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 D ₃

Abstract

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 alpha- and beta-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.

Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers

“…Some of recent studies also show that adequate concentrations of the vitamin D stimulates genetic expression of antimicrobial peptides in human monocytes, neutrophils and other human cell lines (Wang et al, 2004;Gombart et al, 2005;Ustianowski et al, 2005;Cannell et al, 2006;Liu et al, 2006). Also, adult patients with higher concentrations of vitamin D have significantly better lung function compared to patients with lower concentrations of vitamin D (Black and Scragg, 2005).…”

维生素d 在免疫反应和自身免疫性疾病特别是多发性硬化中的作用

“…1,25(OH) 2 D 3 also induces the production of cathelicidin, a peptide involved in the activation of innate immune responses, by macrophages and epithelial cells [44][45][46] .…”

The vitamin D receptor in cancer

“…This control by VDR is underscored by studies showing that vdr -/ -mice are more sensitive to chemicals that induce inflammation than their wild-types counterparts (135) . The normally protective effect of inflammation that occurs under other conditions is lost through this VDR-mediated suppression but is compensated by the induction of a cohort of antimicrobial and antifungal genes via the innate immune response (136)(137)(138) . The induction of antimicrobials not only prevents infection in damaged tissue but can be cytotoxic for cells with increased levels of anion phospholipids within their membranes, a common feature of transformed cells (139) ; experimental results are, however, conflicting.…”