IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7442.html
   My bibliography  Save this article

A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

Author

Listed:
  • Ueli Nachbur

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Che A. Stafford

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Aleksandra Bankovacki

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Yifan Zhan

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Lisa M. Lindqvist

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Berthe K. Fiil

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
    Ludwig Institute for Cancer Research, University of Oxford)

  • Yelena Khakham

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Hyun-Ja Ko

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Jarrod J. Sandow

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Hendrik Falk

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne
    Cancer Therapeutics CRC)

  • Jessica K. Holien

    (ACRF Rational Drug Discovery Centre, St Vincent’s Institute of Medical Research)

  • Diep Chau

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Joanne Hildebrand

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • James E. Vince

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Phillip P. Sharp

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Andrew I. Webb

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Katherine A. Jackman

    (The Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, Austin Campus)

  • Sabrina Mühlen

    (University of Melbourne)

  • Catherine L. Kennedy

    (University of Melbourne)

  • Kym N. Lowes

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • James M. Murphy

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Mads Gyrd-Hansen

    (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen
    Ludwig Institute for Cancer Research, University of Oxford)

  • Michael W. Parker

    (ACRF Rational Drug Discovery Centre, St Vincent’s Institute of Medical Research
    Bio21 Molecular Science and Biotechnology Institute, University of Melbourne)

  • Elizabeth L. Hartland

    (University of Melbourne)

  • Andrew M. Lew

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • David C. S. Huang

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Guillaume Lessene

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • John Silke

    (The Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

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.

Suggested Citation

  • Ueli Nachbur & Che A. Stafford & Aleksandra Bankovacki & Yifan Zhan & Lisa M. Lindqvist & Berthe K. Fiil & Yelena Khakham & Hyun-Ja Ko & Jarrod J. Sandow & Hendrik Falk & Jessica K. Holien & Diep Chau, 2015. "A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7442
    DOI: 10.1038/ncomms7442
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7442
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7442?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. L. S. Tran & L. Ying & K. D’Costa & G. Wray-McCann & G. Kerr & L. Le & C. C. Allison & J. Ferrand & H. Chaudhry & J. Emery & A. De Paoli & N. Colon & S. Creed & M. Kaparakis-Liaskos & J. Como & J. K. , 2023. "NOD1 mediates interleukin-18 processing in epithelial cells responding to Helicobacter pylori infection in mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7442. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.