Interferon-gamma regulation of Clara cell gene expression: In vivo and in vitro

被引:64
作者
Magdaleno, SM
Wang, GY
Jackson, KJ
Ray, MK
Welty, S
Costa, RH
DeMayo, FJ
机构
[1] BAYLOR COLL MED, DEPT CELL BIOL, HOUSTON, TX 77030 USA
[2] BAYLOR COLL MED, DEPT PEDIAT, HOUSTON, TX 77030 USA
[3] UNIV ILLINOIS, COLL MED, DEPT BIOCHEM, CHICAGO, IL 60612 USA
关键词
lung; Clara cells; cell lines; inflammation;
D O I
10.1152/ajplung.1997.272.6.L1142
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:L1142 / L1151
页数:10
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