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Am J Perinatol 2008; 25(8): 481-489
DOI: 10.1055/s-0028-1085067
© Thieme Medical Publishers

Dissociation between the Effects of Oxygen and Pressure on Matrix Metalloproteinase-2, -7, and -9 Expression in Human Airway Epithelial Cells

Thomas L. Miller1 , 3 , Yan Zhu1 , Sean Markwardt1 , Clifford J. Singhaus1 , Aaron S. Chidekel1 , 2 , 3 , Thomas H. Shaffer1 , 2 , 4
  • 1Nemours Research Lung Center, Department of Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware
  • 2Department of Pediatrics, Nemours, Alfred I. duPont Hospital for Children, Wilmington, Delaware
  • 3Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
  • 4Departments of Physiology and Pediatrics, Temple University School of Medicine, Philadelphia, Pennsylvania
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Publication History

Publication Date:
21 August 2008 (online)

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ABSTRACT

We tested the hypothesis that hyperoxia or pressure exposure differentially activates expression of cytokines and/or matrix modeling proteins in human airway epithelial cells. Calu-3 epithelial cell monolayers were cultured on transwell plates with the apical surface exposed to gas. Following establishment of baseline, plates were placed in a chamber and exposed to: control (21% O2; atm), hyperoxia (60% O2; atm), pressure (21% O2; 40 cm H2O), and combination (60% O2; 40 cm H2O). At 72 hour of exposure, monolayers were assessed for integrity, viability, and expression of interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMPs) -2, -7, and -9. Compared with controls, hyperoxia had lower transepithelial resistance (p < 0.001) and greater IL-6 secretion (p < 0.01), and pressure had lower cell viability (p < 0.001) and greater IL-8 secretion (p < 0.001). Hyperoxia resulted in more latent MMP-2 (p < 0.05) and MMP-7 (p < 0.001). Pressure was associated with a rise in MMPs independent of oxygen exposure (p < 0.05). Hyperoxia and pressure differentially affected MMP activities in Calu-3 cells and may lead to the different functional and structural abnormalities observed in these in vitro studies.

KEYWORDS

Conducting airway - mechanical ventilation - matrix modeling - inflammation - Calu-3

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Thomas H ShafferPh.D. 

Nemours Research Lung Center, Department of Biomedical Research

Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803

Email: tshaffer@nemours.org

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