Role of MCP-1 and IL-8 in viral anterior uveitis, and contractility and fibrogenic activity of trabecular meshwork cells

• Published in: Scientific reports Vol. 11; no. 1; p. 14950
• Main Authors: Lee, Jiyoung, Choi, Jin A, Ju, Hyun-Hee, Kim, Ju-Eun, Paik, Soon-Young, Rao, Ponugoti Vasantha
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 22.07.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Actin; Adult; Aqueous Humor - immunology; Cell Movement; Cells, Cultured; Chemokine CCL2 - metabolism; Chemokines; Contractility; Contraction; Cytomegalovirus - pathogenicity; Cytoskeleton; Extracellular matrix; Extracellular Matrix Proteins - metabolism; Eye Infections, Viral - immunology; Eye Infections, Viral - pathology; Fibers; Glaucoma; Guanine nucleotide-binding protein; Herpesvirus 1, Human - pathogenicity; Humans; Inflammation; Interleukin 8; Interleukin-8 - metabolism; Leukocyte migration; Middle Aged; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Myosin; Phosphorylation; Primary Cell Culture; Receptors, CCR2 - metabolism; Receptors, Interleukin-8A - metabolism; Trabecular Meshwork - cytology; Trabecular Meshwork - immunology; Trabecular Meshwork - virology; Uveitis; Uveitis, Anterior - immunology; Uveitis, Anterior - pathology; Uveitis, Anterior - virology; Viral infections
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-94391-2

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.