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Am J Physiol Lung Cell Mol Physiol (April 26, 2002). doi:10.1152/ajplung.00496.2001
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Articles in PresS, published online ahead of print April 26, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00496.2001
Submitted on January 4, 2002
Accepted on April 11, 2002

Glucocorticoid-attenuated response genes induced in the lung during endotoxemia

Jeffrey B Smith1*, Tam T Nguyen1, Heather J Hughes1, Harvey R Herschman2, Daniel P Widney1, Kim C Bui1, and Leonor E Rovai1

1 Department of Pediatrics, UCLA School of Medicine, Los Angeles, CA, USA
2 Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, CA, USA; Department of Molecular Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA; Department of Molecular Biology Institute, UCLA, Los Angeles, CA, USA

* To whom correspondence should be addressed. E-mail: jbsmith{at}ucla.edu.

Cytokines and other mediators whose induction in inflammatory lung disease is attenuated by glucocorticoids are potential targets for development of selective anti-inflammatory treatments. We refer to genes with these regulatory characteristics as Glucocorticoid-Attenuated Response Genes, or GARGs. Systematic identification of GARGs has not been attempted previously in vivo. Using an endotoxemia model in adrenalectomized mice, we constructed a subtracted lung library enriched in endotoxemia-induced genes, and identified candidate GARGs by differential hybridization screening. Northern analysis confirmed induction in the lung during endotoxemia and attenuation by glucocorticoids of 36 genes of diverse types. The majority were genes of unknown function not previously implicated in the pulmonary response to inflammation, including a new member of a 2'-5' oligoadenylate synthetase-like family (murine OASL-2), and a novel lung-inducible Neuralized-related C3HC4 RING protein (LINCR). Our results suggest that a full understanding of glucocorticoid effects on lung inflammation will require elucidation of the roles of an extensive network of glucocorticoid-modulated genes.




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