Docosahexaenoic acid reduces linoleic acid induced monocyte chemoattractant protein‐1 expression via PPARγ and nuclear factor‐κB pathway in retinal pigment epithelial cells

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 PPARγ  was examined using RT-PCR and Western blot analysis. LA at 10, 25, or 50 μM induced expression of MCP ARPE-19 cells in a dose-dependent manner (p < 0.05). DHA at 50 and 100 μM effectively inhibited LA-induced MCP-1 expression and production (p < 0.05) and NF-κB activation. In addition, the culture medium from LA-stimulated ARPE-19 cells could induce tube formation in choroidal endothelial cells (RF6A), whereas 100 μM DHA inhibited tube formation. DHA at 100 μM increased the expression and activity of PPARγ (p < 0.05). Pretreatment with PPARγ inhibitor (GW9662) abolished the inhibitory effect of DHA (100 μM) on LA-induced IκB 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 PPARγ- and NF-κB-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.