Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis.
Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury by Inhibiting Microglia Pyroptosis.
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间充质干细胞通过抑制小胶质细胞焦亡减轻辐射引起的脑损伤
DOI：
10.1155/2017/1948985
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发表时间：
2017
影响因子：
--
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Liao H;Wang H;Rong X;Li E;Xu RH;Peng Y
放射性脑损伤（RI）常见于接受头颈部放射治疗的患者。然而，RI的机制仍不清楚。为探讨放射性视网膜坏死是否与间充质干细胞（mesenchymal stem cells，MSCs）有关，对6-8周龄BALB/c雄性小鼠进行头部照射（15戈伊），2 d后将MSCs移植到双侧皮质，1个月后处死小鼠。同时，照射BV-2小胶质细胞（10戈伊）与MSC共培养24小时。我们观察到照射小鼠脑呈现NLRP 3和caspase-1活化。RT-PCR结果显示，该基因主要表达于小胶质细胞，而不表达于神经元。此外，照射的BV-2细胞显示出焦亡和IL-18和IL-1β的产生增加。RT-PCR还证实了几个炎性体基因在辐照的BV-2细胞中的表达增加，包括NLRP 3和AIM 2。特别是NLRP 3被激活。NLRP 3的敲低导致LDH释放减少。值得注意的是，在体内，MSC移植减轻辐射诱导的NLRP 3和caspase-1激活。此外，在体外，MSC可以减少辐射诱导的caspase-1依赖的细胞凋亡，NLRP 3炎性小体激活和ROS产生。因此，我们的研究结果证明，小胶质细胞的pyroptosis发生在RI。骨髓间充质干细胞可能作为一个有效的治疗工具，在衰减焦亡。
Radiation-induced brain injury (RI) commonly occurs in patients who received head and neck radiotherapy. However, the mechanism of RI remains unclear. We aimed to evaluate whether pyroptosis was involved in RI and the impact of mesenchymal stem cells (MSCs) on it. BALB/c male mice (6–8 weeks) were cranially irradiated (15 Gy), and MSCs were transplanted into the bilateral cortex 2 days later; then mice were sacrificed 1 month later. Meanwhile, irradiated BV-2 microglia cells (10 Gy) were cocultured with MSCs for 24 hours. We observed that irradiated mice brains presented NLRP3 and caspase-1 activation. RT-PCR then indicated that it mainly occurred in microglia cells but not in neurons. Further, irradiated BV-2 cells showed pyroptosis and increased production of IL-18 and IL-1β. RT-PCR also demonstrated an increased expression of several inflammasome genes in irradiated BV-2 cells, including NLRP3 and AIM2. Particularly, NLRP3 was activated. Knockdown of NLRP3 resulted in decreased LDH release. Noteworthily, in vivo, MSCs transplantation alleviated radiation-induced NLRP3 and caspase-1 activation. Moreover, in vitro, MSCs could decrease caspase-1 dependent pyroptosis, NLRP3 inflammasome activation, and ROS production induced by radiation. Thus, our findings proved that microglia pyroptosis occurred in RI. MSCs may act as a potent therapeutic tool in attenuating pyroptosis.
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影响因子：
3.3
作者：
Acharya MM;Christie LA;Hazel TG;Johe KK;Limoli CL
通讯作者：
Limoli CL
DOI：
10.1158/1078-0432.ccr-11-2903
发表时间：
2013-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Greene-Schloesser D;Moore E;Robbins ME
通讯作者：
Robbins ME
影响因子：
64.8
作者：
Shi, Jianjin;Zhao, Yue;Shao, Feng
通讯作者：
Shao, Feng
影响因子：
6.1
作者：
Hwang, SY;Jung, JS;Han, IO
通讯作者：
Han, IO
影响因子：
8.4
作者：
Johannesen, TB;Langmark, F;Lote, K
通讯作者：
Lote, K