Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future

Vitamin D was discovered as the preventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary calcium. However, a variety of studies over the last several years has revealed that vitamin D controls much more than calcium homeostasis. For example, recent research has underlined the key role of vitamin D signaling in regulation of innate immunity in humans. Vitamin D is converted to 25-hydroxyvitamin D (25D), its major circulating form, and then to hormonal 1,25-dihydroxyvitamin D (1,25D) in target cells. We now know that when cells of the immune system such a macrophages sense a bacterial infection they acquire the capacity to convert circulating 25D into 1,25D. Moreover, 1,25D thus produced is a direct inducer of expression of genes encoding antimicrobial peptides, in particular cathelicidin antimicrobial peptide (CAMP). Antimicrobial peptides such as CAMP are vanguards of innate immune responses to bacterial infection and can act as signaling molecules to regulate immune system function. This review covers what we have learned in the past few years about the expression and function of CAMP under physiological and pathophysiological conditions, and addresses the potential future applications of vitamin D analogues to therapeutic regulation of CAMP expression.