| |  Online-Ressource |
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| Verfasst von: | Conzelmann, Michael [VerfasserIn]  |
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| | Wagner, Andreas H. [VerfasserIn] |
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| | Hildebrandt, Anke [VerfasserIn] |
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| | Rodionova, Elena [VerfasserIn] |
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| | Hess, Michael [VerfasserIn] |
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| | Zota, Annika [VerfasserIn] |
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| | Giese, Thomas [VerfasserIn] |
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| | Falk, Christine Susanne [VerfasserIn] |
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| | Ho, Anthony Dick [VerfasserIn] |
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| | Dreger, Peter [VerfasserIn] |
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| | Hecker, Markus [VerfasserIn] |
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| | Luft, Thomas [VerfasserIn] |
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| Titel: | IFN-γ activated JAK1 shifts CD40-induced cytokine profiles in human antigen-presenting cells toward high IL-12p70 and low IL-10 production |
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| Verf.angabe: | Michael Conzelmann, Andreas H. Wagner, Anke Hildebrandt, Elena Rodionova, Michael Hess, Annika Zota, Thomas Giese, Christine S. Falk, Anthony D. Ho, Peter Dreger, Markus Hecker, Thomas Luft |
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| E-Jahr: | 2010 |
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| Jahr: | 13 August 2010 |
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| Umfang: | 13 S. |
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| Fussnoten: | Gesehen am 07.06.2023 |
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| Titel Quelle: | Enthalten in: Biochemical pharmacology |
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| Ort Quelle: | Amsterdam [u.a.] : Elsevier Science, 1958 |
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| Jahr Quelle: | 2010 |
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| Band/Heft Quelle: | 80(2010), 12, Seite 2074-2086 |
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| ISSN Quelle: | 1873-2968 |
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| Abstract: | CD40Ligand (CD40L) represents a strong endogenous danger signal associated with chronic inflammatory disease. CD40L induces activation of antigen-presenting cells (APCs) such as DCs, monocytes, B-cells and endothelial cells. However, CD40 activation alone, whilst inducing IL-10 production, is insufficient to induce interleukin (IL)-12p70 release in human APCs suggesting that additional cytokine signals (e.g. GM-CSF, IL-4 or IFN-γ) are required for the induction of a pro-inflammatory cytokine profile. We demonstrate that IFN-γ-induced Janus kinase 1 (JAK1) enhances CD40-induced IL-12p70 release whilst simultaneously inhibiting IL-10 synthesis, resulting in a pro-inflammatory phenotype of CD40L-activated dendritic cells (DCs). JAK2 mediated enhancing effects on IL-12p70 but did not inhibit IL-10 release, whereas Tyk2 mediated inhibitory effects on IL-12p70 release in this system. The mechanism by which complementary IFN-γ/JAK activities affect IL-12p70 production involves STAT1 activation and de novo induction of interferon-responsive factors (IRF)-1 and IRF-8. Simultaneously, JAK1 was unique in inhibiting IL-10 synthesis via STAT1 and IRF-8 with both transcription factors binding to the IL-10 promoter. We demonstrate that CD40- and JAK/STAT/IRF-signalling pathways are strictly complementary for the induction of a pro-inflammatory cytokine profile in human APCs. This suggests that a number of CD40 effects in chronic inflammatory diseases might be weakened by targeting JAK/STAT. |
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| DOI: | doi:10.1016/j.bcp.2010.07.040 |
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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.
Volltext: https://doi.org/10.1016/j.bcp.2010.07.040 |
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| | DOI: https://doi.org/10.1016/j.bcp.2010.07.040 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Antigen-Presenting Cells |
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| | B-Lymphocytes |
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| | CD40 Antigens |
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| | Cells, Cultured |
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| | Enzyme Activation |
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| | Gene Knockdown Techniques |
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| | Humans |
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| | Interferon Regulatory Factor-1 |
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| | Interferon Regulatory Factors |
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| | Interferon-gamma |
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| | Interleukin-10 |
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| | Interleukin-12 |
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| | Janus Kinase 1 |
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| | Leukocytes, Mononuclear |
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| | RNA, Small Interfering |
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| | Signal Transduction |
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| | STAT1 Transcription Factor |
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| K10plus-PPN: | 1847671756 |
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| Verknüpfungen: | → Zeitschrift |
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IFN-γ activated JAK1 shifts CD40-induced cytokine profiles in human antigen-presenting cells toward high IL-12p70 and low IL-10 production / Conzelmann, Michael [VerfasserIn]; 13 August 2010 (Online-Ressource)
