An in vitro airway wall model of remodeling

Melanie M. Choe, Peter H.S. Sporn, Melody A. Swartz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Recent studies have shown that mechanical forces on airway epithelial cells can induce upregulation of genes involved in airway remodeling in diseases such as asthma. However, the relevance of these responses to airway wall remodeling is still unclear since 1) mechanotransduction is highly dependent on environment (e.g., matrix and other cell types) and 2) inflammatory mediators, which strongly affect remodeling, are also present in asthma. To assess the effects of mechanical forces on the airway wall in a relevant three-dimensional inflammatory context, we have established a tissue culture model of the human airway wall that can be induced to undergo matrix remodeling. Our model contains differentiated human bronchial epithelial cells characterized by tight junctions, cilia formation, and mucus secretion atop a collagen gel embedded with human lung fibroblasts. We found that addition of activated eosinophils and the application of 50% strain to the same system increased the epithelial thickness compared with either condition alone, suggesting that mechanical strain affects airway wall remodeling synergistically with inflammation. This integrated model more closely mimics airway wall remodeling than single-cell, conditioned media, or even two-dimensional coculture systems and is relevant for examining the importance of mechanical strain on airway wall remodeling in an inflammatory environment, which may b e crucial for understanding and treating pathologies such as asthma.

Original languageEnglish (US)
Pages (from-to)L427-L433
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume285
Issue number2 29-2
DOIs
StatePublished - Aug 1 2003

Keywords

  • Airway inflammation
  • Asthma
  • Eosinophils
  • Human bronchial epithelial cells
  • Mechanical stress

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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