| First Author | Li H | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 3 | Pages | 1528-32 |
| PubMed ID | 19596994 | Mgi Jnum | J:151582 |
| Mgi Id | MGI:4354463 | Doi | 10.4049/jimmunol.0901080 |
| Citation | Li H, et al. (2009) Cutting edge: Necrosis activates the NLRP3 inflammasome. J Immunol 183(3):1528-32 |
| abstractText | Cells undergoing necrosis release endogenous danger signals that possess proinflammatory potential. In this study we show that mature IL-1beta and IL-18 are released by necrotic cells but not by apoptotic cells. We identify 7-bromoindirubin-3'-oxime, an indirubin oxime derivative that induces necrosis, as a potent inducer of caspase-1 activation and release of mature IL-1beta and IL-18. Inflammasome activation was triggered by other necrosis-inducing treatments but was not observed in response to apoptosis-inducing stimuli. Necrosis-induced inflammasome activation was mediated by the NLRP3 and ASC molecules. Release of IL-18 and IL-1beta in response to necrosis-inducing stimuli was observed in THP-1 macrophages and the MSTO-211H human mesothelioma cell line independently of LPS priming. Using the in vivo model of naphthalene-induced airway epithelial cell injury, we showed that necrosis activates the ASC inflammasome in vivo. Our study identifies a new mechanism through which necrosis generates proinflammatory molecules that contributes to the sterile inflammatory response. |
