Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells

Introduction. Gastroesophageal reflux has been associated with chronic inflammatory diseases and may be a cause of airway remodelling. Aspiration of gastric fluids may cause damage to airway epithelial cells, not only because acidity is toxic to bronchial epithelial cells, but also since it contains...

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Main Authors: Erik Bathoorn, Paul Daly, Birgit Gaiser, Karl Sternad, Craig Poland, William MacNee, Ellen M. Drost
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:International Journal of Inflammation
Online Access:http://dx.doi.org/10.4061/2011/569416
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author Erik Bathoorn
Paul Daly
Birgit Gaiser
Karl Sternad
Craig Poland
William MacNee
Ellen M. Drost
author_facet Erik Bathoorn
Paul Daly
Birgit Gaiser
Karl Sternad
Craig Poland
William MacNee
Ellen M. Drost
author_sort Erik Bathoorn
collection DOAJ
description Introduction. Gastroesophageal reflux has been associated with chronic inflammatory diseases and may be a cause of airway remodelling. Aspiration of gastric fluids may cause damage to airway epithelial cells, not only because acidity is toxic to bronchial epithelial cells, but also since it contains digestive enzymes, such as pepsin. Aim. To study whether pepsin enhances cytotoxicity and inflammation in airway epithelial cells, and whether this is pH-dependent. Methods. Human bronchial epithelial cells were exposed to increasing pepsin concentrations in varying acidic milieus, and cell proliferation and cytokine release were assessed. Results. Cell survival was decreased by pepsin exposure depending on its concentration (F=17.4) and pH level of the medium (F=6.5) (both P<0.01). Pepsin-induced interleukin-8 release was greater at lower pH (F=5.1; P<0.01). Interleukin-6 induction by pepsin was greater at pH 1.5 compared to pH 2.5 (mean difference 434%; P=0.03). Conclusion. Pepsin is cytotoxic to bronchial epithelial cells and induces inflammation in addition to acid alone, dependent on the level of acidity. Future studies should assess whether chronic aspiration causes airway remodelling in chronic inflammatory lung diseases.
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spelling doaj-art-cf1a99dbe0d840eebf37477dcf9286da2025-02-03T05:46:19ZengWileyInternational Journal of Inflammation2042-00992011-01-01201110.4061/2011/569416569416Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial CellsErik Bathoorn0Paul Daly1Birgit Gaiser2Karl Sternad3Craig Poland4William MacNee5Ellen M. Drost6ELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UKELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UKELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UKELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UKELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UKELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UKELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UKIntroduction. Gastroesophageal reflux has been associated with chronic inflammatory diseases and may be a cause of airway remodelling. Aspiration of gastric fluids may cause damage to airway epithelial cells, not only because acidity is toxic to bronchial epithelial cells, but also since it contains digestive enzymes, such as pepsin. Aim. To study whether pepsin enhances cytotoxicity and inflammation in airway epithelial cells, and whether this is pH-dependent. Methods. Human bronchial epithelial cells were exposed to increasing pepsin concentrations in varying acidic milieus, and cell proliferation and cytokine release were assessed. Results. Cell survival was decreased by pepsin exposure depending on its concentration (F=17.4) and pH level of the medium (F=6.5) (both P<0.01). Pepsin-induced interleukin-8 release was greater at lower pH (F=5.1; P<0.01). Interleukin-6 induction by pepsin was greater at pH 1.5 compared to pH 2.5 (mean difference 434%; P=0.03). Conclusion. Pepsin is cytotoxic to bronchial epithelial cells and induces inflammation in addition to acid alone, dependent on the level of acidity. Future studies should assess whether chronic aspiration causes airway remodelling in chronic inflammatory lung diseases.http://dx.doi.org/10.4061/2011/569416
spellingShingle Erik Bathoorn
Paul Daly
Birgit Gaiser
Karl Sternad
Craig Poland
William MacNee
Ellen M. Drost
Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells
International Journal of Inflammation
title Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells
title_full Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells
title_fullStr Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells
title_full_unstemmed Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells
title_short Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells
title_sort cytotoxicity and induction of inflammation by pepsin in acid in bronchial epithelial cells
url http://dx.doi.org/10.4061/2011/569416
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