{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:53:22Z","timestamp":1791939202839,"version":"4.3.4"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,11,1]],"date-time":"2009-11-01T00:00:00Z","timestamp":1257033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the contribution of pepsin to inflammation attributed to nonacidic gastric reflux via analysis of inflammatory cytokine and cytokine receptor gene expression in pepsin\u2010treated human hypopharyngeal epithelial cells in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Translational research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>This study was performed in an academic research laboratory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>Human hypopharyngeal epithelial cells were incubated with or without pepsin (0.1\u00a0mg\/mL) at pH 7.4, 37\u00b0C, overnight. Expression of 84\u00a0inflammatory cytokines and cytokine receptors was analyzed via RT<jats:sup>2<\/jats:sup> qPCR array.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of a number of inflammatory cytokines and receptors was altered in human hypopharyngeal epithelial cells following overnight treatment with pepsin at neutral pH. Greater than 1.5\u2010fold change in gene expression was detected for CCL20, CCL26, IL8, IL1F10, IL1A, IL5, BCL6, CCR6, and CXCL14 (<jats:italic>P<\/jats:italic> &lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exposure of hypopharyngeal cells to pepsin in a nonacidic environment induces the expression of several pro\u2010inflammatory cytokines and receptors, including those known to be involved in inflammation of esophageal epithelium in response to reflux and which contribute to the pathophysiology of reflux esophagitis. These data indicate that refluxed pepsin may contribute to laryngeal inflammation associated with nonacidic gastric reflux, including that experienced by patients despite maximal acid suppression therapy.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.otohns.2009.08.022","type":"journal-article","created":{"date-parts":[[2009,10,25]],"date-time":"2009-10-25T04:10:08Z","timestamp":1256443808000},"page":"559-563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Pepsin as a causal agent of inflammation during nonacidic reflux"],"prefix":"10.1002","volume":"141","author":[{"given":"Tina L.","family":"Samuels","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin Milwaukee WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Communication Sciences Medical College of Wisconsin Milwaukee WI"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,11]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"PostmaGN HalumSL.Laryngeal and pharyngeal complications of gastroesophageal reflux disease. 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