1,25-Dihydroxyvitamin D3 Modulates Expression of Chemokines and Cytokines in Pancreatic Islets: Implications for Prevention of Diabetes in Nonobese Diabetic Mice

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) is an immune modulator that prevents experimental autoimmune diseases. Receptors for 1,25-(OH)2D3 are present in pancreatic β-cells, the target of an autoimmune assault in nonobese diabetic (NOD) mice. The aim of this study was to investigate the in vivo and in vitro effects of 1,25-(OH)2D3 on β-cell gene expression and death and correlate these findings to in vivo diabetes development in NOD mice. When female NOD mice were treated with 1,25-(OH)2D3 (5 μg/kg per 2 d), there was a decrease in islet cytokine and chemokine expression, which was accompanied by less insulitis. Complementing these findings, we observed that exposure to 1,25-(OH)2D3 in three cell systems INS-1E cell line, fluorescence-activated cell sorting purified rat β-cells, and NOD-severe combined immunodeficient islets) suppressed IP-10 and IL-15 expression in the β-cell itself but did not prevent cytokine-induced β-cell death. This 1,25-(OH)2D3-induced inhibition of chemokine expression in β-cells w...