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Publication : Glucocorticoid-attenuated response genes induced in the lung during endotoxemia.

First Author  Smith JB Year  2002
Journal  Am J Physiol Lung Cell Mol Physiol Volume  283
Issue  3 Pages  L636-47
PubMed ID  12169584 Mgi Jnum  J:79318
Mgi Id  MGI:2387808 Doi  10.1152/ajplung.00496.2001
Citation  Smith JB, et al. (2002) Glucocorticoid-attenuated response genes induced in the lung during endotoxemia. Am J Physiol Lung Cell Mol Physiol 283(3):L636-47
abstractText  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 and a novel lung inducible Neuralized-related C3HC4 RING protein. 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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