{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:46:54Z","timestamp":1753868814602,"version":"3.41.2"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":185,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Growth hormone\u2010releasing hormone (GHRH) is a potent stimulator of growth hormone (GH) secretion from the pituitary gland. Although GHRH is essential for the growth of immune cells, the regulatory effects of its antagonist in granulomatous disease remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we report expression of GHRH receptor (R) in human tissue with sarcoidosis granuloma and demonstrate the anti\u2010inflammatory effects of MIA602 (a GHRH antagonist) in two <jats:italic>in vitro<\/jats:italic> human granuloma models and an <jats:italic>in vivo<\/jats:italic> granuloma model using different methods including ELISA, immunohistochemistry, RNA\u2010seq analysis and flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MIA602 decreases the levels of IL\u20102, IL\u20102R, IL\u20107, IL\u201012, IL\u201017A and TNF\u2010\u03b1 in an <jats:italic>in vitro<\/jats:italic> granuloma model. Further, we show that the anti\u2010inflammatory effect of MIA602 appears to be mediated by a reduction in CD45<jats:sup>+<\/jats:sup>CD68<jats:sup>+<\/jats:sup> cells in granulomatous tissue and upregulation in PD\u20101 expression in macrophages. Analysis of the expression of proteins involved in the mitochondrial stage of apoptosis showed that MIA602 increases the levels of caspase\u20103, BCL\u2010xL\/BAK dimer and MCl\u20101\/Bak dimer in the granuloma. These findings indicate that MIA602 may not induce apoptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings further suggest that GHRH\u2010R is potentially a clinical target for the treatment of granulomatous disease and that MIA602 may be used as a novel therapeutic agent for sarcoidosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1310","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T12:16:33Z","timestamp":1625487393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Activity of the growth hormone\u2010releasing hormone antagonist MIA602 and its underlying mechanisms of action in sarcoidosis\u2010like granuloma"],"prefix":"10.1002","volume":"10","author":[{"given":"Chongxu","family":"Zhang","sequence":"first","affiliation":[{"name":"Section of Pulmonary Miami VA Healthcare System Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runxia","family":"Tian","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Miami VA Healthcare System Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilee M","family":"Dreifus","sequence":"additional","affiliation":[{"name":"School of Medicine University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdolrazagh","family":"Hashemi Shahraki","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Holt","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Miami VA Healthcare System Miami FL USA"},{"name":"Division of Pulmonary and Critical Care University of Miami Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzhi","family":"Cai","sequence":"additional","affiliation":[{"name":"Section of Pulmonary Miami VA Healthcare System Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Griswold","sequence":"additional","affiliation":[{"name":"School of Medicine John P. 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