Heat-shock response down-regulates interleukin-18 expression in murine peritoneal macrophages.
BACKGROUND
The heat-shock response is a self-defence mechanism that protects cells and organisms from a wide range of harmful stresses. Recent studies revealed that it involved the regulation of cytokine expression. Interleukin-18 (IL-18) is an important cytokine in mediating immune response.


RESULTS
We studied interferon-gamma (IFN-gamma)-induced IL-18 expression in heat-shock-treated murine peritoneal macrophages. Our results showed that the heat-shock response significantly inhibited the expression of IFN-gamma-induced pro-inflammatory cytokine IL-18. Interferon consensus sequence binding protein (ICSBP) is a transcription factor that binds to the promoter of IL-18 and regulates the transcription of IL-18. Further research on the down-regulation mechanism showed that the DNA-binding activity of ICSBP was greatly reduced by the heat shock response.


CONCLUSIONS
These results suggest that the inhibitory effect of heat-shock response on IL-18 production in IFN-gamma-stimulated macrophages is related to the suppression of the binding activity of ICSBP.
Wang
Yun
Y
Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People's Republic of China. yunyunwy@hotmail.com
Chang
Zongliang
Z
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D018869:Heat-Shock Response; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma / Q000494:pharmacology; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D020382:Interleukin-18; D012097:Repressor Proteins; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8