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

Lung. 2022 Aug;200(4):463-472. doi: 10.1007/s00408-022-00546-x. Epub 2022 Jun 18.

Abstract

Purpose: Alpha-melanocyte stimulating hormone (α-MSH) is known to have anti-inflammatory effects. However, the anti-inflammatory properties of α-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 α-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 α-MSH decreased inflammatory cytokine levels and downregulated type I interferon pathway genes and related proteins in LOMM and 3D-BSGM models. Treatment with α-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 α-MSH as a potential novel therapeutic agent for treating pulmonary sarcoidosis.

Keywords: Bronchial epithelial cells; In vitro granuloma model; Mice model; Sarcoidosis; Type I interferons; α-MSH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Granuloma / drug therapy
  • Inflammation / metabolism
  • Mice
  • Sarcoidosis* / drug therapy
  • Sarcoidosis, Pulmonary* / drug therapy
  • alpha-MSH / metabolism
  • alpha-MSH / pharmacology
  • alpha-MSH / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • alpha-MSH