{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:55:13Z","timestamp":1791219313159,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100008593","name":"European Respiratory Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004344","name":"Stichting Astma Bestrijding","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004344","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Inflammation"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p><jats:italic>Introduction<\/jats:italic>. 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.<jats:italic>Aim<\/jats:italic>. To study whether pepsin enhances cytotoxicity and inflammation in airway epithelial cells, and whether this is pH-dependent.<jats:italic>Methods<\/jats:italic>. Human bronchial epithelial cells were exposed to increasing pepsin concentrations in varying acidic milieus, and cell proliferation and cytokine release were assessed.<jats:italic>Results<\/jats:italic>. Cell survival was decreased by pepsin exposure depending on its concentration (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>F<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>17.4<\/mml:mn><\/mml:math>) and pH level of the medium (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>F<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>6.5<\/mml:mn><\/mml:math>) (both<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.01<\/mml:mn><\/mml:math>). Pepsin-induced interleukin-8 release was greater at lower pH (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>F<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>5.1<\/mml:mn><\/mml:math>;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.01<\/mml:mn><\/mml:math>). Interleukin-6 induction by pepsin was greater at pH 1.5 compared to pH 2.5 (mean difference 434%;<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.03<\/mml:mn><\/mml:math>).<jats:italic>Conclusion<\/jats:italic>. 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.<\/jats:p>","DOI":"10.4061\/2011\/569416","type":"journal-article","created":{"date-parts":[[2011,8,8]],"date-time":"2011-08-08T12:01:12Z","timestamp":1312804872000},"page":"1-5","source":"Crossref","is-referenced-by-count":19,"title":["Cytotoxicity and Induction of Inflammation by Pepsin in Acid in Bronchial Epithelial Cells"],"prefix":"10.4061","volume":"2011","author":[{"given":"Erik","family":"Bathoorn","sequence":"first","affiliation":[{"name":"ELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UK"},{"name":"Department of Medical Microbiology, University Medical Center Utrecht, 3508 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Daly","sequence":"additional","affiliation":[{"name":"ELEGI, Colt Research 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