Triptolide ameliorates IL-10-deficient mice colitis by mechanisms involving suppression of IL-6/STAT3 signaling pathway and down-regulation of IL-17.
Triptolide is an active component of extracts derived from the medicinal vine Tripterygium Wilfordii Hook. f. (TWHF) whose extracts have been used to treat inflammatory bowel disease (IBD). We have reported that triptolide showed therapeutic activity in a murine IBD model, but the potential mechanism of action of this agent in IBD remains elusive. Accumulated data showed that both T-helper (Th) 1 and Th17 response may contribute to pathogenesis of human IBD and animal colitis. Interleukin (IL)-6/signal transducer and activator of transcription-3 (STAT3) signaling pathway play an important role in Th17 response as well as pathophysiology of IBD. We hypothesized that triptolide would attenuate the experimental colitis by repressing IL-17 and that this would involve down-regulation of IL-6/STAT3 signaling pathway. Histological examination demonstrated that triptolide significantly reduced the severity of colitis in C3H/HeJBir.IL-10-deficeint mice. Triptolide suppressed the IL-6/STAT3 signaling pathway, as well as repressed gene expression of IL-17 in vivo. In addition, triptolide (20ng/ml) in vitro was able to down-regulate the IL-6/STAT3 pathway and reduce IL-17 expression in cultured colonic explants from patients with Crohn's disease (CD).
Li
Yi
Y
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
Yu
Chao
C
Zhu
Wei-Ming
WM
Xie
Ying
Y
Qi
Xin
X
Li
Ning
N
Li
Jie-Shou
JS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects; D003424:Crohn Disease / Q000473:pathology*; D050822:Cytokine Receptor gp130 / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000172:deficiency* / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009924:Organ Culture Techniques; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
D050822:Cytokine Receptor gp130; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D020381:Interleukin-17; D015850:Interleukin-6; D010616:Phenanthrenes; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C494200:Il6st protein, mouse; C494087:Stat3 protein, mouse; C001899:triptolide