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Originally published in Science Express on 26 May 2005
Science 10 June 2005:
Vol. 308. no. 5728, pp. 1618 - 1621
DOI: 10.1126/science.1108228
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Reports

Protection from Experimental Asthma by an Endogenous Bronchodilator

Loretta G. Que,1 Limin Liu,1,2 Yun Yan,1 Gregory S. Whitehead,1 Stephen H. Gavett,4 David A. Schwartz,1 Jonathan S. Stamler1,2,3*

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 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.

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

* To whom correspondence should be addressed: STAML001{at}mc.duke.edu

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