| Literature DB >> 25778803 |
Ueli Nachbur1, Che A Stafford1, Aleksandra Bankovacki1, Yifan Zhan1, Lisa M Lindqvist1, Berthe K Fiil2, Yelena Khakham1, Hyun-Ja Ko1, Jarrod J Sandow1, Hendrik Falk3, Jessica K Holien4, Diep Chau1, Joanne Hildebrand1, James E Vince1, Phillip P Sharp1, Andrew I Webb1, Katherine A Jackman5, Sabrina Mühlen6, Catherine L Kennedy6, Kym N Lowes1, James M Murphy1, Mads Gyrd-Hansen2, Michael W Parker7, Elizabeth L Hartland6, Andrew M Lew1, David C S Huang1, Guillaume Lessene1, John Silke1.
Abstract
Intracellular nucleotide binding and oligomerization domain (NOD) receptors recognize antigens including bacterial peptidoglycans and initiate immune responses by triggering the production of pro-inflammatory cytokines through activating NF-κB and MAP kinases. Receptor interacting protein kinase 2 (RIPK2) is critical for NOD-mediated NF-κB activation and cytokine production. Here we develop and characterize a selective RIPK2 kinase inhibitor, WEHI-345, which delays RIPK2 ubiquitylation and NF-κB activation downstream of NOD engagement. Despite only delaying NF-κB activation on NOD stimulation, WEHI-345 prevents cytokine production in vitro and in vivo and ameliorates experimental autoimmune encephalomyelitis in mice. Our study highlights the importance of the kinase activity of RIPK2 for proper immune responses and demonstrates the therapeutic potential of inhibiting RIPK2 in NOD-driven inflammatory diseases.Entities:
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Year: 2015 PMID： 25778803 DOI： 10.1038/ncomms7442
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919