Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells.
Gamma Radiation Induce Inflammasome Signaling and Pyroptosis in Microvascular Endothelial Cells.
复制标题
伽马辐射诱导微血管内皮细胞炎症小体信号传导和细胞焦亡
DOI：
10.2147/jir.s318812
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发表时间：
2021
影响因子：
4.5
通讯作者：
Zeng L
中科院分区：
文献类型：
--
作者：
Smith AO;Ju W;Adzraku SY;Wenyi L;Yuting C;Qiao J;Xu K;Zeng L
放射治疗的临床益处的延伸是不能仅消除癌细胞并破坏血管龛中的正常细胞如微血管内皮，并将诱导的炎性体信号传导和细胞死亡转化为细胞死亡。这些不幸的损伤产生的电离辐射改变了治疗窗口，并导致复发的恶性肿瘤。因此，我们通过证明辐射诱导的内皮细胞炎性小体和细胞死亡进行体外研究。将微血管内皮细胞在无菌培养皿中培养，然后在37°C下在5%的加湿器中保持12小时/更长时间以达到汇合，并以1.8Gy/min的剂量暴露以达到除对照之外的期望量。照射后24小时收获细胞。我们的研究结果表明，γ射线激活微血管内皮细胞中的NOD样受体（NLR）家族的NLRP 1和NLRP 3复合物。这些复合物激活caspase-1的无活性前体，其裂解为生物活性caspase-1，并增强促炎细胞因子白细胞介素-1 β和白细胞介素-18的产生，诱导依赖性热原，导致产生趋化因子、肿瘤坏死因子-α（TNF-α）和高迁移率族蛋白-1（HMGB-1）。我们还发现辐射可以直接促进caspase-1，其自动切割以激活gasdermin D，从而独立地增强焦亡。总体而言，这些发现表明，减少辐射损伤的不利影响可能具有挑战性，因为γ辐射诱导微血管内皮细胞细胞死亡，并通过不同途径激活炎性体信号传导。
The extend to the clinical benefit of radiation therapy is the inability to eliminate only cancer cells and destroy normal cells such as microvascular endothelial in the vascular niche and turn induced-inflammasome signaling and cell death. These unfortunate injuries generated by ionizing radiation alter the therapeutic window and result in the re-occurrence of the malignancy. Therefore, we engaged in vitro studies by demonstrating radiation-induced inflammasome and cell death in endothelial cells. The microvascular endothelial cells were cultured in a sterile dish, then kept in a humidifier of 5% at 37°C for 12 hours/more to attain confluence, and exposed at a dose of 1.8Gy/min achieve the coveted amounts except for the control. The cells were harvested 24 hours post-irradiation. Our findings indicate that gamma radiation activates the NOD-like receptor (NLR) family of NLRP1 and NLRP3 complex in microvascular endothelial cells. These complexes activate the inactive precursor of caspase-1, which cleaved to bioactive caspase −1 and enhances the production of pro-inflammatory cytokines of interleukin-1β and interleukin-18 that induce the dependent pyroptotic, which results in the production of chemokines, tumor necrosis factor-alpha (TNF-α), and high-mobility group protein-1 (HMGB-1). We also discovered the radiation could directly prompt caspase −1, which auto-cleaved to activate gasdermin D to potentiate pyroptosis independently. Overall, these findings suggested that reducing the unfavorable effect of radiation injuries could be challenging since gamma radiation induces the microvascular endothelial cells to cell death and activates the inflammasome signaling via different pathways.