Decidual lymphatic endothelial cell-derived granulocyte-macrophage colony-stimulating factor induces M1 macrophage polarization via the NF-κB pathway in severe pre-eclampsia
Yun Ji Jung
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorYeji Lee
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorHayan Kwon
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorHyoung-Pyo Kim
Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, The Republic of Korea
Search for more papers by this authorHan-Sung Kwon
Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, The Republic of Korea
Search for more papers by this authorEunhyang Park
Department of Pathology, Yonsei University College of Medicine, Seoul, The Republic of Korea
Search for more papers by this authorJoonHo Lee
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorYoung-Han Kim
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorCorresponding Author
Yong-Sun Maeng
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Correspondence
Ja-Young Kwon and Yong-Sun Maeng, Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, 50–1 Yonsei-ro, Seodaemoon-gu, Seoul, 03722, The Republic of Korea.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Ja-Young Kwon
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Correspondence
Ja-Young Kwon and Yong-Sun Maeng, Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, 50–1 Yonsei-ro, Seodaemoon-gu, Seoul, 03722, The Republic of Korea.
Email: [email protected] and [email protected]
Search for more papers by this authorYun Ji Jung
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorYeji Lee
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorHayan Kwon
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorHyoung-Pyo Kim
Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul, The Republic of Korea
Search for more papers by this authorHan-Sung Kwon
Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, The Republic of Korea
Search for more papers by this authorEunhyang Park
Department of Pathology, Yonsei University College of Medicine, Seoul, The Republic of Korea
Search for more papers by this authorJoonHo Lee
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorYoung-Han Kim
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Search for more papers by this authorCorresponding Author
Yong-Sun Maeng
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Correspondence
Ja-Young Kwon and Yong-Sun Maeng, Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, 50–1 Yonsei-ro, Seodaemoon-gu, Seoul, 03722, The Republic of Korea.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Ja-Young Kwon
Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, Seoul, The Republic of Korea
Correspondence
Ja-Young Kwon and Yong-Sun Maeng, Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Placenta-derived Stem Cell and Genomic Research Lab, Yonsei University College of Medicine, Yonsei University Health System, 50–1 Yonsei-ro, Seodaemoon-gu, Seoul, 03722, The Republic of Korea.
Email: [email protected] and [email protected]
Search for more papers by this authorJa-Young Kwon and Yong-Sun Maeng contributed equally to this study.
Abstract
Problem
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.
Method of Study
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.
Results
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.
Conclusions
In PE, dLECs expressing high levels of GM-CSF via the NF-κB-dependent pathway play a role in inducing decidual M1 macrophage polarization.
CONFLICT OF INTEREST STATEMENT
All authors have read the journal's policy on disclosure of potential conflicts of interest. The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The datasets collected and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Supporting Information
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| aji13744-sup-0001-FigureS1-S2.docx929.1 KB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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