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Peeradech Thichanpiang, David Bates, Kanokpan Wongprasert; Recombinant VEGF165b inhibits TNF-α-induced ICAM-1 expression and monocyte adhesion in primary human retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):153.
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Local inflammation at the retinal pigment epithelial (RPE) cell layer is associated with inflammatory cell migration and secretion of pro-inflammatory cytokines such as Tumor necrosis factor (TNF)-α. TNF-α up-regulates Intercellular Cell Adhesion Molecule (ICAM)-1 expression on RPE that allows binding of lymphocyte function-associated antigen-1 (LFA-1) on leukocytes contributing to leukocyte adhesion at sites of inflammation. VEGF165b is generated by alternative splicing of VEGF-A in the terminal exon 8. VEGF165b is cytoprotective and anti-angiogenic but its effects on inflammation have not been elucidated. Therefore, our aim was to investigate the effects of VEGF165b on TNF-α-induced ICAM-1 expression and monocyte adhesion in RPE cells.
Primary RPE cells were pretreated with 20 ng/ml TNF-α alone, 100 ng/ml VEGF165b alone, 100 ng/ml VEGF165b with 100 ng/ml anti-VEGF165b, 100 ng/ml VEGF165b or 10 nM ZM323881 (VEGFR2 inhibitor) prior to exposure to 20 ng/ml TNF-α for 24 h. After the experiment, cells were lysed for Western blotting and monocyte adhesion assays were performed.
VEGF165b and ZM323881 inhibited TNF-α-induced upregulation of ICAM-1 in RPE cells. VEGF165b was neutralized by antibody to VEGF165b (Figure 1). VEGF165b ameliorated the TNF-α-induced monocyte-RPE adhesion (Figure 2).
These findings indicate that VEGF165b inhibits the TNF-α-mediated upregulation of ICAM-1 expression and increases monocyte-RPE cell adhesion, suggesting an anti-inflammatory property of VEGF165b in the eye.
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