title: Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airways.
abstract: BACKGROUND
  Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan catabolism, is important in generating tolerance at the foetal-maternal interface. Studies using 1-methyl-tryptophan (1-MT), the specific inhibitor of IDO, showed that this enzyme is important in interferon-gamma (IFN-gamma)-dependent inhibition of allergic inflammation in the respiratory airway during immunotherapy.
  
  
  OBJECTIVE
  We investigated the role of IDO in the development of allergic sensitization, leading to allergic inflammation and airway hyper-responsiveness (AHR).
  
  
  METHODS
  We used a mouse model to generate mucosal tolerance to lipopolysaccharide-free ovalbumin (OVA) following repeated intranasal inoculation of OVA over a 3-day period. We tested the successful induction of tolerance by subsequent intraperitoneal (i.p.) sensitization followed by intranasal challenge with OVA. A slow-release pellet of 1-MT implanted into mice was used to block IDO activity prior to repeated intranasal inoculation of OVA. We measured T-cell proliferation in response to OVA, determined airway inflammation, and measured AHR to intranasal methacholine to investigate the role of IDO in sensitization to OVA.
  
  
  RESULTS
  Repeated intranasal administration of OVA generated tolerance and prevented a subsequent sensitization to OVA via the i.p. route. This response was inhibited in mice receiving a slow-release pellet of 1-MT. However, we successfully reconstituted tolerance in mice receiving 1-MT following intra-peritoneal injection of a mixture of kynurenine and hydroxyanthranilic acid.
  
  
  CONCLUSIONS
  Our data suggest that, in addition to their role in IFN-gamma-mediated inhibition of allergic airway inflammation, products of tryptophan catabolism play an important role in the prevention of sensitization to potential allergens in the respiratory airway.
authors: Pulmonary Research Group, Department of Paediatrics, University of Alberta, Edmonton, AB, Canada.
authors: S O
authors: SO
authors: Odemuyiwa
authors: C
authors: C
authors: Ebeling
authors: V
authors: V
authors: Duta
authors: M
authors: M
authors: Abel
authors: L
authors: L
authors: Puttagunta
authors: O
authors: O
authors: Cravetchi
authors: C
authors: C
authors: Majaesic
authors: H
authors: H
authors: Vliagoftis
authors: R
authors: R
authors: Moqbel
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D007108:Immune Tolerance / Q000502:physiology*; D018928:Immunity, Mucosal / Q000187:drug effects*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000485:Allergens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D014364:Tryptophan; D010047:Ovalbumin