IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v418y2002i6894d10.1038_nature00858.html
   My bibliography  Save this article

Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

Author

Listed:
  • Paola Scaffidi

    (DIBIT, Istituto Scientifico San Raffaele)

  • Tom Misteli

    (NIH)

  • Marco E. Bianchi

    (Università Vita Salute San Raffaele)

Abstract

High mobility group 1 (HMGB1) protein is both a nuclear factor and a secreted protein. In the cell nucleus it acts as an architectural chromatin-binding factor that bends DNA and promotes protein assembly on specific DNA targets1,2. Outside the cell, it binds with high affinity to RAGE (the receptor for advanced glycation end products)3 and is a potent mediator of inflammation4,5,6. HMGB1 is secreted by activated monocytes and macrophages4, and is passively released by necrotic or damaged cells7,8,9. Here we report that Hmgb1-/- necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours. Apoptotic cells do not release HMGB1 even after undergoing secondary necrosis and partial autolysis, and thus fail to promote inflammation even if not cleared promptly by phagocytic cells. In apoptotic cells, HMGB1 is bound firmly to chromatin because of generalized underacetylation of histone and is released in the extracellular medium (promoting inflammation) if chromatin deacetylation is prevented. Thus, cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.

Suggested Citation

  • Paola Scaffidi & Tom Misteli & Marco E. Bianchi, 2002. "Release of chromatin protein HMGB1 by necrotic cells triggers inflammation," Nature, Nature, vol. 418(6894), pages 191-195, July.
    • Handle: RePEc:nat:nature:v:418:y:2002:i:6894:d:10.1038_nature00858
    DOI: 10.1038/nature00858
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature00858
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature00858?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Kuo-Tung Tang & Tsu-Yi Hsieh & Ya-Hsuan Chao & Meng-Xian Lin & Yi-Hsing Chen & Der-Yuan Chen & Chi-Chen Lin, 2017. "Plasma levels of high-mobility group box 1 and soluble receptor for advanced glycation end products in primary antiphospholipid antibody syndrome patients," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-13, May.
    2. Lu Zhang & Jianjun Han & Huiyong Wu & Xiaohong Liang & Jianxin Zhang & Jian Li & Li Xie & Yinfa Xie & Xiugui Sheng & Jinming Yu, 2014. "The Association of HMGB1 Expression with Clinicopathological Significance and Prognosis in Hepatocellular Carcinoma: A Meta-Analysis and Literature Review," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-8, October.
    3. Malisa Vittoria Mantonico & Federica Leo & Giacomo Quilici & Liam Sean Colley & Francesco Marchis & Massimo Crippa & Rosanna Mezzapelle & Tim Schulte & Chiara Zucchelli & Chiara Pastorello & Camilla C, 2024. "The acidic intrinsically disordered region of the inflammatory mediator HMGB1 mediates fuzzy interactions with CXCL12," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Meihua Jin & Hiroki Shiwaku & Hikari Tanaka & Takayuki Obita & Sakurako Ohuchi & Yuki Yoshioka & Xiaocen Jin & Kanoh Kondo & Kyota Fujita & Hidenori Homma & Kazuyuki Nakajima & Mineyuki Mizuguchi & Hi, 2021. "Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    5. Wan-Ru Zhuang & Yunfeng Wang & Weidong Nie & Yao Lei & Chao Liang & Jiaqi He & Liping Zuo & Li-Li Huang & Hai-Yan Xie, 2023. "Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Lulu Ren & Jianqin Wan & Xiaoyan Li & Jie Yao & Yan Ma & Fanchao Meng & Shusen Zheng & Weidong Han & Hangxiang Wang, 2024. "Mitochondrial rewiring with small-molecule drug-free nanoassemblies unleashes anticancer immunity," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:nature:v:418:y:2002:i:6894:d:10.1038_nature00858. 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.