The differences in Ca2 signalling dynamics induced by the different PUFAs, selleckchem Pazopanib did not correlate with the activa tion of pERK 1 2 induced by the same PUFAs. AA in duced a slower pERK 1 2 kinetic response than EPA and DHA. DHA gave strongest pERK 1 2 activation after 20 min of treatment compared to AA and EPA, but these differences were not considered significant. We further show that the activation of pERK 1 2 is a result of EGF these pathways are activated differently by EPA, DHA and AA in Caco 2 cells might gain new insights into var iations in the different PUFAs ability to induce the secre tion of GLP 1 and CCK. Increased dietary intake of omega 6 PUFAs, and a lower dietary intake of omega 3 PUFAs are though to contribute to the development of IBD.

There is clear evidence that omega 6 PUFAs exert pro inflammatory events com pared to omega 3 PUFAs. However, our results sug gest that both omega 3 and omega 6 PUFAs exert the same anti inflammatory Inhibitors,Modulators,Libraries effects by inhibiting NF ��B activ ity after binding GPR120 on Caco 2 cells. DHA, EPA and AA were all able to inhibit IL 1B induced breakdown of I��B, but EPA and AA mediated the strongest inhibitory effects. Since this effect was independent of Raf 1 and EGF receptor, we speculate whether GPR120 may inhibit IL 1B signalling in the same manner as TLR4 signalling. These findings challenge the view that only omega 3 PUFAs exert anti inflammatory Inhibitors,Modulators,Libraries effects after binding GPR120. Our results may also be important in the under standing of how long chain PUFAs, not only omega 3 PUFAs influence the inflammatory response in patients with IBD.

In conclusion, our results show that both omega 3 and receptor transactivation involving Raf 1 kinase. Long chain PUFAs are known to activate EGF receptor in other cellular systems, Inhibitors,Modulators,Libraries but this activation has not been linked to GPR120. In the present study, we show that pretreatment with the EGF receptor specific inhibi Inhibitors,Modulators,Libraries tor Iressa, and Raf 1 inhibitor GW5074 abolish ERK1 2 activation induced by EPA. Raf 1 is a crucial kinase in the MAP kinase signalling cascade leading to activation of ERK1 2. EGF receptor can activate the Ras Raf Mek cascade through the activation of Grb2 and SOS. The finding that PKA inhibitor H89 did not influence ERK1 2 activity is in line with previous studies describing GPR120 signalling, where no study has reported activation of PKA after GPR120 activation.

Both cytosolic Ca2 increase and pERK1 2 activation are involved in GPR120 induced secretion of GLP 1 and CCK from intestinal cells. The findings that omega 6 PUFAs activate the same Inhibitors,Modulators,Libraries GPR120 mediated sig nalling events in Caco 2 cells, but differences regarding intensity and kinetics were observed. Previously, anti inflammatory effects of GPR120 have only been linked to omega 3 PUFAs. We show, for the first new time that they might be linked to both omega 3 and omega 6 PUFAs.