Anti-inflammatory property of quercetin through downregulation of ICAM-1 and MMP-9 in TNF-α-activated retinal pigment epithelial cells

Quercetin is a flavonoid polyphenolic compound present in fruits and vegetables that has proven anti-inflammatory activity. The goal of the present investigation was to investigate the effects of quercetin on tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory responses via the expression of ICAM-1 and MMP-9 in human retinal pigment epithelial cells (ARPE-19 cells). Real-time PCR, gelatin zymography, and Western blot analysis showed that TNF-alpha induced the expression of ICAM-1 and MMP-9 protein and mRNA in a time-dependent manner. These effects were attenuated by pretreatment of ARPE-19 cells with quercetin. Quercetin inhibited the TNF-alpha-induced phosphorylation of PKCS, JNK1/2, ERK1/2. Quercetin, rottlerin, SP600125 and U0126 attenuated TNF-alpha-stimulated c-Jun phosphorylation and AP-1 Luc activity. Pretreatment with quercetin, rottlerin, SP600125, or Bay 11-7082 attenuated TNF-alpha-induced NF-kappa B (p65) phosphorylation, translocation and Re1A/p65 Luc activity. TNF-alpha significantly increased MMP-9 promoter activity and THP-1 cell adherence, and these effects were attenuated by pretreatment with quercetin, rottlerin, SP600125, U0126, tanshinone IIA or Bay 117082. These results suggest that quercetin attenuates TNF-alpha-induced ICAM-1 and MMP-9 expression in ARPE-19 cells via the MEK1/2 ERK1/2 and PKC delta JNK1/2 c-Jun or NF-kappa B pathways.