Triptolide suppresses IL-1beta-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts.

ABSTRACT

AIM: To examine the inhibitive 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-1beta. METHODS: SEMF cultures were established from normal colons in patients who underwent gut resection for colorectal carcinoma. Chemokine and MMP-3 expressions were determined by ELISA and RT-PCR. The cytosolic amount of phosphorylation of I kappa B-alpha(p-I kappa B-alpha) was determined by Western blotting. The DNA binding capacity of NF-kappa B was evaluated by electrophoretic mobility shift assays. RESULTS: IL-1beta stimulated protein and mRNA expression of IL-8, MCP-1, and MMP-3 in SEMF. Triptolide inhibited these effects of IL-1beta in a dose-dependent manner. Mechanistic studies revealed that triptolide markedly decreased IL-1beta -induced NF-kappa B DNA binding capacity and cytosolic amount of p-I kappa B-alpha. These results showed that triptolide inhibited IL-1beta -induced chemokine and MMP-3 expression in SEMF through the NF-kappa B pathway. CONCLUSION: Triptolide inhibited IL-1beta -induced chemokine and MMP-3 expression in SEMF by preventing the phosphorylation of I kappa B-alpha.