A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor. Issue 4 (7th January 2014)

• Record Type: Journal Article
• Authors: Kawasaki, H.; Chang, H.‐W.; Tseng, H.‐C.; Hsu, S.‐C.; Yang, S.‐J.; Hung, C.‐H.; Zhou, Y.; Huang, S.‐K.
• Is Part Of: Allergy. Volume 69:Issue 4(2014:Apr.)
• Page Start: 445
• Page End: 452
• Publication Date: 2014-01-07
• Subjects: Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.12346
• Languages: English
• ISSNs: 0105-4538

Abstract

<abstract abstract-type="main" id="all12346-abs-0001"> <title>Abstract</title> <sec id="all12346-sec-0001" sec-type="section"> <title>Background</title> <p>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 <italic>in vitro</italic> and their functional importance <italic>in vivo</italic>.</p> </sec> <sec id="all12346-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>in vivo</italic> 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.</p> </sec> <sec id="all12346-sec-0003" sec-type="section"> <title>Results</title> <p>Kynurenine, but not KA and QA, enhanced IgE‐mediated responses, including degranulation, LTC<sub>4</sub> 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 <italic>in vivo</italic>. 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.</p> </sec> <sec id="all12346-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>