Document Detail

Cigarette smoke decreases innate responses of epithelial cells to rhinovirus infection.
MedLine Citation:
PMID:  20224072     Owner:  NLM     Status:  MEDLINE    
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) reduced the induction of mRNA of the chemokines CXCL10 and CCL5 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 ERK1/2 was unaffected by CSE. HRV-16-stimulated IFN-β mRNA was also significantly reduced by CSE. Because suppression of the IFN response to viral infection was associated with increased viral production, we assessed HRV-16 RNA concentrations. 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.
Jane Eddleston; Rachel U Lee; Astrid M Doerner; Jack Herschbach; Bruce L Zuraw
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-03-11
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  44     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-24     Completed Date:  2011-01-20     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  118-26     Citation Subset:  IM    
Veterans Medical Research Foundation, and Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0732, USA.
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MeSH Terms
Cell Line
Chemokine CCL5 / genetics,  metabolism
Chemokine CXCL10 / genetics,  metabolism
Dose-Response Relationship, Drug
Enzyme Activation
Epithelial Cells / drug effects*,  enzymology,  immunology,  virology
Immunity, Innate / drug effects*
Interferon Regulatory Factor-3 / metabolism
Interferon-beta / genetics,  metabolism
JNK Mitogen-Activated Protein Kinases / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Poly I-C / immunology
RNA, Messenger / metabolism
RNA, Viral / biosynthesis
Respiratory Mucosa / drug effects*,  enzymology,  immunology,  virology
Rhinovirus / genetics,  growth & development,  immunology*
STAT1 Transcription Factor / metabolism
Smoke / adverse effects*
Smoking / adverse effects*
Time Factors
Viral Load
Virus Replication
Grant Support
Reg. No./Substance:
0/CCL5 protein, human; 0/CXCL10 protein, human; 0/Chemokine CCL5; 0/Chemokine CXCL10; 0/IRF3 protein, human; 0/Interferon Regulatory Factor-3; 0/RNA, Messenger; 0/RNA, Viral; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/Smoke; 24939-03-5/Poly I-C; 77238-31-4/Interferon-beta; EC Mitogen-Activated Protein Kinases; EC Protein Kinase 1; EC Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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