Title : PGE2 induces interleukin-8 derepression in human astrocytoma through coordinated DNA demethylation and histone hyperacetylation.

Pub. Date : 2012 Nov

PMID : 23051921






11 Functional Relationships(s)
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1 PGE2 induces interleukin-8 derepression in human astrocytoma through coordinated DNA demethylation and histone hyperacetylation. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
2 We have recently reported that in astrocytoma cells the expression of interleukin-8 (IL-8) is upregulated by prostaglandin E2 (PGE2). Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
3 We have recently reported that in astrocytoma cells the expression of interleukin-8 (IL-8) is upregulated by prostaglandin E2 (PGE2). Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
4 We have recently reported that in astrocytoma cells the expression of interleukin-8 (IL-8) is upregulated by prostaglandin E2 (PGE2). Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
5 We have recently reported that in astrocytoma cells the expression of interleukin-8 (IL-8) is upregulated by prostaglandin E2 (PGE2). Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
6 Here, we have investigated whether IL-8 activation by PGE2 involves changes in DNA methylation and/or histone modifications in 46 astrocytoma specimens, two astrocytoma cell lines and normal astrocytic cells. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
7 IL-8 expression at promoter, mRNA and protein level was explored by transfection, real-time PCR and enzyme immunoassay experiments in cells untreated or treated with PGE2, 5-aza-2"-deoxycytidine (5-aza-dC) and HDAC inhibitors, alone or in combination. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
8 We observed that PGE2 induced IL-8 activation through: (1) demethylation of the single CpG site 5 located at position -83 within the binding region for CEBP-beta in the IL-8 promoter; (2) C/EBP-beta and p300 co-activator recruitment; (3) H3 acetylation enhancement and (4) reduction in DNMT1, DNMT3a, HDAC2 and HDAC3 association to CpG site 5 region. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
9 We observed that PGE2 induced IL-8 activation through: (1) demethylation of the single CpG site 5 located at position -83 within the binding region for CEBP-beta in the IL-8 promoter; (2) C/EBP-beta and p300 co-activator recruitment; (3) H3 acetylation enhancement and (4) reduction in DNMT1, DNMT3a, HDAC2 and HDAC3 association to CpG site 5 region. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
10 Treatment with 5-aza-dC or HDAC inhibitors of class I HDACs strengthened either basal or PGE2-mediated IL-8 expression. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
11 These findings have elucidated an orchestrated mechanism triggered by PGE2 whereby concurrent association of site-specific demethylation and histone H3 hyperacetylation resulted in derepression of IL-8 gene expression in human astrocytoma. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens