Author
Listed:
- Gimena dos Santos
(Northwestern University)
- Micah R. Rogel
(Northwestern University
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
Veterans Administration)
- David Kamp
(Northwestern University
Veterans Administration)
- Dale K. Shumaker
(Northwestern University)
- G. R. Scott Budinger
(Northwestern University
Veterans Administration
Northwestern University)
- Karen M. Ridge
(Northwestern University
Veterans Administration
Northwestern University)
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.
Suggested Citation
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, 2015.
"Vimentin regulates activation of the NLRP3 inflammasome,"
Nature Communications, Nature, vol. 6(1), pages 1-13, May.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7574
DOI: 10.1038/ncomms7574
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