Inhibition of murine T-cell responses by anti-oxidants: the targets of lipo-oxygenase pathway inhibitors.
We have previously established that oxidative phenomena are involved in human T-cell activation (Sekkat, Dornand & Gerber, 1988). In the present work we have studied the effect of different anti-oxidants (scavengers of O2-, .OH and lipo-oxygenase inhibitors) on the stimulation of murine T cells. We report here that all the anti-oxidants used suppressed T-lymphocyte proliferation and IL-2 synthesis, the former effect resulting very likely from the latter. This inhibition was concomitant with the triggering of activation. We also demonstrate that the various anti-oxidants have different biochemical targets. Unlike the other compounds, the phenolic drugs nordihydroguaiaretic acid (NDGA) and butylated hydroxyanisole (BHA), which block lipid peroxidation, affect both signals triggered by the binding of lectin to its receptors: they suppress the rise of intracellular free calcium concentration and inhibit some of the events, depending on the sole protein kinase C activation, namely IL-2 receptor expression and phorbol myristate acetate (PMA)-induced pH change. Our results are discussed within the framework of a possible involvement of reactive oxygen species and of arachidonic acid derivative(s) in T-cell activation and IL-2 production.
Dornand
J
J
CNRS, Laboratoire de Biochimie des Membranes, Montpellier, France.
Gerber
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects*; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D007376:Interleukin-2; D016859:Lipoxygenase Inhibitors; D015375:Receptors, Interleukin-2; D002083:Butylated Hydroxyanisole; D009637:Masoprocol; D002118:Calcium