{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T23:13:50Z","timestamp":1773702830815,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R21 AA028891"],"award-info":[{"award-number":["R21 AA028891"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol: Clinical and Experimental Research"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mechanisms by which alcohol increases the risk of esophageal squamous cell carcinoma remain undefined. Human esophageal myofibroblasts (HEMFs) subjacent to the squamous epithelium are exposed directly to these agents via epithelial barrier defects and indirectly via factors derived from the exposed epithelium. Our aim was to investigate the cellular biology of HEMFs and HEMF\u2010esophageal epithelial cell interactions in response to alcohol and its toxic metabolite acetaldehyde.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An immortalized HEMF and a human esophageal epithelial cell line (Epi) were treated with alcohol (0 to 200\u2009mM) or acetaldehyde (0 to 100\u2009<jats:italic>\u03bc<\/jats:italic>M) in a cyclic fashion or incubated with supernatants collected from treated cells. Healthy cell %, reactive oxygen species (ROS), and proliferation were assessed via flow cytometry, luminescence, scratch wound, and colorimetric assays, respectively. A 15\u2010plex multiplex assay was performed on cell supernatants, followed by IL\u20106 and IL\u20108 qRT\u2013PCR and ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Healthy HEMF decreased to less than 80% at 30\u2009mM alcohol and 70\u2009<jats:italic>\u03bc<\/jats:italic>M acetaldehyde, with microscopic changes at 40\u2009<jats:italic>\u03bc<\/jats:italic>M acetaldehyde. HEMF ROS was detected at 100\u2009mM alcohol and 80\u2009<jats:italic>\u03bc<\/jats:italic>M acetaldehyde. Supernatants from 30\u2009mM alcohol\u2010 or 40\u2009<jats:italic>\u03bc<\/jats:italic>M acetaldehyde\u2010treated HEMFs increased Epi proliferation more than two\u2010fold that of lower doses. In the complementary studies, healthy Epi cells decreased to less than 80% at 50\u2009mM and 70\u2009<jats:italic>\u03bc<\/jats:italic>M acetaldehyde, with microscopic changes at 40\u2009<jats:italic>\u03bc<\/jats:italic>M. Supernatants from Epi treated with 50\u2009mM alcohol or 40\u2009<jats:italic>\u03bc<\/jats:italic>M acetaldehyde increased HEMF proliferation more than two\u2010fold that of lower doses. A multiplex assay of supernatants showed the greatest increase in concentrations of IL\u20106 and IL\u20108 in HEMFs and in Epi treated with higher doses of alcohol or acetaldehyde. Neutralization of IL\u20106 and IL\u20108 in supernatants of HEMFS and esophageal epithelial cells inhibited the proliferation of Epi and HEMFs, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alcohol and acetaldehyde doses in which the majority of HEMFs and epithelial cells are healthy, elicit the production of paracrine mediators with pro\u2010proliferative effects on neighboring cells. Understanding the effect of alcohol and acetaldehyde on HEMFs and HEMF\u2010epithelial interactions could help to identify the molecular basis by which alcohol increases the risk for esophageal cancer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15093","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T06:05:32Z","timestamp":1683007532000},"page":"1297-1311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Direct and indirect effects of alcohol and its toxic metabolite acetaldehyde on human esophageal myofibroblasts and epithelial cells"],"prefix":"10.1111","volume":"47","author":[{"given":"Atousa","family":"Khalatbari","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal and Liver Diseases, Department of Medicine, Swallowing and Esophageal Disorders Center, Keck School of Medicine of USC University of Southern California  Los Angeles California 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