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United States Department of Agriculture

Agricultural Research Service

Research Project: BONE METABOLISM IN OBESITY Title: Ccaat/enhancer-Binding Protein ¿ Is a Critical Regulator of Il-1ß-Induced Il-6 Production in Alveolar Epithelial Cells

Authors
item Yan, Chunguang -
item Wang, Ximo -
item Cao, Jay
item Wu, Min -
item Gao, Hongwei -

Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 19, 2012
Publication Date: April 27, 2012
Repository URL: http://handle.nal.usda.gov/10113/58097
Citation: Yan, C., Wang, X., Cao, J.J., Wu, M., Gao, H. 2012. CCAAT/enhancer-binding protein ¿ is a critical regulator of IL-1ß-induced IL-6 production in alveolar epithelial cells. Proceedings of the National Academy of Sciences. 7(4):e35492. doi:10.1371/journal.pone.0035492.

Interpretive Summary: CCAAT/enhancer binding protein ' (C/EBP') is a member of the C/EBP family of transcription factors and it is highly expressed in immature B cells. C/EBP' has been shown to be an inhibitor of C/EBP transcriptional activators. In the current study, we investigated the role of C/EBP' during lung inflammation. We demonstrate that C/EBP' expression is transiently induced by IL-1ß in lung epithelial cells and contributes to the inhibition of IL-1ß-mediated IL-6 production. Furthermore, we show that C/EBP' inhibits IL-6 expression by inhibiting C/EBPß stimulatory activity and NF-'B activity is not impaired by C/EBP'. Our data suggest that C/EBP' may play an important regulatory role in lung inflammatory responses.

Technical Abstract: CCAAT/enhancer binding protein ' (C/EBP') is a member of the C/EBP family of transcription factors, which is most highly expressed in immature B cells. C/EBP' lacks known activation domains and thus was originally described as an inhibitor of C/EBP transactivation potential. We have previously demonstrated that C/EBP' augments the C/EBPß 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' in regulating gene expression. Furthermore, the expression and function of C/EBP' during inflammation are largely unknown. In this study, we demonstrate that C/EBP' activation was transiently induced by IL-1ß treatment in lung epithelial cells. Importantly, we demonstrate for the first time that C/EBP' plays a critical role in regulating IL-1ß-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' inhibits IL-6 expression by inhibiting C/EBPß but not NF-'B stimulatory activity in MLE12 cells. These findings suggest that C/EBP' 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.

Last Modified: 11/24/2014
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