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A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor
Author(s) -
Kawasaki H.,
Chang H.W.,
Tseng H.C.,
Hsu S.C.,
Yang S.J.,
Hung C.H.,
Zhou Y.,
Huang S.K.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12346
Subject(s) - kynurenine , quinolinic acid , mast cell , aryl hydrocarbon receptor , metabolite , kynurenic acid , chemistry , in vivo , degranulation , pharmacology , receptor , biochemistry , tryptophan , biology , immunology , antagonist , amino acid , microbiology and biotechnology , gene , transcription factor
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 ( A h R ; a unique cellular chemical sensor). However, the involvement of tryptophan metabolites and A h R 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 I g E ‐mediated responses in mouse bone marrow‐derived mast cells ( BMMC s) and in human peripheral blood‐derived cultured mast cells ( HCMC s) and on in vivo anaphylactic responses. For evaluation of A h R involvement, we examined the responses of mast cells from A h R ‐null or A h R ‐wild‐type mice with the use of a known A h R antagonist, CH 223191. Results Kynurenine, but not KA and QA , enhanced I g E ‐mediated responses, including degranulation, LTC 4 release, and IL ‐13 production in BMMC s through the activation of PLC γ1, A kt, MAPK p38, and the increase of intracellular calcium. KYN also enhanced cutaneous anaphylaxis in vivo . These enhancing effects of KYN were not observed in A h R ‐deficient BMMC s and could be inhibited by CH 223191 in BMMC s. Further, KYN had similar enhancing effects on HCMC s, which were inhibited by CH 223191. Conclusion The A h R ‐ KYN axis is potentially important in modulating mast cell responses and represents an example of A h R 's critical involvement in the regulation of allergic responses.