1. Transcriptional regulation of CCSP by interferon-gamma in vitro and in vivo.
- Author
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Ramsay PL, Luo Z, Magdaleno SM, Whitbourne SK, Cao X, Park MS, Welty SE, Yu-Lee LY, and DeMayo FJ
- Subjects
- Animals, Binding Sites physiology, Cell Line, Transformed, DNA-Binding Proteins metabolism, DNA-Binding Proteins physiology, Gene Expression physiology, Hepatocyte Nuclear Factor 3-beta, Interferon Regulatory Factor-1, Mice, Nuclear Proteins metabolism, Phosphoproteins physiology, Promoter Regions, Genetic, Proteins chemistry, Respiratory Mucosa cytology, Respiratory Mucosa metabolism, Stereoisomerism, Trans-Activators metabolism, Gene Expression Regulation physiology, Interferon-gamma physiology, Proteins genetics, Transcription Factors, Transcription, Genetic physiology, Uteroglobin
- Abstract
Interferon gamma (IFN-gamma), a potent cytokine inducing a wide range of immunologic activities, is increased in the airway secondary to viral infection or during an inflammatory response. This increase in IFN-gamma concentration may alter the expression of specific airway epithelial cell genes that regulate adaptation of airway inflammatory responses. One protein induced by IFN-gamma is Clara cell secretory protein (CCSP), which may contribute to the attenuation of airway inflammation. This study was done to investigate the molecular mechanism by which IFN-gamma stimulates the expression of the CCSP gene in mouse transformed Clara cells and transgenic mice. Deletion mapping and linker-scanning mutations demonstrated that IFN-gamma-induced expression of CCSP was regulated, in part, at the level of transcription. In vitro and in vivo studies verified that the minimal IFN-gamma-responsive segment was localized to the proximal 166 bp of the 5'-flanking region. Additionally, IFN-gamma-induced expression of CCSP was mediated indirectly through an interferon regulatory factor-1-mediated increase in hepatocyte nuclear factor-3beta.
- Published
- 2003
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