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We aimed to evaluate the effects of <jats:italic>\u03b1<\/jats:italic>-MSH in a novel <jats:italic>in vitro<\/jats:italic> sarcoidosis model. An <jats:italic>in vitro<\/jats:italic> sarcoidosis-like granuloma model was developed by challenging peripheral blood mononuclear cells (PBMCs) derived from patients with confirmed treatment-na\u00efve sarcoidosis with microparticles generated from <jats:italic>Mycobacterium abscessus<\/jats:italic> cell walls. Unchallenged PBMCsand developed granulomas were treated daily with 10\u2009\u03bcM <jats:italic>\u03b1<\/jats:italic>-MSH or saline as control. Cytokine concentrations in supernatants of culture and in cell extracts were measured using Illumina multiplex Elisa and western blot, respectively. Gene expression was analyzed using RNA-Seq and RT-PCR. Protein secretion and gene expression of IL-7, IL-7R, IFN-<jats:italic>\u03b3<\/jats:italic>, MC1R, NF-\u03baB, phosphorylated NF-\u03baB (p-NF-\u03baB), MARCO, and p-CREB were measured with western blot and RNAseq. A significant increase in IL-7, IL-7R, and IFN-<jats:italic>\u03b3<\/jats:italic> protein expression was found in developed granulomas comparing to microparticle unchallenged PBMCs. IL-7, IL-7R, and IFN-<jats:italic>\u03b3<\/jats:italic> protein expression was significantly reduced in developed granulomas after exposure to <jats:italic>\u03b1<\/jats:italic>-MSH compared with saline treated granulomas. Compared with microparticle unchallenged PBMCs, total NF-\u03baB and p-NF-\u03baB were significantly increased in developed granulomas, while expression of p-CREB was not changed. Treatment with <jats:italic>\u03b1<\/jats:italic>-MSH promoted a significantly higher concentration of p-CREB in granulomas. The anti-inflammatory effects of <jats:italic>\u03b1<\/jats:italic>-MSH were blocked by specific p-CREB inhibition. <jats:italic>\u03b1<\/jats:italic>-MSH has anti-inflammatory properties in this <jats:italic>in vitro<\/jats:italic> granuloma model, which is an effect mediated by induction of phosphorylation of CREB.<\/jats:p>","DOI":"10.1038\/s41598-020-64305-9","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T10:03:28Z","timestamp":1588154608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Anti-inflammatory effects of \u03b1-MSH through p-CREB expression in sarcoidosis like granuloma model"],"prefix":"10.1038","volume":"10","author":[{"given":"Chongxu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Chery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Lazerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman H","family":"Altman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-9062","authenticated-orcid":false,"given":"Michael","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew \u00a0V","family":"Schally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5298-8442","authenticated-orcid":false,"given":"Mehdi","family":"Mirsaeidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"64305_CR1","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1378\/chest.14-1120","volume":"147","author":"M Mirsaeidi","year":"2015","unstructured":"Mirsaeidi, M., Machado, R. 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