| |  Online-Ressource |
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| Verfasst von: | Fitzsimons, Stephen [VerfasserIn]  |
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| | Muñoz-San Martín, María [VerfasserIn] |
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| | Nally, Frances [VerfasserIn] |
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| | Dillon, Eugene [VerfasserIn] |
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| | Fashina, Ifeolutembi A. [VerfasserIn] |
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| | Strowitzki, Moritz [VerfasserIn] |
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| | Ramió-Torrentà, Lluís [VerfasserIn] |
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| | Dowling, Jennifer K. [VerfasserIn] |
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| | De Santi, Chiara [VerfasserIn] |
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| | McCoy, Claire E. [VerfasserIn] |
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| Titel: | Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers |
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| Titelzusatz: | original article |
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| Verf.angabe: | Stephen Fitzsimons, María Muñoz-San Martín, Frances Nally, Eugene Dillon, Ifeolutembi A. Fashina, Moritz J. Strowitzki, Lluís Ramió-Torrentà, Jennifer K. Dowling, Chiara De Santi and Claire E. McCoy |
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| E-Jahr: | 2023 |
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| Jahr: | 12 September 2023 |
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| Umfang: | 19 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Gesehen am 06.12.2023 |
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| Titel Quelle: | Enthalten in: Molecular Therapy / Nucleic Acids |
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| Ort Quelle: | New York, NY : Nature Publ. Group, 2012 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | 33(2023), Seite 941-959 |
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| ISSN Quelle: | 2162-2531 |
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| Abstract: | The modulation of macrophage phenotype from a pro-inflammatory to an anti-inflammatory state holds therapeutic potential in the treatment of inflammatory disease. We have previously shown that arginase-2 (Arg2), a mitochondrial enzyme, is a key regulator of the macrophage anti-inflammatory response. Here, we investigate the therapeutic potential of Arg2 enhancement via target site blockers (TSBs) in human macrophages. TSBs are locked nucleic acid antisense oligonucleotides that were specifically designed to protect specific microRNA recognition elements (MREs) in human ARG2 3′ UTR mRNA. TSBs targeting miR-155 (TSB-155) and miR-3202 (TSB-3202) MREs increased ARG2 expression in human monocyte-derived macrophages. This resulted in decreased gene expression and cytokine production of TNF-α and CCL2 and, for TSB-3202, in an increase in the anti-inflammatory macrophage marker, CD206. Proteomic analysis demonstrated that a network of pro-inflammatory responsive proteins was modulated by TSBs. In silico bioinformatic analysis predicted that TSB-3202 suppressed upstream pro-inflammatory regulators including STAT-1 while enhancing anti-inflammatory associated proteins. Proteomic data were validated by confirming increased levels of sequestosome-1 and decreased levels of phosphorylated STAT-1 and STAT-1 upon TSB treatment. In conclusion, upregulation of Arg2 by TSBs inhibits pro-inflammatory signaling and is a promising novel therapeutic strategy to modulate inflammatory signaling in human macrophages. |
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| DOI: | doi:10.1016/j.omtn.2023.08.023 |
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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.omtn.2023.08.023 |
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| | kostenfrei: Volltext: https://www.sciencedirect.com/science/article/pii/S2162253123002342 |
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| | DOI: https://doi.org/10.1016/j.omtn.2023.08.023 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | arginase-2 |
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| | inflammation |
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| | macrophages |
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| | microRNA |
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| | miR-155 |
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| | MT: Oligonucleotides: Therapies and Applications |
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| | multiple sclerosis |
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| | target site blockers |
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| K10plus-PPN: | 1872108091 |
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| Verknüpfungen: | → Zeitschrift |
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Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers / Fitzsimons, Stephen [VerfasserIn]; 12 September 2023 (Online-Ressource)
