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 (20 ng/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) (C) 2010 Elsevier Ltd All rights reserved