摘要
Heat shock response is a self-defense mecha-nism for protection of cells and organisms from a wide range of harmful stressors. Recent studies revealed that it is in-volved in the regulation of cytokines expression. IL-18 is an important cytokine in mediating immune response. We stud-ied LPS-induced IL-18 expression in heat shock treated RAW264.7 murine macrophages. Our results show that the heat shock response significantly inhibited the expression of LPS-induced pro-inflammatory cytokine IL-18. Further research on the down-regulation mechanism shows that this inhibitory effect is correlated to the great suppression of the binding activity of AP-1, which is a transcription factor binding to the promoter of IL-18 (-1120 to -1083) and regu-lates the transcription of IL-18. Meanwhile, we observed that the phosphorylation of JNK, which is AP-1 upstream kinase, was greatly decreased. These results confirmed that the down-regulation effect on IL-18 production in heat shock response is related to the suppression of the JNK/AP-1 sig-naling pathway.
Heat shock response is a self-defense mecha-nism for protection of cells and organisms from a wide range of harmful stressors. Recent studies revealed that it is in-volved in the regulation of cytokines expression. IL-18 is an important cytokine in mediating immune response. We stud-ied LPS-induced IL-18 expression in heat shock treated RAW264.7 murine macrophages. Our results show that the heat shock response significantly inhibited the expression of LPS-induced pro-inflammatory cytokine IL-18. Further research on the down-regulation mechanism shows that this inhibitory effect is correlated to the great suppression of the binding activity of AP-1, which is a transcription factor binding to the promoter of IL-18 (-1120 to -1083) and regu-lates the transcription of IL-18. Meanwhile, we observed that the phosphorylation of JNK, which is AP-1 upstream kinase, was greatly decreased. These results confirmed that the down-regulation effect on IL-18 production in heat shock response is related to the suppression of the JNK/AP-1 sig-naling pathway.
基金
This work was supported by the National"973"Key Basic Research Program(Grant No.G19999054201)
a fund from Shanghai Institutes for Biological Sciences,the Chinese Academy of Sciences.
关键词
热震反应
巨噬细胞
自卫机制
HSR
环境压力
heat shock response, heat shock protein, IL-18, JNK/AP- 1, macrophage.
