Stat3 is required for cytoprotection of the respiratory epithelium during adenoviral infection

Yohei Matsuzaki, Yan Xu, Machiko Ikegami, Valérie Besnard, Kwon Sik Park, William M. Hull, Susan E. Wert, Jeffrey A. Whitsett

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39 Citations (Scopus)

Abstract

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 ΔΔ mice. Although lung histology and function were unaltered by deletion of Stat3 in vivo, Stat3ΔΔ mice were highly susceptible to lung injury caused by intratracheal administration of AVl-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 Stat3ΔΔ 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 ΔΔ mice were similar, TUNEL staining and caspase-3 were increased in alveolar type II epithelial cells of Stat3ΔΔ mice after exposure to virus. RNA microarray analysis of type II epithelial cells isolated from Stat3ΔΔ mice demonstrated significant changes in expression of numerous genes, including those genes regulating apoptosis, supporting the concept that the susceptibility of StatS-deficient mice to adenovirus was related to the role of StatS in the regulation of cell survival. AVl-Bcl-xL, an El- and E3-deleted, nonproliferative adenovirus expressing the antiapoptotic protein Bcl-xL, protected Stat3ΔΔ mice from adenoviral-induced lung injury. Adenoviral infection of the lungs of Siat3-deficient mice was associated with severe injury of the alveolar and bronchiolar epithelium. Thus, Stat3 plays a critical cytoprotective role that is required for epithelial cell survival and maintenance of alveolar structures during the early phases of pulmonary adenoviral infection.

Original languageEnglish
Pages (from-to)527-537
Number of pages11
JournalJournal of Immunology
Volume177
Issue number1
DOIs
Publication statusPublished - 2006 Jul 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Matsuzaki, Y., Xu, Y., Ikegami, M., Besnard, V., Park, K. S., Hull, W. M., Wert, S. E., & Whitsett, J. A. (2006). Stat3 is required for cytoprotection of the respiratory epithelium during adenoviral infection. Journal of Immunology, 177(1), 527-537. https://doi.org/10.4049/jimmunol.177.1.527