• 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.
• Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA.
• Nat Commun. 2015 Jan 1;6:6574.

AbstractActivation 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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