{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:13:18Z","timestamp":1789564398888,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T00:00:00Z","timestamp":1688428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laboratoire Th\u00e9a"},{"name":"Fondation de la Recherche M\u00e9dicale"},{"name":"French ministerial grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry eye inflammation is a key step in a vicious circle and needs to be better understood in order to break it. The goals of this work were to, first, characterize alarmins and cytokines released by ocular surface cells in the hyperosmolar context and, second, study the role of NFAT5 in this process. Finally, we studied the potential action of these alarmins in ocular surface epithelial cells and macrophages via RAGE pathways. HCE and WKD cell lines were cultured in a NaCl-hyperosmolar medium and the expression of alarmins (S100A4, S100A8, S100A9, and HMGB1), cytokines (IL6, IL8, TNF\u03b1, and MCP1), and NFAT5 were assessed using RT-qPCR, ELISA and multiplex, Western blot, immunofluorescence, and luciferase assays. In selected experiments, an inhibitor of RAGE (RAP) or NFAT5 siRNAs were added before the hyperosmolar stimulations. HCE and WKD cells or macrophages were treated with recombinant proteins of alarmins (with or without RAP) and analyzed for cytokine expression and chemotaxis, respectively. Hyperosmolarity induced epithelial cell inflammation depending on cell type. NFAT5, but not RAGE or alarmins, participated in triggering epithelial inflammation. Furthermore, the release of alarmins induced macrophage migration through RAGE. These in vitro results suggest that NFAT5 and RAGE have a role in dry eye inflammation.<\/jats:p>","DOI":"10.3390\/ijms241311052","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T01:32:18Z","timestamp":1688434338000},"page":"11052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inflammation of Dry Eye Syndrome: A Cellular Study of the Epithelial and Macrophagic Involvement of NFAT5 and RAGE"],"prefix":"10.3390","volume":"24","author":[{"given":"Fanny","family":"Henrioux","sequence":"first","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Navel","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"},{"name":"Ophthalmology Department, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7841-214X","authenticated-orcid":false,"given":"Corinne","family":"Belville","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coline","family":"Charnay","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Antoine","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Chiambaretta","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"},{"name":"Ophthalmology Department, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7452-315X","authenticated-orcid":false,"given":"Vincent","family":"Sapin","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"},{"name":"Biochemistry and Molecular Genetics Department, CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Blanchon","sequence":"additional","affiliation":[{"name":"Team \u201cTranslational Approach to Epithelial Injury and Repair\u201d, Institute Genetics, Reproduction and Development (iGReD), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II pathophysiology report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. 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