当前位置: X-MOL 学术J. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Growth Hormone Reprograms Macrophages toward an Anti-Inflammatory and Reparative Profile in an MAFB-Dependent Manner
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-26 , DOI: 10.4049/jimmunol.1901330
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
Affiliation  

Key Points GH reprograms inflammatory macrophages to an anti-inflammatory phenotype. GH modulates inflammation by altering activin A secretion and MAFB-dependent genes. 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.

中文翻译:

生长激素以依赖于 MAFB 的方式将巨噬细胞重新编程为抗炎和修复特征

关键点 GH 将炎性巨噬细胞重新编程为抗炎表型。GH 通过改变激活素 A 分泌和 MAFB 依赖性基因来调节炎症。生长激素 (GH) 是一种由垂体分泌的多效激素,可调节免疫和炎症反应。在这项研究中,我们表明 GH 在体外和体内调节巨噬细胞的表型和功能可塑性。具体而言,GM-CSF 引发的单核细胞衍生巨噬细胞的 GH 处理促进了抗炎基因的显着富集,并通过 PI3K 介导的激活素 A 下调和 MAFB(抗炎的关键转录因子)的上调抑制了促炎细胞因子谱。人巨噬细胞的极化。这些体外数据与 GH 过度表达小鼠急性葡聚糖硫酸钠诱导结肠炎模型恢复期间炎症缓解和粘膜修复的改善相关。在该模型中,除了 GH 介导的对其他免疫细胞的影响外,我们还观察到来自发炎肠道的巨噬细胞获得抗炎/修复特性。总体而言,这些数据表明 GH 将炎性巨噬细胞重新编程为抗炎表型,并在病理性炎症反应期间提高了分辨率。
更新日期:2020-06-26
down
wechat
bug