{Reference Type}: Journal Article
{Title}: Caspase-3/Gasdermin E-mediated pyroptosis contributes to Ricin toxin-induced inflammation.
{Author}: Xu Y;Dong M;Sun C;Wang Y;Zhao N;Yu K;Lu N;Xu N;Liu W;Wu C;
{Journal}: Toxicol Lett
{Volume}: 396
{Issue}: 0
{Year}: 2024 May 15
{Factor}: 4.271
{DOI}: 10.1016/j.toxlet.2024.04.007
{Abstract}: 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.