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Int Immunopharmacol. 2013 Jun;16(2):268-74. doi: 10.1016/j.intimp.2013.04.018. Epub 2013 Apr 30.

Triptolide induces suppressor of cytokine signaling-3 expression and promotes lamina propria mononuclear cells apoptosis in Crohn's colitis.

Author information

1
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.

Abstract

BACKGROUND:

IL-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.

METHODS:

This study further investigates the mechanism by which triptolide attenuates Crohn's colitis. IL-10 gene-deficient mice (IL-10(-)/(-)) of 10-12weeks 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.

RESULTS:

Our 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.

CONCLUSIONS:

Our 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.

PMID:
23643741
DOI:
10.1016/j.intimp.2013.04.018
[Indexed for MEDLINE]

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