title: CCAAT/enhancer-binding protein γ is a critical regulator of IL-1β-induced IL-6 production in alveolar epithelial cells.
abstract: 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.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yan
authors.forename: Ximo
authors.initials: X
authors.lastname: Wang
authors.forename: Jay
authors.initials: J
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
mesh_terms: D000818:Animals; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D011650:Pulmonary Alveoli / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D023081:CCAAT-Binding Factor; D053583:Interleukin-1beta; D015850:Interleukin-6; D034741:RNA, Small Interfering