PT  - JOURNAL ARTICLE
AU  - Chongxu Zhang
AU  - Runxia Tian
AU  - Emilee M Dreifus
AU  - Gregory Holt
AU  - Renzhi Cai
AU  - Anthony Griswold
AU  - Pablo Bejarano
AU  - Robert Jackson
AU  - Andrew V. Schally
AU  - Mehdi Mirsaeidi
TI  - Activity of the GHRH Antagonist MIA602 and its Underlying Mechanisms of Action in sarcoidosis
AID  - 10.1101/2020.08.19.257915
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.08.19.257915
4099  - http://biorxiv.org/content/early/2020/08/20/2020.08.19.257915.short
4100  - http://biorxiv.org/content/early/2020/08/20/2020.08.19.257915.full
AB  - Growth hormone releasing hormone (GHRH) is a potent stimulator of 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 remains unknown. Here, we report expression of GHRH receptor (R) in human tissue with sarcoidosis granuloma and demonstrate the anti-inflammatory effects of MIA602 (a GHRH antagonist) in two in vitro human granuloma models and an in vivo granuloma model. MIA602 decreases levels of IL2, IL12, and IL17A in in vitro granuloma model.We show further that the anti-inflammatory effect of MIA602 appears to be mediated by reduction in CD45++CD68+ cells in granulomatous tissue and upregulation in PD-1 expression in macrophages.In analysis of expression of proteins involved in the mitochondrial stage of apoptosis, we show that MIA602 increases the levels of caspase 3, BCL-xL/BAK dimer, and MCl-1/Bak dimer in granuloma. These findings indicate that MIA602 may not induce apoptosis.The clinical relevance of our findings further suggest that HGRH-R is potentially a target for treatment of granulomatous disease and MIA602 possibly a novel therapeutic agent for sarcoidosis.Competing Interest StatementThe authors have declared no competing interest.