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Published Online May 26, 2005
Science DOI: 10.1126/science.1108228

Reports

Submitted on December 3, 2004
Accepted on April 26, 2005

Protection from Experimental Asthma by an Endogenous Bronchodilator

Loretta G. Que 1, Limin Liu 2, Yun Yan 1, Gregory S. Whitehead 1, Stephen H. Gavett 3, David A. Schwartz 1, Jonathan S. Stamler 4*

1 Department of Medicine
2 Department of Medicine; Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
3 Experimental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
4 Department of Medicine; Department of Biochemistry, and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.

* To whom correspondence should be addressed.
Jonathan S. Stamler , E-mail: STAML001{at}mc.duke.edu

Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, wild-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR (GSNOR-/-) exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity, and may provide new therapeutic approaches to asthma.


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