Transcriptional regulation of CCSP by interferon-gamma in vitro and in vivo.
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.
Ramsay
P L
PL
Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Luo
Z
Z
Magdaleno
S M
SM
Whitbourne
S K
SK
Cao
X
X
Park
M S
MS
Welty
S E
SE
Yu-Lee
L-Y
LY
DeMayo
F J
FJ
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D051542:Hepatocyte Nuclear Factor 3-beta; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D013237:Stereoisomerism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*; D014598:Uteroglobin
D004268:DNA-Binding Proteins; C496503:Foxa2 protein, mouse; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C556390:Scgb1a1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta; D007371:Interferon-gamma; D014598:Uteroglobin