甲基苯丙胺和HIV-1通过激活AIM2炎性体协同诱导小胶质细胞焦亡。

IF 4.5 2区 医学 Q2 CELL BIOLOGY
Lin Miao, Haowei Wang, Xue Yang, Lisha Xu, Ruike Xu, Hanxin Teng, Yue Zhang, Yingjie Zhao, Genmeng Yang, Xiaofeng Zeng
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引用次数: 0

摘要

目的:人类免疫缺陷病毒(HIV)感染的个体滥用甲基苯丙胺(METH)表现出更严重的神经毒性和认知障碍。焦亡是一种由炎性体介导的程序性细胞死亡途径,与多种神经系统疾病有关。本研究旨在阐明AIM2炎症小体在人脑组织和体外模型中甲基甲氧胺和HIV-1 tat诱导的焦亡中的作用。方法:采用免疫组织化学、免疫荧光和免疫印迹技术,对有冰毒滥用史的hiv感染者的死后脑组织进行焦亡标志物和AIM2炎性体成分的分析。慢病毒诱导BV2小胶质细胞抑制AIM2的表达。采用Western blotting和comet assay评估DNA损伤。通过电镜、免疫印迹和免疫荧光检测热释热相关蛋白的表达。采用CCK8法测定细胞活力。结果:在hiv感染的冰毒使用者的脑组织中观察到焦亡标志物和AIM2炎性体成分水平升高。甲基安非他明和甲基安非他明以时间和浓度依赖的方式协同诱导BV2细胞焦亡,并伴有DNA损伤和AIM2炎性体的激活。AIM2的下调显著降低了热释热相关蛋白的表达。结论:甲氧甲胺素和HIV-1 Tat蛋白通过dsDNA损伤激活AIM2炎性体,协同诱导小胶质细胞焦亡。这些发现表明,靶向AIM2炎性体可能是hiv相关神经认知障碍(HAND)的一种有希望的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Methamphetamine and HIV-1 Tat Synergistically Induce Microglial Pyroptosis Via Activation of the AIM2 Inflammasome.

Objective: Human immunodeficiency virus (HIV)-infected individuals who abuse methamphetamine (METH) exhibit more severe neurotoxicity and cognitive impairment. Pyroptosis, a programmed cell death pathway mediated by the inflammasome, has been implicated in various neurological diseases. This study aimed to elucidate the role of the AIM2 inflammasome in METH- and HIV-1 Tat-induced pyroptosis in human brain tissue and in vitro models.

Methods: Postmortem brain tissue from HIV-infected individuals with a history of METH abuse was analyzed for pyroptosis markers and AIM2 inflammasome components using immunohistochemistry, immunofluorescence, and Western blotting. BV2 microglial cells were lentivirally transduced to knockdown AIM2 expression. DNA damage was assessed using Western blotting and the comet assay. Expression of pyroptosis-related proteins was evaluated by electron microscopy, Western blotting, and immunofluorescence. Cell viability was measured using the CCK8 assay.

Results: Elevated levels of pyroptosis markers and AIM2 inflammasome components were observed in brain tissue from HIV-infected METH users. METH and Tat synergistically induced pyroptosis in BV2 cells in a time- and concentration-dependent manner, accompanied by DNA damage and activation of the AIM2 inflammasome. Knockdown of AIM2 significantly reduced the expression of pyroptosis-related proteins.

Conclusion: METH and HIV-1 Tat proteins synergistically induce microglial pyroptosis by activating the AIM2 inflammasome through dsDNA damage. These findings suggest that targeting the AIM2 inflammasome may be a promising therapeutic strategy for HIV-associated neurocognitive disorder (HAND).

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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
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