{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:07:20Z","timestamp":1771463240551,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T00:00:00Z","timestamp":1659571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["RO1 DC017397"],"award-info":[{"award-number":["RO1 DC017397"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Glucocorticoids (GCs) modulate multiple cellular activities including inflammatory and fibrotic responses. Outcomes of GC treatment for laryngeal disease vary, affording opportunity to optimize treatment. In the current study, three clinically employed GCs were evaluated to identify optimal in vitro concentrations at which GCs mediate favorable anti\u2010inflammatory and fibrotic effects in multiple cell types. We hypothesize a therapeutic window will emerge as a foundation for optimized therapeutic strategies for patients with laryngeal disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>In vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human vocal fold fibroblasts and human macrophages derived from THP\u20101 monocytes were treated with 0.03\u20131000\u2009nM dexamethasone, 0.3\u201310,000\u2009nM methylprednisolone, and 0.3\u201310,000\u2009nM triamcinolone in combination with interferon\u2010\u03b3, tumor necrosis factor\u2010\u03b1, or interleukin\u20104. Real\u2010time polymerase chain reaction was performed to analyze inflammatory (<jats:italic>CXCL10<\/jats:italic>, <jats:italic>CXCl11<\/jats:italic>, <jats:italic>PTGS2<\/jats:italic>, <jats:italic>TNF<\/jats:italic>, <jats:italic>IL1B<\/jats:italic>) and fibrotic (<jats:italic>CCN2<\/jats:italic>, <jats:italic>LOX<\/jats:italic>, <jats:italic>TGM2<\/jats:italic>) genes, and <jats:italic>TSC22D3<\/jats:italic>, a target gene of GC signaling. EC<jats:sub>50<\/jats:sub> and IC<jats:sub>50<\/jats:sub> to alter inflammatory and fibrotic gene expression was calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Interferon\u2010\u03b3 and tumor necrosis factor\u2010\u03b1 increased inflammatory gene expression in both cell types; this response was reduced by GCs. Interleukin\u20104 increased <jats:italic>LOX<\/jats:italic> and <jats:italic>TGM2<\/jats:italic> expression in macrophages; this response was also reduced by GCs. GCs induced <jats:italic>TSC22D3 and CCN2<\/jats:italic> expression independent of cytokine treatment. EC<jats:sub>50<\/jats:sub> for each GC to upregulate <jats:italic>CCN2<\/jats:italic> was higher than the IC<jats:sub>50<\/jats:sub> to downregulate other genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Lower concentrations of GCs repressed inflammatory gene expression and only moderately induced genes involved in fibrosis. These data warrant consideration as a foundation for optimized clinical care paradigms to reduce inflammation and mitigate fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 133:1169\u20131175, 2023<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.30330","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T11:33:45Z","timestamp":1659612825000},"page":"1169-1175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Glucocorticoid Dose Dependency on Gene Expression in Vocal Fold Fibroblasts and Macrophages"],"prefix":"10.1002","volume":"133","author":[{"given":"Ryosuke","family":"Nakamura","sequence":"first","affiliation":[{"name":"Rehabilitation Medicine, NYU Grossman School of Medicine  New York New York 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