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| Verfasst von: | Berberich, Anne [VerfasserIn]  |
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| | Bunse, Theresa [VerfasserIn] |
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| | Litzenburger, Ulrike [VerfasserIn] |
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| | Opitz, Christiane [VerfasserIn] |
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| | Falk, Christine Susanne [VerfasserIn] |
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| | Serafini, Tito [VerfasserIn] |
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| | Wick, Wolfgang [VerfasserIn] |
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| | Platten, Michael [VerfasserIn] |
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| Titel: | Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10 |
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| Verf.angabe: | Anne Hertenstein, Theresa Schumacher, Ulrike Litzenburger, Christiane A. Opitz, Christine S. Falk, Tito Serafini, Wolfgang Wick, Michael Platten |
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| E-Jahr: | 2011 |
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| Jahr: | [15 September 2011] |
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| Umfang: | 10 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Gesehen am 05.10.2022 |
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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: | 2011 |
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| Band/Heft Quelle: | 82(2011), 6 vom: Sept., Seite 632-641 |
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| ISSN Quelle: | 1873-2968 |
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| Abstract: | 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is an orally available anti-allergic drug with structural and functional homologies to immunosuppressive catabolites of the essential amino acid tryptophan and broad anti-inflammatory properties. It has recently been shown to be effective in animal models of multiple sclerosis and rheumatoid arthritis, two autoimmune diseases that are mediated by auto-aggressive Th1-polarized CD4+ T lymphocytes. Here we demonstrate potent suppressive effects of tranilast on the function of naïve human CD4+ T cells. Tranilast inhibited inhibits activation and proliferation of purified CD4+ T cells stimulated through the T cell receptor with an EC50 of less than 10μM, a concentration that is well below plasma levels achieved after oral administration of approved doses of 200-600mg in humans. The antiproliferative effects were less potent on naïve CD8+ T cells. Suppression of CD4+ and CD8+ T cell proliferation was associated with an inhibition of T cell activation. Cytokine analyses of naïve CD4+ T cells revealed that tranilast interferes with the production of cyto- and chemokines driven by signal transducer and activator of transcription 1 (STAT1), notably chemokine (C-X-C motif) ligands (CXCL) 9 and 10. Tranilast limited STAT1 phosphorylation in activated T cells and supplementation of CXCL9 or CXCL10 reversed the anti-proliferative effects of tranilast. These data imply CXCL9 and CXCL10 as novel therapeutic targets of tranilast in Th1-mediated autoimmune diseases and identify phospho-STAT1 and its target chemokines CXCL9 and CXCL10 as potential markers for monitoring the bioactivity of tranilast in humans. |
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| DOI: | doi:10.1016/j.bcp.2011.06.013 |
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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 ; Verlag: https://doi.org/10.1016/j.bcp.2011.06.013 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S0006295211003789 |
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| | DOI: https://doi.org/10.1016/j.bcp.2011.06.013 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Anti-allergic drug |
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| | Multiple sclerosis |
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| | Rheumatoid arthritis |
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| | T cell |
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| | Tryptophan catabolism |
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| K10plus-PPN: | 1818076241 |
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| Verknüpfungen: | → Zeitschrift |
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Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10 / Berberich, Anne [VerfasserIn]; [15 September 2011] (Online-Ressource)
