Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes.
OBJECTIVE
To determine whether vitamin D(3) modulates monocytic expression of intracellular Toll-like receptors (TLRs) 3, 7 and 9.


METHODS
Human monocytes were isolated from peripheral blood and cultured with 100 nM vitamin D(3) for 24, 48 and 72 h. Expression of CD14 and TLR2, TLR3, TLR4, TLR7 and TLR9 were examined by flow cytometry. Monocytes exposed to vitamin D(3) for 48 h were then stimulated with a TLR9 agonist for a further 24 h. The level of IL-6 secretion was measured by ELISA.


RESULTS
CD14 was up-regulated, whereas TLR2, TLR4 and TLR9 expression was down-regulated by vitamin D(3) exposure in a time-dependent manner. TLR3 expression was unaffected by vitamin D(3) and there was no measurable expression of TLR7 on the monocytes. TLR9-induced IL-6 production was impaired in monocytes treated with vitamin D(3) compared with untreated cells.


CONCLUSIONS
The intracellular TLRs are differentially regulated by vitamin D(3), with TLR9 being down-regulated by vitamin D(3) exposure whereas TLR3 was unaffected. This decreased TLR9 expression in monocytes had a downstream functional effect as these cells subsequently secreted less IL-6 in response to TLR9 challenge. This may have significant biological relevance and may be a factor in the association of vitamin D deficiency with susceptibility to autoimmune disease.
Dickie
Laura J
LJ
NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Church
Leigh D
LD
Coulthard
Lydia R
LR
Mathews
Rebeccah J
RJ
Emery
Paul
P
McDermott
Michael F
MF
D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D013223:Statistics as Topic; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism*
D015850:Interleukin-6; D051217:Toll-Like Receptor 9; D002762:Cholecalciferol