Induction of epithelial immune-response genes in a mouse model of viral bronchitis and hyperreactivity

M. J. Walter, N. Kajiwara, D. Sampath, J. Rucker, M. J. Holtzman

Research output: Contribution to journalArticle

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Abstract

Our work indicates that viral replication or Interferon (IFN)-y treatment upregulates expression of a subset of immune-response genes (ICAM-1, RANTES, and Stall) in isolated airway epithelial cells, and that this pathway is also activated during asthmatic airway inflammation and hyperreactivity. To define the determinants for induction of gene expression during viral infection in vivo, we developed a mouse model of viral bronchitis and hyperreactivity using Sendai virus and C57BL/6 mice in which we were able to titer the dose of virus to cause a reversible bronchitis/bronchiolitis with viral antigen and immune cell (predominantly mononuclear cell) infiltrate restricted to these airway sites. The site of viral replication and immune cell influx along the airways correlated closely with localized increases in epithelial levels of Stall, ICAM-1, and RANTES and was accompanied by increased airway reactivity to inhaled methacholine. Comparison of wildtype to same-strain IFN-y (-/-) mice indicated little difference in the response to virus, so that levels of immune cell influx, induction of epithelial immuneresponse genes, and increases in airway reactivity were unchanged by loss of IFN-y production. We submit that these results highlight our proposed importance of innate immunity mediated at the level of the airway epithelial cell. Thus, immunity, inflammation, and hyperreaclivity are all conserved despite the loss of any effects that depend on IFN-y-producing immune cells (T cells and NK cells). The results are consistent with the capacity of airway epithelial cells (that do not produce IFN-y) to use paramyxyoviral machinery to express functional levels of ICAM-1 and RANTES critical for immune cell traffic and activation.

Original languageEnglish
Pages (from-to)A1450
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

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