Peeradech ThichanpiangSteven J. HarperKanokpan WongprasertDavid O. BatesMahidol UniversityUniversity of BristolUniversity of Nottingham2018-11-092018-11-092014-06-10Molecular Vision. Vol.20, (2014), 781-789109005352-s2.0-84902334387https://repository.li.mahidol.ac.th/handle/20.500.14594/34240Purpose: 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.Mahidol UniversityMedicineArticleSCOPUS