Dietary docosahexaenoic acid suppresses T cell protein kinase C theta lipid raft recruitment and IL-2 production.
To date, the proximal molecular targets through which dietary n-3 polyunsaturated fatty acids (PUFA) suppress the inflammatory process have not been elucidated. Because cholesterol and sphingolipid-enriched rafts have been proposed as platforms for compartmentalizing dynamically regulated signaling assemblies at the plasma membrane, we determined the in vivo effects of fish oil and highly purified docosahexaenoic acid (DHA; 22:6n-3) on T cell microdomain lipid composition and the membrane subdomain distribution of signal-transducing molecules (protein kinase C (PKC)theta;, linker for activation of T cells, and Fas/CD95), before and after stimulation. Mice were fed diets containing 5 g/100 g corn oil (control), 4 g/100 g fish oil (contains a mixture of n-3 PUFA) plus 1 g/100 g corn oil, or 4 g/100 g corn oil plus 1 g/100 g DHA ethyl ester for 14 days. Dietary n-3 PUFA were incorporated into splenic T cell lipid raft and soluble membrane phospholipids, resulting in a 30% reduction in raft sphingomyelin content. In addition, polyclonal activation-induced colocalization of PKCtheta; with lipid rafts was reduced by n-3 PUFA feeding. With respect to PKCtheta; effector pathway signaling, both AP-1 and NF-kappaB activation, IL-2 secretion, and lymphoproliferation were inhibited by fish oil feeding. Similar results were obtained when purified DHA was fed. These data demonstrate for the first time that dietary DHA alters T cell membrane microdomain composition and suppresses the PKCtheta; signaling axis.
Fan
Yang-Yi
YY
Molecular and Cell Biology Section, Faculty of Nutrition, Texas A&M University Health Science Center, College Station, TX 77843-2471, USA.
Ly
Lan H
LH
Barhoumi
Rola
R
McMurray
David N
DN
Chapkin
Robert S
RS
D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D021962:Membrane Microdomains / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism
D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D004281:Docosahexaenoic Acids; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta