This information is current as Infection Respiratory Epithelium during Adenoviral Stat 3 Is Required for Cytoprotection of the and

The role of Stat3 in the maintenance of pulmonary homeostasis following adenoviral-mediated lung injury was assessed in vivo. Stat3 was selectively deleted from bronchiolar and alveolar epithelial cells in Stat3 (cid:1)(cid:1) mice. Although lung histology and function were unaltered by deletion of Stat3 in vivo, Stat3 (cid:1)(cid:1) mice were highly susceptible to lung injury caused by intratracheal administration of AV1-GFP, an early (E) region 1- and E3-deleted, nonproliferative adenovirus. Severe airspace enlargement, loss of alveolar septae, and sloughing of the bronchiolar epithelium were observed in Stat3 (cid:1)(cid:1) mice as early as 1 day after exposure to the virus. Although surfactant protein A, B, and C content and surfactant protein-B mRNA expression in Stat3 (cid:1)(cid:1) mice were similar, TUNEL staining and caspase-3 were increased in alveolar type II epithelial cells of Stat3 (cid:1)(cid:1) mice after exposure to virus. RNA microarray analysis of type II epithelial cells isolated from Stat3 (cid:1)(cid:1) mice demonstrated significant changes in expression of numerous genes, including those genes regulating apoptosis, supporting the concept that the susceptibility of Stat3-deficient mice to adenovirus was related to the role of Stat3 in the regulation of cell survival. AV1-Bcl-x L , an E1- and E3-deleted, nonproliferative adenovirus expressing the antiapoptotic protein Bcl-x L , protected Stat3 (cid:1)(cid:1) mice from adenoviral-induced lung injury. Adenoviral

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