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Am J Physiol Lung Cell Mol Physiol 284: L108-L118, 2003. First published August 16, 2002; doi:10.1152/ajplung.00186.2002
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Vol. 284, Issue 1, L108-L118, January 2003

Transcriptional regulation of CCSP by interferon-gamma in vitro and in vivo

P. L. Ramsay1,6,*, Z. Luo6,*, S. M. Magdaleno5, S. K. Whitbourne1, X. Cao1, M. S. Park4, S. E. Welty3, L.-Y. Yu-Lee2, and F. J. DeMayo1,6

Departments of 1 Pediatrics, 2 Medicine, and 6 Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030; 3 Children's Research Institute, Columbus, Ohio 43205; 4 Department of Pediatrics, Ajou University, Suwon, Korea; and 5 Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101

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 .

hepatocyte nuclear factor-3; CCAAT/enhancer-binding protein; mouse transformed Clara cells; thyroid transcription factor-1; interferon regulatory factor-1; Clara cell secretory protein

* P. L. Ramsay and Z. Luo contributed equally to this work.




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