Increased cytokine response of rhinovirus-infected airway epithelial cells in chronic obstructive pulmonary disease
Language: 
English
Abstract: 

RATIONALE: Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection. OBJECTIVES: We hypothesized that airway epithelial cells from patients with COPD maintain a proinflammatory phenotype compared with control subjects, leading to greater RV responses. METHODS: Cells were isolated from tracheobronchial tissues of 12 patients with COPD and 10 transplant donors. Eight patients with COPD had severe emphysema, three had mild to moderate emphysema, and one had no emphysema. All had moderate to severe airflow obstruction, and six met criteria for chronic bronchitis or had at least one exacerbation the previous year. Cells were grown at air-liquid interface and infected with RV serotype 39. Cytokine and IFN expression was measured by ELISA. Selected genes involved in inflammation, oxidative stress, and proteolysis were assessed by focused gene array and real-time polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Compared with control subjects, cells from patients with COPD demonstrated increased mRNA expression of genes involved in oxidative stress and the response to viral infection, including NOX1, DUOXA2, MMP12, ICAM1, DDX58/RIG-I, STAT1, and STAT2. COPD cells showed elevated baseline and RV-stimulated protein levels of IL-6, IL-8/CXCL8, and growth-related oncogene-alpha/CXCL1. COPD cells demonstrated increased viral titer and copy number after RV infection, despite increased IL-29/IFN-lambda1, IL-28A/IFN-lambda2, and IFN-inducible protein-10/CXCL10 protein levels. Finally, RV-infected COPD cultures showed increased mRNA expression of IL28A/IFNlambda2, IL29/IFNlambda1, IFIH1/MDA5, DDX58/RIG-I, DUOX1, DUOX2, IRF7, STAT1, and STAT2. CONCLUSIONS: Airway epithelial cells from patients with COPD show higher baseline levels of cytokine expression and increased susceptibility to RV infection, despite an increased IFN response.

Author(s): 
Schneider, Dina
Ganesan, Shyamala
Comstock, Adam T.
Meldrum, Catherine A.
Mahidhara, Raja
Goldsmith, Adam M.
Curtis, Jeffrey L.
Martinez, Fernando J.
Hershenson, Marc B.
Sajjan, Umadevi
Item Type: 
Journal Article
Publication Title: 
American Journal of Respiratory and Critical Care Medicine
Journal Abbreviation: 
Am. J. Respir. Crit. Care Med.
Publication Date: 
Aug 1, 2010
Publication Year: 
2010
Pages: 
332-340
Volume: 
182
Issue: 
3
ISSN: 
1535-4970
DOI: 
10.1164/rccm.200911-1673OC
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 20395558 PMCID: PMC2921598

Turabian/Chicago Citation

Dina Schneider, Shyamala Ganesan, Adam T. Comstock, Catherine A. Meldrum, Raja Mahidhara, Adam M. Goldsmith, Jeffrey L. Curtis, Fernando J. Martinez, Marc B. Hershenson and Umadevi Sajjan. Aug 1, 2010. "Increased cytokine response of rhinovirus-infected airway epithelial cells in chronic obstructive pulmonary disease." American Journal of Respiratory and Critical Care Medicine 182: 3: 332-340. 10.1164/rccm.200911-1673OC.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1164/rccm.200911-1673OC | issn = 1535-4970 | volume = 182 | pages = 332-340 | last = Schneider | first = Dina | coauthors = Ganesan, Shyamala, Comstock, Adam T., Meldrum, Catherine A., Mahidhara, Raja, Goldsmith, Adam M., Curtis, Jeffrey L., Martinez, Fernando J., Hershenson, Marc B., Sajjan, Umadevi | title = Increased cytokine response of rhinovirus-infected airway epithelial cells in chronic obstructive pulmonary disease | journal = American Journal of Respiratory and Critical Care Medicine | date = Aug 1, 2010 | pmid = | pmc = }} </ref>