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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Inhibition of proliferation of human peripheral blood mononuclear cells by calcium antagonists. Role of interleukin-2. 1079 Dec 90

In T lymphocytes, sustained calcium (Ca2+) influx through Ca2+ channels localized in the plasma membrane is critical for T cell activation and proliferation. Previous studies indicated that voltage-dependent Ca2+ channels (VDCCs) play a role in Ca2+ mobilization during T lymphocyte activation. However, the role of VDCCs in otherwise nonexcitable cells is still poorly understood. We used RT-PCR to identify a transcript encoding the pore-forming alpha1F-subunit of an L-type Ca2+ channel in T lymphocytes. Its identity was confirmed by DNA sequencing. To further investigate the contribution of Ca2+ influx through VDCCs, we assessed the effects of the 1,4-dihydropyridine L-type Ca2+ channel agonist, (+/-) Bay K 8644, and antagonist, nifedipine, on the human Jurkat T cell leukemia line, human peripheral blood T lymphocytes and mouse splenocytes. We found that treatment of T lymphocytes with (+/-) Bay K 8644 increased intracellular Ca2+ and induced the activation of phosphoextracellular-regulated kinase 1/2 (Erk1/2), whereas nifedipine blocked Ca2+ influx, the activity of Erk1/2 and nuclear factor of activated T cells (NFAT), interleukin-2 (IL-2) production, and IL-2 receptor expression. Nifedipine also significantly suppressed splenocyte proliferation in an in vitro mixed lymphocyte reaction and the proliferation of male antigen (H-Y)-specific T cell receptor-transgenic CD8+ T cells in transplanted male mice in vivo. Taken together these novel findings indicate that an L-type Ca2+ channel plays a significant role in the Ca2+ influx pathways mediating T lymphocyte activation and proliferation in vitro and in vivo.
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PMID:Identification and functional characterization of voltage-dependent calcium channels in T lymphocytes. 1295 28