Effects of Vitamin D on Expression of Toll-like Receptors of Monocytes from Patients with Behcet's Disease

PURPOSE: Behcet’s disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology. Although the exact mechanisms of the increased inflammatory response is not yet clear, infectious agents and immunological cross-reaction with the heat-shock proteins (HSP) are considered to play roles in the pathogenesis. Toll-like receptors (TLRs) are involved in the initiation of innate immune response in several immune mediated inflammatory disease including BD by sensing the various microorganisms and triggering the signalling pathways, causing release of cytokines. Recent studies have noticed the immunomodulatory effect of vitamin D3 through down-regulation of TLR expression in human monocytes. To understand the role of vitamin D affecting innate immunity in BD, we focused on the association between the serum vitamin D concentration and the TLR expression in BD. MATERIALS AND METHODS: Serum 25-hydroxyvitamin D levels were measured in the patients with BD, psoriasis and healthy controls. The expression of CD16, TLR 2 and TLR 4 on blood monocytes was detected by flow cytometric analysis and semiquantitative RT-PCR among those groups. Then we correlated the values of serum 25-hydroxyvitamin D levels with the expression of TLRs and the clinical indicators of disease severity (ESR, CRP) among patients and control groups. Then, to assess the influence of Vitamin D on expression and function of TLRs, human monocytes were treated with increasing concentrations of 1,25(OH)2D3 in vitro . RESULTS: We found a trend toward lower 25-hydroxyvitamin D levels in active BD patients compared to controls. The monocytes of active BD patients showed higher expression of TLR2, TLR4 with increased proportion of CD16+ cells compared to the control groups. Interestingly the 25-hydroxyvitamin D levels were inversely correlated with the expression of TLR2, TLR4 and clinical indicators. In vitro study, 1,25(OH)2D3 suppressed the expression of TLR2, TLR4 protein and mRNA in human monocytes in a dose-dependent manner. TNF-α synthesis upon LPS, LTA and HSP60 stimulation was also decreased in 1,25(OH)2D3 treated monocytes in concordance with TLR2, TLR4 down-regulation. And the marked increase of TNF-α response to TLR2, TLR4 ligands was found in active BD monocytes when compared to normal, which was correlated with the higher TLR2, TLR4 expression. CONCLUSION: We found lower serum 25(OH)D levels among active BD patients compared to controls. These results suggest vitamin D deficiency as a possible risk factor for active BD. And treatment of vitamin D deficiency will have a positive impact on immune health. BD patients are known to be rather susceptible to infectious agents which are recognized by TLRs, and HSP60 induced immune-activation is considered as an endogenous “danger signal” in the pathogenesis of BD. Our results could strengthen the notion about immunomodulatory effects of vitamin D to innate immunity-mediated inflammation in BD through down-regulation of TLR2, TLR4 on monocytes.

Author dc:creator

• 도, 정은

Contributors dc:contributor

• 이, 은소
• 대학원 의학과
• 200624302

• Behcet’s disease
• Monocyte
• Toll-like receptor 2
• Toll-like receptor 4
• Vitamin D
• 단핵구
• 베체트병
• 비타민 D

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000006764
000000006764

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1308