CCAAT/enhancer-binding protein γ is a critical regulator of IL-1β-induced IL-6 production in alveolar epithelial cells

• Published in: PloS one 2012-04, Vol.7 (4), p.e35492
• Main Authors: Yan, Chunguang, Wang, Ximo, Cao, Jay, Wu, Min, Gao, Hongwei
• Format: Article
• Language: English
• Subjects: Activation; Alveoli; Anesthesiology; Animals; Apoptosis; Biochemistry; Biology; CCAAT-Binding Factor - metabolism; CCAAT/enhancer-binding protein; Cell Line, Tumor; Cytokines; Cytotoxicity; Deoxyribonucleic acid; Diabetes; DNA; Epithelial cells; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Gene Expression Regulation - physiology; Gene Knockdown Techniques; Histology; Infections; Inflammation; Interleukin 6; Interleukin-1beta - metabolism; Interleukin-1beta - pharmacology; Interleukin-6 - metabolism; Kinases; Leukemia; Lipopolysaccharides; Lungs; Lymphocytes B; Medicine; Mice; Molecular biology; NF-κB protein; Nutrition research; Phosphatase; Proteins; Pseudomonas aeruginosa; Pulmonary Alveoli - cytology; RNA, Small Interfering - genetics; Rodents; Transcription factors; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035492

CCAAT/enhancer binding protein γ (C/EBPγ) is a member of the C/EBP family of transcription factors, which lacks known activation domains. C/EBPγ was originally described as an inhibitor of C/EBP transactivation potential. However, previous study demonstrates that C/EBPγ augments the C/EBPβ stimulatory activity in lipopolysaccharide induction of IL-6 promoter in a B lymphoblast cell line. These data indicate a complexing functional role for C/EBPγ in regulating gene expression. Furthermore, the expression and function of C/EBPγ during inflammation are still largely unknown. In this study, we demonstrate that C/EBPγ activation was induced by IL-1β treatment in lung epithelial cells. Importantly, we demonstrate for the first time that C/EBPγ plays a critical role in regulating IL-1β-induced IL-6 expression in both mouse primary alveolar type II epithelial cells and a lung epithelial cell line, MLE12. We further provide the evidence that C/EBPγ inhibits IL-6 expression by inhibiting C/EBPβ but not NF-κB stimulatory activity in MLE12 cells. These findings suggest that C/EBPγ is a key transcription factor that regulates the IL-6 expression in alveolar epithelial cells, and may play an important regulatory role in lung inflammatory responses.