Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E2 signaling in fat stromal cells.

BACKGROUND: The molecular mechanisms of dietary oils (such as fish oil) and unsaturated fatty acids, which are widely used by the public for anti-inflammation and vascular protection, have not been settled yet. In this study, prostaglandin E(2) (PGE(2))-mediated calcium signaling was used to screen dietary oils and eight unsaturated fatty acids for identification of their anti-inflammatory mechanisms. Isolated fat/stromal cells expressing endogenous PGE(2) receptors and an HEK293 cell line specifically expressing the recombinant human PGE(2) receptor subtype-1 (EP(1)) were cultured and used in live cell calcium signaling assays. The different dietary oils and unsaturated fatty acids were used to affect cell signaling under the specific stimulation of a pathological amount of inflammatory PGE(2). RESULTS: It was identified that fish oil best inhibited the PGE(2) signaling in the primary cultured stromal cells. Second, docosahexaenoic acid (DHA), found in abundance in fish oil, was identified as a key factor of inhibition of PGE(2) signaling. Eicosapentaenoic acid (EPA), another major fatty acid found in fish oil and tested in this study was found to have small effect on EP(1) signaling. The study suggested one of the four PGE(2) subtype receptors, EP(1) as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP(1) expressed in HEK293 cells as a target. CONCLUSION: This study demonstrated the new mechanism behind the positive effects of dietary fish oils in inhibiting inflammation originates from the rich concentration of DHA, which can directly inhibit the inflammatory EP(1)-mediated PGE(2) receptor signaling, and that the inflammatory response stimulated by PGE(2) in the fat stromal cells, which directly related to metabolic diseases, could be down regulated by fish oil and DHA. These findings also provided direct evidence to support the use of dietary oils and unsaturated fatty acids for protection against heart disease, pain, and cancer resulted from inflammatory PGE(2).