Ricin toxin (RT) is a natural plant-derived protein toxin from the seed of castor beans that belongs to a family of type II ribosome-inactivating proteins (RIPs). In addition to its main toxic mechanism of inhibiting the synthesis of cellular proteins, RT can induce the production of inflammatory cytokines and cause inflammatory injury. Macrophages play a crucial role in innate immunity and the adaptive immune response as the first line of host defense against bacterial infections and various types of invading pathogens. Upon activation, macrophages release types of cytokines to remove pathogens. However, the effect of RT on the immune response and its mechanism are not well characterized. In the current study, we investigated the activation of the TLR4-mediated signaling pathway by low-dose RT treatment and its interaction with signaling molecules in the transduction pathway. We found that low-dose RT can activate MyD88- and TRIF-dependent signaling pathways, revealing a possible mechanism by which low-dose RT-activates TLR4-mediated signaling pathways. We also confirmed that the TLR4-induced activation of the inflammatory signaling pathways was produced via its binding to RT. This study may help to identify the most important target molecules and clarify the mechanism of inflammatory injury of ricin.

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Toll 样受体 4 (TLR4) 在巨噬细胞中蓖麻毒素诱导的炎症反应中的关键作用

蓖麻毒素 (RT) 是一种来自蓖麻种子的天然植物蛋白毒素，属于 II 型核糖体灭活蛋白 (RIP) 家族。放疗除了具有抑制细胞蛋白质合成的主要毒性机制外，还可诱导炎性细胞因子的产生，引起炎性损伤。巨噬细胞作为宿主抵御细菌感染和各种入侵病原体的第一道防线，在先天免疫和适应性免疫反应中发挥着至关重要的作用。激活后，巨噬细胞会释放多种细胞因子以清除病原体。然而，RT对免疫反应的影响及其机制尚未得到很好的表征。在目前的研究中，我们研究了低剂量放疗对 TLR4 介导的信号通路的激活及其与转导通路中信号分子的相互作用。我们发现低剂量 RT 可以激活 MyD88 和 TRIF 依赖性信号通路，揭示了低剂量 RT 激活 TLR4 介导的信号通路的可能机制。我们还证实 TLR4 诱导的炎症信号通路激活是通过其与 RT 的结合产生的。该研究可能有助于确定最重要的靶分子，阐明蓖麻毒素炎症损伤的机制。我们还证实 TLR4 诱导的炎症信号通路激活是通过其与 RT 的结合产生的。该研究可能有助于识别最重要的靶分子，阐明蓖麻毒素炎症损伤的机制。我们还证实 TLR4 诱导的炎症信号通路激活是通过其与 RT 的结合产生的。该研究可能有助于确定最重要的靶分子，阐明蓖麻毒素炎症损伤的机制。