Huaier aqueous extract protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NLRP3 inflammasome activation.
Huaier aqueous extract protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NLRP3 inflammasome activation.
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槐耳水提取物通过抑制 NLRP3 炎症小体激活，预防葡聚糖硫酸钠诱导的小鼠实验性结肠炎
DOI：
10.18632/oncotarget.16513
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发表时间：
2017-05-16
期刊：
影响因子：
--
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Wang L;Yu Z;Wei C;Zhang L;Song H;Chen B;Yang Q
赤霉素的使用。（怀尔）作为癌症的一种辅助疗法最近在中国越来越普遍。然而，怀尔是否可以调节宿主的免疫反应，特别是先天免疫，在很大程度上仍然是未知的。NLRP3炎性小体是由NLRP3、ASC和caspase-1组成的多聚体复合物。NLRP3炎性小体响应多种内源性（损伤相关分子模式）和外源性（病原体相关分子模式）刺激，并在宿主防御病原体和溃疡性结肠炎（UC）等多种疾病中发挥关键作用。在本研究中，我们研究了槐儿对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的抗炎作用，并通过靶向NLRP3炎症小体揭示其潜在机制。在C57BL/6小鼠中，口服怀尔减轻了dss引起的结肠缩短和结肠病理损伤。进一步，我们分析了怀尔对巨噬细胞NLRP3炎性体活化的影响。怀尔抑制NLRP3炎性体激活诱导的IL-1β分泌和caspase-1裂解。此外，怀尔通过自噬溶酶体途径促进NLRP3降解，从而降低了NLRP3蛋白的表达。因此，我们的研究结果证明了槐儿在调节NLRP3炎症小体激活中的新功能，并提示槐儿在NLRP3炎症小体相关疾病中的潜在作用。
The use of Trametes robiniophila Murr. (Huaier) as a complementary therapy for cancer has recently become increasingly common in China. However, whether Huaier can regulate host immune responses, especially innate immunity, remains largely unknown. The NLRP3 inflammasome is a multimeric complex consisting of NLRP3, ASC and caspase-1. NLRP3 inflammasomes respond to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli, and play crucial roles in host defense against pathogens and multiple diseases such as ulcerative colitis (UC). In this study, we investigated the anti-inflammatory effect of Huaier in dextran sulfate sodium (DSS)-induced murine colitis and revealed the underlying mechanisms by targeting NLRP3 inflammasomes. In C57BL/6 mice, oral administration of Huaier attenuated DSS-induced colon shortening and colonic pathological damage. Furthermore, we analyzed the effect of Huaier on NLRP3 inflammasome activation in macrophages. Huaier inhibited NLRP3 inflammasome activation-induced IL-1β secretion and caspase-1 cleavage. Moreover, Huaier decreased NLRP3 protein expression via promoting NLRP3 degradation through the autophagy lysosome pathway. Therefore, our findings demonstrate a novel function for Huaier in the regulation of NLRP3 inflammasome activation and suggest a potential role for Huaier in NLRP3 inflammasome-associated diseases.