{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:52:37Z","timestamp":1761155557995},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2012,3,2]],"date-time":"2012-03-02T00:00:00Z","timestamp":1330646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Abnormal Ca2+-mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca2+ signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca2+ level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-\u03b3 and granulocyte\u2013macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3\u2003+\u2003anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50\u2003\u00b5M) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-\u03b3)\/Th2 (IL-10) cytokine production in both groups. The Ca2+ influx was lower in anti-CD3\u2003+\u2003anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50\u2003ng\/ml) of cyclosporin, 1\u2003\u00b5M nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-\u03b3 secretion and NFAT-regulated gene (GM-CSF and IFN-\u03b3) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca2+ channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca2+-calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2012.04563.x","type":"journal-article","created":{"date-parts":[[2012,1,12]],"date-time":"2012-01-12T13:10:50Z","timestamp":1326373850000},"page":"78-86","source":"Crossref","is-referenced-by-count":9,"title":["Combination of nifedipine and subtherapeutic dose of cyclosporin additively suppresses mononuclear cells activation of patients with rheumatoid arthritis and normal individuals via Ca2+\u2013calcineurin\u2013nuclear factor of activated T cells pathway"],"prefix":"10.1093","volume":"168","author":[{"given":"N-S","family":"Lai","sequence":"first","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology"},{"name":"School of Medicine, Tzu Chi University, Hualien"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C-L","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W-Y","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Buddhist Dalin Tzu Chi General Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H-C","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H-B","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Life Science and Institute of Molecular Biology, National Chung Cheng University, Chia-Yi"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C-H","family":"Tung","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M-C","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Allergy, Immunology and Rheumatology"},{"name":"School of Medicine, Tzu Chi University, Hualien"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,3,2]]},"reference":[{"key":"2021122708380856300_b1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ceca.2010.10.003","article-title":"Ca(2+) signaling, genes and the cell cycle","volume":"48","author":"Machaca","year":"2010","journal-title":"Cell Calcium"},{"key":"2021122708380856300_b2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1046\/j.0019-2805.2001.01321.x","article-title":"Calcium channels in 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