title: A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor.
abstract: BACKGROUND
  Tryptophan metabolites have been suggested to play a role in immune modulation, wherein those have recently been shown to be endogenous ligands of aryl hydrocarbon receptor (AhR; a unique cellular chemical sensor). However, the involvement of tryptophan metabolites and AhR in modulating mast cell function remains to be fully defined. We therefore investigated that the functional impacts of tryptophan metabolites on human and mouse mast cell responses in vitro and their functional importance in vivo.
  
  
  METHODS
  Three tryptophan metabolites, kynurenine (KYN), kynurenic acid (KA) and quinolinic acid (QA), were examined in terms of their effect on IgE-mediated responses in mouse bone marrow-derived mast cells (BMMCs) and in human peripheral blood-derived cultured mast cells (HCMCs) and on in vivo anaphylactic responses. For evaluation of AhR involvement, we examined the responses of mast cells from AhR-null or AhR-wild-type mice with the use of a known AhR antagonist, CH223191.
  
  
  RESULTS
  Kynurenine, but not KA and QA, enhanced IgE-mediated responses, including degranulation, LTC4 release, and IL-13 production in BMMCs through the activation of PLCγ1, Akt, MAPK p38, and the increase of intracellular calcium. KYN also enhanced cutaneous anaphylaxis in vivo. These enhancing effects of KYN were not observed in AhR-deficient BMMCs and could be inhibited by CH223191 in BMMCs. Further, KYN had similar enhancing effects on HCMCs, which were inhibited by CH223191.
  
  
  CONCLUSIONS
  The AhR-KYN axis is potentially important in modulating mast cell responses and represents an example of AhR's critical involvement in the regulation of allergic responses.
authors.affiliation: National Health Research Institutes, Zhu-Nan, Taiwan.
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: H-W
authors.initials: HW
authors.lastname: Chang
authors.forename: H-C
authors.initials: HC
authors.lastname: Tseng
authors.forename: S-C
authors.initials: SC
authors.lastname: Hsu
authors.forename: S-J
authors.initials: SJ
authors.lastname: Yang
authors.forename: C-H
authors.initials: CH
authors.lastname: Hung
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: S-K
authors.initials: SK
authors.lastname: Huang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007737:Kynurenine / Q000008:administration & dosage / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D007737:Kynurenine; D007073:Immunoglobulin E; D014364:Tryptophan
keywords: aryl hydrocarbon receptor; kynurenine; mast cell; tryptophan metabolite