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 Ca2+ 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 Ca2+ 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 μM nifedipine could suppress SLE-MNC IFN-γ secretion but 10 μM nifedipine was required for suppressing that of normal MNC. IL-10 secretion by both SLE-MNC and normal MNC was suppressed by 1 μM nifedipine. However, high dose of nifedipine (50 μM) 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 Ca2+ channel blocker-mediated apoptosis and cytokine suppression. We proposed that L-type Ca2+ channel blocker maybe a potential medication for controlling SLE.