin 2 Homo sapiens 122-126 30472069-6 2019 We determined that tacrolimus profoundly suppressed CD4 and CD8 T cell proliferation and significantly suppressed Th1 and Th17 responses, as demonstrated by a reduced frequency of IFN-gamma, IL-2, and IL-17 producing CD4 T cells and reduced frequencies of IFN-gamma and IL-2 producing CD8 T cells. Tacrolimus 19-29 interleukin 2 Homo sapiens 191-195 30472069-6 2019 We determined that tacrolimus profoundly suppressed CD4 and CD8 T cell proliferation and significantly suppressed Th1 and Th17 responses, as demonstrated by a reduced frequency of IFN-gamma, IL-2, and IL-17 producing CD4 T cells and reduced frequencies of IFN-gamma and IL-2 producing CD8 T cells. Tacrolimus 19-29 interleukin 2 Homo sapiens 270-274 31384453-0 2019 Implication of interleukin-2 receptor antibody induction therapy in standard risk renal transplant in the tacrolimus era: a meta-analysis. Tacrolimus 106-116 interleukin 2 Homo sapiens 15-28 31384453-3 2019 The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Tacrolimus 194-204 interleukin 2 Homo sapiens 67-71 25883698-6 2015 Calcineurin inhibitor, which includes cyclosporine, pimecrolimus and tacrolimus, impairs calcineurin-induced up-regulation of IL-2 expression, resulting in increased susceptibility to invasive fungal diseases. Tacrolimus 69-79 interleukin 2 Homo sapiens 126-130 25817300-12 2015 The tacrolimus blood concentrations were significantly higher in patients with the genotype GG of IL-2-330 (P = 0.012) at the third month. Tacrolimus 4-14 interleukin 2 Homo sapiens 98-102 30551354-7 2019 Meanwhile TMP could regulate the Interleukin 10 (IL-10) and FK506 could restrain the Interleukin 2 (IL-2). Tacrolimus 60-65 interleukin 2 Homo sapiens 85-98 30551354-7 2019 Meanwhile TMP could regulate the Interleukin 10 (IL-10) and FK506 could restrain the Interleukin 2 (IL-2). Tacrolimus 60-65 interleukin 2 Homo sapiens 100-104 22447331-8 2013 IL-2 and IL-6 were significantly decreased after the administration of tacrolimus (p = 0.027 and p = 0.024). Tacrolimus 71-81 interleukin 2 Homo sapiens 0-4 23743668-10 2013 Tacrolimus 10 ng/mL reduced the production of IL-2 in CD4 and CD8 T cells by 28.9% and 45.4% (P < 0.05). Tacrolimus 0-10 interleukin 2 Homo sapiens 46-50 23743668-11 2013 Tacrolimus-mediated inhibition of IL-2 was enhanced by verapamil (P < 0.05). Tacrolimus 0-10 interleukin 2 Homo sapiens 34-38 23743668-12 2013 This effect on tacrolimus pharmacodynamics was associated with ABCB1 3435C>T SNP in renal transplant patients: verapamil reduced the percentage of IL-2-producing CD4 and CD8 T cells by 14% and 22% in patients with the CC genotype (P < 0.05) but not in patients with the TT genotype. Tacrolimus 15-25 interleukin 2 Homo sapiens 150-154 23743668-13 2013 Moreover, the ratio of tacrolimus C0 over the percent of IL-2-producing CD8 T cells in CC genotype patients was significantly higher compared with TT genotype patients (P < 0.05), showing a smaller pharmacodynamic effect in CC genotype patients. Tacrolimus 23-33 interleukin 2 Homo sapiens 57-61 24175257-6 2012 Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting the transcription of the early activation genes of interleukin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-alpha, IL-1beta and IL-6. Tacrolimus 25-35 interleukin 2 Homo sapiens 202-220 24028719-9 2013 Compared with control group, the expression of TNF-beta was significantly higher in IL-2 group (73.36% +- 16.73% vs 66.61% +- 16.20%, P < 0.05), significantly lower in FK506 and FK506 plus CsA groups (P < 0.05). Tacrolimus 171-176 interleukin 2 Homo sapiens 84-88 24028719-9 2013 Compared with control group, the expression of TNF-beta was significantly higher in IL-2 group (73.36% +- 16.73% vs 66.61% +- 16.20%, P < 0.05), significantly lower in FK506 and FK506 plus CsA groups (P < 0.05). Tacrolimus 181-186 interleukin 2 Homo sapiens 84-88 24175257-6 2012 Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting the transcription of the early activation genes of interleukin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-alpha, IL-1beta and IL-6. Tacrolimus 37-40 interleukin 2 Homo sapiens 202-220 21640771-9 2011 Moreover, FK506 released from FKBP12-RBC is able to be up-taken by T lymphocytes and inhibit IL-2 expression in vitro as free administered drug. Tacrolimus 10-15 interleukin 2 Homo sapiens 93-97 22974867-0 2012 Long-term interleukin-2 assessment after conversion from a twice-daily to once-daily tacrolimus regimen in stable kidney recipients. Tacrolimus 85-95 interleukin 2 Homo sapiens 10-23 21620040-0 2011 Interleukin-2 profiles shortly after tacrolimus conversion from a twice-daily to once-daily regimen. Tacrolimus 37-47 interleukin 2 Homo sapiens 0-13 21540458-6 2011 Inhibition by IL-2 occurred via a NFAT cell-independent component of the calcineurin pathway, and CD94/NKG2A induction was markedly enhanced in the presence of calcineurin blockers, such as FK506 or using calcineurin-deficient T cells, both in vitro and in vivo. Tacrolimus 190-195 interleukin 2 Homo sapiens 14-18 20159692-6 2010 CONCLUSION: FK506 effectively inhibits the secretion of proinflammatory cytokines including IL-6, IFN-gamma and TNF-alpha and also the secretion of IL-2, IL-12, IL-17, GM-CSF and G-CSF. Tacrolimus 12-17 interleukin 2 Homo sapiens 148-152 20233105-1 2010 Tacrolimus is an immunosuppressive medication in the class of calcineurin inhibitors that acts by inhibiting T-cell and interleukin-2 activity, and is commonly used after allogeneic organ transplant. Tacrolimus 0-10 interleukin 2 Homo sapiens 120-133 20159692-4 2010 RESULTS: Compared with the control group, high-concentration FK506 (20 ng/ml) significantly inhibited the secretions of IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha, GM-CSF and G-CSF. Tacrolimus 61-66 interleukin 2 Homo sapiens 120-124 21195813-10 2011 We found that tacrolimus reduced levels of the IFN-gamma, IL-2, IL-10, and IL-13 cytokines and induced the proliferation of tolerogenic plasmacytoid dendritic cells after treatment. Tacrolimus 14-24 interleukin 2 Homo sapiens 58-62 21176018-6 2011 The use of anti-interleukin-2 inhibitors as induction therapy, with low-dose tacrolimus or in combination with mycophenolate mofetil, has a key role in preventing significant renal dysfunction and reducing infection and rejection. Tacrolimus 77-87 interleukin 2 Homo sapiens 16-29 20671192-5 2010 Likewise, FK506 caused profound inhibition of NK cell proliferation in vitro and suppressed NK cytotoxicity and cytokine secretion in response to IL-2. Tacrolimus 10-15 interleukin 2 Homo sapiens 146-150 18465778-4 2008 Both bisindolylmaleimide-I (BIM-I), a specific protein kinase C (PKC) inhibitor, and the immunosuppressant drug known as Tacrolimus (FK506), an IL-2 inhibitor, prevented mitogen-stimulated IL-2 production in Jurkat cells. Tacrolimus 121-131 interleukin 2 Homo sapiens 189-193 19930321-1 2009 The inhibitory effect of Cyclosporine A (CsA) and Tacrolimus (Tacr) on interleukin 2 (IL-2) are well known, and the importance of Th1-type (IL-2, interferon gamma), and Th2-type (IL-4, IL-6, and IL-10) cytokine secretion in preventing allograft rejection is a controversial issue. Tacrolimus 50-60 interleukin 2 Homo sapiens 71-84 19930321-1 2009 The inhibitory effect of Cyclosporine A (CsA) and Tacrolimus (Tacr) on interleukin 2 (IL-2) are well known, and the importance of Th1-type (IL-2, interferon gamma), and Th2-type (IL-4, IL-6, and IL-10) cytokine secretion in preventing allograft rejection is a controversial issue. Tacrolimus 50-60 interleukin 2 Homo sapiens 86-90 19930321-1 2009 The inhibitory effect of Cyclosporine A (CsA) and Tacrolimus (Tacr) on interleukin 2 (IL-2) are well known, and the importance of Th1-type (IL-2, interferon gamma), and Th2-type (IL-4, IL-6, and IL-10) cytokine secretion in preventing allograft rejection is a controversial issue. Tacrolimus 50-54 interleukin 2 Homo sapiens 71-84 19930321-1 2009 The inhibitory effect of Cyclosporine A (CsA) and Tacrolimus (Tacr) on interleukin 2 (IL-2) are well known, and the importance of Th1-type (IL-2, interferon gamma), and Th2-type (IL-4, IL-6, and IL-10) cytokine secretion in preventing allograft rejection is a controversial issue. Tacrolimus 50-54 interleukin 2 Homo sapiens 86-90 19628039-2 2009 OBJECTIVE: This study examined the effect of FK506 on interleukin-2 (IL-2) and insulin secretion, establishing a novel characteristic of this drug that could explain its diverse adverse effects, and developed an experimental model for the simultaneous analysis of mRNA expression and protein secretion affected by this drug. Tacrolimus 45-50 interleukin 2 Homo sapiens 54-67 19628039-2 2009 OBJECTIVE: This study examined the effect of FK506 on interleukin-2 (IL-2) and insulin secretion, establishing a novel characteristic of this drug that could explain its diverse adverse effects, and developed an experimental model for the simultaneous analysis of mRNA expression and protein secretion affected by this drug. Tacrolimus 45-50 interleukin 2 Homo sapiens 69-73 19628039-3 2009 METHODS: The IL-2 levels when tacrolimus was administered were analysed by Western blot, immunocytochemistry and RT-PCR in a T lymphocyte cellular line (Jurkat) 24 h post-stimulation. Tacrolimus 30-40 interleukin 2 Homo sapiens 13-17 19628039-5 2009 RESULTS: The previously published information describes tacrolimus as only capable of partially blocking IL-2 mRNA expression. Tacrolimus 56-66 interleukin 2 Homo sapiens 105-109 19628039-9 2009 Tacrolimus added before stimulation inhibits only IL-2 synthesis, but blocks IL-2 protein secretion when added 2 h after stimulation. Tacrolimus 0-10 interleukin 2 Homo sapiens 50-54 19628039-9 2009 Tacrolimus added before stimulation inhibits only IL-2 synthesis, but blocks IL-2 protein secretion when added 2 h after stimulation. Tacrolimus 0-10 interleukin 2 Homo sapiens 77-81 19628039-12 2009 CONCLUSIONS: Results of this study indicate that tacrolimus possesses another important effect in addition to the inhibition of IL-2 gene transcription, namely the ability to act as a general inhibitor of the protein secretory pathway. Tacrolimus 49-59 interleukin 2 Homo sapiens 128-132 19138532-4 2009 In contrast, FK506 and MPA selectively inhibited the secretion of IL-2 and IL-13, and MPA unexpectedly increased the production of IL-1beta. Tacrolimus 13-18 interleukin 2 Homo sapiens 66-70 18465778-4 2008 Both bisindolylmaleimide-I (BIM-I), a specific protein kinase C (PKC) inhibitor, and the immunosuppressant drug known as Tacrolimus (FK506), an IL-2 inhibitor, prevented mitogen-stimulated IL-2 production in Jurkat cells. Tacrolimus 133-138 interleukin 2 Homo sapiens 189-193 18570909-7 2008 After binding to a specific immunophillin, cyclosporin and tacrolimus inhibit calcineurine, a serine/threonine phosphatase which plays a major role in cytokines transcription notably IL2 after T-cell activation. Tacrolimus 59-69 interleukin 2 Homo sapiens 183-186 17880416-3 2007 RESULTS: Upon exposure to ciclosporin A (500 ng/mL) or tacrolimus (25 ng/mL) the number of cytokine expressing T cells was almost completely blocked in neonatal T cells while sirolimus (10 ng/mL) only inhibited intracytoplasmatic tumour necrosis factor alpha (TNF-alpha) expression (mean% positive cells; 4.0 +/- 2.1% vs. 1.09 +/- 0.6%, p = 0.003), but mildly stimulated the intracellular expression of interleukin (IL)-2 (24.4 +/- 6.5% vs. 28.1 +/- 7.1%, p = 0.041). Tacrolimus 55-65 interleukin 2 Homo sapiens 403-421 17761346-2 2007 The importance of IL-2 down-regulation in preventing acute rejection in organ transplantation and the development of autoimmune diseases has been demonstrated by the therapeutic usefulness of the widely used immunosuppressants cyclosporine A and FK506. Tacrolimus 246-251 interleukin 2 Homo sapiens 18-22 17880416-4 2007 In cord blood lymphocytes, the inhibitory effect of ciclosporin A and tacrolimus was dose-dependent (e.g. IL-2: control, 12.3 +/- 5.33%, ciclosporin A 5 ng/mL, 10.1 +/- 5.5%; 50 ng/mL, 7.1 +/- 4.7%; 500 ng/mL, 1.2 +/- 0.3%; tacrolimus 0.25 ng/mL, 9.3 +/- 4.9%; 2.5 ng/mL, 6.1 +/- 3.3%; 25 ng/mL, 1.0 +/- 0.6%), while the function of adult lymphocytes was only impaired at high doses of both compounds. Tacrolimus 70-80 interleukin 2 Homo sapiens 106-110 17594193-2 2007 Tacrolimus inhibits the activation of an essential transcription factor for the transcription of cytokine genes in T cells leading to a decreased production of cytokines such as IL-2 and IFN-gamma. Tacrolimus 0-10 interleukin 2 Homo sapiens 178-182 17523132-1 2007 The effect of tacrolimus (FK506) on down-regulation of IL-2 production by T cells is considered to be mainly responsible for its strong suppression of immunological events. Tacrolimus 14-24 interleukin 2 Homo sapiens 55-59 17523132-1 2007 The effect of tacrolimus (FK506) on down-regulation of IL-2 production by T cells is considered to be mainly responsible for its strong suppression of immunological events. Tacrolimus 26-31 interleukin 2 Homo sapiens 55-59 17175263-0 2006 Paradoxical response to tacrolimus assessed by interleukin-2 gene expression. Tacrolimus 24-34 interleukin 2 Homo sapiens 47-60 17565322-5 2007 Interestingly, induction of IL-21 was highly dependent on IL-2 (as in the presence of anti-IL-2, anti-IL-2R alpha-chain, and the immunosuppressive drugs cyclosporine A, tacrolimus, and rapamycin) the transcription of IL-21 was almost completely inhibited, whereas in the presence of exogenous IL-2 the mRNA expression of IL-21 was even more upregulated. Tacrolimus 169-179 interleukin 2 Homo sapiens 28-32 17565322-5 2007 Interestingly, induction of IL-21 was highly dependent on IL-2 (as in the presence of anti-IL-2, anti-IL-2R alpha-chain, and the immunosuppressive drugs cyclosporine A, tacrolimus, and rapamycin) the transcription of IL-21 was almost completely inhibited, whereas in the presence of exogenous IL-2 the mRNA expression of IL-21 was even more upregulated. Tacrolimus 169-179 interleukin 2 Homo sapiens 58-62 17565322-5 2007 Interestingly, induction of IL-21 was highly dependent on IL-2 (as in the presence of anti-IL-2, anti-IL-2R alpha-chain, and the immunosuppressive drugs cyclosporine A, tacrolimus, and rapamycin) the transcription of IL-21 was almost completely inhibited, whereas in the presence of exogenous IL-2 the mRNA expression of IL-21 was even more upregulated. Tacrolimus 169-179 interleukin 2 Homo sapiens 58-62 17000002-1 2007 Inhibition of the interleukin-2 (IL-2) pathway has potent immunosuppressive activity in humans as is evident from the broad therapeutic utility of cyclosporine, rapamycin, tacrolimus, and monoclonal antibodies blocking the high-affinity subunit of the IL-2 receptor (CD25). Tacrolimus 172-182 interleukin 2 Homo sapiens 18-31 17000002-1 2007 Inhibition of the interleukin-2 (IL-2) pathway has potent immunosuppressive activity in humans as is evident from the broad therapeutic utility of cyclosporine, rapamycin, tacrolimus, and monoclonal antibodies blocking the high-affinity subunit of the IL-2 receptor (CD25). Tacrolimus 172-182 interleukin 2 Homo sapiens 33-37 17175263-6 2006 RESULTS: IL-2 mRNA synthesis was suppressed by the presence of tacrolimus in most cases, compared with a control sample. Tacrolimus 63-73 interleukin 2 Homo sapiens 9-13 16378079-1 2005 Tacrolimus (FK506) is a potent immunosuppressive agent that inhibit transcription of cytokines such as IL-2 in T cells. Tacrolimus 0-10 interleukin 2 Homo sapiens 103-107 17098001-8 2006 Comparison of the treatment groups showed that the regimen associated with fever infections included an IL-2 receptor antagonist with tacrolimus, MMF, and S. Tacrolimus 134-144 interleukin 2 Homo sapiens 104-108 16911492-2 2006 An increased prevalence of food allergy noted specifically in children receiving tacrolimus immunosuppression supports the hypothesis that selective suppression of Th1 lymphocytes by the IL-2 inhibitor immunosuppressants CsA, and the more potent drug, tacrolimus , promotes Th2 lymphocytes and an allergic immune response. Tacrolimus 81-91 interleukin 2 Homo sapiens 187-191 16911492-2 2006 An increased prevalence of food allergy noted specifically in children receiving tacrolimus immunosuppression supports the hypothesis that selective suppression of Th1 lymphocytes by the IL-2 inhibitor immunosuppressants CsA, and the more potent drug, tacrolimus , promotes Th2 lymphocytes and an allergic immune response. Tacrolimus 252-262 interleukin 2 Homo sapiens 187-191 16378079-1 2005 Tacrolimus (FK506) is a potent immunosuppressive agent that inhibit transcription of cytokines such as IL-2 in T cells. Tacrolimus 12-17 interleukin 2 Homo sapiens 103-107 16055081-11 2005 Furthermore, Zn2+ and the immunosuppressant FK506 showed an additive inhibitory effect on ConA-induced IL-2 mRNA expression. Tacrolimus 44-49 interleukin 2 Homo sapiens 103-107 16400900-2 2005 OBJECTIVE: To investigate the FK506 sensitivity of interleukin 15 (IL-15)- and IL-2-driven proliferation and apoptosis of anti-CD3-stimulated CB T cells compared with adult peripheral blood (APB) T cells. Tacrolimus 30-35 interleukin 2 Homo sapiens 79-83 12091117-1 2002 BACKGROUND AND OBJECTIVES: FK506 (tacrolimus) is a potent immunosuppressive agent that inhibits interleukin-2 (IL-2) and interferon-g production by CD4+ cells. Tacrolimus 27-32 interleukin 2 Homo sapiens 96-109 15716327-0 2005 Concentrations of cyclosporin A and FK506 that inhibit IL-2 induction in human T cells do not affect TGF-beta1 biosynthesis, whereas higher doses of cyclosporin A trigger apoptosis and release of preformed TGF-beta1. Tacrolimus 36-41 interleukin 2 Homo sapiens 55-59 15149578-7 2004 However, tacrolimus, a potent calcineurin inhibitor and inhibitor of interleukin-2 expression, has shown efficacy in Crohn"s disease, albeit at the cost of substantial potential toxicity. Tacrolimus 9-19 interleukin 2 Homo sapiens 69-82 14709642-2 2004 Previous investigations have demonstrated the occurrence of tacrolimus-resistant production of interleukin-2 (IL-2) in vitro, which may explain in part why rejection episodes are still a frequent problem despite attainment of therapeutic blood concentrations and HLA matching. Tacrolimus 60-70 interleukin 2 Homo sapiens 95-108 14709642-2 2004 Previous investigations have demonstrated the occurrence of tacrolimus-resistant production of interleukin-2 (IL-2) in vitro, which may explain in part why rejection episodes are still a frequent problem despite attainment of therapeutic blood concentrations and HLA matching. Tacrolimus 60-70 interleukin 2 Homo sapiens 110-114 14709642-8 2004 Whole-blood samples from 3 of 11 healthy individuals demonstrated marked suppression of IL-2 mRNA expression (>50%) when tacrolimus was administered in vitro. Tacrolimus 124-134 interleukin 2 Homo sapiens 88-92 14709642-11 2004 Kinetic profiles of IL-2 mRNA expression also revealed individually distinct degrees of calcineurin inhibitor sensitivity in patients undergoing tacrolimus or CsA monotherapy before living-donor kidney transplantation. Tacrolimus 145-155 interleukin 2 Homo sapiens 20-24 12835079-13 2003 Cyclosporine and Tacrolimus, collectively known as calcineurin inhibitors, seems to act on the IL-2 by inhibiting its production thus leading to a decrease in the proliferation of the activated lymphocyte. Tacrolimus 17-27 interleukin 2 Homo sapiens 95-99 12942158-3 2003 The inhibition of calcineurin activation by cyclosporin A and FK-506 blocks T-cell receptor-mediated production of interleukin-2 (IL-2), a growth factor critical for T-cell proliferation. Tacrolimus 62-68 interleukin 2 Homo sapiens 115-128 12942158-3 2003 The inhibition of calcineurin activation by cyclosporin A and FK-506 blocks T-cell receptor-mediated production of interleukin-2 (IL-2), a growth factor critical for T-cell proliferation. Tacrolimus 62-68 interleukin 2 Homo sapiens 130-134 12604780-7 2003 However, contrary to FK506, which blocks IL2 synthesis, we observed that FAP48-FKBP complexes increase IL2 production, thus revealing a previously uncharacterized aspect of the immunosuppressive mechanism of FK506. Tacrolimus 208-213 interleukin 2 Homo sapiens 103-106 12548534-0 2003 Effects of FK506 on myasthenia gravis patients with high interleukin-2 productivity in peripheral blood mononuclear cells. Tacrolimus 11-16 interleukin 2 Homo sapiens 57-70 14561179-4 2002 Cyclosporine and tacrolimus are calcineurin inhibitors that impair the transcription of interleukin 2, reduce the expression of cytokines, and diminish T lymphocyte proliferation. Tacrolimus 17-27 interleukin 2 Homo sapiens 88-101 12091117-1 2002 BACKGROUND AND OBJECTIVES: FK506 (tacrolimus) is a potent immunosuppressive agent that inhibits interleukin-2 (IL-2) and interferon-g production by CD4+ cells. Tacrolimus 27-32 interleukin 2 Homo sapiens 111-115 12091117-1 2002 BACKGROUND AND OBJECTIVES: FK506 (tacrolimus) is a potent immunosuppressive agent that inhibits interleukin-2 (IL-2) and interferon-g production by CD4+ cells. Tacrolimus 34-44 interleukin 2 Homo sapiens 96-109 12091117-1 2002 BACKGROUND AND OBJECTIVES: FK506 (tacrolimus) is a potent immunosuppressive agent that inhibits interleukin-2 (IL-2) and interferon-g production by CD4+ cells. Tacrolimus 34-44 interleukin 2 Homo sapiens 111-115 11987039-4 2002 The mode of action of Fk506 is similar to that of cyclosporin A, i.e. it exerts an inhibitory effect on transcription of interleukin 2 in T lymphocytes. Tacrolimus 22-27 interleukin 2 Homo sapiens 121-134 12372041-1 2002 Tacrolimus inhibits lymphocyte responses by blocking calcium-dependent signalling pathways important in IL-2 generation. Tacrolimus 0-10 interleukin 2 Homo sapiens 104-108 11805719-1 2002 The intracellular class of proteins that bind the interleukin-2 suppressing drugs (cyclosporin, tacrolimus, and sirolimus) are called immunophilins. Tacrolimus 96-106 interleukin 2 Homo sapiens 50-63 11516757-5 2001 Immunosuppressants acting via inhibition of interleukin-2 synthesis, such as CSA or FK506, inhibited the production of GFP in a dose-dependent manner. Tacrolimus 84-89 interleukin 2 Homo sapiens 44-57 11477316-0 2001 Quantitation of immunosuppression by tacrolimus using flow cytometric analysis of interleukin-2 and interferon-gamma inhibition in CD8(-) and CD8(+) peripheral blood T cells. Tacrolimus 37-47 interleukin 2 Homo sapiens 82-95 11477316-1 2001 The authors have determined the frequency of intracellular interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) synthesis by T-cell subsets in whole blood (WB) and isolated lymphocytes in 16 transplant recipients treated with tacrolimus and 10 control patients who were not transplant recipients. Tacrolimus 227-237 interleukin 2 Homo sapiens 59-72 11477316-6 2001 Adding tacrolimus (10 ng/mL) to lymphocyte cultures inhibited (90%) IL-2 production in isolated T cells but not in the whole-blood assay. Tacrolimus 7-17 interleukin 2 Homo sapiens 68-72 11477316-7 2001 The dose of tacrolimus required for a 50% inhibition of IL-2 release in T cells was 10-fold higher in cultures with RBC than without. Tacrolimus 12-22 interleukin 2 Homo sapiens 56-60 11477316-8 2001 Peripheral blood mononuclear cells (PBMC) isolated from tacrolimus-treated whole blood (WB) showed less IL-2 inhibition than did lymphocytes in the WB. Tacrolimus 56-66 interleukin 2 Homo sapiens 104-108 11714196-4 2001 FK506, in a concentration-dependent fashion, inhibited T-cell proliferation and steady-state mRNA expression of IL-2 and IL-7; half-maximal suppression was obtained at 10(-7) to 5 x 10(-8) M. We tested whether FK506 antiproliferative effect could be overcome with exogenously reconstituted rIL-2 and/or rIL-7. Tacrolimus 0-5 interleukin 2 Homo sapiens 112-116 11407316-6 2001 In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokines (IL-2, IFN-gamma), Th2 cytokines (IL-4, IL-5) and IL-3, GM-CSF (produced by both Th1 and Th2). Tacrolimus 116-126 interleukin 2 Homo sapiens 170-174 11258483-5 2000 We further demonstrate that co-expression of a constitutively active NFAT and a constitutively active MEKK1 renders the interleukin-2 promoter in Jurkat T lymphocytes resistant to CsA and FK506, whereas Jurkat cells expressing a constitutively active NFAT alone are still sensitive to CsA or FK506. Tacrolimus 188-193 interleukin 2 Homo sapiens 120-133 11176043-1 2001 Tacrolimus, available for intravenous, oral and now topical administration, is a potent immunosuppressive agent with the ability to block the production of Interleukin-2 (IL-2) and inhibit T-cell proliferation. Tacrolimus 0-10 interleukin 2 Homo sapiens 156-169 11176043-1 2001 Tacrolimus, available for intravenous, oral and now topical administration, is a potent immunosuppressive agent with the ability to block the production of Interleukin-2 (IL-2) and inhibit T-cell proliferation. Tacrolimus 0-10 interleukin 2 Homo sapiens 171-175 11258483-5 2000 We further demonstrate that co-expression of a constitutively active NFAT and a constitutively active MEKK1 renders the interleukin-2 promoter in Jurkat T lymphocytes resistant to CsA and FK506, whereas Jurkat cells expressing a constitutively active NFAT alone are still sensitive to CsA or FK506. Tacrolimus 292-297 interleukin 2 Homo sapiens 120-133 10972232-2 2000 The mechanism of action of cyclosporine and tacrolimus has been explained on the basis of their inhibition of interleukin-2 (IL-2), and induction of transforming growth factor-beta (TGF-beta). Tacrolimus 44-54 interleukin 2 Homo sapiens 110-123 11053632-6 2000 Treatment with Tacr resulted in a decreased expression of costimulatory ligands and adhesion molecules (T cells: CD40L, p < 0.05; CD28 and CD54, p < or = 0.01; B cells: CD25, p = 0.05; CD40, p < 0.001; monocytes: CD40, p < 0.05), which coincided with decreased PHA-stimulated T cell IL-2 responses (398 +/- 153 versus 43 +/- 15 pg/ml, p < 0.05), impaired CD4 helper activity (117% +/- 22% versus 73% +/- 19%, p < 0.05) and increased CD4 suppressor activity (-120% +/- 28% versus -18% +/- 27%, p = 0.02). Tacrolimus 15-19 interleukin 2 Homo sapiens 295-299 10887335-5 2000 RESULTS: Dexamethasone, FK506, and cyclosporin A suppressed the production of IL-2, IL-4, and IL-5 by human helper T cells, which shows a similar concentration-response relationship in each case. Tacrolimus 24-29 interleukin 2 Homo sapiens 78-82 18034554-3 2000 Tacrolimus is a macrolide lactone that inhibits the signal transduction of interleukin-2 (IL-2) via calcineurin inhibition. Tacrolimus 0-10 interleukin 2 Homo sapiens 75-88 18034554-3 2000 Tacrolimus is a macrolide lactone that inhibits the signal transduction of interleukin-2 (IL-2) via calcineurin inhibition. Tacrolimus 0-10 interleukin 2 Homo sapiens 90-94 10555752-7 1999 Growth of tumour cells was also inhibited by the immunosuppressive drugs, cyclosporin A (CsA), FK506 and rapamycin (RPA), known to interfere with the IL-2 pathway in lymphocytes. Tacrolimus 95-100 interleukin 2 Homo sapiens 150-154 10878284-11 2000 Cyclosporine and FK-506 (Tacrolimus) inhibit the phosphatase activity of calcineurin, thereby suppressing the production of IL-2 and other cytokines. Tacrolimus 17-23 interleukin 2 Homo sapiens 124-128 10878284-11 2000 Cyclosporine and FK-506 (Tacrolimus) inhibit the phosphatase activity of calcineurin, thereby suppressing the production of IL-2 and other cytokines. Tacrolimus 25-35 interleukin 2 Homo sapiens 124-128 9112351-2 1997 BACKGROUND: Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. Tacrolimus 24-29 interleukin 2 Homo sapiens 94-107 10515221-10 1999 When we compared the frequencies of cytokine-expressing cells in FK506- and CsA-treated patients, we found that the frequency of IL-2-expressing T cells was significantly lower with FK506 (10.9+/-1.61%) than with CsA (16.3 +/- 1.8%; p = 0.03), whereas the frequencies of the other cytokine-expressing cells were not statistically different between the two groups. Tacrolimus 182-187 interleukin 2 Homo sapiens 129-133 10515221-11 1999 In conclusion, our study clearly demonstrated that studied ex vivo, FK506 and CsA decrease the frequencies of cells expressing IL-2, IL-4 and IL-2/IFN-gamma in vivo but do not affect those expressing IFN-gamma. Tacrolimus 68-73 interleukin 2 Homo sapiens 127-131 10515221-11 1999 In conclusion, our study clearly demonstrated that studied ex vivo, FK506 and CsA decrease the frequencies of cells expressing IL-2, IL-4 and IL-2/IFN-gamma in vivo but do not affect those expressing IFN-gamma. Tacrolimus 68-73 interleukin 2 Homo sapiens 142-146 10515221-12 1999 Meanwhile, the frequency of IL-2-producing T cells was more affected with FK506 than with CsA and was negatively correlated with the CsA trough level. Tacrolimus 74-79 interleukin 2 Homo sapiens 28-32 10515221-13 1999 Finally, our results regarding IL-2 might explain to some extent the higher efficiency of FK506 in vivo than CsA. Tacrolimus 90-95 interleukin 2 Homo sapiens 31-35 9565564-5 1998 The transcriptional response provoked by mT was blocked by the immunosuppressive drug FK506, a potent inhibitor of TCR-mediated IL-2 gene expression. Tacrolimus 86-91 interleukin 2 Homo sapiens 128-132 9620363-3 1998 NFAT acts at the antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is the nuclear target of T cell stimulation signals and the immunosuppressant drugs cyclosporine (Sandimmune) and FK-506 (tacrolimus), which are potent inhibitors of IL-2 gene transcription. Tacrolimus 210-216 interleukin 2 Homo sapiens 78-82 9620363-3 1998 NFAT acts at the antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is the nuclear target of T cell stimulation signals and the immunosuppressant drugs cyclosporine (Sandimmune) and FK-506 (tacrolimus), which are potent inhibitors of IL-2 gene transcription. Tacrolimus 210-216 interleukin 2 Homo sapiens 262-266 9620363-3 1998 NFAT acts at the antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is the nuclear target of T cell stimulation signals and the immunosuppressant drugs cyclosporine (Sandimmune) and FK-506 (tacrolimus), which are potent inhibitors of IL-2 gene transcription. Tacrolimus 218-228 interleukin 2 Homo sapiens 78-82 9620363-3 1998 NFAT acts at the antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is the nuclear target of T cell stimulation signals and the immunosuppressant drugs cyclosporine (Sandimmune) and FK-506 (tacrolimus), which are potent inhibitors of IL-2 gene transcription. Tacrolimus 218-228 interleukin 2 Homo sapiens 262-266 9667420-4 1998 FK506-induced apoptosis was efficiently attenuated by co-addition of ILs including IL-1beta (2 ng/ml), IL-2 (5 ng/ml) and IL-4 (40 ng/ml) into culture. Tacrolimus 0-5 interleukin 2 Homo sapiens 103-107 9667420-6 1998 The data also suggested that cytokine networks including those via IL-1beta and IL-4 in addition to IL-2 prevent FK506-induced apoptosis. Tacrolimus 113-118 interleukin 2 Homo sapiens 100-104 9407429-3 1997 Both tacrolimus and CsA interfere with the early stage of lymphocyte proliferation by blocking interleukin-2 synthesis. Tacrolimus 5-15 interleukin 2 Homo sapiens 95-108 9190906-2 1997 Furthermore we show that IL-10 production by human T cell lines, such as IFN-gamma and IL-2, is inhibited by the immunosuppressive drugs cyclosporin A and FK506. Tacrolimus 155-160 interleukin 2 Homo sapiens 87-91 9112351-2 1997 BACKGROUND: Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. Tacrolimus 12-22 interleukin 2 Homo sapiens 94-107 9878113-0 1998 Distinctive calcineurin-dependent (FK506-sensitive) mechanisms regulate the production of the CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES vs IL-2 and TNF-alpha by activated human T cells. Tacrolimus 35-40 interleukin 2 Homo sapiens 179-183 9182928-4 1997 RESULTS: Interleukin-2 production was suppressed in patients treated with tacrolimus. Tacrolimus 74-84 interleukin 2 Homo sapiens 9-22 9103428-0 1997 IL-2-induced IL-5 synthesis, but not proliferation, of human CD4+ T cells is suppressed by FK506. Tacrolimus 91-96 interleukin 2 Homo sapiens 0-4 9103428-6 1997 Our present findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 stimulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calcineurin-NF-AT system. Tacrolimus 43-48 interleukin 2 Homo sapiens 142-146 9103428-6 1997 Our present findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 stimulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calcineurin-NF-AT system. Tacrolimus 43-48 interleukin 2 Homo sapiens 176-180 9103428-6 1997 Our present findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 stimulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calcineurin-NF-AT system. Tacrolimus 258-263 interleukin 2 Homo sapiens 176-180 9045922-4 1997 Blocking the IL-2 pathway by cyclosporin A, FK506, rapamycin, anti-IL-2 or CD25 antibodies, prevented the development of sensitivity to apoptosis. Tacrolimus 44-49 interleukin 2 Homo sapiens 13-17 9032415-6 1997 The assay is very sensitive and selective for immunosuppressive compounds inhibiting IL-2 gene expression such as cyclosporine (CsA) and FK506, their active metabolites and derivatives, but not for others such as rapamycin. Tacrolimus 137-142 interleukin 2 Homo sapiens 85-89 8786538-1 1996 FK-506 blocks T cell activation by preventing lymphokine gene transcription through formation of a complex with FKBP12 that inhibits calcineurin phosphatase activity. Tacrolimus 0-6 interleukin 2 Homo sapiens 46-56 8939643-3 1996 The immunosuppressants cyclosporin A and FK506, when complexed with immunophilins, inactivate the protein phosphatase calcineurin, resulting in the inhibition of interleukin-2 gene activation. Tacrolimus 41-46 interleukin 2 Homo sapiens 162-175 8974006-3 1996 NFAT acts at the antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is the nuclear target of T cell stimulation signals and the immunosuppressant drugs cyclosporine and FK506, which are potent inhibitors of IL-2 gene transcription. Tacrolimus 197-202 interleukin 2 Homo sapiens 78-82 8974006-3 1996 NFAT acts at the antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is the nuclear target of T cell stimulation signals and the immunosuppressant drugs cyclosporine and FK506, which are potent inhibitors of IL-2 gene transcription. Tacrolimus 197-202 interleukin 2 Homo sapiens 235-239 8669110-7 1996 Noninhibitory doses of CsA (8 nM) or FK506 (0.2 nM) suppressed mitogen-induced IL-2 production by 60-80% when combined with a noninhibitory dose (25 nM) of Ro 31-8220, indicating the potent synergy between these agents. Tacrolimus 37-42 interleukin 2 Homo sapiens 79-83 8906804-4 1996 Interference with the IL-2 pathway was achieved by 1) inhibition of cytokine synthesis using cyclosporin A or FK506, 2) neutralization of IL-2 by anti-IL-2 Ab, 3) inhibition of binding to IL-2R by CD25 mAb, and 4) blocking of IL-2R signaling by rapamycin. Tacrolimus 110-115 interleukin 2 Homo sapiens 22-26 7518678-1 1994 Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin, and calcineurin. Tacrolimus 0-10 interleukin 2 Homo sapiens 91-95 8717522-3 1996 The FKBP12.FK506 complex specifically binds to and inhibits calcineurin, a signaling protein required for transcriptional activation of the interleukin (IL)-2 gene in response to T cell antigen receptor engagement. Tacrolimus 11-16 interleukin 2 Homo sapiens 140-158 9346613-5 1995 FK506 (0.5 ng/ mL) reduced both the percentage of interleukin-2 receptor expressing T cells and the cell surface density of this receptor by 7.1% and 8.7% (P < .01), whereas it only reduced the proportion of HLA-DR expressing T cells by 6.8%. Tacrolimus 0-5 interleukin 2 Homo sapiens 50-63 8557519-2 1995 We demonstrate that CsA and FK506 inhibited IL-2R (CD25) gene transcription and protein expression after stimulation by anti-CD3 or ionomycin, but not by phorbol ester or IL-2. Tacrolimus 28-33 interleukin 2 Homo sapiens 44-48 8846199-6 1995 FK506 strongly suppressed the production of IL-2 (IC50 = 0.01 microM) and GM-CSF (IC50 = 0.03 microM), but was inactive (< 30% inhibition at 1 microM) against IL-5 and IFN-gamma. Tacrolimus 0-5 interleukin 2 Homo sapiens 44-48 7552894-2 1995 Tacrolimus prevents rejection of the transplanted organ by inhibiting the expression of interleukin-2 in T cells and inhibiting T-cell growth and proliferation. Tacrolimus 0-10 interleukin 2 Homo sapiens 88-101 8744655-2 1995 The present study examines the in vitro interactions of classical immunosuppressive agents--FK 506 and Cyclosporine A (CsA) with 2-CdA at the level of T and B cells proliferation, expression receptor for interleukin 2 (R-IL-2) and Ig synthesis. Tacrolimus 92-98 interleukin 2 Homo sapiens 204-217 7974924-2 1994 Several new drugs have been found to be effective immunosuppressive agents: FK 506, a macrolid antibiotic inhibiting lymphokine gene transcription, lymphokine production and secretion, rapamycin, which blocks effects of lymphokine-induced signal transduction, and RS 61443, brequinar and mizoribine, which inhibit DNA/RNA synthesis and lymphocyte proliferation. Tacrolimus 76-82 interleukin 2 Homo sapiens 117-127 7759865-7 1995 p40cdk6 also increased in amount in cells activated in the presence of cyclosporin A or FK506, drugs that inhibit production of IL-2 and cell proliferation, suggesting that initial induction occurred independently of IL-2-mediated cell cycle progression. Tacrolimus 88-93 interleukin 2 Homo sapiens 128-132 7759865-7 1995 p40cdk6 also increased in amount in cells activated in the presence of cyclosporin A or FK506, drugs that inhibit production of IL-2 and cell proliferation, suggesting that initial induction occurred independently of IL-2-mediated cell cycle progression. Tacrolimus 88-93 interleukin 2 Homo sapiens 217-221 7543780-5 1995 Simultaneous addition of Rap and CsA or Rap and FK506 inhibit the IL-2-mediated proliferation of TS1 beta and TS1 alpha beta cells and therefore FK506 does not revert the inhibition mediated by Rap in TS1 alpha beta cells. Tacrolimus 48-53 interleukin 2 Homo sapiens 66-70 7522636-7 1994 Cyclosporin A and FK506 act on two distinct levels of the IL-2 control mechanism. Tacrolimus 18-23 interleukin 2 Homo sapiens 58-62 7522130-2 1994 Although no change in cytoplasmic calcium level ([Ca2+]i) was detectable during antigen-specific signal transduction of 171-CD4+ cells, IL2 induction was inhibited by FK506 and CsA. Tacrolimus 167-172 interleukin 2 Homo sapiens 136-139 7522130-5 1994 We suggest that IL2 secretion induced by antigen presentation to TCR/CD4/p56lck requires an FK506 and cyclosporin A-sensitive step which may be independent of calcium signaling. Tacrolimus 92-97 interleukin 2 Homo sapiens 16-19 7923750-4 1994 Cyclosporine and related agents such as FK-506 and rapamycin selectively inhibit adaptive immune responses by blocking T cell-dependent biosynthesis of lymphokines, particularly interleukin 2 at the level of messenger ribonucleic acid (mRNA) transcription. Tacrolimus 40-46 interleukin 2 Homo sapiens 178-191 7518678-1 1994 Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 kDa or FKBP12), Ca2+, calmodulin, and calcineurin. Tacrolimus 11-16 interleukin 2 Homo sapiens 91-95 11271304-5 1994 Thus, although FK 506 and cyclosporin inhibited calcium-dependent signalling to the IL-2 promoter via inhibition of the protein phosphatase calcineurin, it is possible that IL-2 induction via TCR/CD4 requires an FK 506 (and cyclosporin) sensitive step which is independent of cytoplasmic calcium changes. Tacrolimus 15-21 interleukin 2 Homo sapiens 84-88 7517981-5 1994 In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Tacrolimus 38-44 interleukin 2 Homo sapiens 82-86 7517981-5 1994 In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Tacrolimus 38-44 interleukin 2 Homo sapiens 82-86 7517981-5 1994 In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Tacrolimus 38-44 interleukin 2 Homo sapiens 82-86 7517981-5 1994 In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Tacrolimus 38-44 interleukin 2 Homo sapiens 82-86 7517981-7 1994 Conversely, FK-506 acts as a strong inhibitor of IL-2 production without a prominent effect on IL-2 responsiveness. Tacrolimus 12-18 interleukin 2 Homo sapiens 49-53 7507994-1 1994 The structurally related immunosuppressive macrolides FK-506 and rapamycin (RAP) exert distinct biological effects: inhibition of interleukin-2 production and inhibition of interleukin-2-induced proliferation, respectively, through binding to intracellular receptors, termed FKBPs. Tacrolimus 54-60 interleukin 2 Homo sapiens 130-143 7507994-1 1994 The structurally related immunosuppressive macrolides FK-506 and rapamycin (RAP) exert distinct biological effects: inhibition of interleukin-2 production and inhibition of interleukin-2-induced proliferation, respectively, through binding to intracellular receptors, termed FKBPs. Tacrolimus 54-60 interleukin 2 Homo sapiens 173-186 8186461-2 1994 The expression of GM-CSF and IL-2 is inhibited by immunosuppressive drugs such as cyclosporin A (CsA) and FK506. Tacrolimus 106-111 interleukin 2 Homo sapiens 29-33 8302298-11 1994 The immunosuppressive drugs Cyclosporin A and FK506 completely blocked CD28 and CD3 mediated IL-2 production in these transfectants whereas rapamycin had only a partial inhibitory effect. Tacrolimus 46-51 interleukin 2 Homo sapiens 93-97 7529381-0 1994 In-vitro effects of cyclosporin A, FK506, 6-mercaptopurine, and prednisolone on lymphokine-activated killer cells. Tacrolimus 35-40 interleukin 2 Homo sapiens 80-90 8112299-3 1994 Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, is the FK-506- and CsA-sensitive enzyme required for TcR mediated activation of the IL-2 promoter. Tacrolimus 69-75 interleukin 2 Homo sapiens 146-150 11271304-3 1994 Using 171, 171-CD4 (wild-type) and 171-CD4 (mutant), we found that IL-2 secretion was inhibited by FK 506 and cyclosporin but not by rapamycin. Tacrolimus 99-105 interleukin 2 Homo sapiens 67-71 7689811-0 1993 FK-506 inhibits the IL-2-independent induction of the activation antigen CD 69. Tacrolimus 0-6 interleukin 2 Homo sapiens 20-24 7507316-4 1993 In contrast, rapamycin, a structural analogue of FK 506, interferes with the immune response at a different level, by blocking the response induced by cytokines such as IL-2. Tacrolimus 49-55 interleukin 2 Homo sapiens 169-173 8397339-2 1993 NFAT, a DNA-binding protein required for interleukin-2 gene transcription, is a potential target for calcineurin, cyclosporin A and FK506. Tacrolimus 132-137 interleukin 2 Homo sapiens 41-54 1371623-0 1992 Blockade of interleukin-2 production from cloned T cells by cyclosporine and FK 506 assessed by proliferation assays in vitro. Tacrolimus 77-83 interleukin 2 Homo sapiens 12-25 1374947-0 1992 FK506 as an agonist to induce inhibition of interleukin 2 production. Tacrolimus 0-5 interleukin 2 Homo sapiens 44-57 1380242-3 1992 Cyclosporin A (CsA) and FK506 inhibit the production of IL-2 in T lymphocytes at the level of gene transcription. Tacrolimus 24-29 interleukin 2 Homo sapiens 56-60 1380242-6 1992 However, CsA and FK506 inhibit the appearance of DNA binding activity of factors that bind to the NF-AT and AP-1 sites in the IL-2 enhancer. Tacrolimus 17-22 interleukin 2 Homo sapiens 126-130 1380242-7 1992 Since the induction of NF-AT and AP-1 is induced by the same stimuli that stimulate IL-2 production, these results indicate that the immunosuppressant action of CsA and FK506 is exerted at the level of these trans-activating factors. Tacrolimus 169-174 interleukin 2 Homo sapiens 84-88 1378764-0 1992 Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen-induced primary T lymphocytes. Tacrolimus 18-23 interleukin 2 Homo sapiens 56-60 1378764-3 1992 Cyclosporin A (CsA) and FK506 interfere with normal derepression of the IL-2 gene. Tacrolimus 24-29 interleukin 2 Homo sapiens 72-76 7683641-6 1993 Direct binding studies with [3H]dihydro-FK506 suggest that the ratio of FKBP12-FK506 complex to calcineurin in vivo when IL2 production is inhibited is well correlated with the ratio when calcineurin phosphatase activity is inhibited in vitro. Tacrolimus 40-45 interleukin 2 Homo sapiens 121-124 1281674-0 1992 FK506 and rapamycin selectively enhance degradation of IL-2 and GM-CSF mRNA. Tacrolimus 0-5 interleukin 2 Homo sapiens 55-59 1281674-2 1992 Using Northern analyses and promoter-reporter constructs we analyzed the transcriptional and posttranscriptional effects of FK506 and rapamycin on IL-2, GM-CSF, and IL-2R alpha gene expression. Tacrolimus 124-129 interleukin 2 Homo sapiens 147-151 1281674-3 1992 FK506 completely inhibited activation of the IL-2 promoter, but only partially blocked GM-CSF promoter activity. Tacrolimus 0-5 interleukin 2 Homo sapiens 45-49 1355105-6 1992 Growth of the cells required activation because cyclosporin A and FK506 blocked stimulator cell-induced IL-2 production and proliferation as well as the spontaneous growth of the lines. Tacrolimus 66-71 interleukin 2 Homo sapiens 104-108 1380951-3 1992 While 1 microgram/ml CSA and 0.1 microgram/ml FK 506 completely suppressed PHA-stimulated accumulation of mRNA for IL2, IL4, IL9, GM-CSF, TNF-alpha and IFN-gamma in PBMC, flu, keto and TGF-beta failed to inhibit any (except TNF-alpha blocked by TGF-beta). Tacrolimus 46-52 interleukin 2 Homo sapiens 115-118 1377361-0 1992 FK-506- and CsA-sensitive activation of the interleukin-2 promoter by calcineurin. Tacrolimus 0-6 interleukin 2 Homo sapiens 44-57 1377361-2 1992 The immunosuppressive drugs, cyclosporin A (CsA) and FK-506, prevent T-cell proliferation by inhibiting a Ca(2+)-dependent event required for induction of interleukin-2 transcription. Tacrolimus 53-59 interleukin 2 Homo sapiens 155-168 1377361-6 1992 Here we report that transfection of a calcineurin catalytic subunit increases the 50% inhibitory concentration (IC50) of the immunosuppressants FK-506 and CsA, and that a mutant subunit acts in synergy with phorbol ester alone to activate the interleukin-2 promoter in a drug-sensitive manner. Tacrolimus 144-150 interleukin 2 Homo sapiens 243-256 1373887-5 1992 Both CsA and FK 506 specifically inhibit cellular calcineurin at drug concentrations that inhibit interleukin 2 production in activated T cells. Tacrolimus 13-19 interleukin 2 Homo sapiens 98-111 1371624-0 1992 Enhanced liver regeneration by FK 506 can be blocked by interleukin-1 alpha and interleukin-2. Tacrolimus 31-37 interleukin 2 Homo sapiens 80-93 1371491-10 1992 Further stimulation by addition of anti-CD28 mAb to the cultures resulted in an augmented IL-2 and IFN-gamma production which was resistant to both FK506 and CsA. Tacrolimus 148-153 interleukin 2 Homo sapiens 90-94 1371491-8 1992 When the cells were stimulated by phorbol ester (phorbol 12-myristate 13-acetate, PMA) plus calcium ionophore (ionomycin), FK506 and CsA inhibited, in a dose-dependent manner, the production of IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha. Tacrolimus 123-128 interleukin 2 Homo sapiens 194-198 1384862-0 1992 The effects of FK-506 and cyclosporin A on the proliferation of PHA-stimulated T cells in response to IL-2, IL-4 or IL-6. Tacrolimus 15-21 interleukin 2 Homo sapiens 102-106 1721767-4 1991 Although full recovery was not observed in FK506, this finding indicated that FK506 as well as CsA inhibit IL2 secretion from HTL403. Tacrolimus 78-83 interleukin 2 Homo sapiens 107-110 1715185-0 1991 Cyclosporin A and FK-506 both affect DNA binding of regulatory nuclear proteins to the human interleukin-2 promoter. Tacrolimus 18-24 interleukin 2 Homo sapiens 93-106 1720417-0 1991 The immunosuppressive agent FK506 inhibits in vitro expression of membrane-bound and soluble interleukin-2 receptors on resting but not on activated human lymphocytes. Tacrolimus 28-33 interleukin 2 Homo sapiens 93-106 1712901-0 1991 The immunosuppressant FK-506 specifically inhibits mitogen-induced activation of the interleukin-2 promoter and the isolated enhancer elements NFIL-2A and NF-AT1. Tacrolimus 22-28 interleukin 2 Homo sapiens 85-98 1712901-1 1991 The macrolide FK-506, like the cyclic undecapeptide cyclosporin A (CsA), is a potent immunosuppressant that interferes with the transcriptional activation of several early-phase genes in T lymphocytes, including that for interleukin-2 (IL-2). Tacrolimus 14-20 interleukin 2 Homo sapiens 221-234 1712901-1 1991 The macrolide FK-506, like the cyclic undecapeptide cyclosporin A (CsA), is a potent immunosuppressant that interferes with the transcriptional activation of several early-phase genes in T lymphocytes, including that for interleukin-2 (IL-2). Tacrolimus 14-20 interleukin 2 Homo sapiens 236-240 1712901-2 1991 We compared the effects of FK-506 and CsA on transcription from the 5" upstream activating sequences (UAS) of the human IL-2 gene and several cellular and viral UAS to define cis-acting sites which may be responsive to FK-506. Tacrolimus 27-33 interleukin 2 Homo sapiens 120-124 1712901-7 1991 The induced transcription driven by the IL-2 promoter elements NF-AT1 and NFIL-2A could be blocked completely by FK-506 or CsA. Tacrolimus 113-119 interleukin 2 Homo sapiens 40-44 1715317-0 1991 Comparison of the effects of FK-506, cyclosporin A and rapamycin on IL-2 production. Tacrolimus 29-35 interleukin 2 Homo sapiens 68-72 1717376-1 1991 Cyclosporin (CsA) and FK-506 are structurally distinct fungal metabolites, which exert powerful inhibitory effects on CD4+ T (helper) cell activation and on the secretion of interleukin-2 (IL-2) and other cytokines, including various cell growth factors and interferon-gamma. Tacrolimus 22-28 interleukin 2 Homo sapiens 174-187 1717376-1 1991 Cyclosporin (CsA) and FK-506 are structurally distinct fungal metabolites, which exert powerful inhibitory effects on CD4+ T (helper) cell activation and on the secretion of interleukin-2 (IL-2) and other cytokines, including various cell growth factors and interferon-gamma. Tacrolimus 22-28 interleukin 2 Homo sapiens 189-193 1717376-8 1991 Compared with CsA, the inhibitory action of FK-506 appears more difficult to reverse, e.g., in response to pre-formed IL-2. Tacrolimus 44-50 interleukin 2 Homo sapiens 118-122 1707760-3 1991 Using measurements of the proliferative response, IL-2 production, and changes in intracellular Ca2+ ([Ca2+]i), we demonstrate that FK-506 exerts its inhibitory effect on early events of T-cell activation in a manner indistinguishable from that of CsA. Tacrolimus 132-138 interleukin 2 Homo sapiens 50-54 1726895-3 1991 FK506 is a new immunosuppressant known to inhibit synthesis of interleukin 2 and expression of the membrane bound alpha chain. Tacrolimus 0-5 interleukin 2 Homo sapiens 63-76 1713361-4 1991 FK506 and CsA showed pharmacologic antagonism in inhibiting in vitro proliferation upon phytohemagglutinin, anti-CD3 antibody, and mixed lymphocyte reaction (MLR) stimulation, and interleukin 2 generation by activated normal human peripheral blood lymphocytes. Tacrolimus 0-5 interleukin 2 Homo sapiens 180-193 1715185-1 1991 The structurally unrelated immunosuppressive drugs cyclosporin A (Sandimmun) and FK-506 both interfere with the process of T-cell proliferation by blocking the transcription of the T-cell growth factor interleukin-2 (IL-2). Tacrolimus 81-87 interleukin 2 Homo sapiens 202-215 1715185-1 1991 The structurally unrelated immunosuppressive drugs cyclosporin A (Sandimmun) and FK-506 both interfere with the process of T-cell proliferation by blocking the transcription of the T-cell growth factor interleukin-2 (IL-2). Tacrolimus 81-87 interleukin 2 Homo sapiens 217-221 1715185-3 1991 We present evidence that the binding by regulatory nuclear proteins to the kappa B element of the IL-2 promoter is affected negatively by cyclosporin A and FK-506 at concentrations paralleling their immunosuppressive activity in vivo. Tacrolimus 156-162 interleukin 2 Homo sapiens 98-102 1715185-5 1991 FK-506 is 10 to 100 times more potent than cyclosporin A in its ability to inhibit sequence-specific DNA binding and IL-2 production. Tacrolimus 0-6 interleukin 2 Homo sapiens 117-121 2123553-5 1990 However, an excess of rapamycin is needed to revert FK506-mediated inhibition of IL-2 production, apoptosis, and transcriptional activation of NF-AT, a T-cell-specific transcription factor necessary for IL-2 gene activation. Tacrolimus 52-57 interleukin 2 Homo sapiens 81-85 1707162-0 1991 The immunosuppressives FK 506 and cyclosporin A inhibit the generation of protein factors binding to the two purine boxes of the interleukin 2 enhancer. Tacrolimus 23-29 interleukin 2 Homo sapiens 129-142 1707162-1 1991 Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. Tacrolimus 40-46 interleukin 2 Homo sapiens 152-165 1707162-1 1991 Like Cyclosporin A (CsA), the macrolide FK 506 is a potent immunosuppressive that inhibits early steps of T cell activation, including the synthesis of Interleukin 2 (II-2) and numerous other lymphokines. Tacrolimus 40-46 interleukin 2 Homo sapiens 167-171 1707162-3 1991 At concentrations that block T cell activation, FK 506 and CsA inhibit the proto-enhancer activity of Purine boxes of the II-2 promoter and the generation of lymphocyte-specific factors binding to the Purine boxes. Tacrolimus 48-54 interleukin 2 Homo sapiens 122-126 1701825-5 1990 Therefore, CSA and FK506, while chemically different, seem to act upon a similar pathway that leads to IL-2 gene expression, whereas glucocorticoids do not affect this pathway. Tacrolimus 19-24 interleukin 2 Homo sapiens 103-107 1701570-1 1990 The fungal metabolite FK506 was discovered because it shared an important property, the ability to inhibit production of IL-2, with another well-known immunosuppressive fungal metabolite, CsA. Tacrolimus 22-27 interleukin 2 Homo sapiens 121-125 2123553-2 1990 On the other hand, interleukin 2 (IL-2)-induced signals are blocked by rapamycin but not by FK506. Tacrolimus 92-97 interleukin 2 Homo sapiens 34-38 2123553-5 1990 However, an excess of rapamycin is needed to revert FK506-mediated inhibition of IL-2 production, apoptosis, and transcriptional activation of NF-AT, a T-cell-specific transcription factor necessary for IL-2 gene activation. Tacrolimus 52-57 interleukin 2 Homo sapiens 203-207 2123553-6 1990 Similarly, an excess of FK506 is needed to revert rapamycin-mediated inhibition of IL-2-induced proliferation. Tacrolimus 24-29 interleukin 2 Homo sapiens 83-87