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Corticosteroids and Montelukast: Effects on Airway Epithelial and Human Umbilical Vein Endothelial Cells

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Abstract

Our primary objective was to investigate the possible contribution of controller medications to asthmatic airway remodeling, by (1) comparing the apoptotic and necrotic effects of several corticosteroids and montelukast on cultured airway human bronchial surface epithelial (16HBE) and submucosal (Calu3) cells; (2) measuring epithelial shedding potential and desmosome length in response to a cytokine challenge, with or without co-administered corticosteroids; and (3) studying corticosteroids and montelukast effects on inter-cellular adhesion molecule (ICAM) expression in both 16HBE and human umbilical vein endothelial cells (HUVEC). For this purpose, apoptosis, necrosis, and ICAM expression were quantified by flow cytometry, with 16HBE cells sensitive to both the apoptotic and necrotic effects of dexamethasone and montelukast; Calu3 cells sensitive only to budesonide. Transmission electron microscopy revealed decreased desmosome length in the presence of cytokines (TNF-α and INF-γ), with corticosteroids counteracting this reduction. Dexamethasone, beclomethasone, and montelukast decreased versus increased ICAM-1 expression in airway epithelial cells and HUVEC, respectively. For conclusions, bronchial surface epithelial and submucosal cells exhibit a different sensitivity profile toward dexamethasone, budesonide, and montelukast, with corticosteroids preventing cytokineinduced desmosomal damage in 16HBE cells. The studied drugs led to increased ICAM-1 expression in endothelium, potentially facilitating inflammatory cell migration into lung tissue.

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Acknowledgements

The technical assistance of Leif Ljung is gratefully acknowledged. This study was financially supported by the Swedish Asthma Allergy Association, the Swedish Heart–Lung Foundation, and the Swedish Science Research Council.

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Author notes

  1. G. M. Roomans & Z. Servetnyk

    Present address: School of Health and Medical Sciences, University Hospital, Örebro University, 70185, Örebro, Sweden

Authors and Affiliations

  1. Department of Medical Cell Biology, University of Uppsala, Box 571, 75123, Uppsala, Sweden

    K. Andersson, E. B. Shebani, N. Makeeva, G. M. Roomans & Z. Servetnyk

  2. Department of Medicine, St. Luke-Roosevelt Hospital Center, University Hospital of Columbia University College of Physicians and Surgeons, 1000 Tenth Avenue, Room 3A, New York, NY, 10019, USA

    Z. Servetnyk

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  1. K. Andersson
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Correspondence to Z. Servetnyk.

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Andersson, K., Shebani, E.B., Makeeva, N. et al. Corticosteroids and Montelukast: Effects on Airway Epithelial and Human Umbilical Vein Endothelial Cells. Lung 188, 209–216 (2010). https://doi.org/10.1007/s00408-010-9227-6

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  • DOI: https://doi.org/10.1007/s00408-010-9227-6

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