C3 SYNTHESIS BY A549 ALVEOLAR EPITHELIAL-CELLS IS INCREASED BY INTERFERON-GAMMA AND DEXAMETHASONE

The third component of complement, C3, is produced in the lung by seve ral cell types including alveolar epithelial cells. Since interferon-g amma (IFN-gamma) and dexamethasone regulate C3 gene expression in non- pulmonary cells, and because IFN-gamma and dexamethasone interact to r egulate the functional activity of alveolar epithelial cells, we inves tigated the effects of IFN-gamma and dexamethasone on C3 production by A549 human alveolar epithelial cells. Treatment of A549 cells with IF N-gamma a one increased C3 production in a time- and dose-dependent ma nner. Maximal increase in C3 production occurred after stimulation of A549 cells with 500 IU/ml IFN-gamma for 3 days and was 3.4-fold greate r than control. Dexamethasone (0.1 muM) stimulation of A549 cells incr eased C3 production 6.7-fold over controls on day 3. Treatment of A549 cells with IFN-gamma plus dexamethasone resulted in an 11- to 13-fold increase in C3 synthesis. C3 mRNA levels were increased in A549 cells treated with IFN-gamma and dexamethasone individually and in combinat ion suggesting that IFN-gamma and dexamethasone increase C3 synthesis by a pre-translational mechanism. IFN-gamma and dexamethasone did not alter the two-chain structure of the C3 molecule produced by A549 cell s, as assessed by Western blotting. We speculate that IFN-gamma and gl ucocorticoids may be important in the local regulation of C3 synthesis in the lung.