Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation

文献类型： 外文期刊

第一作者： Xu, Yuxin

作者： Xu, Yuxin;Wu, Congmei;Dong, Mingxin;Sun, Chengbiao;Wang, Yan;Zhao, Na;Yu, Kaikai;Liu, Wensen;Xu, Na;Wang, Yan;Lu, Nan

作者机构：

关键词： Ricin toxin; Pyroptosis; Caspase-3; GSDME; Inflammation

期刊名称：TOXICOLOGY LETTERS （ 影响因子：3.5； 五年影响因子：3.8 ）

ISSN： 0378-4274

年卷期： 2024 年 396 卷

页码：

收录情况： SCI

摘要： Ricin toxin (RT) is highly cytotoxic and can release a considerable amount of pro-inflammatory factors due to depurination, causing excessive inflammation that may aggravate the harm to the body. Pyroptosis, a type of gasdermin-mediated cell death, is a contributor to the exacerbation of inflammation. Accumulating evidence indicate that pyroptosis plays a significant role in the pathogen infection and tissue injury, suggesting a potential correlation between pyroptosis and RT-induced inflammation. Here, we aim to demonstrate this correlation and explore its molecular mechanisms. Results showed that RT triggers mouse alveolar macrophage MH-S cells pyroptosis by activating caspase-3 and cleaving Gasgermin E (GSDME). In contrast, inhibition of caspase-3 with Z-DEVD-FMK (inhibitor of caspase-3) or knockdown of GSDME attenuates this process, suggesting the essential role of caspase-3/GSDME-mediated pyroptosis in contributing to RT-induced inflammation. Collectively, our study enhances our understanding of a novel mechanism of ricin cytotoxicity, which may emerge as a potential target in immunotherapy to control the RT-induced inflammation.

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