Stretch induces cytokine release by alveolar epithelial cells in vitro.
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 (51)Cr release assay, or the release of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. 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.
Thoracic Diseases Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
N E
NE
Vlahakis
M A
MA
Schroeder
A H
AH
Limper
R D
RD
Hubmayr
D015152:Blotting, Northern; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002857:Chromium