INTERFERON-GAMMA STIMULATES HUMAN CLARA CELL SECRETORY PROTEIN-PRODUCTION BY HUMAN AIRWAY EPITHELIAL-CELLS

Clara cell secretory protein (CCSP) is an inhibitor of secretory phosp holipase A(2). It is produced by airway epithelial cells and is presen t in airway secretions. Because interferon (IFN)-gamma can induce gene expression in airway epithelial cells and may modulate the inflammato ry response in the airway, it was of interest to study the effect of t his cytokine on epithelial cell CCSP mRNA expression and CCSP protein synthesis. A human bronchial epithelial cell Line (BEAS-2B) was used f or this study. CCSP mRNA was detected by ribonuclease protection assay . IFN-gamma was found to increase CCSP mRNA-expression ina time- and d ose-dependent manner. The CCSP mRNA level increased after IFN-gamma (3 00 U/ml) treatment for 8-36 h, with the peak increase at 18 h. Immunob loting of CCSP protein also demonstrated that IFN-gamma induced the sy nthesis and secretion of CCSP protein in a time-dependent manner. Nucl ear run-on, CCSP reporter gene activity assay, and CCSP mRNA half-life assay demonstrated that IFN-gamma-induced increases in CCSP gene expr ession were mediated, at least in part, at the posttranscriptional lev el. The present study demonstrates that IFN-gamma can induce increases in steady-state mRNA levels and protein synthesis of human CCSP prote in in airway epithelial cells and may modulate airway inflammatory res ponses ill this manner.