title: Role of indoleamine 2,3-dioxygenase in an inflammatory model of murine gingiva.
abstract: OBJECTIVE
  Indoleamine 2,3-dioxygenase (IDO) is one of the major pathways for metabolism of tryptophan in a variety of cells, including immune cells. Increasing evidence indicates that IDO is a critical player in establishing the balance between immunity and tolerance and ultimately in the maintenance of homeostasis. By inducing inflammation in gingival tissue, we tested the hypothesis that IDO is a pivotal player in regulating the immune and inflammatory responses of gingiva.
  
  
  METHODS
  We utilized the IDO knockout mouse model in conjunction with lipopolysaccharide (LPS)-induced inflammation. Accordingly, wild-type and IDO knockout mice were injected with LPS or vehicle in the anterior mandibular gingiva, twice over a 2-wk period, which was followed by procurement of gingival tissue for histopathology and preparation of tissue for flow cytometry-based studies.
  
  
  RESULTS
  Clinical and histological examinations revealed a marked adverse impact of IDO deficiency on gingival inflammation. These observations were consistent with a more marked increase in the number of cells positive for the proinflammatory cytokine interleukin (IL)-17, but no significant change in the number of cells positive for the anti-inflammatory cytokine IL-10, in LPS-treated IDO knockout mice. Consistent with the more marked proinflammatory impact of IDO deficiency, the percentage of regulatory T cells was much reduced in gingival tissue of LPS-treated IDO knockout mice than in gingival tissue of wild-type mice. These proinflammatory changes were accompanied with a prominent increase in apoptotic and necrotic cell death in gingival tissue of IDO knockout mice compared with wild-type mice.
  
  
  CONCLUSIONS
  Collectively, our findings support a major role for IDO in the development of gingival inflammation, as an example of an inflammatory condition, and lay the foundation for subsequent studies to explore it as a novel immunotherapy target.
authors.affiliation: Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA.|The 3rd Department, Plastic Surgery Hospital (Institute), CAMS&PUMC, Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Pashley
authors.affiliation: Department of Oral Rehabilitation, Dental College of Georgia, Augusta University, Augusta, GA, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Al-Hashim
authors.affiliation: Department of Oral Health and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Abdelsayed
authors.affiliation: Department of Surgery, Section of Plastic Surgery, School of Medicine, Augusta University, Augusta, GA, USA.
authors.forename: J
authors.initials: J
authors.lastname: C Yu
authors.affiliation: Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Mozaffari
authors.affiliation: Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA, USA.|Department of Surgery, Section of Plastic Surgery, School of Medicine, Augusta University, Augusta, GA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Baban
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005891:Gingivitis / Q000201:enzymology* / Q000473:pathology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides
keywords: Tregs; apoptosis; gingivitis; indoleamine 2,3-dioxygenase; inflammation; periodontitis