| First Author | Kovarova M | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 4 | Pages | 2006-16 |
| PubMed ID | 22753929 | Mgi Jnum | J:189777 |
| Mgi Id | MGI:5446983 | Doi | 10.4049/jimmunol.1201065 |
| Citation | Kovarova M, et al. (2012) NLRP1-dependent pyroptosis leads to acute lung injury and morbidity in mice. J Immunol 189(4):2006-16 |
| abstractText | Acute inflammation in response to both exogenous and endogenous danger signals can lead to the assembly of cytoplasmic inflammasomes that stimulate the activation of caspase-1. Subsequently, caspase-1 facilitates the maturation and release of cytokines and also, under some circumstances, the induction of cell death by pyroptosis. Using a mouse line lacking expression of NLRP1, we show that assembly of this inflammasome in cells is triggered by a toxin from anthrax and that it initiates caspase-1 activation and release of IL-1beta. Furthermore, NLRP1 inflammasome activation also leads to cell death, which escalates over 3 d following exposure to the toxin and culminates in acute lung injury and death of the mice. We show that these events are not dependent on production of IL-1beta by the inflammasome but are dependent on caspase-1 expression. In contrast, muramyl dipeptide-mediated inflammasome formation is not dependent on NLRP1 but NLRP3. Taken together, our findings show that assembly of the NLRP1 inflammasome is sufficient to initiate pyroptosis, which subsequently leads to a self-amplifying cascade of cell injury within the lung from which the lung cannot recover, eventually resulting in catastrophic consequences for the organism. |
