Interferon (IFN)-γ is a proinflammatory cytokine with a crucial role in intercellular communication during innate and acquired immune responses. IFN-γ interacts with many cell types, among which endothelial cells. Here, we show that pharmacological and low-dose kinetically activated (SKA) IFN-γ exert different effects on endothelial cells by activating different signal transduction pathways. Pharmacological concentrations of IFN-γ activate JAK/STAT pathway, inducing the overexpression of the CDKN1A p21, which in turn inhibits cell growth. Conversely, low-dose SKA IFN-γ does not activate the canonical JAK/STAT pathway but induces the phosphorylation of ERK. ERK activation is responsible for the induction of endothelial cell migration. Interestingly, ERK activation occurs only in the presence of kinetically activate low-dose IFN-γ, underlying the importance of mechanical forces to potentiate IFN-γ activity.

中文翻译：

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药理或低剂量 IFN-γ 在内皮细胞中的不同作用是由不同的细胞内信号通路介导的

干扰素 (IFN)-γ 是一种促炎细胞因子，在先天性和获得性免疫反应期间的细胞间通讯中起关键作用。IFN-γ 与许多细胞类型相互作用，其中包括内皮细胞。在这里，我们表明药理学和低剂量动力学激活 (SKA) IFN-γ 通过激活不同的信号转导途径对内皮细胞发挥不同的作用。药理浓度的 IFN-γ 激活 JAK/STAT 通路，诱导 CDKN1A p21 的过表达，进而抑制细胞生长。相反，低剂量 SKA IFN-γ 不会激活经典的 JAK/STAT 通路，但会诱导 ERK 的磷酸化。ERK 激活负责诱导内皮细胞迁移。有趣的是，ERK 激活仅在存在动力学激活的低剂量 IFN-γ 时发生，