J. Virol. doi:10.1128/JVI.02583-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
TGF-
Enhances RSV Replication and TNF-
Induction in Human Epithelial Cells
Kelly L. McCann
and
Farhad Imani*
Laboratory of Respiratory Biology, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709
* To whom correspondence should be addressed. Email:
imani{at}niehs.nih.gov.
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Abstract |
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Asthma is characterized as a chronic inflammatory disease associated with significant tissue remodeling. Patients with asthma are more susceptible to viral-induced exacerbation which subsequently can lead to increased rates of hospitalization and mortality. While the most common cause of asthma-related deaths is from respiratory viral infections, the underlying factor in the lung environment which renders asthmatic subjects more susceptible to viral exacerbation are not yet identified. Since TGF-
is a critical cytokine for lung tissue remodeling and asthma phenotype, we have focused on the effects of TGF-
on viral replication and viral-induced inflammation. Treatment of human epithelial cells with TGF-
increased respiratory syncytial virus replication by approximately 4 fold. TNF-
mRNA and protein expression were also significantly increased above RSV infection alone. The increase in RSV replication and TNF-
expression after TGF-
treatment was concomitant with an increase in viral-induced p38 MAPK activation. Our data reveal a novel effect for TGF-
on RSV replication and provide a potential mechanism for the exaggerated inflammatory response observed in asthmatic subjects during respiratory viral infections.