Back to Search
Start Over
Critical role for CCAAT/enhancer-binding protein β in immune complex-induced acute lung injury.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2012 Aug 01; Vol. 189 (3), pp. 1480-90. Date of Electronic Publication: 2012 Jun 25. - Publication Year :
- 2012
-
Abstract
- C/EBPs, particularly C/EBPβ and C/EBPδ, 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/EBPβ and C/EBPδ in acute lung inflammation and injury. In this study, we show that both C/EBPβ and C/EBPδ 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/EBPβ 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-α, 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/EBPδ deficiency had no effect on IgG immune complex-induced lung injury. IgG immune complex-stimulated C/EBPβ-deficient alveolar macrophages released significantly less TNF-α, IL-6, MIP-2, keratinocyte cell-derived chemokine, and MIP-1α compared with wild-type cells. Similar decreases in IgG immune complex-induced inflammatory mediator production were observed following small interfering RNA ablation of C/EBPβ in a murine alveolar macrophage cell line. These findings implicate C/EBPβ as a critical regulator of IgG immune complex-induced inflammatory responses and injury in the lung.
- Subjects :
- Acute Lung Injury genetics
Acute Lung Injury pathology
Animals
Antigen-Antibody Complex adverse effects
CCAAT-Enhancer-Binding Protein-beta biosynthesis
CCAAT-Enhancer-Binding Protein-beta deficiency
CCAAT-Enhancer-Binding Protein-delta deficiency
CCAAT-Enhancer-Binding Protein-delta genetics
CCAAT-Enhancer-Binding Protein-delta physiology
Cell Line
Disease Models, Animal
Immunoglobulin G administration & dosage
Immunoglobulin G adverse effects
Inflammation Mediators administration & dosage
Inflammation Mediators adverse effects
Inflammation Mediators physiology
Macrophages, Alveolar immunology
Macrophages, Alveolar metabolism
Macrophages, Alveolar pathology
Male
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Acute Lung Injury immunology
Antigen-Antibody Complex administration & dosage
CCAAT-Enhancer-Binding Protein-beta physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 189
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 22732594
- Full Text :
- https://doi.org/10.4049/jimmunol.1200877