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Modulation of Glutaredoxin-1 Expression in a Mouse Model of Allergic Airway Disease

Department of Respiratory Medicine, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; and Department of Pathology, University of Vermont, Burlington, Vermont

Correspondence and requests for reprints should be addressed to Yvonne M. W. Janssen-Heininger, Department of Pathology, University of Vermont, HSRF Building, Room 216A, Burlington VT 05405. E-mail: yjanssen{at}uvm.edu

Abstract

Glutaredoxins (GRX) are antioxidant enzymes that preferentially catalyze the reduction of protein-glutathione mixed disulfides. The formation of mixed disulfides with GSH is known as S-glutathionylation, a post-translational modification that is emerging as an important mode of redox signaling. Since asthma is a disease that is associated with increased oxidative stress and altered antioxidant defenses, we investigated the expression of GRX in a murine model of allergic airway disease. Sensitization and challenge of C57BL/6 mice with ovalbumin resulted in increased expression of GRX1 mRNA, as well as increased amounts of GRX1 protein and total GRX activity in the lung. Because GRX1 expression is prominent in bronchial epithelium, we isolated primary epithelial cells from mouse trachea to investigate the presence of GRX. Primary tracheal epithelial cells were found to express both GRX1 and 2 mRNA and detectable GRX activity. Treatment with IFN- increased the expression of GRX1 and overall GRX activity, resulting in attenuation of protein S-glutathionylation. In contrast, TGF-1 caused decreased GRX1 expression and overall GRX activity, leading to markedly enhanced protein S-glutathionylation. GRX1 joins the cadre of antioxidant defenses known to be modulated during allergic airway inflammation.

Key Words: glutaredoxin • asthma • epithelium • IFN- • TGF-

CLINICAL RELEVANCE Glutaredoxin-1 can contribute to the disease pathology through alterations in protein S-glutathionylation.