Cutting edge:: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression

The hormonal form of vitamin D-3, 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)(2)D-3 signals through the vitamin D receptor, a ligand-stimulated transcription factor that recognizes specific DNA sequences called vitamin D response elements. In this study, we show that 1,25(OH)(2)D-3 is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin beta2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)(2)D-3-dependent gene expression. 1,25(OH)(2)D-3 induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)(2)D-3 along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)(2)D-3 induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)(2)D-3 thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.