[HTML][HTML] Vimentin regulates activation of the NLRP3 inflammasome

G Dos Santos, MR Rogel, MA Baker, JR Troken… - Nature …, 2015 - nature.com
G Dos Santos, MR Rogel, MA Baker, JR Troken, D Urich, L Morales-Nebreda, JA Sennello…
Nature communications, 2015nature.com
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 …
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.
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