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.
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Authors | P 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 |
Journal | American 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 |
PMID | 12388333
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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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
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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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