IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms3909.html
   My bibliography  Save this article

Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway

Author

Listed:
  • Xinshou Ouyang

    (Section of Digestive Diseases, Yale University
    Section of Digestive Diseases)

  • Ayaz Ghani

    (Section of Digestive Diseases, Yale University)

  • Ahsan Malik

    (Section of Digestive Diseases, Yale University)

  • Tuere Wilder

    (New York University School of Medicine)

  • Oscar Rene Colegio

    (Yale University)

  • Richard Anthony Flavell

    (Yale University)

  • Bruce Neil Cronstein

    (New York University School of Medicine)

  • Wajahat Zafar Mehal

    (Section of Digestive Diseases, Yale University
    Section of Digestive Diseases)

Abstract

Inflammasome pathways are important in chronic diseases; however, it is not known how the signalling is sustained after initiation. Inflammasome activation is dependent on stimuli such as lipopolysaccharide (LPS) and ATP that provide two distinct signals resulting in rapid production of interleukin (IL)-1β, with the lack of response to repeat stimulation. Here we report that adenosine is a key regulator of inflammasome activity, increasing the duration of the inflammatory response via the A2A receptor. Adenosine does not replace signals provided by stimuli such as LPS or ATP but sustains inflammasome activity via a cAMP/PKA/CREB/HIF-1α pathway. In the setting of the lack of IL-1β responses after previous exposure to LPS, adenosine can supersede this tolerogenic state and drive IL-1β production. These data reveal that inflammasome activity is sustained, after initial activation, by A2A receptor-mediated signalling.

Suggested Citation

  • Xinshou Ouyang & Ayaz Ghani & Ahsan Malik & Tuere Wilder & Oscar Rene Colegio & Richard Anthony Flavell & Bruce Neil Cronstein & Wajahat Zafar Mehal, 2013. "Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway," Nature Communications, Nature, vol. 4(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3909
    DOI: 10.1038/ncomms3909
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms3909
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms3909?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
    ---><---

    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:4:y:2013:i:1:d:10.1038_ncomms3909. 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.