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 Dietary Prevention of Obesity-related Disease Research: Grand Forks, ND
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ARS Home Plains Area Grand Forks, North Dakota Grand Forks Human Nutrition Research Center Dietary Prevention of Obesity-related Disease Research Research Publications at this Location





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Title:   Author  item
                                            YAN, CHUNGUANG - Harvard Medical Schoolitem
                                            WANG, XIMO - Nankai Universityitem
                                            Cao, Jayitem
                                            WU, MIN - University Of North Dakotaitem
                                            GAO, HONGWEI - Harvard Medical School
  Submitted to: Proceedings of the National Academy of Sciences (PNAS)
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/19/2012
                                    Publication  Date: 4/27/2012
                                    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.


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