Macrophages are the effector immune cells with plasticity to differentiate as M1 (classically activated) and M2 (alternatively activated) phenotypes. Prostaglandins (PGs) have various important roles and are involved in the regulation of macrophage activation. However, the role of PGF2α in macrophage activation remains unclear. We investigated the role of PGF2α receptor (FP)-mediated signaling in the M1 macrophage polarization using murine macrophage RAW264.7 cells. Stimulation with lipopolysaccharide (LPS) + interferon (IFN)-γ increased the mRNA expression of the M1 macrophage markers such as inducible nitric oxide synthase, tumor necrosis factor-α, and CD11c. Pre-treatment with AL8810, an FP receptor antagonist, further enhanced the expression of these genes. In contrast, treatment with fluprostenol, an FP receptor agonist, decreased the LPS + IFN-γ-induced expression of M1 markers. LPS-induced M1 macrophage polarization was dependent on the activation of NF-κB p65. Treatment with IκB kinase β inhibitor reduced AL8810-induced mRNA expression of the M1 markers. Stimulation with LPS + IFN-γ increased the expression of IL-10. Pre-treatment with AL8810 lowered LPS + IFN-γ-induced IL-10 expression, and further enhanced LPS + IFN-γ-stimulated nuclear translocation of NF-κB p65. In contrast, co-treatment with IL-10 reversed AL8810-induced nuclear translocation of NF-κB p65. These results indicate that the FP receptor signaling was involved in the control of M1 polarization of macrophages via IL-10-regulated nuclear translocation of NF-κB p65.

中文翻译：

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IL-1调节NF-κBp65的核易位，FP受体在M1巨噬细胞极化中的作用。

巨噬细胞是效应免疫细胞，具有可塑性，可以区分为M1（经典激活）和M2（交替激活）表型。前列腺素（PG）具有各种重要作用，并参与巨噬细胞活化的调节。但是，PGF2α在巨噬细胞活化中的作用尚不清楚。我们调查了使用鼠巨噬细胞RAW264.7细胞在M1巨噬细胞极化中PGF2α受体（FP）介导的信号传导的作用。脂多糖（LPS）+干扰素（IFN）-γ刺激增加M1巨噬细胞标志物的mRNA表达，例如诱导型一氧化氮合酶，肿瘤坏死因子-α和CD11c。FP受体拮抗剂AL8810的预处理进一步增强了这些基因的表达。相反，用FP受体激动剂氟前列腺素治疗，降低LPS +IFN-γ诱导的M1标记的表达。LPS诱导的M1巨噬细胞极化取决于NF-κBp65的激活。用IκB激酶β抑制剂治疗可降低AL8810诱导的M1标记物mRNA表达。LPS +IFN-γ刺激可增加IL-10的表达。AL8810预处理可降低LPS +IFN-γ诱导的IL-10表达，并进一步增强LPS +IFN-γ刺激的NF-κBp65核移位。相反，与IL-10共同治疗可逆转AL8810诱导的NF-κBp65核易位。这些结果表明FP受体信号传导通过IL-10调节的NF-κBp65核转位参与巨噬细胞的M1极化控制。用IκB激酶β抑制剂治疗可降低AL8810诱导的M1标记物mRNA表达。LPS +IFN-γ刺激可增加IL-10的表达。AL8810预处理可降低LPS +IFN-γ诱导的IL-10表达，并进一步增强LPS +IFN-γ刺激的NF-κBp65核移位。相反，与IL-10共同治疗可逆转AL8810诱导的NF-κBp65核易位。这些结果表明FP受体信号传导通过IL-10调节的NF-κBp65核转位参与巨噬细胞的M1极化控制。用IκB激酶β抑制剂治疗可降低AL8810诱导的M1标记物mRNA表达。LPS +IFN-γ刺激可增加IL-10的表达。AL8810预处理可降低LPS +IFN-γ诱导的IL-10表达，并进一步增强LPS +IFN-γ刺激的NF-κBp65核移位。相反，与IL-10共同治疗可逆转AL8810诱导的NF-κBp65核易位。这些结果表明FP受体信号传导通过IL-10调节的NF-κBp65核转位参与巨噬细胞的M1极化控制。并进一步增强LPS +IFN-γ刺激的NF-κBp65核移位。相反，与IL-10共同治疗可逆转AL8810诱导的NF-κBp65核易位。这些结果表明FP受体信号传导通过IL-10调节的NF-κBp65核转位参与巨噬细胞的M1极化控制。并进一步增强LPS +IFN-γ刺激的NF-κBp65核移位。相反，与IL-10共同治疗可逆转AL8810诱导的NF-κBp65核易位。这些结果表明，FP受体信号传导通过IL-10调节的NF-κBp65核转位参与巨噬细胞的M1极化控制。