Redox regulation of mast cell histamine release in thioredoxin-1 (TRX) transgenic mice.
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 (FcepsilonRI) 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-alpha) 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.
1Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Aoi
A
Son
Hajime
H
Nakamura
Norihiko
N
Kondo
Yoshiyuki
Y
Matsuo
Wenrui
W
Liu
Shin-ichi
S
Oka
Yasuyuki
Y
Ishii
Junji
J
Yodoi
D000818:Animals; D002417:Cattle; D003713:Dendritic Cells / Q000378:metabolism; D004140:Dinitrophenols / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006636:Histamine Release; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004140:Dinitrophenols; D006241:Haptens; D015850:Interleukin-6; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; C515559:Txn1 protein, mouse; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D013879:Thioredoxins