Heat shock response inhibits IL-18 expression through the JNK pathway in murine peritoneal macrophages.
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.
Wang
Yun
Y
Department of Cell Biology, The Third Military Medical University, Chongqing 400038, China.
Li
Changlin
C
Wang
Xingyu
X
Zhang
Jinsong
J
Chang
Zongliang
Z
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
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