title: Both 25-hydroxyvitamin-D3 and 1,25-dihydroxyvitamin-D3 reduces inflammatory response in human periodontal ligament cells.
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.
authors.affiliation: Division of Oral Biology, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria.
authors.forename: Oleh
authors.initials: O
authors.lastname: Andrukhov
authors.affiliation: Department of Biomedical Science, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Olena
authors.initials: O
authors.lastname: Andrukhova
authors.affiliation: Division of Oral Biology, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria ; Department of Restorative Science, School of Dentistry, Health Science University of Mongolia, Ulan Bator, Mongolia.
authors.forename: Ulamnemekh
authors.initials: U
authors.lastname: Hulan
authors.affiliation: Division of Oral Biology, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria ; Department of Stomatology, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Division of Orthodontics, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bantleon
authors.affiliation: Division of Oral Biology, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria ; Division of Orthodontics, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Rausch-Fan
mesh_terms: D002112:Calcifediol / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000819:agonists / Q000235:genetics; D016209:Interleukin-8 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016966:Porphyromonas gingivalis / Q000737:chemistry; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D002112:Calcifediol; D002117:Calcitriol; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D018167:Receptors, Calcitriol; D000093242:Interleukin-6 Inhibitors; C111835:CCL2 protein, human; C508600:IL6 protein, human