Both 25-Hydroxyvitamin-D3 and 1,25-Dihydroxyvitamin-D3 Reduces Inflammatory Response in Human Periodontal Ligament Cells

Periodontitis is an inflammatory disease leading to the destruction of periodontal tissue. Vitamin D-3 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 D-3 metabolism might play a role in the progression of periodontitis. The aim of the present study was to examine the effects of 25(OH)D-3, which is stable form of vitamin D-3 in blood, and biologically active form 1,25(OH)(2)D-3 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)D-3 or 1,25(OH)(2)D-3 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)D-3 and 1,25(OH)(2)D-3 in a dose-dependent manner. In primary hPdLCs, both 25(OH)D-3 and 1,25(OH)(2)D-3 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)D-3 and 1,25(OH)(2)D-3 was abolished by specific knockdown of vitamin D-3 receptor by siRNA. Our data suggest that vitamin D-3 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.