Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behcet's disease.
OBJECTIVE
Recent studies have shown the immunomodulatory effect of vitamin D(3) through down-regulation of Toll-like receptor (TLR) expression in human monocytes. To understand the implication of innate immunity with the role of vitamin D affecting TLR expression in Behçet's disease (BD), we focused on the association between the TLR expression and the serum vitamin D concentration in BD.


METHODS
The expression of TLR2, TLR4 and CD16 on monocytes was detected by flow cytometric analysis and RT-PCR. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured in the patients with BD, psoriasis and healthy controls, and then the expression of TLRs was correlated with the value of serum 25(OH)D levels. To assess the influence of vitamin D(3) on expression and function of TLRs in vitro, human monocytes were treated with increasing concentrations of 1,25(OH)(2)D(3).


RESULTS
We found that the monocytes of active BD patients showed higher expressions of TLR2 and TLR4 than those of controls, and serum 25(OH)D levels tended to be lower in active BD. Furthermore, 25(OH)D levels were inversely correlated with the expressions of TLR2, TLR4 and clinical indicators. In vitro analysis showed that vitamin D(3) was found to dose-dependently suppress the protein and mRNA expressions of TLR2 and TLR4. TNF-alpha synthesis was also decreased upon TLR ligand stimulation in vitamin D(3)-treated monocytes.


CONCLUSIONS
These results suggest that the inflammation triggered through TLR2 and TLR4 is important in the pathogenesis of BD. And it seems possible that vitamin D may be used as a therapeutic option by modulating TLR2 and TLR4 expression of monocytes in BD.
Do
J E
JE
Department of Dermatology, Ajou University School of Medicine, 5 Wonchon-Dong, Yeongtong-Gu, Suwon 443-721, South Korea.
Kwon
S Y
SY
Park
S
S
Lee
E-S
ES
D000328:Adult; D001528:Behcet Syndrome / Q000097:blood*; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051195:Toll-Like Receptor 2 / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000097:blood; D051193:Toll-Like Receptors / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D016207:Cytokines; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002117:Calcitriol