title: Indoleamine 2,3-dioxygenase expression and regulation in chronic periodontitis.
abstract: BACKGROUND
  Indoleamine 2,3-dioxygenase (IDO) is an intracellular tryptophan-oxidizing enzyme with immunosuppressive characteristics. Its expression and regulation in periodontal tissues are unknown. The aim of this study was to determine IDO expression in healthy gingiva and chronic periodontitis lesions. In addition, the effect of inflammatory cytokines and bacterial products on the expression and activity of DOI in human gingival fibroblasts (HGFs) was assessed.
  
  
  METHODS
  Human gingival tissue samples were obtained from patients who underwent periodontal surgery. IDO expression in healthy gingiva and periodontitis lesions was determined by immunohistochemistry. HGF cells were treated with interferon-gamma (IFN-gamma), interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccharides from Porphyromonas gingivalis (PgLPS). IDO mRNA expression was determined by reverse transcription-polymerase chain reaction. The IDO enzymatic activity was determined by measuring the kynurenine level using a colorimetric method.
  
  
  RESULTS
  In gingival tissues, IDO expression was detected in epithelial cells, fibroblasts, endothelial cells, and inflammatory mononuclear cells. IDO expression was higher in periodontitis lesions than in healthy gingiva. HGFs did not constitutively express IDO. IFN-gamma strongly induced IDO expression and activity in HGFs, in a dose-dependent manner. IL-1beta, TNF-alpha, and PgLPS were also able to induce IDO expression in HGF cells. IFN-gamma in combination with IL-1beta, TNF-alpha, or PgLPS showed enhanced IDO expression.
  
  
  CONCLUSIONS
  IDO was expressed in human gingiva, and the expression was upregulated in chronic periodontitis. The increased IDO expression in periodontitis lesions may be due, in part, to the activation of HGFs by inflammatory cytokines and bacterial products.
authors.affiliation: Department of Periodontology, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Nisapakultorn
authors.forename: Jittima
authors.initials: J
authors.lastname: Makrudthong
authors.forename: Noppadol
authors.initials: N
authors.lastname: Sa-Ard-Iam
authors.forename: Pimprapa
authors.initials: P
authors.lastname: Rerkyen
authors.forename: Rangsini
authors.initials: R
authors.lastname: Mahanonda
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
mesh_terms: D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000201:enzymology*; D003124:Colorimetry; D003238:Connective Tissue / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016966:Porphyromonas gingivalis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma