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Transcriptional regulation of CCSP by interferon-gamma in vitro and in vivo.

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.
AuthorsP L Ramsay, Z Luo, S M Magdaleno, S K Whitbourne, X Cao, M S Park, S E Welty, L-Y Yu-Lee, F J DeMayo
JournalAmerican journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 284 Issue 1 Pg. L108-18 (Jan 2003) ISSN: 1040-0605 [Print] United States
PMID12388333 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA-Binding Proteins
  • Foxa2 protein, mouse
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • Scgb1a1 protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta
  • Interferon-gamma
  • Uteroglobin
Topics
  • Animals
  • Binding Sites (physiology)
  • Cell Line, Transformed
  • DNA-Binding Proteins (metabolism, physiology)
  • Gene Expression (physiology)
  • Gene Expression Regulation (physiology)
  • Hepatocyte Nuclear Factor 3-beta
  • Interferon Regulatory Factor-1
  • Interferon-gamma (physiology)
  • Mice
  • Nuclear Proteins (metabolism)
  • Phosphoproteins (physiology)
  • Promoter Regions, Genetic
  • Proteins (chemistry, genetics)
  • Respiratory Mucosa (cytology, metabolism)
  • Stereoisomerism
  • Trans-Activators (metabolism)
  • Transcription Factors
  • Transcription, Genetic (physiology)
  • Uteroglobin

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