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Cellular and Molecular Bioengineering

, Volume 3, Issue 4, pp 415–427 | Cite as

Influence of Transmural Pressure and Cytoskeletal Structure on NF-κB Activation in Respiratory Epithelial Cells

  • Yan Huang
  • Caroline Haas
  • Samir N. Ghadiali
Article

Abstract

Respiratory epithelial cells are exposed to complex mechanical forces which are often modulated during pathological conditions such as Otitis Media and acute lung injury. The transduction of these mechanical forces into altered inflammatory signaling may play an important role in the persistence of disease conditions and inflammation. In this study, we investigated how static and oscillatory pressures altered the activation of NF-κB inflammatory pathways and how changes in the actin cytoskeleton influenced the mechanotransduction of pressure into NF-κB activation. An in vitro system was used to apply static and oscillatory pressures to alveolar epithelial cells cultured at an air–liquid interface. Latrunculin A and Jasplakinolide were used to alter the cytoskeleton and tight-junction structure and ELISA was used to monitor activation of NF-κB. Results indicate that both static and oscillatory pressures can activate NF-κB and that this activation is magnitude-dependent at low oscillation frequencies only. Jasplakinolide treated cells did not exhibit significant changes in normalized NF-κB activation compared to unloaded controls while Latrunculin treated cells exhibited increases in normalized NF-κB activation only at low frequency or static pressures. These results indicate that altering the actin cytoskeleton may be a useful way to mitigate the mechanotransduction of pressure forces into inflammatory signaling.

Keywords

Mechanotransduction Otitis Media Acute lung injury Ventilation induced lung injury Inflammation Compressive stress Calcium signaling IκBα 

Notes

Acknowledgments

This work was supported in part by NIH/NIDCD grants DC007230 and DC007667 and NSF CAREER grant 0852417.

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Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  • Yan Huang
    • 1
    • 3
  • Caroline Haas
    • 1
  • Samir N. Ghadiali
    • 1
    • 2
    • 3
  1. 1.Department of Biomedical EngineeringThe Ohio State UniversityColumbusUSA
  2. 2.Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal MedicineOhio State University Medical CenterColumbusUSA
  3. 3.Davis Heart and Lung Research InstituteThe Ohio State UniversityColumbusUSA

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