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Growth Hormone Reprograms Macrophages toward an Anti-Inflammatory and Reparative Profile in an MAFB-Dependent Manner.

J Immunol. 2020 Aug 01;205(3):776-788. Epub 2020 Jun 26
Blanca Soler Palacios 1 , Concha Nieto 2 , Pilar Fajardo 1 , Arturo González de la Aleja 2 , Nuria Andrés 1 , Ángeles Dominguez-Soto 2 , Pilar Lucas 1 , Ana Cuenda 1 , José Miguel Rodríguez-Frade 1 , Carlos Martínez-A 1 , Ricardo Villares 1 , Ángel L Corbí 3 , Mario Mellado 4
Blanca Soler Palacios 1 , Concha Nieto 2 , Pilar Fajardo 1 , Arturo González de la Aleja 2 , Nuria Andrés 1 , Ángeles Dominguez-Soto 2 , Pilar Lucas 1 , Ana Cuenda 1 , José Miguel Rodríguez-Frade 1 , Carlos Martínez-A 1 , Ricardo Villares 1 , Ángel L Corbí 3 , Mario Mellado 4
+ et al

[No authors listed]

Author information
  • 1 Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain; and.
  • 2 Departamento de Biología Molecular y Celular, Centro de Investigaciones Biológicas/Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain.
  • 3 Departamento de Biología Molecular y Celular, Centro de Investigaciones Biológicas/Consejo Superior de Investigaciones Científicas, 28040 Madrid, Spain acorbi@cib.csic.es mmellado@cnb.csic.es.
  • 4 Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain; and acorbi@cib.csic.es mmellado@cnb.csic.es.

摘要


Growth hormone (GH), a pleiotropic hormone secreted by the pituitary gland, regulates immune and inflammatory responses. In this study, we show that GH regulates the phenotypic and functional plasticity of macrophages both in vitro and in vivo. Specifically, GH treatment of GM-CSF-primed monocyte-derived macrophages promotes a significant enrichment of anti-inflammatory genes and dampens the proinflammatory cytokine profile through PI3K-mediated downregulation of activin A and upregulation of MAFB, a critical transcription factor for anti-inflammatory polarization of human macrophages. These in vitro data correlate with improved remission of inflammation and mucosal repair during recovery in the acute dextran sodium sulfate-induced colitis model in GH-overexpressing mice. In this model, in addition to the GH-mediated effects on other immune cells, we observed that macrophages from inflamed gut acquire an anti-inflammatory/reparative profile. Overall, these data indicate that GH reprograms inflammatory macrophages to an anti-inflammatory phenotype and improves resolution during pathologic inflammatory responses.