Mesenchymal stem/stromal cells (MSCs) and macrophages are critical components in many tissue microenvironments, including that in adipose tissue. The close interaction between MSCs and macrophages modulates various adipose-related disease development. However, the effects of macrophages on the fate of MSCs remain largely elusive. We here studied the effect of macrophages on the adipogenic differentiation of MSCs. Macrophages were obtained from THP-1 cells treated with phorbol-12-myristate-13-acetate (PMA). The induced matured macrophages were then induced to undergo classically activated macrophage (M1) or alternatively activated macrophage (M2) polarization with Iipopolysaccharide (LPS)/interferon (IFN)-γ and interleukin (IL)-4/IL-13, respectively. The supernatants derived from macrophages under different conditions were applied to cultured human adipose tissue-derived mesenchymal stem/stromal cells (hADSCs) undergoing adipogenic differentiation. Adipogenic differentiation was evaluated by examining Oil Red O staining of lipid droplets and the expression of adipogenesis-related genes with real-time quantitative polymerase chain reaction (Q-PCR) and western blot analysis. The adipogenic differentiation of hADSCs was impaired when treated with macrophage-derived supernatants, especially that from the M1-polarized macrophage (M1-sup). The inhibitory effect was found to be mediated by the inflammatory cytokines, mainly tumor necrosis factor-α (TNF-α) and IL-1β. Blocking TNF-α and IL-1β with neutralizing antibodies partially alleviated the inhibitory effect of M1-sup. Macrophage-derived supernatants inhibited the adipogenic differentiation of hADSCs in vitro, irrespective of the polarization status (M0, M1 or M2 macrophages). M1-sup was more potent because of the higher expression of pro-inflammatory cytokines. Our findings shed new light on the interaction between hADSCs and macrophages and have implications in our understanding of disrupted adipose tissue homeostasis under inflammation.

中文翻译：

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巨噬细胞通过产生促炎细胞因子来抑制脂肪组织衍生的间充质干/基质细胞的脂肪形成分化。

间充质干/基质细胞 (MSCs) 和巨噬细胞是许多组织微环境中的关键成分，包括脂肪组织中的微环境。间充质干细胞和巨噬细胞之间的密切相互作用调节了各种脂肪相关疾病的发展。然而，巨噬细胞对 MSCs 命运的影响在很大程度上仍然难以捉摸。我们在这里研究了巨噬细胞对 MSCs 成脂分化的影响。从用 phorbol-12-myristate-13-acetate (PMA) 处理的 THP-1 细胞获得巨噬细胞。然后诱导诱导的成熟巨噬细胞经历经典激活的巨噬细胞 (M1) 或分别与脂多糖 (LPS)/干扰素 (IFN)-γ 和白细胞介素 (IL)-4/IL-13 激活的巨噬细胞 (M2) 极化。将不同条件下巨噬细胞来源的上清液应用于培养的人脂肪组织来源的间充质干/基质细胞 (hADSCs) 进行成脂分化。通过使用实时定量聚合酶链反应 (Q-PCR) 和蛋白质印迹分析检查脂滴的油红 O 染色和脂肪生成相关基因的表达来评估脂肪形成分化。当用巨噬细胞衍生的上清液处理时，hADSCs 的脂肪形成分化受到损害，尤其是来自 M1 极化巨噬细胞 (M1-sup) 的上清液。发现抑制作用由炎性细胞因子介导，主要是肿瘤坏死因子-α（TNF-α）和IL-1β。用中和抗体阻断 TNF-α 和 IL-1β 部分减轻了 M1-sup 的抑制作用。无论极化状态（M0、M1 或 M2 巨噬细胞）如何，巨噬细胞衍生的上清液在体外抑制 hADSCs 的脂肪形成分化。由于促炎细胞因子的更高表达，M1-sup 更有效。我们的研究结果为 hADSCs 和巨噬细胞之间的相互作用提供了新的线索，并有助于我们理解炎症下脂肪组织稳态的破坏。