Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E2 signaling in fat stromal cells
1 Science Department, Bellaire High School, Bellaire, TX, 77401, USA
2 University of Houston, College of Pharmacy, Houston, TX, 77204, USA
3 The Center for Experimental Therapeutics and Pharmacoinformatics, Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, USA
BMC Complementary and Alternative Medicine 2012, 12:143 doi:10.1186/1472-6882-12-143Published: 31 August 2012
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 E2 (PGE2)-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 PGE2 receptors and an HEK293 cell line specifically expressing the recombinant human PGE2 receptor subtype-1 (EP1) 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 PGE2.
It was identified that fish oil best inhibited the PGE2 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 PGE2 signaling. Eicosapentaenoic acid (EPA), another major fatty acid found in fish oil and tested in this study was found to have small effect on EP1 signaling. The study suggested one of the four PGE2 subtype receptors, EP1 as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP1 expressed in HEK293 cells as a target.
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 EP1-mediated PGE2 receptor signaling, and that the inflammatory response stimulated by PGE2 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 PGE2.