Triptolide suppresses IL-1β-induced chemokine and stromelysin-1 gene expression in human colonic sub

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:meimeilaile
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Aim:To examine the inhibitive effects of triptolide on the expression of IL-8,monocyte chemotactic protein(MCP)-1,and matrix metalloproteinases(MMP)-3in subepithelial myofibroblasts(SEMF)stimulated with IL-1β.Methods:SEMFcultures were established from normal colons in patients who underwent gutresection for colorectal carcinoma.Chemokine and MMP-3 expressions weredetermined by ELISA and RT-PCR.The cytosolic amount of phosphorylation ofIκB-α(p-IκB-α)was determined by Western blotting.The DNA binding capacityof NF-κB was evaluated by electrophoretic mobility shift assays.Results:IL-1βstimulated protein and mRNA expression of IL-8,MCP-1,and MMP-3 in SEMF.Triptolide inhibited these effects of IL-1β in a dose-dependent manner.Mecha-nistic studies revealed that triptolide markedly decreased IL-1β-induced NF-κBDNA binding capacity and cytosolic amount of p-IκB-α.These results showedthat triptolide inhibited IL-1β-induced chemokine and MMP-3 expression in SEMFthrough the NF-κB pathway.Conclusion:Triptolide inhibited IL-1β-inducedchemokine and MMP-3 expression in SEMF by preventing the phosphorylationof IκB-α. Aim: To examine the inhibititive effects of triptolide on the expression of IL-8, monocyte chemotactic protein (MCP) -1, and matrix metalloproteinases (MMP) -3 in subepithelial myofibroblasts (SEMF) stimulated with IL-1β. Methods: SEMFcultures were established from normal colons in patients who underwent gutrection for colorectal carcinoma. Chemokine and MMP-3 expressions were determined by ELISA and RT-PCR. The cytosolic amount of phosphorylation of IκB-α (p-IκB-α) was determined by Western blotting. capacity of NF-κB was evaluated by electrophoretic mobility shift assays. Results: IL-1βstimulated protein and mRNA expression of IL-8, MCP-1, and MMP-3 in SEMF.Triptolide inhibited these effects of IL-1β in a dose- dependent manner. Mecha-nistic studies that that triptolide markedly decreased IL-1β-induced NF-κB DNA binding capacity and cytosolic amount of p-IκB-α. thesese results showed that triptolide inhibited IL-1β-induced chemokine and MMP-3 expression in SEMFthrough the NF-κB pa thway.Conclusion: Triptolide inhibited IL-1β-induced chemokine and MMP-3 expression in SEMF by preventing the phosphorylation of IκB-α.
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