Cutting Edge: 1,25-Dihydroxyvitamin D3 Is a Direct Inducer of Antimicrobial Peptide Gene Expression
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Abstract
The hormonal form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is an immune system modulator and induces expression of the TLR coreceptor CD14. 1,25(OH)(2)D(3) 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)(2)D(3) is a direct regulator of antimicrobial innate immune responses. The promoters of the human cathelicidin antimicrobial peptide (camp) and defensin beta2 (defB2) genes contain consensus vitamin D response elements that mediate 1,25(OH)(2)D(3)-dependent gene expression. 1,25(OH)(2)D(3) induces antimicrobial peptide gene expression in isolated human keratinocytes, monocytes and neutrophils, and human cell lines, and 1,25(OH)(2)D(3) along with LPS synergistically induce camp expression in neutrophils. Moreover, 1,25(OH)(2)D(3) induces corresponding increases in antimicrobial proteins and secretion of antimicrobial activity against pathogens including Pseudomonas aeruginosa. 1,25(OH)(2)D(3) thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections.
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The record
- Venue
- The Journal of Immunology
- Topic
- Antimicrobial Peptides and Activities
- Field
- Immunology and Microbiology
- Canadian institutions
- McGill University and Génome Québec Innovation CentreUniversité de MontréalMcGill University
- Funders
- —
- Keywords
- CathelicidinAntimicrobial peptidesAntimicrobialBeta defensinBiologyCalcitriol receptorInnate immune systemGene expressionPeptideDefensinImmune systemMicrobiologyGeneCell biologyMolecular biologyBiochemistryImmunology
- Has abstract in OpenAlex
- yes