CCAAT/Enhancer-Binding Protein \(\gamma\) Is a Critical Regulator of IL-1\(\beta\)-Induced IL-6 Production in Alveolar Epithelial Cells

Abstract

CCAAT/enhancer binding protein (\gamma) (C/EBPγ) is a member of the C/EBP family of transcription factors, which lacks known activation domains. C/EBP(\gamma) was originally described as an inhibitor of C/EBP transactivation potential. However, previous study demonstrates that C/EBP(\gamma) augments the C/EBP(\beta) stimulatory activity in lipopolysaccharide induction of IL-6 promoter in a B lymphoblast cell line. These data indicate a complexing functional role for C/EBP(\gamma) in regulating gene expression. Furthermore, the expression and function of C/EBP(\gamma) during inflammation are still largely unknown. In this study, we demonstrate that C/EBP(\gamma) activation was induced by IL-1(\beta) treatment in lung epithelial cells. Importantly, we demonstrate for the first time that C/EBP(\gamma) plays a critical role in regulating IL-1(\beta)-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/EBP(\gamma) inhibits IL-6 expression by inhibiting C/EBP(\beta) but not NF-(\kappa)B stimulatory activity in MLE12 cells. These findings suggest that C/EBP(\gamma) 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.