| First Author | Wu J | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 7 | Pages | 3590-9 |
| PubMed ID | 23436933 | Mgi Jnum | J:194745 |
| Mgi Id | MGI:5474691 | Doi | 10.4049/jimmunol.1200860 |
| Citation | Wu J, et al. (2013) Activation of NLRP3 Inflammasome in Alveolar Macrophages Contributes to Mechanical Stretch-Induced Lung Inflammation and Injury. J Immunol 190(7):3590-9 |
| abstractText | Mechanical ventilation of lungs is capable of activating the innate immune system and inducing sterile inflammatory response. The proinflammatory cytokine IL-1beta is among the definitive markers for accurately identifying ventilator-induced lung inflammation. However, mechanisms of IL-1beta release during mechanical ventilation are unknown. In this study, we show that cyclic stretch activates the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes and induces the release of IL-1beta in mouse alveolar macrophages via caspase-1- and TLR4-dependent mechanisms. We also observed that NADPH oxidase subunit gp91(phox) was dispensable for stretch-induced cytokine production, whereas mitochondrial generation of reactive oxygen species was required for stretch-induced NLRP3 inflammasome activation and IL-1beta release. Further, mechanical ventilation activated the NLRP3 inflammasomes in mouse alveolar macrophages and increased the production of IL-1beta in vivo. IL-1beta neutralization significantly reduced mechanical ventilation-induced inflammatory lung injury. These findings suggest that the alveolar macrophage NLRP3 inflammasome may sense lung alveolar stretch to induce the release of IL-1beta and hence may contribute to the mechanism of lung inflammatory injury during mechanical ventilation. |
