TY - JOUR
T1 - Effects of paramyxoviral infection on airway epithelial cell foxj1 expression, ciliogenesis, and mucociliary function
AU - Look, Dwight C.
AU - Walter, Michael J.
AU - Williamson, Michael R.
AU - Pang, Liyi
AU - You, Yingjian
AU - Sreshta, J. Nicholas
AU - Johnson, Joyce E.
AU - Zander, Dani S.
AU - Brody, Steven L.
N1 - Funding Information:
Supported by awards from the National Institutes of Health (to D. C. L., M. J. W., and S. L. B.), the Cystic Fibrosis Foundation (to D. C. L.), and the American Lung Association (to D. C. L. and M. J. W.)
PY - 2001/12
Y1 - 2001/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035190108&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)63057-X
DO - 10.1016/S0002-9440(10)63057-X
M3 - Article
C2 - 11733356
AN - SCOPUS:0035190108
SN - 0002-9440
VL - 159
SP - 2055
EP - 2069
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -