TNF-α-induced ICAM-1 expression and monocyte adhesion in human RPE cells is mediated in part through autocrine VEGF stimulation

• Main Authors: Peeradech Thichanpiang, Steven J. Harper, Kanokpan Wongprasert, David O. Bates
• Other Authors: Mahidol University
• Format: Article
• Published: 2018
• Subjects: Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/34240

Purpose: Local inflammation at the RPE cell layer is associated with inflammatory cell migration and secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-α. TNF-α upregulates intercellular adhesion molecule (ICAM)-1 expression on the RPE, which allows lymphocyte function-associated antigen-1 (LFA-1) to bind on leukocytes that contribute to leukocyte adhesion at sites of inflammation. Vascular endothelial growth factor (VEGF)-A165b is generated by alternative splicing of VEGF-A in the terminal exon, exon 8. VEGF-A165b is cytoprotective and antiangiogenic, but its effects on inflammation have not yet been elucidated. Therefore, we tested the hypothesis that VEGF-A165b regulates TNF-α-induced ICAM-1 expression and monocyte adhesion in RPE cells. Methods: Primary RPE cells were pretreated with TNF-α alone, VEGF-A165b alone, VEGF-A165b with anti-VEGF-A165b, or the VEGFR-2 inhibitor ZM323881 before exposure to TNF-α for 24 h. Western blotting and monocyte adhesion as - says were performed. Results: VEGF-A165b and ZM323881 inhibited TNF-α-induced upregulation of ICAM-1 in RPE cells. The effect of VEGF-A165b was neutralized by an antibody to VEGF-A165b. VEGF-A165b ameliorated TNF-α-induced monocyte-RPE adhesion. Conclusions: These findings indicate that VEGF-A165b inhibits TNF-α-mediated upregulation of ICAM-1 expression and increases monocyte-RPE cell adhesion, suggesting an anti-inflammatory property of VEGF-A165b in the eye. © 2014 Molecular Vision.