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| Verfasst von: | Klement, Lukas [VerfasserIn]  |
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| | Jansakun, Chutima [VerfasserIn] |
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| | Yan, Bin [VerfasserIn] |
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| | Staffer, Simone [VerfasserIn] |
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| | Tuma-Kellner, Sabine [VerfasserIn] |
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| | Altamura, Sandro [VerfasserIn] |
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| | Muckenthaler, Martina [VerfasserIn] |
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| | Merle, Uta [VerfasserIn] |
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| | Chamulitrat, Walee [VerfasserIn] |
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| Titel: | Myeloid-specific deletion of group VIA calcium-independent phospholipase A2 induces pro-inflammatory LPS response predominantly in male mice via MIP-1α activation |
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| Verf.angabe: | Lukas Klement, Chutima Jansakun, Bin Yan, Simone Staffer, Sabine Tuma-Kellner, Sandro Altamura, Martina Muckenthaler, Uta Merle, Walee Chamulitrat |
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| E-Jahr: | 2024 |
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| Jahr: | March 2024 |
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| Umfang: | 14 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Online verfügbar: 9. Januar 2024 ; Gesehen am 07.06.2024 |
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| Titel Quelle: | Enthalten in: Biochimica et biophysica acta. Molecular basis of disease |
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| Ort Quelle: | Amsterdam : Elsevier, 1990 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 1870(2024), 3 vom: März, Artikel-ID 167016, Seite 1-14 |
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| ISSN Quelle: | 1879-260X |
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| Abstract: | Polymorphisms of group VIA calcium-independent phospholipase A2 (PLA2G6) are associated with blood C-reactive protein suggesting its role in inflammation. We showed that myeloid-specific Pla2g6-deficiency in Pla2g6M−/− mice led to exaggerated inflammation and fibrosis in a lean fatty liver model. We here investigated whether these mutants display alteration in immune response after treatment with E. coli lipopolysaccharides (LPS) under acute (a single dose) and persistent (four doses) conditions. Without LPS treatment, male Pla2g6M−/− (but not Flox) mice at 12 months of age exhibited splenomegaly and hepatic necrosis, and ~ 30 % of them exhibited autoimmune hepatitis showing lymphoplasma cells with CD3(+) and CD45R(+) staining. Under acute LPS, male mutants showed an elevation of plasma MIP-1α and immunoglobulinA as well as upregulation of hepatic apoptosis and fibrosis PARP-1, Bax, MCP-1, α-SMA, and collagen I proteins. Their bone-marrow-derived macrophages also showed an elevation of MIP-1α release upon LPS stimulation in vitro. Female mutants under acute LPS showed a moderate increase in plasma KC/CXCL1, MCP-1, and IL10, and they showed no remarkable increase in hepatic fibrosis under acute or persistent LPS. Male mutants under persistent LPS displayed an elevation of aspartate aminotransferase, blood eosinophils, and hepatic apoptosis. Moreover, ~30 % of these mutants exhibited eosinophilic sclerosing portal hepatitis associated with an upregulated protein expression of hepatic CD8α, CD68, eosinophilic cationic protein, and Ly6G. Thus, myeloid-PLA2G6 deficiency led to an autoimmune and LPS-induced inflammatory liver disease via MIP-1α in a male-predominant manner. Our results may be applicable to patients with PLA2G6 mutations who undergo bacterial infection and sepsis. |
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| DOI: | doi:10.1016/j.bbadis.2024.167016 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1016/j.bbadis.2024.167016 |
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| | kostenfrei: Volltext: https://www.sciencedirect.com/science/article/pii/S0925443924000012 |
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| | DOI: https://doi.org/10.1016/j.bbadis.2024.167016 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Endotoxin |
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| | Group VIA phospholipase A2 |
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| | Liver inflammation |
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| | Macrophage inflammatory protein-1α |
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| | sepsis |
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| | Sex dimorphism |
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| K10plus-PPN: | 1890917192 |
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| Verknüpfungen: | → Zeitschrift |
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Myeloid-specific deletion of group VIA calcium-independent phospholipase A2 induces pro-inflammatory LPS response predominantly in male mice via MIP-1α activation / Klement, Lukas [VerfasserIn]; March 2024 (Online-Ressource)
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