title: Increased cytokine response of rhinovirus-infected airway epithelial cells in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: University of Michigan, Ann Arbor, MI 48109-5688, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Schneider
authors.forename: Shyamala
authors.initials: S
authors.lastname: Ganesan
authors.forename: Adam T
authors.initials: AT
authors.lastname: Comstock
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Meldrum
authors.forename: Raja
authors.initials: R
authors.lastname: Mahidhara
authors.forename: Adam M
authors.initials: AM
authors.lastname: Goldsmith
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Curtis
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
authors.forename: Umadevi
authors.initials: U
authors.lastname: Sajjan
mesh_terms: D000368:Aged; D001980:Bronchi / Q000166:cytology; D016022:Case-Control Studies; D002478:Cells, Cultured; D003139:Common Cold / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D012229:Rhinovirus / Q000276:immunology*; D014132:Trachea / Q000166:cytology; D019562:Viral Load
chemical_list: D016207:Cytokines; D012333:RNA, Messenger
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