The lysosome rupture-activated TAK1-JNK pathway regulates NLRP3 inflammasome activation

Masahiro Okada; Atsushi Matsuzawa; Akihiko Yoshimura; Hidenori Ichijo

doi:10.1074/jbc.M114.579961

The lysosome rupture-activated TAK1-JNK pathway regulates NLRP3 inflammasome activation

Masahiro Okada, Atsushi Matsuzawa, Akihiko Yoshimura, Hidenori Ichijo

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

153 Citations (Scopus)

Abstract

Results: Inhibition of CaMKII, TAK1, or JNK specifically suppressed lysosome rupture-induced NLRP3 inflammasome activation.

Background: The mechanisms underlying lysosome rupture-mediated inflammasome activation are not understood.

Conclusion: Activation of the Ca²⁺-CaMKII-TAK1-JNK pathway in lysosome rupture is necessary for complete activation of the NLRP3 inflammasome.

Significance: Our results suggest novel roles for the Ca²⁺-CaMKII-TAK1-JNK pathway in the regulation of the inflammasome and propose potential therapeutic targets for inflammatory diseases.

Original language	English
Pages (from-to)	32926-32936
Number of pages	11
Journal	Journal of Biological Chemistry
Volume	289
Issue number	47
DOIs	https://doi.org/10.1074/jbc.M114.579961
Publication status	Published - 2014 Nov 21

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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abstract = "Results: Inhibition of CaMKII, TAK1, or JNK specifically suppressed lysosome rupture-induced NLRP3 inflammasome activation.Background: The mechanisms underlying lysosome rupture-mediated inflammasome activation are not understood.Conclusion: Activation of the Ca2+-CaMKII-TAK1-JNK pathway in lysosome rupture is necessary for complete activation of the NLRP3 inflammasome.Significance: Our results suggest novel roles for the Ca2+-CaMKII-TAK1-JNK pathway in the regulation of the inflammasome and propose potential therapeutic targets for inflammatory diseases.",

author = "Masahiro Okada and Atsushi Matsuzawa and Akihiko Yoshimura and Hidenori Ichijo",

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AU - Ichijo, Hidenori

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AB - Results: Inhibition of CaMKII, TAK1, or JNK specifically suppressed lysosome rupture-induced NLRP3 inflammasome activation.Background: The mechanisms underlying lysosome rupture-mediated inflammasome activation are not understood.Conclusion: Activation of the Ca2+-CaMKII-TAK1-JNK pathway in lysosome rupture is necessary for complete activation of the NLRP3 inflammasome.Significance: Our results suggest novel roles for the Ca2+-CaMKII-TAK1-JNK pathway in the regulation of the inflammasome and propose potential therapeutic targets for inflammatory diseases.

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The lysosome rupture-activated TAK1-JNK pathway regulates NLRP3 inflammasome activation

Abstract

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