Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5833983 | International Immunopharmacology | 2013 | 7 Pages |
â¢Triptolide increased the expression of SOCS3 protein both in vivo and in vitro.â¢Triptolide decreased Bcl-2 and Bcl-xl productions in LPMC in vivo and in vitro.â¢Triptolide enhanced programmed cell death in LP-T cells in vivo and in vitro.â¢Defective LP-T apoptosis in Crohn's disease may sustainably reverted by triptolide.â¢Triptolide potentially regulated IL-6/STAT3/SOCS3 signaling pathway.
BackgroundIL-6/STAT3/SOCS3 signaling pathway plays an important role in the pathogenesis of Crohn's disease by induction of the antiapoptotic factors Bcl-2 and Bcl-xl in lamina propria mononuclear cells (LPMCs). We previously reported that triptolide showed therapeutic activity in mouse colitis by mechanisms involving suppression of IL-6 trans-signaling. IL-10 gene-deficient mice with established colitis were used for the experiments with triptolide administration.MethodsThis study further investigates the mechanism by which triptolide attenuates Crohn's colitis. IL-10 gene-deficient mice (IL-10â/â) of 10-12Â weeks with established colitis were used for the experiments with chronic triptolide administration. Apoptosis of lamina propria mononuclear cells (LPMCs) were measured by flow cytometry. SOCS, Bcl-2, Bcl-xl and Bax were determined by Western blot. Furthermore, an in vitro study was performed by using cultured intestine from CD patients to observe the direct effects of triptolide.ResultsOur data indicated triptolide promoted apoptosis in LPMCs in vivo. Interestingly, triptolide significantly induced the apoptosis of LP-CD4-positive but not LP-CD4-negative cells. Triptolide significantly induced SOCS3 protein and reduced STAT3 target anti-apoptotic genes Bcl-2 and Bcl-xl in LPMCs. The results were confirmed by an in vitro study using colonic explants cultured with triptolide.ConclusionsOur results indicated that triptolide therapy may restore the homeostatic balance of LP-T cell apoptosis within the gut, and demonstrate a novel mechanism of action of triptolide therapy mediated through regulation IL-6/STAT3/SOCS3 signaling pathway.
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