A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor

H. Kawasaki, H. W. Chang, H. C. Tseng, S. C. Hsu, S. J. Yang, C. H. Hung, Y. Zhou, S. K. Huang

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62 引文 斯高帕斯(Scopus)

摘要

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. Conclusion 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.

原文英語
頁(從 - 到)445-452
頁數8
期刊Allergy: European Journal of Allergy and Clinical Immunology
69
發行號4
DOIs
出版狀態已發佈 - 4月 2014

ASJC Scopus subject areas

  • 免疫學和過敏
  • 免疫學

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