Mechanical compression attenuates normal human bronchial epithelial wound healing.
BACKGROUND
Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer.


METHODS
Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1) unperturbed control cells, 2) single scrape wound only, 3) static compression (6 hours of 30 cmH2O), and 4) 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled.


RESULTS
We found that mechanical compression and scrape injury increase TGF-beta2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF.


CONCLUSIONS
Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.
Arold
Stephen P
SP
Department of Biomedical Engineering, University of California, Irvine, USA. scgeorge@uci.edu
Malavia
Nikita
N
George
Steven C
SC
D000199:Actins / Q000378:metabolism; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011312:Pressure; D020545:Respiratory Mucosa / Q000293:injuries / Q000473:pathology*; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
D000199:Actins; D019332:Endothelin-1; D018836:Inflammation Mediators; D053781:Transforming Growth Factor beta2; D003571:Cytochalasin B; D004815:Epidermal Growth Factor; D015232:Dinoprostone