| First Author | Yan C | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 3 | Pages | 1480-90 |
| PubMed ID | 22732594 | Mgi Jnum | J:189783 |
| Mgi Id | MGI:5446989 | Doi | 10.4049/jimmunol.1200877 |
| Citation | Yan C, et al. (2012) Critical role for CCAAT/enhancer-binding protein beta in immune complex-induced acute lung injury. J Immunol 189(3):1480-90 |
| abstractText | C/EBPs, particularly C/EBPbeta and C/EBPdelta, are known to participate in the regulation of many genes associated with inflammation. However, very little is known regarding the activation and functions of C/EBPbeta and C/EBPdelta in acute lung inflammation and injury. In this study, we show that both C/EBPbeta and C/EBPdelta activation are triggered in lungs and in alveolar macrophages following intrapulmonary deposition of IgG immune complexes. We further show that mice carrying a targeted deletion of the C/EBPbeta gene displayed significant attenuation of the permeability index (lung vascular leak of albumin), lung neutrophil accumulation (myeloperoxidase activity), total number of WBCs, and neutrophils in bronchoalveolar lavage fluids compared with wild-type mice. Moreover, the mutant mice expressed considerably less TNF-alpha, IL-6, and CXC/CC chemokine and soluble ICAM-1 proteins in bronchoalveolar lavage fluids, and corresponding mRNAs in the IgG immune complex-injured lung, compared with wild-type mice. These phenotypes were associated with a significant reduction in morphological lung injury. In contrast, C/EBPdelta deficiency had no effect on IgG immune complex-induced lung injury. IgG immune complex-stimulated C/EBPbeta-deficient alveolar macrophages released significantly less TNF-alpha, IL-6, MIP-2, keratinocyte cell-derived chemokine, and MIP-1alpha compared with wild-type cells. Similar decreases in IgG immune complex-induced inflammatory mediator production were observed following small interfering RNA ablation of C/EBPbeta in a murine alveolar macrophage cell line. These findings implicate C/EBPbeta as a critical regulator of IgG immune complex-induced inflammatory responses and injury in the lung. |
