Vitamin D3 ameliorates herpes simplex virus-induced Behçet's disease-like inflammation in a mouse model through down-regulation of Toll-like receptors.

Abstract

OBJECTIVES: This study was conducted to understand the role of vitamin D3 through the regulation of Toll like receptors (TLRs) and cytokines in herpes simplex virus-induced Behçet's disease (BD)-like mice.

METHODS: Serum 25-hydroxyvitamin D (1,25(OH)2D3) levels were measured in BD-like mice, as well as virus injected and asymptomatic appearance BD normal mice (BDN). The frequencies of TLRs of peritoneal macrophages were compared by FACS. To determine the effect of vitamin D3 in vitro, peritoneal macrophages were isolated and then incubated with 1,25(OH)2D3. To identify the mechanism of improvement of BD-like symptoms induced by 1,25(OH)2D3, mice were orally administered 1,25(OH)2D3.

RESULTS: The serum 25-hydroxyvitamin D levels in BD-like mice were 12.4 ± 5.4ng/ml, while they were 17.5 ± 7.2ng/ml in BDN mice. The frequency of TLR2 in BD-like mice was 32.91 ± 20.88%, while it was 12.73 ± 7.67% in BDN. The frequency of TLR4 was 26.09 ± 10.20% in BD-like mice and 9.72 ± 5.30% in BDN. In a 72 h culture of peritoneal macrophages in 10-8 M 1,25(OH)2D3, the frequency of TLR2 was 25.0 ± 2.7%, while it was 37.3 ± 5.8% in the control group. The frequency of TLR4 was 18.9 ± 5.3% with 1,25(OH)2D3, while it was 30.3 ± 0.1% in the control group. Treatment with 1,25(OH)2D3 improved the symptoms in six out of 11 BD-like mice and downregulated the frequency of TLR2 and TLR4. Moreover, 1,25(OH)2D3 influenced Interleukin-6 and TNF-alpha expression in the sera of BD-like mice.

CONCLUSIONS: Vitamin D improved BD-like symptoms by down-regulating the expression of TLRs and pro-inflammatory cytokines in in vivo mouse models.