Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance

Norihiro Kikuchi, Yukio Ishii, Yuko Morishima, Yuichi Yageta, Norihiro Haraguchi, Ken Itoh, Masayuki Yamamoto, Nobuyuki Hizawa

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Background: Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant and Th1/Th2 balances may play an important role in many of the processes of inflammation and fibrosis. The transcription factor Nrf2 acts as a critical regulator for various inflammatory and immune responses by controlling oxidative stress. We therefore investigated the protective role of Nrf2 against the development of pulmonary fibrosis.Methods: To generate pulmonary fibrosis, both wild-type C57BL/6 mice and Nrf2-deficient mice of the same background were administered bleomycin intratracheally.Results: The survival of Nrf2-deficient mice after bleomycin administration was significantly lower than that of wild-type mice. The degree of bleomycin-induced initial pulmonary inflammation and pulmonary fibrosis was much more severe in Nrf2-deficient mice than in wild-type mice. The expression of antioxidant enzymes and phase II detoxifying enzymes was significantly reduced in the lungs of Nrf2-deficient mice, concomitant with an elevation of lung 8-isoprostane level, compared with wild-type mice. The expression of Th2 cytokines, such as interleukin-4 and interleukin-13, was significantly elevated in the lungs of Nrf2-deficient mice with an increase in the number of Th2 cells that express GATA-binding protein 3.Conclusions: The results indicated that Nrf2 protects against the development of pulmonary fibrosis by regulating the cellular redox level and lung Th1/Th2 balance. Thus, Nrf2 might be an important genetic factor in the determination of susceptibility to pulmonary fibrosis.

Original languageEnglish
Article number31
JournalRespiratory Research
Volume11
DOIs
Publication statusPublished - 2010 Mar 18

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance'. Together they form a unique fingerprint.

  • Cite this