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- Title
A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor.
- Authors
Kawasaki, H.; Chang, H.‐W.; Tseng, H.‐C.; Hsu, S.‐C.; Yang, S.‐J.; Hung, C.‐H.; Zhou, Y.; Huang, S.‐K.
- 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 ( Ah R; a unique cellular chemical sensor). However, the involvement of tryptophan metabolites and Ah 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 Ig E-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 Ah R involvement, we examined the responses of mast cells from Ah R-null or Ah R-wild-type mice with the use of a known Ah R antagonist, CH223191. Results Kynurenine, but not KA and QA, enhanced Ig E-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 Ah R-deficient BMMCs and could be inhibited by CH223191 in BMMCs. Further, KYN had similar enhancing effects on HCMCs, which were inhibited by CH223191. Conclusion The Ah R- KYN axis is potentially important in modulating mast cell responses and represents an example of Ah R's critical involvement in the regulation of allergic responses.
- Subjects
KYNURENINE; MAST cells; ARYL hydrocarbon receptors; METABOLITES; IMMUNE system; LABORATORY mice
- Publication
Allergy, 2014, Vol 69, Issue 4, p445
- ISSN
0105-4538
- Publication type
Article
- DOI
10.1111/all.12346