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

• Published in: Molecular vision 2014-06, Vol.20, p.781-789
• Main Authors: Thichanpiang, Peeradech, Harper, Steven J, Wongprasert, Kanokpan, Bates, David O
• Format: Article
• Language: English
• Subjects: Autocrine Communication - drug effects; Cell Adhesion - drug effects; Cell Count; Cells, Cultured; Gene Expression Regulation - drug effects; Humans; Intercellular Adhesion Molecule-1 - metabolism; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Neovascularization, Physiologic - drug effects; Protein Isoforms - metabolism; Retinal Pigment Epithelium - cytology; Tumor Necrosis Factor-alpha - pharmacology; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1090-0535; 1090-0535

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)-A(165)b is generated by alternative splicing of VEGF-A in the terminal exon, exon 8. VEGF-A(165)b is cytoprotective and antiangiogenic, but its effects on inflammation have not yet been elucidated. Therefore, we tested the hypothesis that VEGF-A(165)b regulates TNF-α-induced ICAM-1 expression and monocyte adhesion in RPE cells. Primary RPE cells were pretreated with TNF-α alone, VEGF-A(165)b alone, VEGF-A(165)b with anti-VEGF-A(165)b, or the VEGFR-2 inhibitor ZM323881 before exposure to TNF-α for 24 h. Western blotting and monocyte adhesion assays were performed. VEGF-A(165)b and ZM323881 inhibited TNF-α-induced upregulation of ICAM-1 in RPE cells. The effect of VEGF-A(165)b was neutralized by an antibody to VEGF-A(165)b. VEGF-A(165)b ameliorated TNF-α-induced monocyte-RPE adhesion. These findings indicate that VEGF-A(165)b inhibits TNF-α-mediated upregulation of ICAM-1 expression and increases monocyte-RPE cell adhesion, suggesting an anti-inflammatory property of VEGF-A(165)b in the eye.