Dietary omega-3 polyunsaturated fatty acids reduce IFN-gamma receptor expression in mice

Enrichment of immune cells in vivo or in vitro with omega-3 polyunsaturated fatty acid (n-3 PUFA) has been reported to diminish their response to inte rferon-gamma (IFN-gamma), We hypothesized that the n-3 PUFA-induced hypores ponsiveness to IFN-gamma is mediated, in part, by a reduction in the number of IFN-gamma receptors (IFNGR) expressed on the surface of these cells. To test this hypothesis, we fed mice experimental diets containing low or hig h amounts of n-3 PUFA, Thioglycollate-elicited peritoneal macrophages (PEC) were collected and tested for binding and internalization of [I-125]-label ed recombinant murine IFN-gamma, High n-3 PUFA intake was associated with a significant (n = 2,p < 0.01) reduction in [I-125]-IFN-gamma binding withou t affecting binding affinity (K-d) When studies were performed at 37 degree s C, high n-3 PUFA intake reduced internalization of [I-125]-rmIFN-gamma by 20%-30% (n = 2, p < 0.001). Results from flow cytometric analysis of IFNGR -1 expression on the surface of murine splenocytes were in agreement with t he binding studies. Further, total cellular IFNGR-1 from PEC and splenocyte s was examined via immunoprecipitation and Western blotting, High n-3 PUFA diet was associated with a 50% decline (n = 3-6, p < 0.05) in total IFNGR-1 in both immune cell populations studied. These data suggest that reduced I FNGR expression may be responsible for immune cell hyporesponsiveness to IF N-gamma, which may, in part, explain some of the immunomodulatory and anti- inflammatory effects associated with the consumption of diets high in n-3 P UFA.