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• W4382981621 abstract "Direct interactions between macrophages and lymphatic vessels have been shown previously. In pre-eclampsia (PE), macrophages are dominantly polarized into a proinflammatory M1 phenotype and lymphangiogenesis is defective in the decidua. Here, we investigated whether decidual lymphatic endothelial cells (dLECs) affect macrophage polarization in PE.THP-1 macrophages were cocultured with dLECs or cultured in the conditioned medium (CM) of dLECs. Macrophage polarization was measured using flow cytometry. Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in dLECs was measured using qRT-PCR and ELISA. The activation of nuclear translocation of nuclear factor-κ (NF-κB), an upstream signaling molecule of GM-CSF, was assessed by immunocytochemical localization of p65. Through GM-CSF knockdown and NF-κB inhibition in dLEC, we evaluated whether the GM-CSF/NF-κB pathway of PE dLEC affects decidual macrophage polarization.The ratio of inflammatory M1 macrophages with HLA-DR+ /CD80+ markers significantly increased following coculturing with PE dLECs or culturing in PE dLEC CM, indicating that the PE dLEC-derived soluble factor acts in a paracrine manner. GM-CSF expression was significantly upregulated in PE dLECs. Recombinant human GM-CSF induced macrophage polarization toward an M1-like phenotype, whereas its knockdown in PE dLECs suppressed it, suggesting PE dLECs induce M1 macrophage polarization by secreting GM-CSF. The NF-κB p65 significantly increased in PE dLECs compared to the control, and pretreatment with an NF-κB inhibitor significantly suppressed GM-CSF production from PE dLECs.In PE, dLECs expressing high levels of GM-CSF via the NF-κB-dependent pathway play a role in inducing decidual M1 macrophage polarization." @default.
• W4382981621 created "2023-07-04" @default.
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• W4382981621 date "2023-07-02" @default.
• W4382981621 modified "2023-10-17" @default.
• W4382981621 title "Decidual lymphatic endothelial cell‐derived granulocyte‐macrophage colony‐stimulating factor induces M1 macrophage polarization via the NF‐κB pathway in severe pre‐eclampsia" @default.
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• W4382981621 doi "https://doi.org/10.1111/aji.13744" @default.
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• W4382981621 hasPublicationYear "2023" @default.
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