Eicosapentaenoic acid and docosahexaenoic acid modulate MAP kinase enzyme activity in human T-cells.
In order to investigate the implication of docosahexacnoic acid (DHA) and eicosapentaenoic acid (EPA) in T signalling, we assessed their effects on the activation of two mitogen activated protein (MAP) kinases, i.e. extracellularly-regulated kinases 1 and 2 (ERK1/ERK2) in Jurkat T-cells. The n-3 polyunsaturated fatty acids (PUFAs) alone failed to induce MAP kinase (MAPK) enzyme activity. To elucidate whether DHA and EPA act via protein kinase C (PKC) dependent and independent pathways, we employed their respective activators, i.e. phorbol 12-myristate 13-acetate (PMA) and antiCD3 antibodies. We observed that U0126, an inhibitor of MAPK kinase-ERK kinase 1/2 (MEK1/2), abolished the actions of these two agents on MAPK activation, suggesting that they act upstream of MEK1/2. Further EPA and DHA diminished both the PMA- and antiCD3 antibodies-induced enzyme activity of ERK1/ERK2 in Jurkat T-cells. Interestingly, okadaic acid (OA), a phosphatase inhibitor seems to act downstream of MEK1/2 as U0126 failed to inhibit the OA-induced MAPK activation. It is noteworthy that EPA and DHA not only failed to curtail the OA-induced MAPK activity but also these n-3 PUFAs at 20 microM potentiated the action of OA. Therefore, EPA and DHA seem to modulate MAPK activation upstream and downstream of MEK1/2. On the hand, arachidonic acid, an n-6 PUFA potentiated the MAPK enzyme activity. In conclusion, our study shows that EPA and DHA may regulate T-cells functions by modulating MAPK enzyme activity.
Denys
Anne
A
University of Burgundy, Department of Physiology, UPRES Lipids and Nutrition, Faculty of Life Sciences, Dijon, France.
Hichami
Aziz
A
Khan
Naim Akhtar
NA
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid; D004789:Enzyme Activation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000906:Antibodies; D017252:CD3 Complex; D005231:Fatty Acids, Unsaturated; D019319:Okadaic Acid; D004281:Docosahexaenoic Acids; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D015118:Eicosapentaenoic Acid; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate