期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 51, 期 2, 页码 516-521出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.04.040
关键词
Atopic asthma; Human; Alveolar macrophage; Oxidative stress; NRF2; Superoxide dismutase; Antioxidant; Vitamin E; Segmental allergen challenge; BAL fluid; In vivo; Free radicals
资金
- NIH [K23 HL080030-04, M01 RR-00095, P30 ES000267, 5RO1 CA104590, 5RO1 CA 115556, 5RO1 CA102353, AI 079253]
Asthma is a chronic inflammatory airway disease associated with increased generation of reactive oxidant species and disturbed antioxidant defenses. NRF2 is the master transcription factor that regulates the expression of Phase II antioxidant and detoxifying enzymes. Disruption of NRF2 augments oxidative stress and inflammation in a mouse model of asthma, suggesting a protective role for NRF2 in the lungs in vivo. Yet, little is known about the regulation and function of NRF2 in human asthmatics. Using segmental allergen challenge, a well-established experimental model of IgE-mediated asthma exacerbation in human atopic asthmatics, we investigated the effects of a specific allergen and the modulatory role of vitamin E on NRF2 and a NRF2-target gene, superoxide dismutase, in alveolar macrophages recovered from the airways at 24 h after allergen instillation in vivo. Allergen-provoked airway inflammation in sensitive asthmatics caused a profound inhibition of macrophage NRF2 activity and superoxide dismutase, rendering them incapable of responding to the NRF2 inducers. Prolonged treatment with high doses of the antioxidant vitamin E lessened this allergen-induced drop in alveolar macrophage NRF2. These results are the first to demonstrate that NRF2 expression in human asthmatics is compromised upon allergen challenge but can be rescued by vitamin E in vivo. (C) 2011 Elsevier Inc. All rights reserved.
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