Growth Hormone Reprograms Macrophages toward an Anti-Inflammatory and Reparative Profile in an MAFB-Dependent Manner.
Blanca Soler PalaciosConcha NietoPilar FajardoArturo González de la AlejaNuria AndrésÁngeles Dominguez-SotoPilar LucasAna CuendaJosé Miguel Rodríguez-FradeCarlos Martínez-ARicardo VillaresÁngel L CorbíMario MelladoPublished in: Journal of immunology (Baltimore, Md. : 1950) (2020)
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.
Keyphrases
- growth hormone
- anti inflammatory
- transcription factor
- endothelial cells
- cell proliferation
- oxidative stress
- type diabetes
- signaling pathway
- squamous cell carcinoma
- gene expression
- big data
- machine learning
- immune response
- genome wide
- dna methylation
- poor prognosis
- artificial intelligence
- adipose tissue
- acute respiratory distress syndrome
- skeletal muscle
- intensive care unit
- dna binding
- insulin resistance
- induced pluripotent stem cells
- wild type