title: Heat shock response inhibits IL-18 expression through the JNK pathway in murine peritoneal macrophages.
abstract: Heat shock response has been implicated in cytoprotective effects from cellular damage and in the regulation of cytokine expression. We report the effect of heat shock on LPS-induced expression of IL-18, an important cytokine that has diverse immune regulatory effects on T cells, B cells, NK cells, and nonimmune cells. The augmentation of LPS-induced IL-18 mRNA and protein was significantly suppressed in murine peritoneal macrophages after 43 degrees C heat shock treatment. In addition, the JNK MAPK inhibitor SP600125 inhibited IL-18 mRNA transcription in a dose-dependent manner. To examine the possibility that the inhibition of IL-18 may be mediated through the inactivation of JNK, the activity of JNK was measured by using Western blot and kinase assays. Our data show that heat shock response decreased LPS-induced phosphorylation of JNK and its downstream substrate c-Jun. AP-1, a transcriptional factor composed of c-Jun, could regulate the expression of IL-18. Also, its DNA-binding activity was reduced by the heat shock response. These findings suggest that treatment of heat stress results in inhibition of IL-18 production in macrophages mainly through the JNK/AP-1 signaling pathway.
authors.affiliation: Department of Cell Biology, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Changlin
authors.initials: C
authors.lastname: Li
authors.forename: Xingyu
authors.initials: X
authors.lastname: Wang
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
authors.forename: Zongliang
authors.initials: Z
authors.lastname: Chang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D018869:Heat-Shock Response; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D020382:Interleukin-18; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases