IJMS, Vol. 18, Pages 2497: Quercetin Mitigates Inflammatory Responses Induced by Vascular Endothelial Growth Factor in Mouse Retinal Photoreceptor Cells through Suppression of Nuclear Factor Kappa B (International Journal of Molecular Sciences)
Retinal vascular endothelial growth factor (VEGF) increased by neovascularization is well known as a pathogenic factor in ocular neovascular diseases. However, it is still unclear how retinal neurons are damaged by VEGF. The aims of this study are to demonstrate the inflammatory protein expression regulated by VEGF using mouse photoreceptor-derived cells and the protective effect of quercetin against VEGF-induced inflammatory response. Expression and phosphorylation of protein and expression of mRNA were detected by immunoblot and reverse transcriptase polymerase chain reaction. VEGF-induced degradation of limiting membrane and translocation of nuclear factor kappa B (NF-?B) were analyzed by immunocytochemistry. VEGF treatment activated angiogenic signaling pathway in photoreceptor cells. In addition, adhesion molecules and matrix metalloproteinases were increased in VEGF-treated photoreceptor cells. All these events were reversed by quercetin. Zona occludins-1 and ?-catenin decreased by VEGF were recovered by quercetin. NF-?B signaling pathway regulated by VEGF through phosphorylations of mitogen-activated protein kinases (MAPK) and protein kinase B (Akt) was suppressed by quercetin. These results suggest that quercetin suppressed VEGF-induced excessive inflammatory response in retinal photoreceptor cells by inactivation of NF-?B signals through inhibition of MAPKs and Akt. These data may provide a basic information for development of pharmaceuticals or nutraceuticals for treatment of retinal diseases caused by excessive VEGF.