title: Gene expression profiles of alveolar type II cells of chronic obstructive pulmonary disease: a case-control study.
abstract: OBJECTIVE
  The aim of this study was to identify the gene expression pattern specific in alveolar epithelial type II cells (ATII cells) isolated from patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Case control.
  
  
  METHODS
  Two hospitals in Japan.
  
  
  METHODS
  Three patients without COPD and three patients with COPD in microarray analyses. Five smokers without COPD and nine smokers with COPD in the following analyses.   PRIMARY AND SECONDARY OUTCOME MEASURED:  Primary outcome included identification of differentially expressed genes and activated or inhibited pathways in ATII cells of the patients with COPD, compared to those of the patients without COPD, using Affymetrix gene expression arrays. Secondary outcome included validation of the results of microarray analyses by quantitative reverse transcription-PCR.
  
  
  RESULTS
  We isolated ATII cells from COPD and non-COPD lungs using fluorescence-activated cell sorting. We performed Affymetrix gene expression arrays on both types of ATII cells. Gene set enrichment analyses revealed that two major gene sets were enriched in ATII cells from COPD lungs: interferon-responsive gene sets and gene sets associated with cell cycle progression. Gene ontology term enrichment analyses indicated that among the interferon-stimulated genes, ATII cells in COPD expressed genes such as PSMB8, PSMB9, TAP1 and TAP2 associated with the antigen processing and presentation pathway. We validated the results of the microarray analyses using quantitative reverse transcriptase-PCR. In addition, FACS analysis indicated that the percentage of ATII cells to CD45-negative lung cells isolated from COPD lungs were significantly increased more than that from non-COPD lungs.
  
  
  CONCLUSIONS
  Our study demonstrated that interferon-stimulated genes involved in the antigen processing and presentation pathway and genes involved in cell cycle progression were enriched in ATII cells of the patients with COPD. These pathways might alter phenotypes of ATII cells in COPD lungs.
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease,  Tohoku University Graduate School of Medicine, Sendai,  Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujino
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ota
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takaya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Nagatomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo