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Respir Res. 2010 Mar 18;11:31. doi: 10.1186/1465-9921-11-31.

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

Author information

1
Department of Respiratory Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. ishii-y@md.tsukuba.ac.jp

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.

PMID:
20298567
PMCID:
PMC2846897
DOI:
10.1186/1465-9921-11-31
[Indexed for MEDLINE]
Free PMC Article

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