Role of MCP-1 and IL-8 in viral anterior uveitis, and contractility and fibrogenic activity of trabecular meshwork cells.
Role of MCP-1 and IL-8 in viral anterior uveitis, and contractility and fibrogenic activity of trabecular meshwork cells.
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DOI：
10.1038/s41598-021-94391-2
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发表时间：
2021-07-22
影响因子：
4.6
通讯作者：
Rao PV
中科院分区：
文献类型：
--
作者：
Lee J;Choi JA;Ju HH;Kim JE;Paik SY;Rao PV
炎症趋化因子单核细胞趋化蛋白（MCP）-1和IL-8由正常小梁细胞（TM）产生，并在原发性开角型青光眼（POAG）和与病毒感染相关的高血压性前葡萄膜炎的房水中升高。然而，它们在TM细胞和房水流出中的作用仍不清楚。在此，我们探讨了MCP-1和IL-8在房水外流和病毒性前葡萄膜炎中可能参与TM细胞的生理学。我们发现，刺激人TM细胞与MCP-1和IL-8诱导的肌动蛋白应力纤维和粘着斑的形成，肌球蛋白轻链磷酸化，和TM细胞的收缩显着增加。MCP-1和IL-8也表现出细胞外基质蛋白的升高和TM细胞的迁移。当TM细胞感染HSV-1和CMV病毒时，细胞骨架收缩和Rho-GTPase活化显着增加。病毒感染的TM细胞的MCP-1和IL-8的表达显着增加。总之，这些结果表明，MCP-1和IL-8诱导TM细胞收缩性，纤维化活性，和可塑性，这被认为是增加抵抗水流出的病毒性前葡萄膜炎和POAG。
The inflammatory chemokines, monocyte chemoattractant protein (MCP)-1 and IL-8, are produced by normal trabecular meshwork cells (TM) and elevated in the aqueous humor of primary open angle glaucoma (POAG) and hypertensive anterior uveitis associated with viral infection. However, their role in TM cells and aqueous humor outflow remains unclear. Here, we explored the possible involvement of MCP-1 and IL-8 in the physiology of TM cells in the context of aqueous outflow, and the viral anterior uveitis. We found that the stimulation of human TM cells with MCP-1 and IL-8 induced significant increase in the formation of actin stress fibers and focal adhesions, myosin light chain phosphorylation, and the contraction of TM cells. MCP-1 and IL-8 also demonstrated elevation of extracellular matrix proteins, and the migration of TM cells. When TM cells were infected with HSV-1 and CMV virus, there was a significant increase in cytoskeletal contraction and Rho-GTPase activation. Viral infection of TM cells revealed significantly increased expression of MCP-1 and IL-8. Taken together, these results indicate that MCP-1 and IL-8 induce TM cell contractibility, fibrogenic activity, and plasticity, which are presumed to increase resistance to aqueous outflow in viral anterior uveitis and POAG.
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