Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice

• DOI: 10.1084/jem.20050538
• Publication Date: 2005-07-05T18:28:11Z
• Authors: Tirumalai Rangasamy; Jia Guo; Wayne A. Mitzner; Jessica Roman; Anju Singh; Allison D. Fryer; Masayuki Yamamoto; Thomas W. Kensler; Rubin M. Tuder; Steve N. Georas; Shyam Biswal
• Keywords: Chemokine CCL11; Male; Mice, Knockout; 0301 basic medicine; DNA, Complementary; Base Sequence; NF-E2-Related Factor 2; Ovalbumin; NF-kappa B; Article; Antioxidants; Asthma; Acetylcysteine; 3. Good health; DNA-Binding Proteins; Mice; Oxidative Stress; 03 medical and health sciences; Gene Expression Regulation; Chemokines, CC; Animals; Bronchoalveolar Lavage Fluid; Lung; Oxidation-Reduction

Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect antioxidant responses speculated exacerbate asthma severity, this difficult demonstrate with certainty. Nuclear erythroid 2 p45-related factor (Nrf2) is redox-sensitive basic leucine zipper transcription that involved transcriptional regulation many genes. We show disruption Nrf2 gene leads severe allergen-driven airway inflammation and hyperresponsiveness mice. Enhanced asthmatic response as result ovalbumin sensitization challenge Nrf2-disrupted mice was associated more pronounced mucus cell hyperplasia infiltration eosinophils into lungs than seen wild-type littermates. resulted increased expression T helper type cytokines interleukin (IL)-4 IL-13 bronchoalveolar lavage fluid splenocytes after allergen challenge. The enhanced severity from pathway lowered status caused by lower basal expression, well marked attenuation, induction multiple Our studies suggest responsiveness Nrf2-directed pathways may act major determinant susceptibility allergen-mediated asthma.