Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation
| العنوان: | Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation |
|---|---|
| المؤلفون: | Bart Everts, Leonard R. Pelgrom, Joost M. Lambooij, Isabel Stoetzel, Maria Embgenbroich, Joachim L. Schultze, Vanessa van Harmelen, Jonas Schulte-Schrepping, Hendrik J. P. van der Zande, Hanno Pijl, Kristian Händler, Lisa R. Hoving, Laura Schlautmann, Karin de Ruiter, Sven Burgdorf, Anna Zawistowska-Deniziak, Leonie Hussaarts, Ko Willems van Dijk, Bruno Guigas, Maria Yazdanbakhsh, Marjolein A. Wijngaarden, Noemí García-Tardón |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America 118(31), e2103304118 (2021). doi:10.1073/pnas.2103304118 Proc Natl Acad Sci U S A Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences, 118(31). NATL ACAD SCIENCES |
| بيانات النشر: | NATL ACAD SCIENCES, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, obesity, Phosphatase, metabolism [Mannose Receptor], immunometabolism, metaflammation, drug effects [Gene Expression Regulation], macrophage, Diet, High-Fat, Proinflammatory cytokine, 03 medical and health sciences, Mice, Random Allocation, 0302 clinical medicine, In vivo, Macrophage, Animals, drug effects [Macrophage Activation], Protein kinase B, Cells, Cultured, mannose receptor, Inflammation, pharmacology [Membrane Proteins], Mice, Knockout, Multidisciplinary, Chemistry, Macrophages, Membrane Proteins, metabolism [Cytokines], Macrophage Activation, Biological Sciences, Animal Feed, In vitro, Cell biology, Gastrointestinal Microbiome, 030104 developmental biology, genetics [Cytokines], Gene Expression Regulation, 030220 oncology & carcinogenesis, Cytokines, metabolism [Macrophages], ddc:500, physiology [Macrophage Activation], chemistry [Mannose Receptor], Mannose receptor, Proto-oncogene tyrosine-protein kinase Src |
| الوصف: | Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to an Src/Akt/ NF-kappa B-mediated cellular reprogramming toward an inflammatory phenotype both in vitro and in vivo. Remarkably, increased serum sMR levels were observed in obese mice and humans and directly correlated with body weight. Importantly, enhanced sMR levels increase serum proinflammatory cytokines, activate tissue macrophages, and promote insulin resistance. Altogether, our results reveal sMR as regulator of proinflammatory macrophage activation, which could constitute a therapeutic target for metaflammation and other hyperinflammatory diseases. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd4853dd491738c9d4b4c81a0e54327c https://hdl.handle.net/1887/3214620 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fd4853dd491738c9d4b4c81a0e54327c |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |