The suppressive effect of triptolide on chronic colitis and TNF-alpha/TNFR2 signal pathway in interleukin-10 deficient mice.

Abstract

Recent studies have suggested a critical role of TNFR2 signaling associated with NF-kappaB activation in the pathogenesis of Crohn's disease. Triptolide, an extract from Tripterygium wilfordii Hook, has both anti-immune and anti-inflammatory effects. In this study, we evaluated its possible therapeutic effects on colitis in interleukin-10 deficient mice, a murine model of Crohn's disease. Triptolide was administered to IL-10(-/-) mice intraperitoneally every other day for 8 weeks. The severity of colitis in IL-10(-/-) mice was obviously reduced after triptolide treatment, with a reduction in the numbers of CD4+ T cells and macrophages in lamina propria. Triptolide also significantly decreased the production of TNF-alpha and IFN-gamma in colon. Furthermore, triptolide suppressed TNFR2 expression and NF-kappaB activation in colon of IL-10(-/-) mice. These data suggested that triptolide could ameliorate Th1-mediated chronic colitis and disordered immune state in IL-10(-/-) mice. A possible mechanism could be inhibiting TNF-alpha/TNFR2 signal pathway.

• Authors: Xiaowei Wei, Jianfeng Gong, Juan Zhu, Pengfei Wang, Ning Li, Weiming Zhu, Jieshou Li
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 129 Issue 2 Pg. 211-8 (Nov 2008) ISSN: 1521-7035 [Electronic] United States
• PMID: 18757245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• Epoxy Compounds
• Immunosuppressive Agents
• NF-kappa B
• Phenanthrenes
• Receptors, Tumor Necrosis Factor, Type II
• Tumor Necrosis Factor-alpha
• Interleukin-10
• triptolide

Topics

• Animals
• Chronic Disease
• Colitis (prevention & control)
• Diterpenes (pharmacology, therapeutic use)
• Epoxy Compounds (pharmacology, therapeutic use)
• Immunosuppressive Agents (therapeutic use)
• Interleukin-10 (deficiency, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors)
• Phenanthrenes (pharmacology, therapeutic use)
• Receptors, Tumor Necrosis Factor, Type II (antagonists & inhibitors, genetics, physiology)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, physiology)