Modification of gene expression of the small airway epithelium in response to cigarette smoking

Ben Gary Harvey, Adriana Heguy, Philip L. Leopold, Brendan J. Carolan, Barbara Ferris, Ronald Crystal

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

The earliest morphologic evidence of changes in the airways associated with chronic cigarette smoking is in the small airways. To help understand how smoking modifies small airway structure and function, we developed a strategy using fiberoptic bronchoscopy and brushing to sample the human small airway (10th-12th order) bronchial epithelium to assess gene expression (Affymetrix HG-U133A and HG-133 Plus 2.0 array) in phenotypically normal smokers (n = 16, 25 ± 7 pack-years) compared to matched nonsmokers (n = 17). Compared to samples from large (second to third order) bronchi, the small airway samples had a higher proportion of ciliated cells, but less basal, undifferentiated, and secretory cells, and contained Clara cells. Even though the smokers were phenotypically normal, microarray analysis of gene expression of the small airway epithelium of the smokers compared to the nonsmokers demonstrated up- and downregulation of genes in multiple categories relevant to the pathogenesis of chronic obstructive lung disease (COPD), including genes coding for cytokines/innate immunity, apoptosis, mucin, response to oxidants and xenobiotics, and general cellular processes. In the context that COPD starts in the small airways, these gene expression changes in the small airway epithelium in phenotypically normal smokers are candidates for the development of therapeutic strategies to prevent the onset of COPD.

Original languageEnglish
Pages (from-to)39-53
Number of pages15
JournalJournal of Molecular Medicine
Volume85
Issue number1
DOIs
Publication statusPublished - 1 Jan 2007
Externally publishedYes

    Fingerprint

Keywords

  • COPD
  • Microarray
  • Smoking

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this