Action of Docosa-Hexaenoic Acid is their interference with MAP kinase signaling in mouse CD4+ T cells

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assessed their effects on the activation of two mitogen activated protein (MAP) kinases, i.e. extracellularly-regulated kinases 1 and 2 (ERK1/ERK2) in mouse CD4+ T cells. The n-3 polyunsaturated fatty acids (PUFAs) alone failed to induce MAP kinase (MAPK) enzyme activity. To elucidate whether DHA act via protein kinase C (PKC) dependent and independent pathways, we employed their respective activators, i.e. phorbol 12-myristate 13-acetate (PMA) and anti-CD3 antibodies. DHA diminished the PMA- and anti-CD3-induced phosphorylation of ERK1/ERK2 CD4+ T cells. In the present study, PMA acts mainly via protein kinase C (PKC) whereas anti-CD3 antibodies act via PKC-dependent and–independent mechanisms. We observed that DHA inhibited PMA-stimulated PKC enzyme activity. Together these results suggest that DHA modulate ERK1/ERK2 activation upstream of MEK via PKC-dependent and independent pathways and that these actions may be implicated in DHA-induced immunosuppression. Our study shows that DHA inhibits cell cycle progression.

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