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stimulates human Clara cell secretory protein
production by human airway epithelial cells
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892
Clara cell secretory protein (CCSP) is an
inhibitor of secretory phospholipase
A2. It is produced by airway
epithelial cells and is present in airway secretions. Because
interferon (IFN)-
can induce gene expression in airway epithelial
cells and may modulate the inflammatory response in the airway, it was
of interest to study the effect of this cytokine on epithelial cell
CCSP mRNA expression and CCSP protein synthesis. A human bronchial
epithelial cell line (BEAS-2B) was used for this study. CCSP mRNA was
detected by ribonuclease protection assay. IFN-
was found to
increase CCSP mRNA expression in a time- and dose-dependent manner. The CCSP mRNA level increased after IFN-
(300 U/ml) treatment for 8-36 h, with the peak increase at 18 h. Immunobloting of CCSP protein also demonstrated that IFN-
induced the synthesis and secretion of CCSP protein in a time-dependent manner. Nuclear run-on,
CCSP reporter gene activity assay, and CCSP mRNA half-life assay
demonstrated that IFN-
-induced increases in CCSP gene expression were mediated, at least in part, at the posttranscriptional level. The
present study demonstrates that IFN-
can induce increases in
steady-state mRNA levels and protein synthesis of human CCSP protein in
airway epithelial cells and may modulate airway inflammatory responses
in this manner.
cytokines; airway inflammation; airway secretion
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