NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages.
NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages.
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NLRP3炎症小体激活介导骨髓源性巨噬细胞辐射诱导的细胞焦亡
DOI：
10.1038/cddis.2016.460
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发表时间：
2017-02-02
影响因子：
9
通讯作者：
Lu GC
中科院分区：
文献类型：
--
作者：
Liu YG;Chen JK;Zhang ZT;Ma XJ;Chen YC;Du XM;Liu H;Zong Y;Lu GC
放射治疗的临床益处的限制不是不能消除肿瘤细胞，而是限制了其在不破坏正常组织和诱导炎症的情况下消除肿瘤细胞的能力。最近的证据表明，炎性小体是介导辐射诱导的细胞和组织损伤所必需的。在这项研究中，使用原代培养的骨髓源性巨噬细胞（BMDM）和小鼠辐射模型，我们探讨了NLRP 3炎性小体激活和继发性pyroptosis辐射诱导的免疫细胞死亡的作用。我们观察到在10和20戈伊照射组中，焦亡比例增加，Caspase-1活化升高。Nlrp 3基因敲除可显著降低Caspase-1（p10）和IL-1β的表达量以及细胞凋亡比例。此外，体内研究表明，9.5戈伊的辐射促进边缘区细胞中的Caspase-1活化并诱导小鼠死亡，这两者都可以通过敲除Nlrp 3而显著抑制。因此，基于这些发现，我们得出结论，NLRP 3炎性小体激活介导BMDM中辐射诱导的焦亡。靶向NLRP 3炎性小体和焦亡可能是减轻辐射损伤的有效策略。
A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death. We observed an increasing proportion of pyroptosis and elevating Caspase-1 activation in 10 and 20 Gy radiation groups. Nlrp3 knock out significantly diminished the quantity of cleaved-Caspase-1 (p10) and IL-1β as well as the proportion of pyroptosis. Additionally, in vivo research shows that 9.5 Gy of radiation promotes Caspase-1 activation in marginal zone cells and induces death in mice, both of which can be significantly inhibited by knocking out Nlrp3. Thus, based on these findings, we conclude that the NLRP3 inflammasome activation mediates radiation-induced pyroptosis in BMDMs. Targeting NLRP3 inflammasome and pyroptosis may serve as effective strategies to diminish injury caused by radiation.