| First Author | dos Santos G | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 6574 | PubMed ID | 25762200 |
| Mgi Jnum | J:221886 | Mgi Id | MGI:5641798 |
| Doi | 10.1038/ncomms7574 | Citation | dos Santos G, et al. (2015) Vimentin regulates activation of the NLRP3 inflammasome. Nat Commun 6:6574 |
| abstractText | Activation of the NLRP3 inflammasome and subsequent maturation of IL-1beta 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-1beta 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-1beta levels and attenuated lung injury and fibrosis following bleomycin exposure. Furthermore, decreased active caspase-1 and IL-1beta 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. |
