Human Cathelicidin is Vitamin D Driven

Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3

Adrian F. Gombart*,1, Niels Borregaard{dagger} and H. Phillip Koeffler*

The innate immune system of mammals provides a rapid response to repel assaults from numerous infectious agents including bacteria, viruses, fungi, and parasites. A major component of this system is a diverse combination of cationic antimicrobial peptides that include the - and ß-defensins and cathelicidins. In this study, we show that 1,25-dihydroxyvitamin D₃ and three of its analogs induced expression of the human cathelicidin antimicrobial peptide (CAMP) gene. This induction was observed in acute myeloid leukemia (AML), immortalized keratinocyte, and colon cancer cell lines, as well as normal human bone marrow (BM) -derived macrophages and fresh BM cells from two normal individuals and one AML patient. The induction occurred via a consensus vitamin D response element (VDRE) in the CAMP promoter that was bound by the vitamin D receptor (VDR). Induction of CAMP in murine cells was not observed and expression of CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-type levels. Comparison of mammalian genomes revealed evolutionary conservation of the VDRE in a short interspersed nuclear element or SINE in the CAMP promoter of primates that was absent in the mouse, rat, and canine genomes. Our findings reveal a novel activity of 1,25-dihydroxyvitamin D₃ and the VDR in regulation of primate innate immunity.

We humans only have one cathelicidin (pronounced cath-i-li-cye-den) antimicrobial peptide, which is known as LL-37 and FALL-39. CAMP is a potent antimicrobial substance that is part of our immune system that is used to destroy pathogens identified in the body, such as bacteria, fungi, parasites, etc. Another recent study I reviewed has informed me that this, our only cathelicidin, is dependent on vitamin D for its production.