Omega-3 and omega-6 PUFAs induce the same GPR120-mediated signalling events, but with different kinetics and intensity in Caco-2 cells

Background: Omega-3 PUFAs are known to have anti-inflammatory properties, and different mechanisms are involved. GPR120 is a G-protein coupled receptor that has recently received attention because of its anti-inflammatory signalling properties after binding omega-3 PUFAs. However, both omega-3 and omega-6 PUFAs are natural GPR120 ligands. The aim of this study was to study possible differences in GPR120-mediated signalling events after treatment with different long-chain PUFAs in intestinal epithelial cells. We also investigated possible GPR120-mediated anti-inflammatory effects of different long-chain PUFAs that may be relevant in the understanding of how dietary PUFAs influence inflammatory responses in inflammatory diseases such as IBD. Methods: We used Caco-2 cells as a model system to study GPR120-mediated signalling events because we found this cell line to express GPR120, but not GPR40, another plasma membrane receptor for medium- and long chain fatty acids. Increase in cytosolic Ca2+ concentration, activation of MAP kinase ERK1/2 and the inhibition of IL-1 beta induced NF-kappa B activity were studied to reveal potential differences in the activation of GPR120 by the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the omega-6 PUFA arachidonic acid (AA). Results: We found that EPA, DHA and AA enhanced the cytosolic concentration of the second messenger Ca2+ with the same efficiency, but with different kinetics. Both omega-3 and omega-6 PUFAs activated MAP kinase ERK1/2, but differences regarding kinetics and intensity were also observed in this pathway. ERK1/2 activation was shown to be dependent upon EGFR and Raf-1. We further investigated the ability of EPA, DHA and AA to inhibit NF-kappa B activity in Caco-2 cells. All PUFAs tested were able to inhibit IL-1 beta induced breakdown of I kappa B alpha after binding to GPR120, but with different potency. Conclusions: Our results show that EPA, DHA and AA elicit the same signalling events, but with different kinetics and efficiency through GPR120 in Caco-2 cells. We show, for the first time, that both omega-3 and omega-6 PUFAs inhibit NF-kappa B activation in intestinal epithelial cells. Our results may be important for understanding how dietary PUFAs influence inflammatory processes relevant in delineating effects of PUFAs in the treatment of IBD.