RT Journal Article
SR Electronic
T1 Cutting Edge: 1,25-Dihydroxyvitamin D<sub>3</sub> Is a Direct Inducer of Antimicrobial Peptide Gene Expression
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 2909
OP 2912
DO 10.4049/jimmunol.173.5.2909
VO 173
IS 5
A1 Wang, Tian-Tian
A1 Nestel, Frederick P.
A1 Bourdeau, Véronique
A1 Nagai, Yoshihiko
A1 Wang, Qiuyu
A1 Liao, Jie
A1 Tavera-Mendoza, Luz
A1 Lin, Roberto
A1 Hanrahan, John W.
A1 Mader, Sylvie
A1 White, John H.
YR 2004
UL http://www.jimmunol.org/content/173/5/2909.abstract
AB The hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)2D3 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)2D3 is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin β2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)2D3-dependent gene expression. 1,25(OH)2D3 induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)2D3 along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)2D3 induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)2D3 thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.