| First Author | Yan C | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 2 | Pages | 420-30 |
| PubMed ID | 23177475 | Mgi Jnum | J:192313 |
| Mgi Id | MGI:5464919 | Doi | 10.1016/j.ajpath.2012.10.013 |
| Citation | Yan C, et al. (2013) CCAAT/Enhancer-Binding Protein delta Is a Critical Mediator of Lipopolysaccharide-Induced Acute Lung Injury. Am J Pathol 182(2):420-30 |
| abstractText | Although inflammation plays a central role in the pathogenesis of acute lung injury, the molecular mechanisms underlying inflammatory responses in acute lung injury are poorly understood, and therapeutic options remain limited. CCAAT/enhancer-binding proteins, C/EBPbeta and C/EBPdelta, are expressed in the lung and have been implicated in the regulation of inflammatory mediators. However, their functions in lung pathobiological characteristics are not well characterized. Herein, we show that C/EBPbeta and C/EBPdelta are activated in mouse lung after intrapulmonary deposition of lipopolysaccharide (LPS). Mice carrying a targeted deletion of the C/EBPdelta gene displayed significant attenuation of the lung permeability index (lung vascular leak of albumin), lung neutrophil accumulation (myeloperoxidase activity), and neutrophils in bronchial alveolar lavage fluids compared with wild-type mice. These phenotypes were consistent with morphological evaluation of lung, which showed reduced inflammatory cell influx and minimal intra-alveolar hemorrhage. Moreover, mutant mice expressed considerably less tumor necrosis factor-alpha, IL-6, and macrophage inflammatory protein-2 in bronchial alveolar lavage fluids in LPS-injured lung compared with wild-type mice. In contrast, C/EBPbeta deficiency had no effect on LPS-induced lung injury. By using small-interfering RNA-mediated knockdown for C/EBPdelta, we demonstrate, for the first time to our knowledge, that C/EBPdelta plays a critical role for the tumor necrosis factor-alpha, IL-6, and macrophage inflammatory protein-2 production in LPS-stimulated alveolar macrophages. These findings demonstrate that C/EBPdelta, but not C/EBPbeta, plays an important role in LPS-induced lung inflammatory responses and injury. |
