Effects of paramyxoviral infection on airway epithelial cell foxj1 expression, ciliogenesis, and mucociliary function

Dwight C. Look, Michael J. Walter, Michael R. Williamson, Liyi Pang, Yingjian You, J. Nicholas Sreshta, Joyce E. Johnson, Dani S. Zander, Steven L. Brody

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

To elucidate molecular mechanisms underlying the association between respiratory viral infection and predisposition to subsequent bacterial infection, we used in vivo and in vitro models and human samples to characterize respiratory virus-induced changes in airway epithelial cell morphology, gene expression, and mucociliary function. Mouse paramyxoviral bronchitis resulted in airway epithelial cell infection and a distinct pattern of epithelial cell morphology changes and altered expression of the differentiation markers β-tubulin-IV, Clara cell secretory protein, and Foxj1. Furthermore, changes in gene expression were recapitulated using an in vitro epithelial cell culture system and progressed independent of the host inflammatory response. Restoration of mature airway epithelium occurred in a pattern similar to epithelial cell differentiation and ciliogenesis in embryonic lung development characterized by sequential proliferation of undifferentiated cells, basal body production, Foxj1 expression, and β-tubulin-IV expression. The effects of virus-induced alterations in morphology and gene expression on epithelial cell function were illustrated by decreased airway mucociliary velocity and impaired bacterial clearance. Similar changes in epithelial cell Foxj1 expression were also observed in human paramyxoviral respiratory infection. Taken together, these model systems of paramyxoviral respiratory infection mimic human pathology and identify epithelial cell Foxj1 expression as an early marker of epithelial cell differentiation, recovery, and function.

Original languageEnglish (US)
Pages (from-to)2055-2069
Number of pages15
JournalAmerican Journal of Pathology
Volume159
Issue number6
DOIs
StatePublished - Dec 2001

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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