Vimentin regulates activation of the NLRP3 inflammasome

Gimena dos Santos, Micah R. Rogel, Margaret A. Baker, James R. Troken, Daniela Urich, Luisa Morales-Nebreda, Joseph A. Sennello, Mikhail A. Kutuzov, Albert Sitikov, Jennifer M. Davis, Anna P. Lam, Paul Cheresh, David Kamp, Dale K. Shumaker, G. R. Scott Budinger and Karen M. Ridge ()
Additional contact information
Gimena dos Santos: Northwestern University
Micah R. Rogel: Northwestern University
Margaret A. Baker: Northwestern University
James R. Troken: Northwestern University
Daniela Urich: Northwestern University
Luisa Morales-Nebreda: Northwestern University
Joseph A. Sennello: Northwestern University
Mikhail A. Kutuzov: Northwestern University
Albert Sitikov: Northwestern University
Jennifer M. Davis: Northwestern University
Anna P. Lam: Northwestern University
Paul Cheresh: Northwestern University
David Kamp: Northwestern University
Dale K. Shumaker: Northwestern University
G. R. Scott Budinger: Northwestern University
Karen M. Ridge: Northwestern University

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract Activation of the NLRP3 inflammasome and subsequent maturation of IL-1β have been implicated in acute lung injury (ALI), resulting in inflammation and fibrosis. We investigated the role of vimentin, a type III intermediate filament, in this process using three well-characterized murine models of ALI known to require NLRP3 inflammasome activation. We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim−/− mice challenged with LPS, bleomycin and asbestos. Bone marrow chimeric mice lacking vimentin have reduced IL-1β levels and attenuated lung injury and fibrosis following bleomycin exposure. Furthermore, decreased active caspase-1 and IL-1β levels are observed in vitro in Vim−/− and vimentin-knockdown macrophages. Importantly, we show direct protein–protein interaction between NLRP3 and vimentin. This study provides insights into lung inflammation and fibrosis and suggests that vimentin may be a key regulator of the NLRP3 inflammasome.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7574

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DOI: 10.1038/ncomms7574

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