ORIGINAL ARTICLE

Cell Research (2006)16:230-239
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Redox regulation of mast cell histamine release in thioredoxin-1 (TRX) transgenic mice

Aoi Son¹, Hajime Nakamura², Norihiko Kondo¹, Yoshiyuki Matsuo¹, Wenrui Liu¹, Shin-ichi Oka¹, Yasuyuki Ishii³, Junji Yodoi^1,2

¹Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; ²Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan; ³Research Unit for Clinical Allergy, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan

Correspondence: Junji Yodoi Tel: +81-75-751-4024; Fax: +81-75-761-5766; E-mail: yodoi@virus.kyoto-u.ac.jp

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Thioredoxin-1 (TRX) is a stress-inducible redox-regulatory protein with antioxidative and anti-inflammatory effects. Here we show that the release of histamine from mast cells elicited by cross-linking of high-affinity receptor for IgE (FcεRI) was significantly suppressed in TRX transgenic (TRX-tg) mice compared to wild type (WT) mice. Intracellular reactive oxygen species (ROS) of mast cells stimulated by IgE and antigen was also reduced in TRX-tg mice compared to WT mice. Whereas there was no difference in the production of cytokines (IL-6 and TNF-α) from mast cells in response to 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulation in TRX-tg and WT mice. Immunological status of TRX-tg mice inclined to T helper (Th) 2 dominant in primary immune response, although there was no difference in the population of dendritic cells (DCs) and regulatory T cells. We conclude that the histamine release from mast cells in TRX-tg mice is suppressed by inhibition of ROS generation. As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.

Cell Research (2006) 16:230-239. doi:10.1038/sj.cr.7310031; published online 16 February 2006

Keywords:thioredoxin, redox, mast cell, histamine release, allergy