Interferon-gamma regulation of Clara cell gene expression: in vivo and in vitro
Magdaleno, S.M.; Wang, G.; Jackson, K.J.; Ray, M.K.; Welty, S.; Costa, R.H.; DeMayo, F.J.
American Journal of Physiology 272(6 Pt 1): L1142-L1151
1997
ISSN/ISBN: 0002-9513 PMID: 9227516 Document Number: 478919
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.