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 interferon-y (IFN-gamma). We hypothesized that the n-3 PUFA-induced hyporesponsiveness 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 high amounts of n-3 PUFA. Thioglycollate-elicited peritoneal macrophages (PEC) were collected and tested for binding and internalization of [125I]-labeled recombinant murine IFN-gamma. High n-3 PUFA intake was associated with a significant (n = 2, p < 0.01) reduction in [125I]-IFN-gamma binding without affecting binding affinity (Kd). When studies were performed at 37 degrees C, high n-3 PUFA intake reduced internalization of [125I]-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 the binding studies. Further, total cellular IFNGR-1 from PEC and splenocytes 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 IFNGR expression may be responsible for immune cell hyporesponsiveness to IFN-gamma, which may, in part, explain some of the immunomodulatory and anti-inflammatory effects associated with the consumption of diets high in n-3 PUFA.
Feng
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Graduate Nutritional Sciences Program, College of Agriculture, Food & Natural Resources, University of Missouri Columbia 65211, USA.
Keisler
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DH
Fritsche
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KL
D000818:Animals; D015153:Blotting, Western; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D017471:Receptors, Interferon / Q000096:biosynthesis*; D011994:Recombinant Proteins; D000096743:Interferon gamma Receptor
D015525:Fatty Acids, Omega-3; D007371:Interferon-gamma; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D000096743:Interferon gamma Receptor