BACKGROUND: Polyunsaturated fatty acids (PUFAs) modulate immune responses particularly by affecting T cell function and are applied clinically as adjuvant immunosuppressants in the treatment of various inflammatory diseases. However, the molecular mechanisms of PUFA-induced immunosuppressive effects are not yet elucidated. Membrane lipid rafts are functional plasma membrane microdomains characterized by a unique lipid environment. Since lipid interactions are crucial for the formation of lipid rafts, the immunomodulatory effects of PUFAs may be due to changes of fatty acid composition in lipid rafts. AIM OF THE STUDY: We investigated the effects of eicosapentaenoic acid (EPA, 20:5 n - 3) supplementation on modulating lipid composition and fatty acyl substitution in their cytoplasmic and exoplasmic lipid leaflet in lipid rafts. METHODS: The human Jurkat E6-1 T cells were cultured in EPA-supplemented medium and the cells treated with stearic acid served as a control. Lipid rafts were isolated by discontinuous sucrose density gradient ultracentrifugation. The lipids in raft and soluble fractions from EPA-treated and control T cells were extracted and separated by gas chromatography. Raft phospholipids were analyzed by mass spectrometry. RESULTS: Our results showed that EPA treatment could alter lipid composition resulting in a considerable increase of unsaturated fatty acyl chains in lipid rafts from EPA-treated T cells compared with control cells. Effective incorporation of EPA to rafts was not only in the exoplasmic but also in the cytoplasmic membrane lipid leaflet. EPA treatment altered the lipid environment in lipid rafts. EPA presented an inhibiting effect on Jurkat T cells proliferation and inhibited IL-2Ralpha expression on the surface of T cells. CONCLUSIONS: Our data provided evidence for an important modification in lipid composition of membrane lipid rafts and T cell function by EPA supplementation.
BACKGROUND:Polyunsaturated fatty acids (PUFAs) modulate immune responses particularly by affecting T cell function and are applied clinically as adjuvant immunosuppressants in the treatment of various inflammatory diseases. However, the molecular mechanisms of PUFA-induced immunosuppressive effects are not yet elucidated. Membrane lipid rafts are functional plasma membrane microdomains characterized by a unique lipid environment. Since lipid interactions are crucial for the formation of lipid rafts, the immunomodulatory effects of PUFAs may be due to changes of fatty acid composition in lipid rafts. AIM OF THE STUDY: We investigated the effects of eicosapentaenoic acid (EPA, 20:5 n - 3) supplementation on modulating lipid composition and fatty acyl substitution in their cytoplasmic and exoplasmic lipid leaflet in lipid rafts. METHODS: The human Jurkat E6-1 T cells were cultured in EPA-supplemented medium and the cells treated with stearic acid served as a control. Lipid rafts were isolated by discontinuous sucrose density gradient ultracentrifugation. The lipids in raft and soluble fractions from EPA-treated and control T cells were extracted and separated by gas chromatography. Raft phospholipids were analyzed by mass spectrometry. RESULTS: Our results showed that EPA treatment could alter lipid composition resulting in a considerable increase of unsaturated fatty acyl chains in lipid rafts from EPA-treated T cells compared with control cells. Effective incorporation of EPA to rafts was not only in the exoplasmic but also in the cytoplasmic membrane lipid leaflet. EPA treatment altered the lipid environment in lipid rafts. EPA presented an inhibiting effect on Jurkat T cells proliferation and inhibited IL-2Ralpha expression on the surface of T cells. CONCLUSIONS: Our data provided evidence for an important modification in lipid composition of membrane lipid rafts and T cell function by EPA supplementation.
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