IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms2608.html
   My bibliography  Save this article

TRPM2 links oxidative stress to NLRP3 inflammasome activation

Author

Listed:
  • Zhenyu Zhong

    (Stritch School of Medicine, Loyola University Chicago)

  • Yougang Zhai

    (Stritch School of Medicine, Loyola University Chicago)

  • Shuang Liang

    (Graduate Program of Molecular Biology, Cardinal Bernardin Cancer Center, Stritch School of Medicine, Loyola University Chicago)

  • Yasuo Mori

    (Laboratory of Molecular Biology, Graduate School of Engineering, Kyoto University)

  • Renzhi Han

    (Stritch School of Medicine, Loyola University Chicago)

  • Fayyaz S. Sutterwala

    (Inflammation Program, Carver College of Medicine, University of Iowa
    Veterans Affairs Medical Center)

  • Liang Qiao

    (Stritch School of Medicine, Loyola University Chicago)

Abstract

Exposure to particulate crystals can induce oxidative stress in phagocytes, which triggers NLRP3 inflammasome-mediated interleukin-1β secretion to initiate undesirable inflammatory responses that are associated with both autoinflammatory and metabolic diseases. Although mitochondrial reactive oxygen species have a central role in NLRP3 inflammasome activation, how reactive oxygen species signal assembly of the NLRP3 inflammasome remains elusive. Here, we identify liposomes as novel activators of the NLRP3 inflammasome and further demonstrate that liposome-induced inflammasome activation also requires mitochondrial reactive oxygen species. Moreover, we find that stimulation with liposomes/crystals induced reactive oxygen species-dependent calcium influx via the TRPM2 channel and that macrophages deficient in TRPM2 display drastically impaired NLRP3 inflammasome activation and interleukin-1β secretion. Consistently, Trpm2−/− mice are resistant to crystal-/liposome-induced interleukin-1β-mediated peritonitis in vivo. Together, these results identify TRPM2 as a key factor that links oxidative stress to the NLRP3 inflammasome activation. Therefore, targeting TRPM2 may be effective for the treatment of NLRP3 inflammasome-associated inflammatory disorders.

Suggested Citation

  • Zhenyu Zhong & Yougang Zhai & Shuang Liang & Yasuo Mori & Renzhi Han & Fayyaz S. Sutterwala & Liang Qiao, 2013. "TRPM2 links oxidative stress to NLRP3 inflammasome activation," Nature Communications, Nature, vol. 4(1), pages 1-11, June.
  • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2608
    DOI: 10.1038/ncomms2608
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms2608
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/ncomms2608?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. Jia-Rui Zhang & Shi-Yu Shen & Meng-Ying Zhai & Zu-Qi Shen & Wei Li & Ling-Feng Liang & Shu-Yuan Yin & Qiu-Qin Han & Bing Li & Yu-Qiu Zhang & Jin Yu, 2024. "Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress," Nature Communications, Nature, vol. 15(1), pages 1-15, 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:4:y:2013:i:1:d:10.1038_ncomms2608. 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.