Role of indoleamine 2,3-dioxygenase in an inflammatory model of murine gingiva

X. Qin, J. Y. Liu, T. Wang, D. H. Pashley, A. H. Al-Hashim, R. Abdelsayed, J. C Yu, M. S. Mozaffari, B. Baban

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background and 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. Material and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalJournal of Periodontal Research
Volume52
Issue number1
DOIs
StatePublished - Feb 1 2017

Keywords

  • Tregs
  • apoptosis
  • gingivitis
  • indoleamine 2,3-dioxygenase
  • inflammation
  • periodontitis

ASJC Scopus subject areas

  • Periodontics

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