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Journal of Lipid Research, Vol. 46, 752-758, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

n-3 PUFAs modulate T-cell activation via protein kinase C- and - and the NF-B signaling pathway

Anne Denys, Aziz Hichami and Naim Akhtar Khan¹

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

¹ To whom correspondence should be addressed. e-mail: naim.khan{at}u-bourgogne.fr

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 A₂ (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)- and -. The two n-3 PUFAs also inhibited the nuclear translocation of nuclear factor B (NF-B) 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 A₂, modulate IL-2 gene expression by exerting their action on two PKC isoforms and NF-B in Jurkat T-cells.

Abbreviations: AACOCF3, arachidonyl trifluoromethyl ketone; BEL, bromoenol lactone; BpB, 4-bromo-phenacyl-bromide; cPLA₂, cytosolic phospholipase A₂; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; ERK, extracellular signal-regulated kinase; I-B, inhibitor B; IL-2, interleukin-2; iPLA₂, calcium-independent phospholipase A₂; MAPK, mitogen-activated protein kinase; NF-B, nuclear factor B; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI/PS, phosphatidylinositol/phosphatidylserine; PKC, protein kinase C; PLA₂, phospholipase A₂; PMA, phorbol 12-myristate 13-acetate; sPLA₂, secreted phospholipase A₂

Supplementary key words fatty acids • mitogen-activated protein kinase • polyunsaturated fatty acids • nuclear factor B

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