Conclusions
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.
Methods
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.
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)-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.
Results
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. Conclusions: 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.