Project supported by the National Natural Science Foundation of China (No 30571797).
Triptolide suppresses IL-1β-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts1
Article first published online: 10 JAN 2007
Acta Pharmacologica Sinica
Volume 28, Issue 1, pages 81–88, January 2007
How to Cite
TAO, Q.-s., REN, J.-a. and LI, J.-s. (2007), Triptolide suppresses IL-1β-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts. Acta Pharmacologica Sinica, 28: 81–88. doi: 10.1111/j.1745-7254.2006.00482.x
- Issue published online: 10 JAN 2007
- Article first published online: 10 JAN 2007
- Received 2006-07-30Accepted 2006-09-06
- matrix metallopro-teinase;
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.