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玉米赤霉烯酮通过自噬调控 NF-κB 激活诱导 INS-1 细胞中 NLRP3 依赖性细胞焦亡。

Zearalenone induces NLRP3-dependent pyroptosis via activation of NF-κB modulated by autophagy in INS-1 cells.

机构信息

Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian 116044, Liaoning, PR China; Department of Teaching Affairs, the Second Affiliated Hospital of Dalian Medical University, Dalian 116023, PR China.

Experimental Teaching Center of Public Health, Dalian Medical University, 9 W Lvshun South Road, Dalian, 116044, PR China.

出版信息

Toxicology. 2019 Dec 1;428:152304. doi: 10.1016/j.tox.2019.152304. Epub 2019 Oct 3.

Abstract

Zearalenone (ZEA), one of the mycotoxins widely found in food and feed, can stimulate an inflammatory reaction. In the present study, we demonstrated that ZEA induced the activation of NLRP3 inflammasome even pyroptotic cell death in rat Insulinoma Cell Line (INS-1). Meanwhile, according to the results of western blot and TEM, the level of autophagy was elevated by ZEA, which protected against the activation of NLRP3 inflammasome and inflammatory response caused by ZEA. Furthermore, we indicated that ZEA-induced NF-κB p65 activation contributed to the activation of the NLRP3 inflammasome, inflammatory response, and pyroptosis in INS-1 cells, which were indicated by western blot and immunofluorescence, and the activation of NF-κB p65 induced by ZEA was autophagy-dependent. This study demonstrates that ZEA induces NLRP3-dependent pyroptosis via activation of NF-κB modulated by autophagy in INS-1 cells.

摘要

玉米赤霉烯酮(ZEA)是一种广泛存在于食品和饲料中的真菌毒素,可刺激炎症反应。本研究表明,ZEA 可诱导大鼠胰岛素瘤细胞系(INS-1)中 NLRP3 炎性体的激活甚至焦亡性细胞死亡。同时,根据 Western blot 和 TEM 的结果,ZEA 可上调自噬水平,从而防止 ZEA 引起的 NLRP3 炎性体激活和炎症反应。此外,我们表明 ZEA 诱导的 NF-κB p65 激活有助于 INS-1 细胞中 NLRP3 炎性体的激活、炎症反应和焦亡,这是通过 Western blot 和免疫荧光检测到的,并且 ZEA 诱导的 NF-κB p65 激活依赖于自噬。本研究表明,ZEA 通过自噬调节的 NF-κB 激活诱导 INS-1 细胞中 NLRP3 依赖性细胞焦亡。

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