Docosahexaenoic acid reduces linoleic acid induced monocyte chemoattractant protein-1 expression via PPAR gamma and nuclear factor-kappa B pathway in retinal pigment epithelial cells

摘要

Scope: To investigate whether docosahexaenoic acid (DHA) could inhibit linoleic acid (LA) induced monocyte chemoattractant protein (MCP)-1 expression in human retinal pigment epithelial (RPE) cells. Methods and results: ARPE-19 cells were pretreated with DHA and then exposed to LA. The expression of MCP-1 and PPAR gamma was examined using RT-PCR and Western blot analysis. LA at 10, 25, or 50 mu M induced expression of MCP ARPE-19 cells in a dose-dependent manner (p < 0.05). DHA at 50 and 100 mu M effectively inhibited LA-induced MCP-1 expression and production (p < 0.05) and NF-kappa B activation. In addition, the culture medium from LA-stimulated ARPE-19 cells could induce tube formation in choroidal endothelial cells (RF6A), whereas 100 mu M DHA inhibited tube formation. DHA at 100 mu M increased the expression and activity of PPAR gamma (p < 0.05). Pretreatment with PPAR gamma inhibitor (GW9662) abolished the inhibitory effect of DHA (100 mu M) on LA-induced I kappa B degradation, p65 translocation, and MCP-1 expression in ARPE-19 cells (p < 0.05), as well as tube formation in RF6A. Conclusion: DHA reduced LA-induced MCP-1 expression via a PPAR gamma- and NF-kappa B-dependent pathway in ARPE-19 cells. These results suggest the molecular mechanisms underlying the beneficial effects of increased consumption of DHA and reduced consumption of LA on age-related macular degeneration.