The p38 Mitogen-activated Kinase Pathway Regulates the Human Interleukin-10 Promoter via the Activation of Sp1 Transcription Factor in Lipopolysaccharide-stimulated Human Macrophages

摘要: Interleukin-10 (IL-10), a pleiotropic cytokine that inhibits inflammatory and cell-mediated immune responses, is produced by wide variety of cell types including T B cells monocytes/macrophages. Regulation pro- anti-inflammatory cytokines has been suggested to involve distinct signaling pathways. In this study, we investigated the regulation human IL-10 (hIL-10) promoter in monocytic line THP-1 following activation with lipopolysaccharide (LPS). Analysis hIL-10 sequences revealed DNA located between base pairs −652 −571 are necessary for transcription. A computer analysis sequence existence consensus Sp1, PEA1, YY1, Epstein-Barr virus-specific nuclear antigen-2 (EBNA-2)-like transcription factors. transfected plasmid containing mutant Sp1 abrogated activity, whereas plasmids EBNA-2-like factors did not influence activity. To understand events upstream activation, role p38 extracellular signal-regulated kinase mitogen-activated protein kinases using their specific inhibitors. SB202190 SB203580, p38-specific inhibitors, inhibited LPS-induced production. contrast, PD98059, inhibitor kinases, failed modulate Furthermore, SB203580 as well activity sequence. These results suggest regulates which turn gene.