Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production

被引：168

作者：

Gong, Zizhen ^{[1
,2
,3
]}

Zhao, Shengnan ^{[1
,2
,3
]}

Zhou, Jiefei ^{[1
,2
,3
]}

Yan, Junkai ^{[1
,2
,3
]}

Wang, Lingyu ^{[1
,2
,3
]}

Du, Xixi ^{[1
,2
,3
]}

Li, Hui ^{[4
]}

Chen, Yingwei ^{[2
,3
]}

Cai, Wei ^{[1
,2
,3
]}

Wu, Jin ^{[1
,2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Pediat Surg, Xinhua Hosp, Sch Med, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Shanghai Inst Pediat Res, Sch Med, Shanghai, Peoples R China

[3] Shanghai Key Lab Pediat Gastroenterol & Nutr, Shanghai, Peoples R China

[4] Shanghai Univ Med & Hlth Sci, Dept Pathol, Shanghai, Peoples R China

来源：

MOLECULAR IMMUNOLOGY | 2018年 / 104卷

基金：

上海市自然科学基金;

关键词：

Curcumin; NLRP3; inflammasome; IL-1; beta; Inflammatory bowel diseases; Dextran sulfate sodium; INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; INTESTINAL INFLAMMATION; INTERLEUKIN-1; INFLAMMASOMES; EXPRESSION; MECHANISM; PREVENTS; INCREASE; THERAPY;

D O I：

10.1016/j.molimm.2018.09.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Background NLRP3 inflammasome mediates IL-1 beta maturation, therefore plays a vital role in the development of IBD. Curcumin is known for possessing strong anti-inflammatory property. Objective: The present study was to investigate the protective effects of curcumin on dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome activation and IL-1 beta production. Methods: LPS-primed macrophages were treated with curcumin prior to DSS triggering NLRP3 inflammasome activation, IL-1j3 secretion and ASC oligomerization were observed. The mechanisms of curcumin in the inhibition of DSS-induced inflammasome activation were explored. Curcumin or caspase-1/NLRP3 inhibitor was administrated respectively in DSS-induced colitis mouse model. The changes of body weight, disease activity index, colon length were measured. Additionally, mature IL-1 beta and other inflammatory cytokines, MPO activity and histopathological damage were analyzed for the evaluation of colitis severity. Results: NLRP3 inflammasome activation was dramatically inhibited by curcumin in DSS-stimulated macrophages, as evidenced by decreased IL-1 beta secretion, less caspase-1 activation and ASC specks. Mechanistically, curcumin prevented DSS-induced K+ efflux, intracellular ROS formation and cathepsin B release, three major cellular events mediating NLRP3 inflammasome activation. In DSS-induced colitis, curcumin administration significantly ameliorated colitis symptoms by reducing weight loss, DAI and colon length shortening. Meanwhile, curcumin significantly decreased the expression of multiple inflammatory cytokines (including mature IL-1 beta, IL-6, MCP-1), MPO activity, caspase-1 activity as well as histopathological damage. Furthermore, blockage of NLRP3 inflammasome activation in vivo with specific NLRP3 inhibitor abrogated the further inhibitory effect of curcumin on DSS-induced colitis. Conclusion: Curcumin could strongly suppress DSS-induced NLRP3 inflammsome activation and alleviate DSSinduced colitis in mice, thus it may be a promising candidate drug in clinical application for IBD therapy.

引用

页码：11 / 19

页数：9

共 45 条

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