Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10
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 anima...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
[15 September 2011]
|
| In: |
Biochemical pharmacology
Year: 2011, Jahrgang: 82, Heft: 6, Pages: 632-641 |
| ISSN: | 1873-2968 |
| DOI: | 10.1016/j.bcp.2011.06.013 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bcp.2011.06.013 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006295211003789 
|
| Verfasserangaben: | Anne Hertenstein, Theresa Schumacher, Ulrike Litzenburger, Christiane A. Opitz, Christine S. Falk, Tito Serafini, Wolfgang Wick, Michael Platten |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1818076241 | ||
| 003 | DE-627 | ||
| 005 | 20230710112459.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 221005s2011 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bcp.2011.06.013 |2 doi | |
| 035 | |a (DE-627)1818076241 | ||
| 035 | |a (DE-599)KXP1818076241 | ||
| 035 | |a (OCoLC)1389780140 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Berberich, Anne |d 1988- |e VerfasserIn |0 (DE-588)1034064096 |0 (DE-627)743980654 |0 (DE-576)381718697 |4 aut | |
| 245 | 1 | 0 | |a Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10 |c Anne Hertenstein, Theresa Schumacher, Ulrike Litzenburger, Christiane A. Opitz, Christine S. Falk, Tito Serafini, Wolfgang Wick, Michael Platten |
| 264 | 1 | |c [15 September 2011] | |
| 300 | |b Illustrationen | ||
| 300 | |a 10 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 05.10.2022 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Anti-allergic drug | |
| 650 | 4 | |a Multiple sclerosis | |
| 650 | 4 | |a Rheumatoid arthritis | |
| 650 | 4 | |a T cell | |
| 650 | 4 | |a Tryptophan catabolism | |
| 700 | 1 | |a Bunse, Theresa |d 1985- |e VerfasserIn |0 (DE-588)105282112X |0 (DE-627)789079070 |0 (DE-576)408553731 |4 aut | |
| 700 | 1 | |a Litzenburger, Ulrike |e VerfasserIn |0 (DE-588)1030343454 |0 (DE-627)735097054 |0 (DE-576)378142003 |4 aut | |
| 700 | 1 | |a Opitz, Christiane |d 1979- |e VerfasserIn |0 (DE-588)132405121 |0 (DE-627)522675913 |0 (DE-576)299125041 |4 aut | |
| 700 | 1 | |a Falk, Christine Susanne |d 1966- |e VerfasserIn |0 (DE-588)173109195 |0 (DE-627)674145453 |0 (DE-576)133960943 |4 aut | |
| 700 | 1 | |a Serafini, Tito |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wick, Wolfgang |d 1970- |e VerfasserIn |0 (DE-588)120297736 |0 (DE-627)080586929 |0 (DE-576)186221320 |4 aut | |
| 700 | 1 | |a Platten, Michael |d 1971- |e VerfasserIn |0 (DE-588)121627780 |0 (DE-627)081431848 |0 (DE-576)261969811 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochemical pharmacology |d Amsterdam [u.a.] : Elsevier Science, 1958 |g 82(2011), 6 vom: Sept., Seite 632-641 |h Online-Ressource |w (DE-627)30631777X |w (DE-600)1496199-4 |w (DE-576)081952929 |x 1873-2968 |7 nnas |a Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10 |
| 773 | 1 | 8 | |g volume:82 |g year:2011 |g number:6 |g month:09 |g pages:632-641 |g extent:10 |a Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.bcp.2011.06.013 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0006295211003789 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20221005 | ||
| 993 | |a Article | ||
| 994 | |a 2011 | ||
| 998 | |g 121627780 |a Platten, Michael |m 121627780:Platten, Michael |d 910000 |d 911100 |e 910000PP121627780 |e 911100PP121627780 |k 0/910000/ |k 1/910000/911100/ |p 8 |y j | ||
| 998 | |g 120297736 |a Wick, Wolfgang |m 120297736:Wick, Wolfgang |d 910000 |d 911100 |e 910000PW120297736 |e 911100PW120297736 |k 0/910000/ |k 1/910000/911100/ |p 7 | ||
| 998 | |g 132405121 |a Opitz, Christiane |m 132405121:Opitz, Christiane |d 50000 |e 50000PO132405121 |k 0/50000/ |p 4 | ||
| 998 | |g 1030343454 |a Litzenburger, Ulrike |m 1030343454:Litzenburger, Ulrike |d 140000 |e 140000PL1030343454 |k 0/140000/ |p 3 | ||
| 998 | |g 105282112X |a Bunse, Theresa |m 105282112X:Bunse, Theresa |d 140000 |e 140000PB105282112X |k 0/140000/ |p 2 | ||
| 998 | |g 1034064096 |a Berberich, Anne |m 1034064096:Berberich, Anne |d 50000 |e 50000PB1034064096 |k 0/50000/ |p 1 |x j | ||
| 999 | |a KXP-PPN1818076241 |e 4194643461 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"id":{"eki":["1818076241"],"doi":["10.1016/j.bcp.2011.06.013"]},"title":[{"title_sort":"Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10","title":"Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10"}],"recId":"1818076241","note":["Gesehen am 05.10.2022"],"language":["eng"],"origin":[{"dateIssuedDisp":"[15 September 2011]","dateIssuedKey":"2011"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"roleDisplay":"VerfasserIn","family":"Berberich","role":"aut","display":"Berberich, Anne","given":"Anne"},{"family":"Bunse","roleDisplay":"VerfasserIn","given":"Theresa","display":"Bunse, Theresa","role":"aut"},{"roleDisplay":"VerfasserIn","family":"Litzenburger","given":"Ulrike","role":"aut","display":"Litzenburger, Ulrike"},{"roleDisplay":"VerfasserIn","family":"Opitz","given":"Christiane","role":"aut","display":"Opitz, Christiane"},{"family":"Falk","roleDisplay":"VerfasserIn","display":"Falk, Christine Susanne","role":"aut","given":"Christine Susanne"},{"given":"Tito","display":"Serafini, Tito","role":"aut","family":"Serafini","roleDisplay":"VerfasserIn"},{"given":"Wolfgang","role":"aut","display":"Wick, Wolfgang","roleDisplay":"VerfasserIn","family":"Wick"},{"family":"Platten","roleDisplay":"VerfasserIn","given":"Michael","role":"aut","display":"Platten, Michael"}],"name":{"displayForm":["Anne Hertenstein, Theresa Schumacher, Ulrike Litzenburger, Christiane A. Opitz, Christine S. Falk, Tito Serafini, Wolfgang Wick, Michael Platten"]},"physDesc":[{"noteIll":"Illustrationen","extent":"10 S."}],"relHost":[{"recId":"30631777X","pubHistory":["1.1958 -"],"id":{"issn":["1873-2968"],"zdb":["1496199-4"],"eki":["30631777X"]},"title":[{"title":"Biochemical pharmacology","title_sort":"Biochemical pharmacology"}],"disp":"Suppression of human CD4+ T cell activation by 3,4-dimethoxycinnamonyl-anthranilic acid (tranilast) is mediated by CXCL9 and CXCL10Biochemical pharmacology","note":["Gesehen am 21.02.20"],"language":["eng"],"origin":[{"publisher":"Elsevier Science","dateIssuedDisp":"1958-","dateIssuedKey":"1958","publisherPlace":"Amsterdam [u.a.]"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"part":{"year":"2011","extent":"10","pages":"632-641","text":"82(2011), 6 vom: Sept., Seite 632-641","issue":"6","volume":"82"},"physDesc":[{"extent":"Online-Ressource"}]}]} | ||
| SRT | |a BERBERICHASUPPRESSIO1520 | ||