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Budesonide and fluticasone propionate exertdifferential effects on human bronchial epithelial cells exposed to streptococcus pneumoniae and viral mimetic

H. Irene Heijink, Marnix Jonker, Dirkje S. Postma, Maarten van den Berge
European Respiratory Journal 2016 48: PA5061; DOI: 10.1183/13993003.congress-2016.PA5061
H. Irene Heijink
1Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
2Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
3GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
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Marnix Jonker
1Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
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Dirkje S. Postma
2Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
3GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
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Maarten van den Berge
2Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
3GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
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Abstract

Rationale: Clinical data from large cohorts of COPD patients suggest an increased risk of pneumonia in patients treated with fluticasone propionate (FP) vs no use of inhaled corticosteroids (Thorax 2013;68:1029) and vs budesonide (BUD) (BMJ 2013;346:f3306).Mechanisms underlying this difference are unknown. We hypothesized that BUD and FP differentially affect the susceptibility to bacterial infection upon concomitant viral exposure.

Methods: We assessed the effect of 2-hour pre-treatment with equipotent concentrations of BUD (16 nM) and FP (10 nM) on adhesion and/or internalization of S. pneumoniae and barrier function (trans-epithelial resistance; TER) in the human bronchial epithelial 16HBE cells upon concomitant exposure to viral mimetic poly-(I:C). Data were normalized to the poly-(I:C) response.

Results: Exposure to poly-(I:C) increased the adhesion and/or internalization of S. pneumoniaeadministered to the apical side of the cells 2-fold (p<0.05). This increase was prevented by BUD (p<0.05) but not by FP. The exposure to S. pneumoniaecaused a 7-fold (p<0.01) reduction in TER, which was further decreased 2-fold (p<0.05) by concomitant exposure to poly-(I:C). The poly-(I:C) effect was counteracted by BUD (p<0.05) but not by FP.

Conclusions: BUD, but not FP, counteracted S. pneumoniae adhesion and/or internalization and barrier dysfunction upon concomitant exposure to viral mimetic, suggesting that BUD is more effective than FP in the protection of the epithelial barrier against secondary bacterial infection. This may contribute to the difference in the risk of pneumonia between FP and BUD in COPD.

Supported by AstraZeneca.

  • COPD - mechanism
  • Cell biology
  • Pneumonia
  • Copyright ©the authors 2016
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Budesonide and fluticasone propionate exertdifferential effects on human bronchial epithelial cells exposed to streptococcus pneumoniae and viral mimetic
H. Irene Heijink, Marnix Jonker, Dirkje S. Postma, Maarten van den Berge
European Respiratory Journal Sep 2016, 48 (suppl 60) PA5061; DOI: 10.1183/13993003.congress-2016.PA5061

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Budesonide and fluticasone propionate exertdifferential effects on human bronchial epithelial cells exposed to streptococcus pneumoniae and viral mimetic
H. Irene Heijink, Marnix Jonker, Dirkje S. Postma, Maarten van den Berge
European Respiratory Journal Sep 2016, 48 (suppl 60) PA5061; DOI: 10.1183/13993003.congress-2016.PA5061
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