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Airway cell involvement in intermittent hypoxia-induced airway inflammation

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Abstract

Purpose

Respiratory inflammation has been described in patients with obstructive sleep apnea syndrome, but it is unknown whether the increased neutrophil and interleukin (IL)-8 levels observed in induced sputum reflect systemic or local airway inflammation. We assessed the potential role of resident cells in intermittent hypoxia-induced airway inflammation.

Methods

Airway epithelial cells (AEC) and bronchial smooth muscle cells (BSMC) were exposed to intermittent hypoxia (IH) in vitro. Cell supernatants were assessed for matrix metalloproteinase, growth factor, and cytokine expression. The role of IH on neutrophil and BSMC migration capacities was evaluated, and the effect of supernatants from IH-exposed or control AEC was tested.

Results

Compared to normoxic conditions, 24 h of exposure to IH induced a significant increase of MMP-9 and MMP-2 expression and pro-MMP-9 activation (p < 0.05), and IL-8 (p < 0.05), platelet-derived growth factor (PDGF)-AA (p < 0.05), and vascular endothelial growth factor (VEGF) (p < 0.05) expression by AEC and VEGF expression (p = 0.04) by BSMC. Neutrophil chemotaxis and BSMC migration were enhanced by IH and supernatants of IH-exposed AEC (112.00 ± 4.80 versus 0.69 ± 0.43 %, p = 0.0053 and 247 ± 76 versus 21 ± 23, p = 0.009 respectively). This enhanced BSMC migration was totally abolished in the presence of an antibody blocking PDGF-AA.

Conclusions

These data suggest a specific inflammatory response of airway cells to IH, independently of systemic events.

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Abbreviations

AECs:

Airway epithelial cells

BSMCs:

Bronchial smooth muscle cells

FCS:

Fetal calf serum

IH:

Intermittent hypoxia

IL:

Interleukin

MMPs:

Matrix metalloproteinases

Nx:

Normoxia

OSAS:

Obstructive sleep apnea syndrome

PBS:

Phosphate buffered saline

PDGF:

Platelet-derived growth factor

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We are very grateful to D. Bokar-Thire and L. Margarit for their technical assistance and to Dr A. Saul for his English expertise. We are very grateful to Bernadette Lescure at the microassay platform (Institut de Recherche en Santé, IFR65, Paris, France) for cytokines assays. This work was funded by the nonprofit Air-Liquide Foundation and INSERM.

Conflict of interest

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. INSERM, U955, Equipe 13, Créteil, France

    C. Philippe, J F. Papon, D. Isabey & A. Coste

  2. APHP, Groupe Hospitalier Pitié Salpêtrière, Unité des Pathologies du Sommeil, 47-83, Bd de l’hôpital, 75651, Paris, France

    C. Philippe

  3. INSERM, U773, Equipe 8, Paris, France

    Y. Boussadia & C. Clérici

  4. INSERM, U955, Equipe 11, Créteil, France

    V. Prulière-Escabasse

  5. Centre Hospitalier Intercommunal de Créteil, Service d’ORL, Créteil, France

    V. Prulière-Escabasse, J F. Papon & A. Coste

  6. Université Paris Est, Faculté de Médecine, Créteil, France

    V. Prulière-Escabasse, J F. Papon & A. Coste

  7. INSERM, UMRS 933, Paris, France

    E. Escudier

  8. APHP, Hôpital Armand-Trousseau, Service de Génétique et Embryologie Médicales, Paris, France

    E. Escudier

  9. APHP, Hôpital Bichat, Service de Physiologie - Explorations Fonctionnelles, DHU FIRE, Paris, France

    C. Clérici & M P. d’Ortho

  10. Université Paris Diderot, Sorbonne Paris Cité, 75018, Paris, France

    C. Clérici & M P. d’Ortho

Authors
  1. C. Philippe
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  2. Y. Boussadia
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  3. V. Prulière-Escabasse
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  4. J F. Papon
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  5. C. Clérici
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  6. D. Isabey
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  7. A. Coste
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  8. E. Escudier
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  9. M P. d’Ortho
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Corresponding author

Correspondence to C. Philippe.

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Philippe, C., Boussadia, Y., Prulière-Escabasse, V. et al. Airway cell involvement in intermittent hypoxia-induced airway inflammation. Sleep Breath 19, 297–306 (2015). https://doi.org/10.1007/s11325-014-1019-4

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  • DOI: https://doi.org/10.1007/s11325-014-1019-4

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