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

Authors
Ramsay, PL; Luo, Z; Magdaleno, SM; Whitbourne, SK; Cao, X; Park, MS; Welty, SE; Yu-Lee, LY; DeMayo, FJ
Citation
American journal of physiology. Lung cellular and molecular physiology, 284(1):108-118, 2003
Journal Title
American journal of physiology. Lung cellular and molecular physiology
ISSN
1040-06051522-1504
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.
MeSH terms
AnimalsBinding Sites/physiologyCell Line, TransformedDNA-Binding Proteins/metabolismDNA-Binding Proteins/physiologyGene Expression/physiologyGene Expression Regulation/physiology*Hepatocyte Nuclear Factor 3-betaInterferon Regulatory Factor-1Interferon-gamma/physiology*MiceNuclear Proteins/metabolismPhosphoproteins/physiologyPromoter Regions, GeneticProteins/chemistryProteins/genetics*Respiratory Mucosa/cytologyRespiratory Mucosa/metabolismStereoisomerismTrans-Activators/metabolismTranscription Factors*Transcription, Genetic/physiology*Uteroglobin*
DOI
10.1152/ajplung.00186.2002
PMID
12388333
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Journal Papers > School of Medicine / Graduate School of Medicine > Pediatrics & Adolescent Medicine
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