title: cAMP elevators inhibit LPS-induced IL-12 p40 expression by interfering with phosphorylation of p38 MAPK in murine peritoneal macrophages.
abstract: cAMP mediated signaling may play a suppressive role in immune response. We previously found that the cAMP-elevators (CTx and 8-Br-cAMP) inhibited IL-12, IL-la, IL-6 gene expression, but increased the transcriptional levels of IL-10 and IL-1Ra in LPS-treated murine peritoneal macrophages. The present study examined a possible molecular mechanism involved in cAMP elevators-induced inhibition of IL-12 p40 expression in response to LPS. Our data demonstrated that cAMP elevators downregulated IL-12 p40 mRNA expression and IL-12 p70 production in murine peritoneal macrophages. Subsequent studies revealed that cAMP-elevators blocked phosphorylation of p38 MAPK, but did not affect the activity of NF-kappaB binding to IL-12 promoter (-136/-112). This is the first report that cAMP elevators inhibit LPS-induced IL-12 production by a mechanism that is associated, at least in part, with p38-dependent inhibition by cAMP signaling pathways.
authors.affiliation: Laboratory of Immune Signaling Transduction, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wei Guo
authors.initials: WG
authors.lastname: Feng
authors.forename: Yi Bing
authors.initials: YB
authors.lastname: Wang
authors.forename: Jin Song
authors.initials: JS
authors.lastname: Zhang
authors.forename: Xing Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Chang Lin
authors.initials: CL
authors.lastname: Li
authors.forename: Zong Liang
authors.initials: ZL
authors.lastname: Chang
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000819:agonists / Q000031:analogs & derivatives / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D007107:Immune System / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D012333:RNA, Messenger; D018664:Interleukin-12; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases