{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:47Z","timestamp":1779148847183,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammation, hyaluronan production, and adipogenesis are the main pathological events leading to thyroid eye disease (TED). \u03b1-Melanocytemelanocyte-stimulating hormone (\u03b1-MSH) is a well-known tridecapeptidetreatment for several inflammatory disorders including sepsis syndrome, acute respiratory distress syndrome, rheumatoid arthritis, and encephalitis. Here, we investigated the effect of \u03b1-MSH treatment on TED. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Lactate Dehydrogenase (LDH) assays were performed to analyze the effect of \u03b1-MSH on cell viability and it\u2019s toxicity. Using primary cultures of orbital fibroblasts from TED patients and non-TED as control, we examined the effects of \u03b1-MSH on proinflammatory cytokine production induced by interleukin (IL)-1\u03b2, further analyzed by real-time reverse transcription-polymerase chain reaction (qPCR) and western blotting. Immunofluorescence staining assay and qPCR were performed to examine proopiomelanocortin (POMC) expression, the upstream neuropeptide of \u03b1-MSH in TED patients and non-TED control. Treatment with non-cytotoxic concentrations of \u03b1-MSH resulted in the dose-dependent inhibition of mRNA and protein levels (p &lt; 0.05) for IL-1\u03b2-induced inflammatory cytokines: IL-6, IL-8, MCP-1, ICAM-1, and COX-2. The expression of POMC mRNA and protein were significantly higher in TED patients compared to non-TED control (p &lt; 0.05). Our data show significant inhibitory effects of \u03b1-MSH on inflammation, POMC production in orbital fibroblasts. At present, this is the first in vitro preclinical evidence of \u03b1-MSH therapeutic effect on TED. These findings indicate that POMC and \u03b1-MSH may play a role in the immune regulation of TED and can be a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms222011225","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T22:52:47Z","timestamp":1634683967000},"page":"11225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic Effect of \u03b1-MSH in Primary Cultured Orbital Fibroblasts Obtained from Patients with Thyroid Eye Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-9247","authenticated-orcid":false,"given":"Pei-Wen","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0005-1476","authenticated-orcid":false,"given":"Pei-Jhen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"},{"name":"Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 813414, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Hong","family":"Tai","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 813414, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7020-5296","authenticated-orcid":false,"given":"Youn-Shen","family":"Bee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan"},{"name":"Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 813414, Taiwan"},{"name":"Department of Optometry, Shu-Zen Junior College of Medicine and Management, Kaohsiung 813414, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1016\/j.ophtha.2011.06.003","article-title":"Smoking and strabismus surgery in patients with thyroid eye disease","volume":"118","author":"Rajendram","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/cxo.12472","article-title":"Thyroid eye disease: A review","volume":"100","author":"Weiler","year":"2017","journal-title":"Clin. 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