British journal of pharmacology · 2018
Cambogin suppresses dextran sulphate sodium-induced colitis by enhancing Treg cell stability and function.
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Lu Yue, Kim Na-Mi, Jiang Yi-Wen, Zhang Hong, Zheng Dan, Zhu Fu-Xiang, Liang Rui, Li Bin, Xu Hong-Xi
Аннотация
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, and an impaired immune response plays a critical role in IBD. The current drugs and therapies for IBD treatment are of limited use, therefore, there is a need to find 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 a Treg-cell-mediated effect on the immune response.
EXPERIMENTAL APPROACH: Chronic colitis was established in mice using 2% DSS, and cambogin (10 mg·kg-1 , p.o.) was administered for 10 days. Body weight, colon length and colon histology were assessed. Cytokine production was measured using elisa and quantitative real-time PCR. To evaluate the mechanism of cambogin, human CD4+ CD25hi CD127lo Treg cells were isolated from peripheral blood mononuclear cells. Major signalling profiles involved in Treg cell stability were measured.
KEY RESULTS: Cambogin attenuated diarrhoea, colon shortening and colon histological injury and IL-6, IFN-γ and TNF-α production in DSS-treated mice. Cambogin also up-regulated Treg cell numbers in both the spleen and mesenteric lymph nodes. Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7-mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS-treated cells.
CONCLUSIONS AND IMPLICATIONS: The effect of cambogin on DSS-induced colitis is expedited by a Treg-cell-mediated modification of the immune response, suggesting that cambogin could be applied as a novel agent for treating colitis and other Treg cell-related diseases.
EXPERIMENTAL APPROACH: Chronic colitis was established in mice using 2% DSS, and cambogin (10 mg·kg-1 , p.o.) was administered for 10 days. Body weight, colon length and colon histology were assessed. Cytokine production was measured using elisa and quantitative real-time PCR. To evaluate the mechanism of cambogin, human CD4+ CD25hi CD127lo Treg cells were isolated from peripheral blood mononuclear cells. Major signalling profiles involved in Treg cell stability were measured.
KEY RESULTS: Cambogin attenuated diarrhoea, colon shortening and colon histological injury and IL-6, IFN-γ and TNF-α production in DSS-treated mice. Cambogin also up-regulated Treg cell numbers in both the spleen and mesenteric lymph nodes. Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7-mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS-treated cells.
CONCLUSIONS AND IMPLICATIONS: The effect of cambogin on DSS-induced colitis is expedited by a Treg-cell-mediated modification of the immune response, suggesting that cambogin could be applied as a novel agent for treating colitis and other Treg cell-related diseases.