Abstract
Periodontitis is an inflammatory disease leading to the destruction of periodontal tissue. Vitamin D3 is an important hormone involved in the preservation of serum calcium and phosphate levels, regulation of bone metabolism and inflammatory response. Recent studies suggest that vitamin D3 metabolism might play a role in the progression of periodontitis. The aim of the present study was to examine the effects of 25(OH)D3, which is stable form of vitamin D3 in blood, and biologically active form 1,25(OH)2D3 on the production of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) by cells of periodontal ligament. Commercially available human periodontal ligament fibroblasts (hPdLF) and primary human periodontal ligament cells (hPdLC) were used. Cells were stimulated with either Porphyromonas gingivalis lipopolysaccharide (LPS) or heat-killed P. ginigvalis in the presence or in the absence of 25(OH)D3 or 1,25(OH)2D3 at concentrations of 10–100 nM. Stimulation of cells with either P. gingivalis LPS or heat-killed P. gingivalis resulted in a significant increase of the expression levels of IL-6, IL-8, and MCP-1 in gene as well as in protein levels, measured by qPCR and ELISA, respectively. The production of these pro-inflammatory mediators in hPdLF was significantly inhibited by both 25(OH)D3 and 1,25(OH)2D3 in a dose-dependent manner. In primary hPdLCs, both 25(OH)D3 and 1,25(OH)2D3 inhibited the production of IL-8 and MCP-1 but have no significant effect on the IL-6 production. The effect of both 25(OH)D3 and 1,25(OH)2D3 was abolished by specific knockdown of vitamin D3 receptor by siRNA. Our data suggest that vitamin D3 might play an important role in the modulation of periodontal inflammation via regulation of cytokine production by cells of periodontal ligament. Further studies are required for better understanding of the extents of this anti-inflammatory effect and its involvement in the progression of periodontal disease.
Highlights
Vitamin D3 is known to play an important role in the bone metabolism and mineral homeostasis [1]
The effect of 25(OH)D3 and 1,25(OH)2D3 on the gene expression levels of pro-inflammatory mediators IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) in human periodontal ligament fibroblasts (hPdLF) in response to stimulation with P. gingivalis LPS and heat-killed P. gingivalis is shown on the Figures 2 and 3, respectively
We focused on the measurements of the expression of IL-6, IL-8, and MCP-1, which are produced by periodontal ligament cells and are thought to play an important role in the progression of periodontal disease
Summary
Vitamin D3 is known to play an important role in the bone metabolism and mineral homeostasis [1]. Vitamin D3 is first converted by liver to 25(OH)D3 (calcifediol), which has a half life time of about 15 day [2]. Calcifideol could be further converted into the active form of vitamin D3 calcitriol (1,25(OH)2D3) by specific enzyme 25(OH)D1a-hydroxylase. The half life time of 1,25(OH)2D3 is about 15 h [2] and its biological effects are mediated by activation of the vitamin D3 receptor (VDR), a member of the nuclear receptor superfamily [3]. For a long time it was thought that the expression of 1a-hydroxylase is limited to kidney, but this enzyme is found to be expressed in numerous extrarenal tissues [4]. There are accumulating evidences that vitamin D3 is involved in the regulation of immune response [5]
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