Vitamin d-directed rheostatic regulation of monocyte antibacterial responses

Research output: Contribution to journalJournal articleResearchpeer-review

John S Adams, Songyang Ren, Philip T Liu, Rene F Chun, Venu Lagishetty, Adrian F Gombart, Niels Borregaard, Robert L Modlin, Martin Hewison

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D) enhances innate immunity by inducing the cathelicidin antimicrobial peptide (hCAP). In monocytes/macrophages, this occurs primarily in response to activation of TLR, that induce expression of the vitamin D receptor and localized synthesis of 1,25(OH)(2)D from precursor 25-hydroxyvitamin D(3) (25OHD). To clarify the relationship between vitamin D and innate immunity, we assessed changes in hCAP expression in vivo and ex vivo in human subjects attending a bone clinic (n = 50). Of these, 38% were vitamin D-insufficient (<75 nM 25OHD) and received supplementation with vitamin D (50,000 IU vitamin D(2) twice weekly for 5 wk). Baseline 25OHD status or vitamin D supplementation had no effect on circulating levels of hCAP. Therefore, ex vivo changes in hCAP for each subject were assessed using peripheral blood monocytes cultured with 10% autologous serum (n = 28). Under these vitamin D "insufficient" conditions the TLR2/1 ligand 19 kDa lipopeptide or the TLR4 ligand LPS, monocytes showed increased expression of the vitamin D-activating enzyme CYP27b1 (5- and 5.5-fold, respectively, both p < 0.01) but decreased expression of hCAP mRNA (10-fold and 30-fold, both p < 0.001). Following treatment with 19 kDa, expression of hCAP: 1) correlated with 25OHD levels in serum culture supplements (R = 0.649, p < 0.001); 2) was significantly enhanced by exogenous 25OHD (5 nM); and 3) was significantly enhanced with serum from vivo vitamin D-supplemented patients. These data suggest that a key role of vitamin D in innate immunity is to maintain localized production of antibacterial hCAP following TLR activation of monocytes
Udgivelsesdato: 2009/4/1
Original languageEnglish
JournalJournal of Immunology
Volume182
Issue number7
Pages (from-to)4289-4295
Number of pages6
ISSN0022-1767
DOIs
Publication statusPublished - 2009

Bibliographical note

Keywords: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Antimicrobial Cationic Peptides; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Humans; Immunity, Innate; Male; Middle Aged; Monocytes; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptor 4; Vitamin D; Vitamin D Deficiency

ID: 17215578