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Objective(s): Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of IL-17, IL- 23, IL-4 and IFN-γ were assessed in activated chromatin-induced mouse model for SLE. Materials and Methods: Five groups of mice were included in this study; Group one received active chromatin +CFA + PBS; Group 2 received vitamin D3 starting 2 weeks before disease induction; Group 3 received vitamin D3 (50 ng/day) starting with the disease establishment; Group 4 received non active chromatin +CFA + PBS; Group 5 received CFA + PBS. On day 56 splenocytes were isolated and gene expression of interleukin IL-17, IL-23, IL-4 and IFN-γ were analyzed by Real-Time PCR method. Proteinuria and serum anti-dsDNA and Th17 levels were measured using commercial kits. Results: The results showed that IL-17, IL-23, and IFN-γ mRNA expression, and IL-17 titers were decreased remarkably and that of IL-4 increased in mice which received vitamin D3 before SLE induction. Administration of vitamin D3 after the establishment of SLE failed to affect the IL-17 or IL- 23 mRNA levels. Lastly, pre-treatment of mice with vitamin D3 decreased the anti-ds DNA antibody titer. Conclusion: Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE. [ABSTRACT FROM AUTHOR]

Objective(s): Genetic and environmental factors are involved in the pathogenesis of systemic lupus erythematosus (SLE). Autoreactive lymphocytes are cleared through apoptosis and any disturbance in the apoptosis or clearance of apoptotic cells may disturb tolerance and lead to autoimmunity. Vitamin D has anti-proliferative effects and controls cell cycle progression. In this study we investigated the effects of vitamin D on cell cycle and apoptosis induction in lupus patients. Materials and Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 25 SLE patients were cultured in the presence of 50 nM of 1,25(OH)2D3; then one part of the cells were stained with FITC labeled Annexin V and PI and were analyzed for apoptosis determination. For gene expression assessment of FasL, Bcl-2 and Bax, RNA was extracted from one another part of the cells, cDNA was synthesized and gene expression analysis was performed using Real time PCR. An additional part of the cells were treated with PI and the cell cycle was analyzed using flowcytometer. Results: The mean number of early apoptotic cells in vitamin D treated cells decreased significantly (18.48±7.9%) compared to untreated cells (22.02±9.4%) (P=0.008). Cell cycle analysis showed a significant increase in G1 phase in vitamin D treated cells (67.33±5.2%) compared to non treated ones (60.77±5.7%) (P =0.02). Vitamin D up-regulated the expression levels of Bcl-2 by (18.87 fold increase), and down-regulated expression of Bax (23%) and FasL (25%). Conclusion: Vitamin D has regulatory effects on cell cycle progression, apoptosis and apoptosis related molecules in lupus patients. [ABSTRACT FROM AUTHOR]