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Inflammasome activation by danger signals: extracellular ATP and pH

Takato Takenouchi
  • Corresponding author
  • Animal Immune and Cell Biology Research Unit, Division of Animal Sciences, National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki 305-8634, Japan
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/ Mitsutoshi Tsukimoto
  • Corresponding author
  • Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
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/ Makoto Hashimoto
  • Corresponding author
  • Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-0057, Japan
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/ Hiroshi Kitani
  • Corresponding author
  • Animal Immune and Cell Biology Research Unit, Division of Animal Sciences, National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki 305-8634, Japan
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Published Online: 2014-11-17 | DOI: https://doi.org/10.2478/infl-2014-0008


Extracellular ATP has been recognized as a danger signal that alerts the innate immune system. High extracellular concentrations of ATP can trigger the maturation and secretion of pro-inflammatory cytokines (e.g., interleukin-1β and interleukin-18) through the inflammasome-dependent activation of caspase-1. The P2X7 receptor, an ATP-gated cation channel, plays a pivotal role in ATP-induced NLRP3 inflammasome assembly. Recently, intriguing evidence has emerged that acidic extracellular pH acts as a danger signal that activates inflammasomes. Extracellular acidification frequently occurs at sites of inflammation, infection, or injury. In addition, large amounts of ATP are readily released into the extracellular space from damaged cells at such sites. Thus, it is assumed that the ATP/P2X7 receptor pathway regulates the inflammatory response under acidic extracellular conditions. Here, we briefly discuss the mutual effects of extracellular ATP and pH on inflammasome activation and consider their roles in the regulation of inflammation.

Keywords : inflammasome; interleukin-1β; ATP; extracellular acidosis; P2X7 receptor


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About the article

Received: 2014-09-02

Accepted: 2014-09-22

Published Online: 2014-11-17

Citation Information: Inflammasome, ISSN (Online) 2300-102X, DOI: https://doi.org/10.2478/infl-2014-0008.

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© 2014 Takato Takenouchi et al.. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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