3 years ago

Cambogin suppresses dextran sulphate sodium-induced colitis by enhancing Treg cell stability and function

Rui Liang, Hong-Xi Xu, Yi-Wen Jiang, Hong Zhang, Bin Li, Na-Mi Kim, Fu-Xiang Zhu, Dan Zheng, Yue Lu
BACKGROUND AND PURPOSE Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of gastrointestinal tract, and the dysfunction of immune regulation plays a critical role in IBD. Reflecting the limited use of current drugs and therapies for IBD treatment, it is necessary to explore novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via Treg-cell-mediated immune modulation. EXPERIMENTAL APPROACH Chronic colitis was established using 2% DSS in mice, and cambogin (10 mg·kg -1) was orally administered to mice for 10 d. Body weight, colon length and colon histology were assessed. Cytokine production was measured using ELISA and qRT-PCR. To evaluate the mechanism of cambogin, human CD4+CD25hiCD127lo Treg cells were isolated from peripheral blood mononuclear cells (PBMCs). Major signaling profiles involved in Treg cell stability were measured. KEY RESULTS Administration of cambogin attenuated diarrhoea, colon shortening and colon histological injury and IL-6, IFNγ and TNF-α production. Cambogin also up-regulated Treg cell numbers in both the spleen and mesenteric lymph nodes (MLN). Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro. We also observed that cambogin promoted USP7-mediated Foxp3 deubiquitination and increased Foxp3 protein expression under LPS treatment. CONCLUSIONS AND IMPLICATIONS These results demonstrated the effect of cambogin in DSS-induced colitis via Treg-cell-mediated immune modulation, suggesting that this compound could be applied as a novel agent for treating colitis and other Treg cell-related diseases.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bph.14150

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