PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 24756886-7 2014 RESULTS: (1) Morphine induces robust BV-2 cell activation, as evidenced by increased p38 mitogen-activated protein kinase phosphorylation, nuclear factor-kappaB translocation and mRNA expression of pro-inflammatory cytokines [including interleukin-1beta (IL-1beta), IL-6 and tumour necrosis factor-alpha], inducible nitric oxide synthase and Toll-like receptor-4, and these changes are inhibited by resveratrol. Morphine 13-21 toll-like receptor 4 Mus musculus 342-362 23960234-7 2013 Morphine pretreatment prevented TLR4-dependent ERK and IKK phosphorylation. Morphine 0-8 toll-like receptor 4 Mus musculus 32-36 24824631-0 2014 Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence. Morphine 49-57 toll-like receptor 4 Mus musculus 0-20 24824631-2 2014 Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. Morphine 65-73 toll-like receptor 4 Mus musculus 38-42 23960234-11 2013 In conclusion, our results show that activation of mu and delta opioid receptors with morphine suppresses TLR4-induced TNF release in mast cells, preventing the IKK-dependent phosphorylation of SNAP-23, which is necessary for TNF exocytosis, and this inhibition correlates with the formation of a beta-arrestin-2/TRAF6 complex. Morphine 86-94 toll-like receptor 4 Mus musculus 106-110 22926420-2 2013 It has been suggested that morphine activates microglia through its action on the toll-like receptor 4 (TLR4) in the spinal cord, leading to suppression of the morphine effect. Morphine 27-35 toll-like receptor 4 Mus musculus 82-102 22926420-2 2013 It has been suggested that morphine activates microglia through its action on the toll-like receptor 4 (TLR4) in the spinal cord, leading to suppression of the morphine effect. Morphine 27-35 toll-like receptor 4 Mus musculus 104-108 22926420-2 2013 It has been suggested that morphine activates microglia through its action on the toll-like receptor 4 (TLR4) in the spinal cord, leading to suppression of the morphine effect. Morphine 160-168 toll-like receptor 4 Mus musculus 82-102 22926420-2 2013 It has been suggested that morphine activates microglia through its action on the toll-like receptor 4 (TLR4) in the spinal cord, leading to suppression of the morphine effect. Morphine 160-168 toll-like receptor 4 Mus musculus 104-108 22926420-9 2013 CD11b mRNA expression was increased after morphine treatment both in TLR4-knockout and wild-type mice. Morphine 42-50 toll-like receptor 4 Mus musculus 69-73 25542736-1 2015 Increasing evidence demonstrates induction of proinflammatory Toll-like receptor (TLR) 2 and TLR4 signaling by morphine and, TLR4 signaling by alcohol; thus indicating a common site of drug action and a potential novel innate immune-dependent hypothesis for opioid and alcohol drug interactions. Morphine 111-119 toll-like receptor 4 Mus musculus 93-97 22240038-6 2012 Morphine, when added to RAW 264.7 cells and when injected into mice (s.c. 20mg/kg) is in fact able to decrease TLR4 both at mRNA and protein level in RAW cells and peritoneal macrophages. Morphine 0-8 toll-like receptor 4 Mus musculus 111-115 22240038-9 2012 Experiments with MOR KO mice and with DAMGO (MOR specific agonist) confirm that the effect of morphine on TLR4 mRNA in peritoneal macrophages is due to the MOR activation. Morphine 94-102 toll-like receptor 4 Mus musculus 106-110 20381591-11 2010 While tricyclics had no effect on basal pain responsivity, they potentiated morphine analgesia in rank-order with their potency as TLR4 inhibitors. Morphine 76-84 toll-like receptor 4 Mus musculus 131-135 19679181-4 2010 Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Morphine 0-8 toll-like receptor 4 Mus musculus 39-43 19679181-4 2010 Morphine non-stereoselectively induced TLR4 signaling in vitro, blocked by a classical TLR4 antagonist and non-stereoselectively by naloxone. Morphine 0-8 toll-like receptor 4 Mus musculus 87-91 19679181-5 2010 Pharmacological blockade of TLR4 signaling in vivo potentiated acute intrathecal morphine analgesia, attenuated development of analgesic tolerance, hyperalgesia, and opioid withdrawal behaviors. Morphine 81-89 toll-like receptor 4 Mus musculus 28-32 19679181-6 2010 TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. Morphine 51-59 toll-like receptor 4 Mus musculus 0-4 19679181-6 2010 TLR4 opposition to opioid actions was supported by morphine treatment of TLR4 knockout mice, which revealed a significant threefold leftward shift in the analgesia dose response function, versus wildtype mice. Morphine 51-59 toll-like receptor 4 Mus musculus 73-77 19679181-8 2010 Selectivity in the response was identified since morphine-3-glucuronide, a morphine metabolite with no opioid receptor activity, displayed significant TLR4 activity, whilst the opioid receptor active metabolite, morphine-6-glucuronide, was devoid of such properties. Morphine 49-57 toll-like receptor 4 Mus musculus 151-155 19744765-9 2009 RESULTS: Although LPS induced premature labor and decreased the delivery time to gestational day 16, morphine treatment significantly decreased the incidence of LPS-induced premature labor by 50% and increased the delivery time to gestational day 17.6. Morphine 101-109 toll-like receptor 4 Mus musculus 161-164 19744765-13 2009 CONCLUSION: Morphine increases the gestational duration and decreases the preterm delivery rate induced by LPS probably through modulation in NO release. Morphine 12-20 toll-like receptor 4 Mus musculus 107-110 34557761-4 2021 Considering the psychoactive substances morphine, cocaine, and methamphetamine act as xenobiotic-associated molecular patterns and can be specifically sensed by the innate immune receptor Toll-like receptor 4 (TLR4), here we sought to delineate whether nicotine and/or its metabolite cotinine may be recognized by the innate immune system via myeloid differentiation protein 2 (MD2), an accessory protein of TLR4 that is responsible for ligand recognition. Morphine 40-48 toll-like receptor 4 Mus musculus 188-208 34557761-4 2021 Considering the psychoactive substances morphine, cocaine, and methamphetamine act as xenobiotic-associated molecular patterns and can be specifically sensed by the innate immune receptor Toll-like receptor 4 (TLR4), here we sought to delineate whether nicotine and/or its metabolite cotinine may be recognized by the innate immune system via myeloid differentiation protein 2 (MD2), an accessory protein of TLR4 that is responsible for ligand recognition. Morphine 40-48 toll-like receptor 4 Mus musculus 210-214 34557761-4 2021 Considering the psychoactive substances morphine, cocaine, and methamphetamine act as xenobiotic-associated molecular patterns and can be specifically sensed by the innate immune receptor Toll-like receptor 4 (TLR4), here we sought to delineate whether nicotine and/or its metabolite cotinine may be recognized by the innate immune system via myeloid differentiation protein 2 (MD2), an accessory protein of TLR4 that is responsible for ligand recognition. Morphine 40-48 toll-like receptor 4 Mus musculus 408-412 33549727-0 2021 Microglial TLR4-induced TAK1 phosphorylation and NLRP3 activation mediates neuroinflammation and contributes to chronic morphine-induced antinociceptive tolerance. Morphine 120-128 toll-like receptor 4 Mus musculus 11-15 35121060-3 2022 Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. Morphine 0-8 toll-like receptor 4 Mus musculus 27-47 35121060-3 2022 Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. Morphine 0-8 toll-like receptor 4 Mus musculus 49-53 35121060-5 2022 We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Morphine 31-39 toll-like receptor 4 Mus musculus 94-98 35121060-13 2022 CONCLUSION: Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4. Morphine 12-20 toll-like receptor 4 Mus musculus 98-102 33549727-5 2021 RESULTS: Repeated treatment with morphine increased total expression of spinal TLR4, TAK1, and NLRP3 and phosphorylation of TAK1 in wild-type mice. Morphine 33-41 toll-like receptor 4 Mus musculus 79-83 33549727-1 2021 BACKGROUND AND PURPOSE: The aim of this work was to investigate the role and signal transduction of toll-like receptor 4 (TLR4), TGF-beta-activated kinase 1 (TAK1) and nod-like receptor protein 3 (NLRP3) in microglial in the development of morphine-induced antinociceptive tolerance. Morphine 240-248 toll-like receptor 4 Mus musculus 100-120 33549727-6 2021 TLR4 knockout attenuated morphine-induced tolerance and inhibited the chronic morphine-induced increase in NLRP3 and phosphorylation of TAK1. Morphine 25-33 toll-like receptor 4 Mus musculus 0-4 33549727-6 2021 TLR4 knockout attenuated morphine-induced tolerance and inhibited the chronic morphine-induced increase in NLRP3 and phosphorylation of TAK1. Morphine 78-86 toll-like receptor 4 Mus musculus 0-4 33061523-0 2020 Spinal TLR4/P2X7 Receptor-Dependent NLRP3 Inflammasome Activation Contributes to the Development of Tolerance to Morphine-Induced Antinociception. Morphine 113-121 toll-like receptor 4 Mus musculus 7-11 33549727-10 2021 CONCLUSIONS: Microglial TLR4 regulates TAK1 expression and phosphorylation and results in NLRP3 activation contributes to the development of morphine tolerance through regulating neuroinflammation. Morphine 141-149 toll-like receptor 4 Mus musculus 24-28 33549727-11 2021 Targeting TLR4-TAK1-NLRP3 signaling to regulate neuro-inflammation will be alternative therapeutics and strategies for chronic morphine-induced antinociceptive tolerance. Morphine 127-135 toll-like receptor 4 Mus musculus 10-14 33061523-14 2020 Knockout of TLR4 alleviated morphine tolerance and chronic morphine-induced upregulation of spinal NLRP3. Morphine 28-36 toll-like receptor 4 Mus musculus 12-16 33061523-14 2020 Knockout of TLR4 alleviated morphine tolerance and chronic morphine-induced upregulation of spinal NLRP3. Morphine 59-67 toll-like receptor 4 Mus musculus 12-16 33061523-17 2020 Conclusion: This study demonstrates that the NLRP3 inflammasome in microglia plays a crucial role in morphine tolerance and that both TLR4- and P2X7R-dependent pathways are required for NLRP3 inflammasome activation over the course of the development of morphine-induced tolerance. Morphine 254-262 toll-like receptor 4 Mus musculus 134-138 30044299-11 2019 Furthermore, spinal cord toll-like receptor-4 levels 3 weeks after fracture were higher in fracture mice given morphine than those given oliceridine. Morphine 111-119 toll-like receptor 4 Mus musculus 25-45 31921165-5 2019 Beginning with a paper published in 2005, evidence was presented that morphine is immune-stimulating via binding to MD2, a molecule associated with Toll-like Receptor 4 (TLR4), the receptor for bacterial lipopolysaccharide (LPS). Morphine 70-78 toll-like receptor 4 Mus musculus 148-168 31921165-5 2019 Beginning with a paper published in 2005, evidence was presented that morphine is immune-stimulating via binding to MD2, a molecule associated with Toll-like Receptor 4 (TLR4), the receptor for bacterial lipopolysaccharide (LPS). Morphine 70-78 toll-like receptor 4 Mus musculus 170-174 31921165-9 2019 Since engagement of TLR4 is universally accepted to result in immune activation by up-regulation of NF-kappaB, if morphine were binding to TLR4, it would be predicted that opioids would have been found to be pro-inflammatory, which they were not. Morphine 114-122 toll-like receptor 4 Mus musculus 20-24 31921165-9 2019 Since engagement of TLR4 is universally accepted to result in immune activation by up-regulation of NF-kappaB, if morphine were binding to TLR4, it would be predicted that opioids would have been found to be pro-inflammatory, which they were not. Morphine 114-122 toll-like receptor 4 Mus musculus 139-143 31921165-10 2019 Further, morphine is immunosuppressive in mice with a defective TLR4 receptor. Morphine 9-17 toll-like receptor 4 Mus musculus 64-68 31921165-13 2019 It is proposed that an occult variable in experiments where morphine is being proposed to activate TLR4 is actually underlying sepsis induced by the opioid. Morphine 60-68 toll-like receptor 4 Mus musculus 99-103 30418215-10 2019 Treatment with a Toll-like receptor 4 antagonist TAK242 improved nociceptive sensitization for about 2 weeks in morphine-treated fracture mice (F(1, 198) = 73.36, P < 0.001, fracture + morphine + TAK242 vs. fracture + morphine, n = 10 per group). Morphine 112-120 toll-like receptor 4 Mus musculus 17-37 31057724-8 2019 The expression of TLR4 gene only was reduced in groups under treatment with morphine and morphine plus nalmefene relative to the control group and in the other groups increased. Morphine 76-84 toll-like receptor 4 Mus musculus 18-22 31057724-8 2019 The expression of TLR4 gene only was reduced in groups under treatment with morphine and morphine plus nalmefene relative to the control group and in the other groups increased. Morphine 89-97 toll-like receptor 4 Mus musculus 18-22 31057724-10 2019 Conclusion: However, in this study it was found that despite decreasing the size of lesion in all treated groups, expression of TLR4 in the morphine, nalmefene, morphine plus nalmefene treated groups compared to the control group was decreased. Morphine 140-148 toll-like receptor 4 Mus musculus 128-132 31057724-10 2019 Conclusion: However, in this study it was found that despite decreasing the size of lesion in all treated groups, expression of TLR4 in the morphine, nalmefene, morphine plus nalmefene treated groups compared to the control group was decreased. Morphine 161-169 toll-like receptor 4 Mus musculus 128-132 31289487-8 2019 Morphine, an additional ligand for TLR4, aggravated the NETs induced by lung cancer cells. Morphine 0-8 toll-like receptor 4 Mus musculus 35-39 30418215-10 2019 Treatment with a Toll-like receptor 4 antagonist TAK242 improved nociceptive sensitization for about 2 weeks in morphine-treated fracture mice (F(1, 198) = 73.36, P < 0.001, fracture + morphine + TAK242 vs. fracture + morphine, n = 10 per group). Morphine 185-193 toll-like receptor 4 Mus musculus 17-37 30418215-10 2019 Treatment with a Toll-like receptor 4 antagonist TAK242 improved nociceptive sensitization for about 2 weeks in morphine-treated fracture mice (F(1, 198) = 73.36, P < 0.001, fracture + morphine + TAK242 vs. fracture + morphine, n = 10 per group). Morphine 185-193 toll-like receptor 4 Mus musculus 17-37 29096659-1 2017 BACKGROUND: Morphine tolerance is a clinical challenge, and its pathogenesis is closely related to the neuroinflammation mediated by Toll-like receptor 4 (TLR4). Morphine 12-20 toll-like receptor 4 Mus musculus 133-153 30662412-2 2018 Both mu opioid receptor (MOR) encoded by Oprm1/OPRM1 gene and toll like receptor 4 (TLR4) have been reported to mediate these morphine effects and a current question is whether microglia express the Oprm1 transcript and MOR protein. Morphine 126-134 toll-like receptor 4 Mus musculus 62-82 30662412-2 2018 Both mu opioid receptor (MOR) encoded by Oprm1/OPRM1 gene and toll like receptor 4 (TLR4) have been reported to mediate these morphine effects and a current question is whether microglia express the Oprm1 transcript and MOR protein. Morphine 126-134 toll-like receptor 4 Mus musculus 84-88 29178967-0 2017 Blocking ATP-sensitive potassium channel alleviates morphine tolerance by inhibiting HSP70-TLR4-NLRP3-mediated neuroinflammation. Morphine 52-60 toll-like receptor 4 Mus musculus 91-95 29178967-2 2017 Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. Morphine 19-27 toll-like receptor 4 Mus musculus 65-85 29178967-2 2017 Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. Morphine 19-27 toll-like receptor 4 Mus musculus 87-91 29178967-2 2017 Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. Morphine 162-170 toll-like receptor 4 Mus musculus 65-85 29178967-2 2017 Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. Morphine 162-170 toll-like receptor 4 Mus musculus 87-91 29178967-3 2017 In our study, we investigated whether other existing alternative pathways caused morphine-induced activation of TLR4 in microglia. Morphine 81-89 toll-like receptor 4 Mus musculus 112-116 29178967-17 2017 CONCLUSIONS: Our study indicated that morphine-induced extracellular HSP70 was an alternative way for the activation of TLR4-NLRP3 in analgesic tolerance. Morphine 38-46 toll-like receptor 4 Mus musculus 120-124 29096659-1 2017 BACKGROUND: Morphine tolerance is a clinical challenge, and its pathogenesis is closely related to the neuroinflammation mediated by Toll-like receptor 4 (TLR4). Morphine 12-20 toll-like receptor 4 Mus musculus 155-159 27939249-8 2017 Interestingly, this protocol of morphine administration also led to TLR4-independent NF-kappaB activation, at time points where M3G was not detected, presumably via elevation of circulating cytokines including, but not limited to, TNFalpha. Morphine 32-40 toll-like receptor 4 Mus musculus 68-72 27855689-11 2016 RESULTS: We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin. Morphine 23-31 toll-like receptor 4 Mus musculus 181-201 27855689-11 2016 RESULTS: We found that morphine-activated BV-2 cells, including the upregulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, pro-inflammatory cytokines, and Toll-like receptor-4 (TLR-4) mRNA expression, which was inhibited by metformin. Morphine 23-31 toll-like receptor 4 Mus musculus 203-208 25962524-0 2015 Toll-like receptor 4 contributes to the inhibitory effect of morphine on colonic motility in vitro and in vivo. Morphine 61-69 toll-like receptor 4 Mus musculus 0-20 25400125-11 2015 (3) Co-administration of paeoniflorin suppresses morphine-increased expression of toll-like receptor-4 both in BV-2 cells and within the spinal cord following chronic morphine treatment. Morphine 49-57 toll-like receptor 4 Mus musculus 82-102 25400125-11 2015 (3) Co-administration of paeoniflorin suppresses morphine-increased expression of toll-like receptor-4 both in BV-2 cells and within the spinal cord following chronic morphine treatment. Morphine 167-175 toll-like receptor 4 Mus musculus 82-102 25962524-7 2015 This is the first report that morphine-induced inhibition of colonic peristalsis is alleviated by TLR4 antagonism. Morphine 30-38 toll-like receptor 4 Mus musculus 98-102 25386959-3 2014 Prolonged morphine exposure exacerbates pain by activating the innate immune toll-like receptor-4 (TLR4) in the central nervous system. Morphine 10-18 toll-like receptor 4 Mus musculus 77-97 25386959-3 2014 Prolonged morphine exposure exacerbates pain by activating the innate immune toll-like receptor-4 (TLR4) in the central nervous system. Morphine 10-18 toll-like receptor 4 Mus musculus 99-103