Volume 10 Supplement 1

Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2013

Open Access

Cyclic stretch augments human rhinovirus induced inflammatory responses in airway epithelial cells

  • Sergei Nikitenko1Email author,
  • Sami Shariff1,
  • Jason Arnason1,
  • Chris Shelfoon1,
  • Cora Kooi1,
  • David Proud1 and
  • Richard Leigh1
Allergy, Asthma & Clinical Immunology201410(Suppl 1):A71

https://doi.org/10.1186/1710-1492-10-S1-A71

Published: 3 March 2014

Background

Structural cells of the airways are subject to normal mechanical stretch during respiration [1]. Mechanical stretch acts as a mechanism of cell activation, and mechanotransduction pathways have been shown to activate pro-inflammatory genes [2]. Human rhinovirus (HRV) infections are a major cause of asthma exacerbations, and mechanical forces are likely to be more pronounced during asthma exacerbations [3]. Moreover, smoking is associated with worse clinical outcomes in asthma. Previous studies have shown that HRV infection, cigarette smoke extract (CSE), or mechanical stretch each induce CXCL8 production in bronchial epithelial cells [46]. In this study, we sought to determine whether mechanical stretch interacts with HRV infection and CSE to further upregulate airway inflammation.

Methods

Studies were performed using primary human bronchial epithelial cells (HBEC), the human bronchial epithelial cell line BEAS-2B. Cells were treated with CS (FlexCell FX-4000), HRV-16 or with a combination of CS+HRV-16. Protein and mRNA levels were measured using ELISA (R&D Systems) and real-time RT-PCR (Applied Biosystems).

Results

Mechanical stretch and HRV infection each significantly increased CXCL8 release in BEAS-2B and HBE cells compared to static controls (p<0.001). When studied in combination, there was a significant synergistic increase in CXCL8 in BEAS-2B (p<0.001). Ultraviolet (UV) inactivation of HRV attenuated this increase in CXCL8 release. Mechanical stretch and HRV infection each increased CXCL8 mRNA levels compared to static controls, with the combination resulting in further enhanced induction (p<0.01). CSE alone did not significantly increase CXCL8 production in BEAS-2B. However, the combination of CSE+HRV significantly enhanced CXCL8 release compared to medium control (p<0.001) and HRV alone (p<0.05), and this increase was significantly further augmented by mechanical stretch (p<0.001).

Conclusions

Mechanical stretching of BEAS-2B and HBE cells increased HRV-induced CXCL8 mRNA and protein levels, confirming that this effect is, at least in part, regulated at the transcriptional level. Moreover, the combination of mechanical stretch and HRV infection, as might occur during asthma exacerbations, resulted in a synergistic enhancement of CXCL8 expression, compared to either stimulus alone. CSE further enhanced HRV-induced and stretch-induced CXCL8 release, and the combination of all three variables potentiated this effect. Since levels of CXCL8 have been linked to increased airway neutrophils and symptom severity, mechanical stretch, if it also enhances CXCL8 production induced during HRV infections in vivo, may contribute to the pathogenesis of airway inflammation in HRV-induced asthma exacerbations.

Declarations

Acknowledgements

The funding sources for this study include AllerGen NCE Inc., Queen Elizabeth II Masters Scholarship, Canadian Institutes of Health Research, and the GSK-CIHR Professorship in Inflammatory Lung Disease.

Authors’ Affiliations

(1)
Snyder Institute for Chronic Diseases, University of Calgary

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Copyright

© Nikitenko et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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