αB-Crystallin Alleviates Endotoxin-Induced Retinal Inflammation and Inhibits Microglial Activation and Autophagy.
αB-Crystallin Alleviates Endotoxin-Induced Retinal Inflammation and Inhibits Microglial Activation and Autophagy.
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αB-晶状体蛋白减轻内毒素引起的视网膜炎症并抑制小胶质细胞活化和自噬
DOI：
10.3389/fimmu.2021.641999
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发表时间：
2021
影响因子：
7.3
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Wang F;Jiang Z;Lou B;Duan F;Qiu S;Cheng Z;Ma X;Yang Y;Lin X
αB-Crystallin 是小热休克蛋白 (sHSP) 家族的成员，通过抑制多种疾病中的小胶质细胞活化来发挥免疫调节和神经保护作用。然而，其对内毒素引起的葡萄膜炎（EIU）的作用尚不清楚。自噬可能与小胶质细胞活化有关，αB-晶状体蛋白参与某些细胞自噬的调节。 αB-晶状体蛋白在小胶质细胞自噬中的作用尚不清楚。本研究旨在探讨 αB-晶状体蛋白对培养的 BV2 细胞和 EIU 小鼠模型中视网膜小胶质细胞自噬、小胶质细胞激活和神经炎症的作用。我们的结果表明，αB-晶状体蛋白在 mRNA 和蛋白质水平上减少了典型促炎细胞因子的释放，在形态上抑制了小胶质细胞的活化，并在体外抑制了自噬相关分子的表达和自噬溶酶体的数量。在 EIU 小鼠模型中，通过光学相干断层扫描和视网膜电图评估，αB-晶状体蛋白治疗减轻了眼部炎症细胞因子的释放和炎症的代表性体征，减少了神经节细胞的凋亡，并挽救了视网膜炎症结构和功能损伤。综上所述，这些结果表明 αB-晶状体蛋白抑制小胶质细胞的活化并抑制小胶质细胞自噬，最终减少内毒素诱导的神经炎症。总之，αB-晶状体蛋白为影响小胶质细胞自噬和减轻眼部炎症疾病症状提供了一种新颖且有前景的选择。
αB-Crystallin, a member of the small heat shock protein (sHSP) family, plays an immunomodulatory and neuroprotective role by inhibiting microglial activation in several diseases. However, its effect on endotoxin-induced uveitis (EIU) is unclear. Autophagy may be associated with microglial activation, and αB-crystallin is involved in the regulation of autophagy in some cells. The role of αB-crystallin in microglial autophagy is unknown. This study aimed to explore the role of αB-crystallin on retinal microglial autophagy, microglial activation, and neuroinflammation in both cultured BV2 cells and the EIU mouse model. Our results show that αB-crystallin reduced the release of typical proinflammatory cytokines at both the mRNA and protein level, inhibited microglial activation in morphology, and suppressed the expression of autophagy-related molecules and the number of autophagolysosomes in vitro. In the EIU mouse model, αB-crystallin treatment alleviated the release of ocular inflammatory cytokines and the representative signs of inflammation, reduced the apoptosis of ganglion cells, and rescued retinal inflammatory structural and functional damage, as evaluated by optical coherence tomographic and electroretinography. Taken together, these results indicate that αB-crystallin inhibits the activation of microglia and supresses microglial autophagy, ultimately reducing endotoxin-induced neuroinflammation. In conclusion, αB-crystallin provides a novel and promising option for affecting microglial autophagy and alleviating symptoms of ocular inflammatory diseases.
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DOI：
10.1158/1078-0432.ccr-11-0915
发表时间：
2011-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Mineharu Y;King GD;Muhammad AK;Bannykh S;Kroeger KM;Liu C;Lowenstein PR;Castro MG
通讯作者：
Castro MG
影响因子：
5.3
作者：
Klopstein, Armelle;Santos-Nogueira, Eva;Lopez-Vales, Ruben
通讯作者：
Lopez-Vales, Ruben
影响因子：
7.3
作者：
Kovaleva M;Johnson K;Steven J;Barelle CJ;Porter A
通讯作者：
Porter A
自噬对于超细颗粒诱导的气道上皮炎症和粘液过度产生至关重要
影响因子：
13.3
作者：
Chen, Zhi-Hua;Wu, Yin-Fang;Shen, Hua-Hao
通讯作者：
Shen, Hua-Hao
抑制 Notch1 信号传导通过调节视网膜小胶质细胞偏振减轻内毒素引起的炎症
影响因子：
7.3
作者：
Cheng, Zhixing;Yang, Yao;Lin, Xiaofeng
通讯作者：
Lin, Xiaofeng