Stretch induces cytokine release by alveolar epithelial cells in vitro

Nicholas E. Vlahakis, Mark A. Schroeder, Andrew H. Limper, Rolf D. Hubmayr

Research output: Contribution to journalArticlepeer-review

344 Scopus citations


Mechanical ventilation can injure the lung, causing edema and alveolar inflammation. Interleukin-8 (IL-8) plays an important role in this inflammatory response. We postulated that cyclic cell stretch upregulates the production and release of IL-8 by human alveolar epithelium in the absence of structural cell damage or paracrine stimulation. To test this hypothesis, alveolar epithelial cells (A549 cells) were cultured on a deformable silicoelastic membrane. When stretched by 30% for up to 48 h, the cells released 49 ± 34% more IL-8 (P < 0.001) than static controls. Smaller deformations (20% stretch) produced no consistent increase in IL-8. Stretch of 4 h duration increased IL-8 gene transcription fourfold above baseline. Stretch had no effect on cell proliferation, cell viability as assessed by 51Cr release assay, or the release of granulocyte-macrophage colony- stimulating factor and tumor necrosis factor-α. We conclude that deformation per se can trigger inflammatory signaling and that alveolar epithelial cells may be active participants in the alveolitis associated with ventilator- induced lung injury.

Original languageEnglish (US)
Pages (from-to)L167-L173
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 21-1
StatePublished - Jul 1999


  • Alveolar epithelium
  • Deformation
  • Inflammation
  • Interleukin-8
  • Mechanical forces

ASJC Scopus subject areas

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


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