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姜黄素抑制DSS诱导的小鼠肠上皮细胞NLRP3炎性小体活化及IL-1β分泌
作者:杜惜惜  龚自珍  吴瑾 
单位:上海交通大学医学院 附属新华医院/上海市儿科医学研究所, 上海 200092
关键词:姜黄素 葡聚糖硫酸钠 炎性小体 白细胞介素1β 肠上皮细胞 小鼠 
分类号:R574.62;R-33
出版年·卷·期(页码):2019·38·第三期(418-423)
摘要:

目的:研究葡聚糖硫酸钠(DSS)诱导肠上皮细胞NLRP3炎性小体活化及姜黄素对其的抑制作用。方法:用脂多糖(LPS)预激活小鼠肠上皮细胞,以不同浓度DSS刺激细胞,ELISA法检测培养上清白细胞介素(IL)-1β水平;以NLRP3炎性小体特异性抑制剂及多种炎性小体活化通路阻断剂进行干预,检测对IL-1β分泌的影响;进而以姜黄素处理细胞,ELISA法、免疫荧光法观察姜黄素对DSS诱导的IL-1β分泌及胞质中凋亡相关斑点样蛋白(ASC)斑点形成的抑制情况。结果:DSS可剂量依赖性地诱导LPS预致敏小鼠肠上皮细胞释放IL-1β;NLRP3特异性抑制剂、炎性小体活化通路阻断剂均可明显减少DSS诱导的IL-1β分泌(P<0.01);姜黄素预处理细胞可显著下调IL-1β水平、抑制胞内ASC斑点形成。结论:姜黄素能有效阻遏DSS诱导的肠上皮细胞NLRP3炎性小体活化、减少促炎性细胞因子IL-1β分泌,可能是其治疗肠道炎症的重要机制之一。

Objective:To investigate the effects and mechanisms of NLRP3 inflamasome activation induced by dextran sulphate sodium(DSS) on murine intestinal epithelial cells and the inhibitive role of curcumin in this process. Methods:LPS-primed murine intestinal epithelial cells were stimulated with DSS at different concentrations, and the interleukin(IL)-1β levels in the cell culture supernatant were measured by ELISA. Specific NLRP3 inflammasome inhibitor and multiple inflammasome activation pathway antagonists were respectively adopted to evaluate the corresponding effects on the IL-1β production induced by DSS. Furthermore, ELISA and immunofluorescence were used to determine the suppressive effects of curcumin on IL-1β secretion and intracellular ASC specks formation. Results:DSS could dose-dependently induce the secretion of IL-1β in LPS-primed murine intestinal epithelial cells. Specific NLRP3 inflammasome inhibitor as well as inflammasome activation pathway antagonists significantly decreased the DSS-induced IL-1β secretion(P<0.01). Pretreatment of the intestinal epithelial cells with curcumin could dramatically reduce the IL-1β release and ASC specks formation. Conclusion:Curcumin could effectively block DSS-induced activation of NLRP3 inflammasome and secretion of pro-inflammatory cytokine IL-1β in the intestinal epithelial cells, which may be one of the most important mechanisms that contribute to its anti-inflammatory effect on colitis.

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