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...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.展开更多
The p49 gene from baculovirus Spodoptera lit-toralis nucleopolyhedrovirus (SlNPV) was able to suppress apoptosis of Sf9 cells induced by virus infection. Ectopically expressed P49 protein had the capacity to inhibit t...The p49 gene from baculovirus Spodoptera lit-toralis nucleopolyhedrovirus (SlNPV) was able to suppress apoptosis of Sf9 cells induced by virus infection. Ectopically expressed P49 protein had the capacity to inhibit the activity of Caspases, being the executioner of apoptosis. Digestion of P49 with human Caspase or Bm-Caspase both yielded 10 and 40 kD fragments. Checking the sequence of P49, we found that the motif 91-TVTDG-95 of P49 was the sequence recog-nized by Caspases. The mutant of P49, Asp94Ala, could not be cut by both caspases and lost its caspases inhibition. Meanwhile, Thr91Ala mutant permitted the cleavage and partially retained its activity of caspases inhibition. We also found that P49 was a substrate of upstream initiator caspase and downstream effector Caspases, indicating that P49 was a broad specificity Caspase inhibitor.展开更多
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.
文摘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The work was supported by the National Natural Science Foundation of China(Grant No.39470398).
文摘The p49 gene from baculovirus Spodoptera lit-toralis nucleopolyhedrovirus (SlNPV) was able to suppress apoptosis of Sf9 cells induced by virus infection. Ectopically expressed P49 protein had the capacity to inhibit the activity of Caspases, being the executioner of apoptosis. Digestion of P49 with human Caspase or Bm-Caspase both yielded 10 and 40 kD fragments. Checking the sequence of P49, we found that the motif 91-TVTDG-95 of P49 was the sequence recog-nized by Caspases. The mutant of P49, Asp94Ala, could not be cut by both caspases and lost its caspases inhibition. Meanwhile, Thr91Ala mutant permitted the cleavage and partially retained its activity of caspases inhibition. We also found that P49 was a substrate of upstream initiator caspase and downstream effector Caspases, indicating that P49 was a broad specificity Caspase inhibitor.
