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Keywords:

  • triptolide;
  • chemokine;
  • matrix metallopro-teinase;
  • myofibroblast

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-1β. 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 IκB-α (p-IκB-α) was determined by Western blotting. The DNA binding capacity of NF-κB was evaluated by electrophoretic mobility shift assays. Results: IL-1β stimulated 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. Mechanistic studies revealed that triptolide markedly decreased IL-1β-induced NF-κB DNA binding capacity and cytosolic amount of p-IκB-α. These results showed that triptolide inhibited IL-1 β-induced chemokine and MMP-3 expression in SEMF through the NF-κB pathway. Conclusion: Triptolide inhibited IL-1 β-induced chemokine and MMP-3 expression in SEMF by preventing the phosphorylation of IκB-α.