%0 Journal Article
%T Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation.
%A Xu Y
%A Dong M
%A Sun C
%A Wang Y
%A Zhao N
%A Yu K
%A Lu N
%A Xu N
%A Liu W
%A Wu C
%J Toxicol Lett
%V 396
%N 0
%D 2024 May 15
%M 38642674
%F 4.271
%R 10.1016/j.toxlet.2024.04.007
%X 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.