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Interferon-gamma regulation of Clara cell gene expression: in vivo and in vitro.
- Source :
-
The American journal of physiology [Am J Physiol] 1997 Jun; Vol. 272 (6 Pt 1), pp. L1142-51. - Publication Year :
- 1997
-
Abstract
- This report demonstrates that Clara cell 10-kDa protein (CC10) mRNA levels are regulated by interferon-gamma (IFN-gamma). An analysis of total lung RNA from mice given IFN-gamma intratracheally showed increased levels of CC10 mRNA compared to control animals but no significant increases in surfactant proteins B and C. These results were confirmed in a Clara cell line, mtCC1-2, generated from the lungs of a transgenic mouse expressing the SV40 large T antigen under the control of a Clara cell-specific promoter. Significant increases in mtCC1-2 CC10 mRNA levels were observed in a time- and a dose-dependent manner. The expression of transacting factors hepatocyte nuclear factors 3 alpha and 3 beta (HNF-3 alpha and HNF-3 beta) were also analyzed, and a transient increase in the expression of HNF-3 beta but not HNF-3 alpha was detected. Deoxyribonuclease I footprint analysis identified a signal transducer and activator of transcription (STAT) binding site (at nucleotides -293 to -284 of CC10) adjacent to two thyroid transcription factor-1 (TTF-1) binding sites, suggesting a potential interaction between STAT1 and TTF-1. This report reinforces the hypothesis that CC10 functions as an anti-inflammatory protein and that increases in CC10 protein may provide additional protection from inflammation and disease in the lung.
- Subjects :
- Animals
Cell Line, Transformed
Cell Nucleus metabolism
DNA Primers
Enzyme Inhibitors
Female
Hepatocyte Nuclear Factor 3-alpha
Hepatocyte Nuclear Factor 3-beta
Lung metabolism
Male
Mice
Mice, Inbred ICR
Mice, Transgenic
Polymerase Chain Reaction
Promoter Regions, Genetic
Proteins genetics
RNA, Messenger biosynthesis
Recombinant Proteins
Transcription Factors biosynthesis
Transcription Factors metabolism
DNA-Binding Proteins biosynthesis
Interferon-gamma pharmacology
Lung cytology
Lung drug effects
Nuclear Proteins biosynthesis
Protein Biosynthesis
Transcription, Genetic drug effects
Uteroglobin
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9513
- Volume :
- 272
- Issue :
- 6 Pt 1
- Database :
- MEDLINE
- Journal :
- The American journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 9227516
- Full Text :
- https://doi.org/10.1152/ajplung.1997.272.6.L1142