Tumor necrosis factor-alpha aggravates gliosis and inflammation of activated retinal Muller cells
Tumor necrosis factor-alpha aggravates gliosis and inflammation of activated retinal Muller cells
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DOI：
10.1016/j.bbrc.2020.07.102
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发表时间：
2020-10-20
影响因子：
3.1
通讯作者：
Wang, Zhongfeng
中科院分区：
文献类型：
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作者：
Hu, Xin;Xu, Meng-Xi;Wang, Zhongfeng
肿瘤坏死因子-α（TNF-α）是从活化的视网膜神经胶质细胞释放的主要炎症因子，与青光眼的发病机制有关。在这项研究中，我们研究了TNF-α是否以及如何影响激活的视网膜Muller细胞的功能条件。我们的研究结果表明，在第I组代谢型谷氨酸受体（mGluR I）激动剂DHPG激活的培养的Muller细胞，TNF-α处理加重细胞胶质增生，表现为胶质细胞酸性蛋白（GFAP）的表达显着增加。TNF-α处理DHPG激活的Muller细胞降低细胞增殖并诱导细胞凋亡。在正常的Muller细胞中，TNF-α处理增加了白细胞抑制因子（LIF）、细胞间粘附分子（ICAM）、血管细胞粘附分子（VCAM）和趋化因子C-C-基序配体2（CCL 2）的mRNA水平，当Muller细胞被预激活时，这些mRNA水平可以显著减弱。然而，TNF-α诱导的炎症因子，如TNF-α，诱导型一氧化氮合酶（iNOS）和白细胞介素-6（IL-6）的mRNA水平的升高，在正常的Muller细胞仍然保持较高的水平时，Muller细胞被预激活。此外，TNF-α诱导的细胞因子变化部分由NF-κ B信号通路介导。提示TNF-α可促进活化的Muller细胞的胶质增生和炎症反应，从而加重青光眼RGC的损伤。(c)2020爱思唯尔公司All rights reserved.
Tumor necrosis factor-alpha (TNF-alpha), a major inflammatory factor released from activated retinal glial cells, is implicated in the pathogenesis of glaucoma. In this study, we investigated whether and how TNF-alpha may affect functional conditions of activated retinal Muller cells. Our results showed that in the group I metabotropic glutamate receptor (mGluR I) agonist DHPG-activated cultured Muller cells, TNF-a treatment aggravated cell gliosis, as evidenced by significantly increased expression of glial fibrillary acidic protein (GFAP). TNF-alpha treatment of the DHPG-activated Muller cells decreased cell proliferation and induced cell apoptosis. In normal Muller cells, TNF-alpha treatment increased the mRNA levels of leukocyte inhibitory factor (LIF), intercellular cell adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and chemokine C-C-motif ligand 2 (CCL2), which could be significantly attenuated when Muller cells were pre-activated. However, TNF-alpha-induced elevation in mRNA levels of inflammatory factors, such as TNF-alpha, inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6), in normal Muller cells still kept higher levels when Muller cells were pre-activated. Furthermore, the TNF-alpha-induced changes of cytokines were partially mediated by NF-kappa B signaling pathway. Our results suggest that TNF-alpha may promote gliosis and inflammatory response of activated Muller cells, thus aggravating RGC injury in glaucoma. (c) 2020 Elsevier Inc. All rights reserved.