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 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.
Lu
Ming-Chi
MC
Division of Allergy, Immunology and Rheumatology, Buddhist DaLin Tzu-Chi General Hospital, Chia-Yi, Taiwan.
Lai
Ning-Sheng
NS
Yu
Hui-Chun
HC
Hsieh
Song-Chou
SC
Tung
Chien-Hsueh
CH
Yu
Chia-Li
CL
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D019703:Calcineurin / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D050778:NFATC Transcription Factors / Q000276:immunology / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; D016753:Interleukin-10; D007371:Interferon-gamma; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases; D009543:Nifedipine