Einzeltreffer — DigiBib

Introduction: Retinoic Acid Related Orphan Nuclear Receptor gamma T (RORγT) is a lineage specifying transcription factor for IL-17 expressing cells, which may contribute to the pathogenesis of Inflammatory Bowel Disease (IBD). VPR-254 is a selective in vitro inhibitor of RORγT.

Aims: The main goals of our study were twofold: (1) To determine if ex vivo treatment with VPR-254 reduced relevant cytokine (IL-17 and IL-21) secretion from colonic strips of mice with colitis; (2) To determine if treatment of mice with VPR-254 attenuated parameters of colitis, using three murine IBD models.

Methods: VPR-254 was evaluated ex vivo in a colonic strip assay, using tissue from mice with Dextran sulfate sodium (DSS)-induced colitis. In vivo, VPR-254 was evaluated for efficacy in DSS, Trintirobenzenesulfonic acid (TNBS) and Anti-CD40 antibody-induced murine models of colitis.

Results: VPR-254 reduced the production of key pro-inflammatory cytokines (e.g., IL-17) in ex vivo and in vivo models of colitis. This small molecule inhibitor of RORγT also improved various morphometric and histological parameters associated with three diverse murine models of IBD.

Conclusion: Our results support the concept that an inhibitor of ROR-gamma T may have potential utility for the treatment of IBD.

Titel:	VPR-254: an inhibitor of ROR-gamma T with potential utility for the treatment of inflammatory bowel disease.
Autor/in / Beteiligte Person:	Fitzpatrick, LR ; Small, J ; O'Connell, R ; Talbott, G ; Alton, G ; Zapf, J
Link:	Full Text Finder (Volltext)
Zeitschrift:	Inflammopharmacology, Jg. 28 (2020-04-01), Heft 2, S. 499-511
Veröffentlichung:	Basel ; Boston : Birkhäuser ; <i>Original Publication</i>: Dordrecht, The Netherlands ; Norwell, MA, USA : Kluwer Academic Publishers, c1991-, 2020
Medientyp:	academicJournal
ISSN:	1568-5608 (electronic)
DOI:	10.1007/s10787-019-00643-z
Schlagwort:	Adult Animals CHO Cells Cricetulus Dextran Sulfate Disease Models, Animal Female Humans Inflammatory Bowel Diseases physiopathology Interleukin-17 metabolism Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, SCID Cytokines metabolism Inflammatory Bowel Diseases drug therapy Nuclear Receptor Subfamily 1, Group F, Member 3 antagonists & inhibitors
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Inflammopharmacology] 2020 Apr; Vol. 28 (2), pp. 499-511. <i>Date of Electronic Publication: </i>2019 Sep 23. MeSH Terms: Cytokines / metabolism ; Inflammatory Bowel Diseases / drug therapy ; Nuclear Receptor Subfamily 1, Group F, Member 3 / *antagonists & inhibitors ; Adult ; Animals ; CHO Cells ; Cricetulus ; Dextran Sulfate ; Disease Models, Animal ; Female ; Humans ; Inflammatory Bowel Diseases / physiopathology ; Interleukin-17 / metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID References: Inflamm Bowel Dis. 2006 May;12(5):382-8. (PMID: 16670527) ; J Leukoc Biol. 2015 Mar;97(3):499-510. (PMID: 25548251) ; Elife. 2016 Jan 18;5:e10066. (PMID: 26780670) ; Nat Med. 2016 Mar;22(3):319-23. (PMID: 26878233) ; Nat Rev Gastroenterol Hepatol. 2015 May;12(5):271-83. (PMID: 25971811) ; Mol Med Rep. 2012 Dec;6(6):1255-60. (PMID: 23008075) ; Int J Inflam. 2012;2012:389404. (PMID: 22506136) ; Gastroenterology. 2008 Apr;134(4):1038-48. (PMID: 18395085) ; J Exp Med. 2011 Jan 17;208(1):125-34. (PMID: 21173107) ; Front Immunol. 2018 Oct 22;9:2307. (PMID: 30405600) ; Biochem Pharmacol. 2018 Apr;150:35-45. (PMID: 29369782) ; Nature. 2010 Apr 29;464(7293):1371-5. (PMID: 20393462) ; J Immunol. 2019 Jan 1;202(1):79-92. (PMID: 30478092) ; Genome Biol. 2016 Mar 30;17:58. (PMID: 27029486) ; Inflammopharmacology. 2014 Dec;22(6):341-9. (PMID: 24715223) ; Aliment Pharmacol Ther. 2016 Jan;43(1):30-51. (PMID: 26515897) ; Immunity. 2006 Aug;25(2):309-18. (PMID: 16919486) ; Inflamm Bowel Dis. 2010 Oct;16(10):1763-77. (PMID: 20310011) ; World J Gastroenterol. 2013 Aug 7;19(29):4702-17. (PMID: 23922467) ; Eur J Immunol. 2012 Sep;42(9):2232-7. (PMID: 22949321) ; Cell Death Dis. 2019 Apr 8;10(4):315. (PMID: 30962426) ; Gastroenterology. 2009 Jan;136(1):257-67. (PMID: 18992745) ; Mucosal Immunol. 2014 Jan;7(1):143-54. (PMID: 23715173) ; Gut. 2009 Sep;58(9):1207-17. (PMID: 18483078) ; J Exp Med. 2019 Jan 7;216(1):133-151. (PMID: 30518599) ; Curr Pharm Des. 2012;18(9):1292-310. (PMID: 22316157) ; Immunity. 2008 Jan;28(1):29-39. (PMID: 18164222) ; Dig Dis Sci. 2012 Jul;57(7):1822-31. (PMID: 22466098) ; Br J Nutr. 2008 Sep;100(3):530-41. (PMID: 18279557) ; Inflamm Res. 2019 Jun;68(6):493-509. (PMID: 30972425) ; Eur J Immunol. 2015 Jun;45(6):1667-79. (PMID: 25820779) ; Acta Pharmacol Sin. 2015 Jan;36(1):71-87. (PMID: 25500868) ; Mucosal Immunol. 2012 May;5(3):240-7. (PMID: 22354322) ; J Exp Med. 2011 Jun 6;208(6):1127-33. (PMID: 21576383) ; Bioorg Med Chem Lett. 2009 Oct 1;19(19):5560-4. (PMID: 19720530) ; J Med Chem. 2018 Dec 27;61(24):10976-10995. (PMID: 30010338) ; J Pharmacol Exp Ther. 2012 Sep;342(3):850-60. (PMID: 22691298) ; Cytokine. 2013 May;62(2):262-71. (PMID: 23557800) Grant Information: 1R43 DK099896 United States DK NIDDK NIH HHS; 2R44 DK098896 United States DK NIDDK NIH HHS; 1R43 DK099896 United States DK NIDDK NIH HHS; 2R44 DK098896 United States DK NIDDK NIH HHS Contributed Indexing: Keywords: Colitis; Inflammatory bowel disease; Mice; Rorγt; VPR-254 Substance Nomenclature: 0 (Cytokines) ; 0 (Interleukin-17) ; 0 (Nuclear Receptor Subfamily 1, Group F, Member 3) ; 9042-14-2 (Dextran Sulfate) Entry Date(s): Date Created: 20190925 Date Completed: 20210104 Latest Revision: 20210110 Update Code: 20240513

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

VPR-254: an inhibitor of ROR-gamma T with potential utility for the treatment of inflammatory bowel disease.