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pubmed:abstractText |
We investigated the mechanisms by which lipoxygenase (LO) inhibitors decrease interleukin-2 (IL-2) production in Jurkat cells. We demonstrate that the inhibition, linked to blockade of the [Ca2+]i rise involving T cell receptor (TCR) triggering, resulted from the action of these compounds on the signal transduction pathway, upstream from inositol triphosphate synthesis. IL2 secretion induced by phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187, which bypasses the breakdown of inositol phospholipids induced by the ligand-receptor interaction, was still suppressed by LO inhibitors which implies that these drugs also have an inhibitory effect on other target(s). None of the three protein kinase C (PKC)-dependent events investigated was affected in Jurkat cells stimulated in the presence of LO inhibitors. Furthermore, these compounds did not inhibit IL2 production in PMA-treated Jurkat cells cultured with vanadate, which mimics the tyrosine kinase activation pathway and induces IL2 secretion. This suggests that in addition to their effect on the phosphatidylinositol diphosphate pathway-dependent [Ca2+]i rise, LO inhibitors might affect the tyrosine kinase pathway in TCR-activated Jurkat cells, but probably not the PKC-dependent pathway. These results are consistent with a role for LO metabolite(s) in signal transduction pathways.
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