Cigarette smoke decreases innate responses of epithelial cells to rhinovirus infection

Jane Eddleston*, Rachel U. Lee, Astrid M. Doerner, Jack Herschbach, Bruce L. Zuraw

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Exposure to cigarette smoke is associated with a significant increase in the risk for respiratory viral infections.The airway epithelium is the primary target for both cigarette smoke and respiratory viral infection. We investigated the effects of cigarette smoke on the response of airway epithelial cells to rhinovirus infection. We found that pre-exposure of BEAS-2B cells or primary normal human bronchial epithelial cells (NHBEs) to cigarette smoke extract (CSE) reducedthe induction ofmRNAof the chemokinesCXCL10andCCL5 by either the viral mimic polyinosine-polycytidylic acid (Poly I:C) or human rhinovirus 16 (HRV-16) infection. The HRV-16-induced release of CXCL10 and CCL5 was also significantly suppressed by CSE. Activation of the IFN mediator STAT-1 and the activation of JNK by poly I:C and HRV-16 were partially suppressed by pre-exposure to CSE. In contrast, the poly I:C-induced and HRV-16-induced phosphorylation of ERK+/2 was unaffected by CSE. HRV-16-stimulated IFN-b mRNA was also significantly reduced by CSE. Because suppression of the IFN response to viral infection was associated with increased viral production,weassessed HRV-16RNAconcentrations. Exposure to CSE resulted in an increase in HRV-16 RNA at 48 hours after the infection of BEAS-2B cells. These data demonstrate that exposure to CSE alters the response of airway epithelial cells to HRV infection, leading to decreased activation of the IFN-STAT-1 and SAP-JNK pathways, the suppression of CXCL10 and CCL5 production, and increased viral RNA. A diminished, early epithelial-initiated antiviral response to rhinovirus infection could contribute to the increased susceptibility of subjects to prolonged respiratory viral infections after exposure to cigarette smoke.

Original languageEnglish
Pages (from-to)118-126
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume44
Issue number1
DOIs
StatePublished - 1 Jan 2010
Externally publishedYes

Keywords

  • Cigarette smoke
  • Epithelial cells
  • Respiratory infections
  • Rhinovirus

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