Inhibition of proliferation of human peripheral blood mononuclear cells by calcium antagonists. Role of interleukin-2.
To evaluate the role of interleukin-2 (IL-2) in the inhibition of the proliferation of human peripheral blood mononuclear cells (PBMC) by calcium channel blockade, the effect of nifedipine, which blocks the L-type calcium channel on the proliferation, the IL-2 expression and the IL-2 production in human PBMC, was compared with the effect of mibefradil, which blocks both L- and T-type calcium channels with a more selective blockade of T-type channels. The rate of [3H]-thymidine incorporation into control and concanavalin A-induced PBMC in the presence or absence of the calcium channel blockers nifedipine or mibefradil (1, 10 or 50 microM) was assayed in the cells cultured for 3 days. The cellular cytotoxicity and the cell number in growing cultures was also determined in nifedipine- or mibefradil-treated control or stimulated cells. Restoration of the proliferative response in nifedipine- or mibefradil-treated cells was investigated by addition of exogenous IL-2. IL-2 receptor expression in the cells was monitored using antiactivated T-cell antigen (Tac) antibody, and the IL-2 production in the cell supernatants of the cultures was determined by an enzyme amplified sensitive immunoassay. Nifedipine and mibefradil concentration-dependently reduced the cell number and [3H]-thymidine incorporation or the do novo DNA synthesis in control and concanavalin A-stimulated human PBMC. The proliferative response of nifedipine- or mibefradil-treated cells was restored by addition of exogenous IL-2. The normal expression of IL-2 receptors was preserved while the IL-2 production was blocked in the presence of nifedipine or mibefradil.
Petrov
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V
Department of Molecular and Cardiovascular Research, KULeuven, Leuven, Belgium.
Lijnen
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P
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020748:Mibefradil / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000187:drug effects
D002121:Calcium Channel Blockers; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D020748:Mibefradil; D007770:L-Lactate Dehydrogenase; D009543:Nifedipine