Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
Department of Interdisciplinary Research on Medicine and Photonics, Institute of Post-LED Photonics, Tokushima University, Tokushima, Japan.
Front Immunol. 2023 Jan 27;14:1065790. doi: 10.3389/fimmu.2023.1065790. eCollection 2023.
FXR is a key molecule that modulates anti-inflammatory activity in the intestinal-liver axis. Although FXR has pleiotropic functions including regulation of liver inflammation and activation of macrophages, it remains unclear whether it is involved in macrophage polarization. In this paper we demonstrated that stimulation of macrophages derived from the bone marrow using an FXR agonist activated polarization toward M2 but not M1 macrophages. The treatment of mice with chitin skewed macrophage polarization towards M2 macrophages, while co-treatment with an FXR agonist further promoted the polarization toward M2 macrophages . This skewed polarization towards M2 macrophages by an FXR agonist was accompanied by increased expression of signaling molecules related to the retinoic acid receptor. Inhibition of the retinoic acid receptor suppressed FXR agonist-mediated M2 macrophage polarization, indicating that this polarization was, at least, partly dependent on the retinoic acid receptor pathway. These data demonstrate that FXR has a role in polarization toward M2 macrophages and suggest a possible therapeutic potential of FXR agonists in M2 macrophage-related conditions.
FXR 是调节肠-肝轴抗炎活性的关键分子。尽管 FXR 具有多种功能，包括调节肝脏炎症和激活巨噬细胞，但尚不清楚它是否参与巨噬细胞极化。在本文中，我们证明了 FXR 激动剂刺激骨髓来源的巨噬细胞可激活向 M2 型极化，但不激活向 M1 型极化。壳聚糖处理的小鼠巨噬细胞向 M2 型极化倾斜，而同时用 FXR 激动剂处理则进一步促进向 M2 型极化。这种 FXR 激动剂向 M2 型巨噬细胞的极化伴随着与维甲酸受体相关的信号分子表达增加。维甲酸受体的抑制抑制了 FXR 激动剂介导的 M2 型巨噬细胞极化，表明这种极化至少部分依赖于维甲酸受体途径。这些数据表明 FXR 在向 M2 型巨噬细胞极化中起作用，并提示 FXR 激动剂在与 M2 型巨噬细胞相关的疾病中具有潜在的治疗作用。
Zotero 插件
