Interferon-gamma regulation of Clara cell gene expression: in vivo and in vitro.
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.
Magdaleno
S M
SM
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Wang
G
G
Jackson
K J
KJ
Ray
M K
MK
Welty
S
S
Costa
R H
RH
DeMayo
F J
FJ
D000818:Animals; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors; D005260:Female; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D007371:Interferon-gamma / Q000494:pharmacology*; D008168:Lung / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014598:Uteroglobin
D017931:DNA Primers; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C496500:Foxa1 protein, mouse; C496503:Foxa2 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C556390:Scgb1a1 protein, mouse; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D007371:Interferon-gamma; D014598:Uteroglobin