CD137 signaling plays an important role in the formation and development of atherosclerotic plaques. The purpose of the present study was to investigate the effects of CD137 signaling on macrophage polarization during atherosclerosis and to explore the underlying mechanisms. The effect of CD137 signaling on macrophage phenotype in atherosclerotic plaques was determined by intraperitoneal injection of agonist-CD137 recombinant protein in apolipoprotein E-deficient (ApoE-/-) mice, an established in vivo model of atherosclerosis. Murine peritoneal macrophages and RAW 264.7 cells were treated with AS1517499 and siPPARδ (peroxisome proliferator-activated receptor δ) to study the role of STAT6 (signal transducers and activators of transcription 6)/PPARδ signaling in CD137-induced M2 macrophage polarization in vitro. Results from both in vivo and in vitro experiments showed that CD137 signaling can transform macrophages into the M2 phenotype during the process of atherosclerotic plaque formation and regulate the angiogenic features of M2 macrophages. Furthermore, activation of the CD137 signaling pathway induces phosphorylation of STAT6 and enhances the expression of PPARδ. We further found that macrophage M2 polarization is reduced when the STAT6/PPARδ pathway is inhibited. Together, these data show a role for the STAT6/PPARδ signaling pathway in the CD137 signaling-induced M2 macrophage polarization pathway.

中文翻译：

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CD137 信号通过 STAT6/PPARδ 通路在动脉粥样硬化中诱导巨噬细胞 M2 极化。

CD137 信号在动脉粥样硬化斑块的形成和发展中起重要作用。本研究的目的是研究 CD137 信号传导对动脉粥样硬化过程中巨噬细胞极化的影响并探索其潜在机制。CD137 信号转导对动脉粥样硬化斑块中巨噬细胞表型的影响是通过在载脂蛋白 E 缺陷 (ApoE-/-) 小鼠中腹腔注射激动剂-CD137 重组蛋白来确定的，这是一种已建立的动脉粥样硬化体内模型。用 AS1517499 和 siPPARδ（过氧化物酶体增殖物激活受体 δ）处理鼠腹膜巨噬细胞和 RAW 264.7 细胞，以研究 STAT6（信号转导和转录激活因子 6）/PPARδ 信号在体外 CD137 诱导的 M2 巨噬细胞极化中的作用。体内外实验结果表明，CD137信号通路可以在动脉粥样硬化斑块形成过程中将巨噬细胞转化为M2表型，并调节M2巨噬细胞的血管生成特征。此外，CD137 信号通路的激活诱导 STAT6 磷酸化并增强 PPARδ 的表达。我们进一步发现，当 STAT6/PPARδ 通路被抑制时，巨噬细胞 M2 极化减少。总之，这些数据显示了 STAT6/PPARδ 信号通路在 CD137 信号诱导的 M2 巨噬细胞极化通路中的作用。CD137 信号通路的激活诱导 STAT6 磷酸化并增强 PPARδ 的表达。我们进一步发现，当 STAT6/PPARδ 通路被抑制时，巨噬细胞 M2 极化减少。总之，这些数据显示了 STAT6/PPARδ 信号通路在 CD137 信号诱导的 M2 巨噬细胞极化通路中的作用。CD137 信号通路的激活诱导 STAT6 磷酸化并增强 PPARδ 的表达。我们进一步发现，当 STAT6/PPARδ 通路被抑制时，巨噬细胞 M2 极化减少。总之，这些数据显示了 STAT6/PPARδ 信号通路在 CD137 信号诱导的 M2 巨噬细胞极化通路中的作用。