title: Vitamin D inhibits the growth of and virulence factor gene expression by Porphyromonas gingivalis and blocks activation of the nuclear factor kappa B transcription factor in monocytes.
abstract: OBJECTIVE
  Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed.
  
  
  METHODS
  A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites.
  
  
  RESULTS
  Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 μg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model.
  
  
  CONCLUSIONS
  Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy.
authors: Oral Ecology Research Group, Faculty of Dentistry, Université Laval, Quebec City, QC, Canada.
authors: D
authors: D
authors: Grenier
authors: Oral Ecology Research Group, Faculty of Dentistry, Université Laval, Quebec City, QC, Canada.
authors: M-P
authors: MP
authors: Morin
authors: Oral Ecology Research Group, Faculty of Dentistry, Université Laval, Quebec City, QC, Canada.
authors: J
authors: J
authors: Fournier-Larente
authors: Department of Stomatology, Hubei University of Science and Technology, Xianning, Hubei, China.
authors: H
authors: H
authors: Chen
mesh_terms: D018829:Adhesins, Bacterial / Q000187:drug effects / Q000235:genetics; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000235:genetics; D004338:Drug Combinations; D036781:Fimbriae Proteins / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D037102:Lectins / Q000187:drug effects / Q000235:genetics; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000187:drug effects / Q000235:genetics; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics; D020298:U937 Cells / Q000187:drug effects; D037521:Virulence Factors / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D004338:Drug Combinations; D000080867:Gingipain Cysteine Endopeptidases; C098582:HagB protein, Porphyromonas gingivalis; D037102:Lectins; D016328:NF-kappa B; D014157:Transcription Factors; D037521:Virulence Factors; C118756:dihydroxy-vitamin D3; C063055:fimbrillin; C114923:hemagglutinin A, Porphyromonas gingivalis; D014807:Vitamin D; D008795:Metronidazole; D036781:Fimbriae Proteins; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases
keywords: Porphyromonas gingivalis; chronic periodontitis; cytokine; host modulatory therapy; macrophage