Background information: 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.