Nifedipine suppresses Th1/Th2 cytokine production and increased apoptosis of anti-CD3 + anti-CD28-activated mononuclear cells from patients with systemic lupus erythematosus via calcineurin pathway

Increased Ca(2+) influx is found in mononuclear cells (MNC) of patients with systemic lupus erythematosus (SLE). The role of calcineurin and potential implication of calcium channel blocker to suppress the abnormal Ca(2+) influx in SLE remain to be determined. In the present study, we found that the...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 129(2008), 3 vom: 10. Dez., Seite 462-70
1. Verfasser: Lu, Ming-Chi (VerfasserIn)
Weitere Verfasser: Lai, Ning-Sheng, Yu, Hui-Chun, Hsieh, Song-Chou, Tung, Chien-Hsueh, Yu, Chia-Li
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2008
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Adaptor Proteins, Signal Transducing CABIN1 protein, human CD28 Antigens CD3 Complex Calcium Channel Blockers Calcium Channels, L-Type Cytokines FASLG protein, human mehr... Fas Ligand Protein NFATC Transcription Factors NFATC1 protein, human Interleukin-10 130068-27-8 Interferon-gamma 82115-62-6 Calcineurin EC 3.1.3.16 Phosphoric Monoester Hydrolases EC 3.1.3.2 Nifedipine I9ZF7L6G2L
Beschreibung
Zusammenfassung:Increased Ca(2+) influx is found in mononuclear cells (MNC) of patients with systemic lupus erythematosus (SLE). The role of calcineurin and potential implication of calcium channel blocker to suppress the abnormal Ca(2+) influx in SLE remain to be determined. In the present study, we found that the expression and phosphatase activity of calcineurin, but not calcineurin inhibitor in SLE-MNC were greater than normal MNC. Functionally, 1 microM nifedipine could suppress SLE-MNC IFN-gamma secretion but 10 microM nifedipine was required for suppressing that of normal MNC. IL-10 secretion by both SLE-MNC and normal MNC was suppressed by 1 microM nifedipine. However, high dose of nifedipine (50 microM) suppressed NFATc1 activation in SLE-MNC and enhanced apoptosis of anti-CD3 + anti-CD28-activated SLE-MNC irrelevant to expression of Fas ligand. These data suggest that SLE-MNC overexpressed calcineurin and hyper-responded to L-type Ca(2+) channel blocker-mediated apoptosis and cytokine suppression. We proposed that L-type Ca(2+) channel blocker maybe a potential medication for controlling SLE
Beschreibung:Date Completed 04.12.2008
Date Revised 16.11.2017
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2008.08.001