n-3 PUFAs modulate T-cell activation via protein kinase C-alpha and -epsilon and the NF-kappaB signaling pathway.
We elucidated the mechanisms of action of two n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in Jurkat T-cells. Both DHA and EPA were principally incorporated into phospholipids in the following order: phosphatidylcholine < phosphatidylethanolamine < phosphatidylinositol/phosphatidylserine. Furthermore, two isoforms of phospholipase A(2) (i.e., calcium-dependent and calcium-independent) were implicated in the release of DHA and EPA, respectively, during activation of these cells. The two fatty acids inhibited the phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane translocation of protein kinase C (PKC)-alpha and -epsilon. The two n-3 PUFAs also inhibited the nuclear translocation of nuclear factor kappaB (NF-kappaB) and the transcription of the interleukin-2 (IL-2) gene in PMA-activated Jurkat T-cells. Together, these results demonstrate that DHA and EPA, being released by two isoforms of phospholipase A(2), modulate IL-2 gene expression by exerting their action on two PKC isoforms and NF-kappaB in Jurkat T-cells.
Denys
Anne
A
University of Burgundy, Department of Physiology, Unité Propre de Recherche et de l'Enseignement Supérieur (UPRES) Lipids and Nutrition, Faculty of Life Sciences, Dijon 21000, France.
Hichami
Aziz
A
Khan
Naim Akhtar
NA
D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*
D015525:Fatty Acids, Omega-3; D007376:Interleukin-2; D007527:Isoenzymes; D016328:NF-kappa B; D010703:Phorbol Esters; D010743:Phospholipids; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C496628:PRKCA protein, human; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D010741:Phospholipases A