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

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 inflammatio...

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Veröffentlicht in:Toxicology letters 2024-05, Vol.396, p.19-27
Hauptverfasser: Xu, Yuxin, Dong, Mingxin, Sun, Chengbiao, Wang, Yan, Zhao, Na, Yu, Kaikai, Lu, Nan, Xu, Na, Liu, Wensen, Wu, Congmei
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Sprache:eng
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Zusammenfassung: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. •RT induces pyroptosis in mouse alveolar macrophage MH-S cells.•GSDME is an actuator of RT-induced pyroptosis in MH-S cells.•Activation of caspase-3 is associated with GSDME cleavage in RT induced pyroptosis.
ISSN:0378-4274
1879-3169
DOI:10.1016/j.toxlet.2024.04.007