Role of Nrf2 in host defense against influenza virus in cigarette smoke-exposed mice |
| |
Authors: | Yageta Yuichi Ishii Yukio Morishima Yuko Masuko Hironori Ano Satoshi Yamadori Tadahiro Itoh Ken Takeuchi Kaoru Yamamoto Masayuki Hizawa Nobuyuki |
| |
Affiliation: | 1Department of Respiratory Medicine;3Department of Infectious Biology, University of Tsukuba, Tsukuba, Japan;2Center for Advanced Medical Research, Hirosaki University School of Medicine, Hirosaki, Japan;4Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan |
| |
Abstract: | Influenza virus is a common respiratory tract viral infection. Although influenza can be fatal in patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease, its pathogenesis is not fully understood. The Nrf2-mediated antioxidant system is essential to protect the lungs from oxidative injury and inflammation. In the present study, we investigated the role of Nrf2 in protection against influenza virus-induced pulmonary inflammation after cigarette smoke exposure with both in vitro and in vivo approaches. For in vitro analyses, peritoneal macrophages isolated from wild-type and Nrf2-deficient mice were treated with poly(I:C) and/or cigarette smoke extract. For in vivo analysis, these mice were infected with influenza A virus with or without exposure to cigarette smoke. In Nrf2-deficient macrophages, NF-κB activation and the induction of its target inflammatory genes were enhanced after costimulation with cigarette smoke extract and poly(I:C) compared with wild-type macrophages. The induction of antioxidant genes was observed for the lungs of wild-type mice but not those of Nrf2-deficient mice after cigarette smoke exposure. Cigarette smoke-exposed Nrf2-deficient mice showed higher rates of mortality than did wild-type mice after influenza virus infection, with enhanced peribronchial inflammation, lung permeability damage, and mucus hypersecretion. Lung oxidant levels and NF-κB-mediated inflammatory gene expression in the lungs were also enhanced in Nrf2-deficient mice. Our data indicate that the antioxidant pathway controlled by Nrf2 is pivotal for protection against the development of influenza virus-induced pulmonary inflammation and injury under oxidative conditions. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|