Anti-inflammatory Properties of the Alpha-Melanocyte-Stimulating Hormone in Models of Granulomatous Inflammation

Purpose Alpha-melanocyte stimulating hormone ([alpha]-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of [alpha]-MSH on normal bronchial epithelial cells are largely unknown, especially in the context of in vitro sarcoidosis models. Methods We evaluated the anti-inflammatory effects of [alpha]-MSH on two different in vitro sarcoidosis models (lung-on-membrane model; LOMM and three-dimensional biochip pulmonary sarcoidosis model; 3D-BSGM) generated from NBECs and an in vivo sarcoidosis mouse model. Results Treatment with [alpha]-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with [alpha]-MSH also significantly decreased macrophages and cytotoxic T-cells counts in a sarcoidosis mice model. Conclusion Our results confirm the direct role of type I IFNs in the pathogenesis of sarcoid lung granulomas and highlight [alpha]-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis. Graphical Abstract
Author(s): Abdolrazagh Hashemi Shahraki [sup.1], Runxia Tian [sup.2], Chongxu Zhang [sup.2], Nevis L. Fregien [sup.2], Pablo Bejarano [sup.3], Mehdi Mirsaeidi [sup.1] Author Affiliations: (1) grid.15276.37, 0000 0004 1936 8091, Division [...]