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.
摘要：
蓖麻毒素（RT）具有高度的细胞毒性，由于去嘌呤作用，可以释放大量的促炎因子，引起过度的炎症，可能会加剧对身体的伤害。焦亡,一种gasdermin介导的细胞死亡，是炎症恶化的原因。越来越多的证据表明，焦亡在病原体感染和组织损伤中起着重要作用，提示焦亡与RT诱导的炎症之间存在潜在的相关性。这里,我们旨在证明这种相关性并探索其分子机制。结果表明，RT通过激活caspase-3和裂解GasgerminE（GSDME）触发小鼠肺泡巨噬细胞MH-S细胞的焦亡。相比之下,用Z-DEVD-FMK（caspase-3的抑制剂）抑制caspase-3或GSDME的敲减会减弱此过程，提示caspase-3/GSDME介导的焦亡在促成RT诱导的炎症中的重要作用。总的来说，我们的研究增强了我们对蓖麻毒素细胞毒性新机制的理解，这可能成为免疫疗法中控制RT诱导的炎症的潜在靶标。
