Department of Critical Care Medicine, the People's Hospital of China Three Gorges University, Yichang, 443110, Hubei, China.
Inflammation. 2018 Oct;41(5):1815-1824. doi: 10.1007/s10753-018-0824-5.
Platelets contribute to inflammation and their activation has been suggested as versatile effectors of sepsis. Activation of platelets promotes secretion of CD40L that induces sepsis and multiple organ dysfunction syndrome (MODS). However, the mechanisms regulate platelet-derived CD40L are not fully understood. Activation of PI3K/Akt pathway has been reported as a key component of sepsis, whereas the role of PI3K/Akt pathway in platelet-derived CD40L is unknown. In this study, we identified PI3K/Akt pathway as a key regulator of CD40L secretion by platelets. Significantly, inhibition of PI3K/Akt pathway by Ly294002 attenuated platelet activation and CD40L production. Moreover, PI3K/Akt pathway blocking suppresses vascular endothelial cells in vivo. Furthermore, the expression of biomarkers that represent the severity of sepsis, such as ICAM-1, VCAM-1, and E-selectin, was also suppressed by Ly294002. Altogether, our results confirm the pivotal role of PI3K/Akt pathway in sepsis and its inhibition might be a potential therapeutic target.
血小板参与炎症反应，其激活被认为是脓毒症的多功能效应物。血小板的激活促进了 CD40L 的分泌，从而诱导了脓毒症和多器官功能障碍综合征（MODS）。然而，调节血小板衍生的 CD40L 的机制尚不完全清楚。PI3K/Akt 通路的激活已被报道为脓毒症的一个关键组成部分，而 PI3K/Akt 通路在血小板衍生的 CD40L 中的作用尚不清楚。在这项研究中，我们确定了 PI3K/Akt 通路是血小板 CD40L 分泌的关键调节剂。值得注意的是，通过 Ly294002 抑制 PI3K/Akt 通路可减弱血小板的激活和 CD40L 的产生。此外，PI3K/Akt 通路阻断可抑制体内血管内皮细胞。此外，Ly294002 还抑制了代表脓毒症严重程度的生物标志物的表达，如 ICAM-1、VCAM-1 和 E-选择素。总之，我们的结果证实了 PI3K/Akt 通路在脓毒症中的关键作用，抑制其活性可能是一种潜在的治疗靶点。
