C-Reactive Protein Promotes Inflammation through Fc gamma R-Induced Glycolytic Reprogramming of Human Macrophages
| Autor: | Alwin J. van der Ham, Lathees Sritharan, Willianne Hoepel, Jeroen den Dunnen, Dominique Baeten, Leonie de Boer, Melissa Newling, Bart Everts, Sebastian A. J. Zaat, R Bisoendial, Renée H. Fiechter |
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| Přispěvatelé: | Clinical Immunology and Rheumatology, Graduate School, AGEM - Digestive immunity, AII - Inflammatory diseases, Medical Microbiology and Infection Prevention |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Phosphorylcholine
Immunology Syk Context (language use) Inflammation Phosphatidylinositol 3-Kinases medicine Humans Syk Kinase Immunology and Allergy Receptor Cells Cultured biology Kinase Chemistry Receptors IgG Toll-Like Receptors C-reactive protein Atherosclerosis Cellular Reprogramming C-Reactive Protein Liver biology.protein Cytokines Tumor necrosis factor alpha Inflammation Mediators Signal transduction medicine.symptom Glycolysis Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of Immunology, 203(1), 225-235. AMER ASSOC IMMUNOLOGISTS Journal of immunology (Baltimore, Md., 203(1), 225-235. American Association of Immunologists |
| ISSN: | 0022-1767 |
| Popis: | C-reactive protein (CRP) is an acute-phase protein produced in high quantities by the liver in response to infection and during chronic inflammatory disorders. Although CRP is known to facilitate the clearance of cell debris and bacteria by phagocytic cells, the role of CRP in additional immunological functions is less clear. This study shows that complexed CRP (phosphocholine [PC]:CRP) (formed by binding of CRP to PC moieties), but not soluble CRP, synergized with specific TLRs to posttranscriptionally amplify TNF, IL-1β, and IL-23 production by human inflammatory macrophages. We identified FcγRI and IIa as the main receptors responsible for initiating PC:CRP–induced inflammation. In addition, we identified the underlying mechanism, which depended on signaling through kinases Syk, PI3K, and AKT2, as well as glycolytic reprogramming. These data indicate that in humans, CRP is not only a marker but also a driver of inflammation by human macrophages. Therefore, although providing host defense against bacteria, PC:CRP–induced inflammation may also exacerbate pathology in the context of disorders such as atherosclerosis. |
| Databáze: | OpenAIRE |
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