Summary
We have shown that free radical scavengers inhibit IL2 synthesis and that reactive oxygen species are induced upon T cell activation. Because of their physiological relevance, we concentrated our study on lipoxygenase (LO) inhibitors. We investigated the mechanisms by which LO inhibitors decrease IL2 production in Jurkat cells. We demonstrated that the inhibition, linked to blockade of the [Ca2+]i rise involving TCR triggering, resulted from the action of these compounds on the signal transduction, upstream from inositol-triphosphate synthesis. When the breakdown of inositol phospholipids induced by the ligand-receptor interaction was bypassed, e.g. after PMA+A23187 stimulation, IL2 secretion was also suppressed by LO inhibitors, but at much higher concentrations. This indicates that the event depending upon ligand receptor binding are the main target of LO inhibitors. None of three PKC-dependent events investigated were 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 maintains protein phosphorylation on tyrosine residues and induces IL2 secretion. This suggests that LO inhibitors might affect the tyrosine kinase pathway in TCR- activated Jurkat cells. These results are consistent with a role for LO metabolite(s) in signal transduction pathways. However, some other redox mechanism might be involved at other steps of IL2 synthesis, as indicated by the partial effect of LO inhibitors when the ligand-receptor binding is by-passed, and by the effect of other types of anti-oxidants.
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Gerbert, M., Dornand, J. (1994). Implication of Oxydative Phenomena in T Cell Activation. In: Pasquier, C., Olivier, R.Y., Auclair, C., Packer, L. (eds) Oxidative Stress, Cell Activation and Viral Infection. Molecular and Cell Biology Updates. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7424-3_22
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