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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
Author(s) -
Gombart Adrian F.,
Borregaard Niels,
Koeffler H. Phillip
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3284com
Subject(s) - cathelicidin , calcitriol receptor , antimicrobial peptides , peptide , myeloid cells , vitamin d and neurology , receptor , gene , myeloid , antimicrobial , microbiology and biotechnology , biology , immunology , genetics , endocrinology , biochemistry
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 α‐ and β‐defensins and cathelicidins. In this study, we show that 1,25‐dihydroxyvitamin D 3 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 D 3 and the VDR in regulation of primate innate immunity. Gombart, A. F., Borregaard, N., Koeffler, H. P. 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 . FASEB J. 19, 1067–1077 (2005)