Peroxiredoxin I is a negative regulator of Th2-dominant allergic asthma.
Peroxiredoxin (Prx) I, a ubiquitous antioxidant enzyme, is known to protect against inflammation; however, its role in the allergic inflammation remains unidentified. We determined whether intristic Prx I protects against allergic asthma traits using Prx-I knockout (-/-) mice. Prx I (-/-) and wild-type (WT) mice were immunized with ovalbumin (OVA) plus aluminum potassium sulfate (Alum: Th2 adjuvant) and subsequently challenged with OVA. Twenty-four hours after the last OVA challenge, leukocyte influx including eosinophils into bronchoalveolar lavage fluid was significantly greater in Prx I (-/-) mice compared to that in WT mice. On the other hand, when these mice were immunized with OVA+complete Freund's adjuvant (Th1 adjuvant), opposite phenomenon was observed. In the presence of OVA/Alum, peribronchial inflammatory leukocyte infiltration, cholinergic airway resistance, and the lung expression of interleukin (IL)-2 were significantly greater and that of interferon-gamma was significantly lesser in Prx I (-/-) than in WT mice. In vitro, OVA/Alum-sensitized Prx I (-/-) T cells proliferated more profoundly than WT T cells when they were cocultured with syngeneic bone marrow-generated dendritic cells. These results indicate that endogenous Prx I protects against allergen-related Th2-type airway inflammation and hyperresponsiveness, at least partly, via the suppression of the lung expression of IL-2 and regulation of the Th1/Th2 balance in addition to its antioxidative properties. Furthermore, Prx I can inhibit allergen-specific T-cell proliferation through immunological synapse. Our findings implicate an alternative therapeutic value of Prx I in the treatment of Th2-skewed allergic airway inflammatory diseases such as atopic asthma.
Inoue
Ken-ichiro
K
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan. inoue.kenichirou@nies.go.jp
Takano
Hirohisa
H
Koike
Eiko
E
Warabi
Eiji
E
Yanagawa
Toru
T
Yanagisawa
Rie
R
Ishii
Tetsuro
T
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008168:Lung / Q000033:anatomy & histology / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide; D054464:Peroxiredoxins / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D016210:Methacholine Chloride; D009569:Nitric Oxide; D054464:Peroxiredoxins