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 several cell types including alveolar epithelial cells. Since interferon-gamma (IFN-gamma) and dexamethasone regulate C3 gene expression in non-pulmonary cells, and because IFN-gamma and dexamethasone interact to regulate the functional activity of alveolar epithelial cells, we investigated the effects of IFN-gamma and dexamethasone on C3 production by A549 human alveolar epithelial cells. Treatment of A549 cells with IFN-gamma alone increased C3 production in a time-and dose-dependent manner. 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 greater than control. Dexamethasone (0.1 microM) stimulation of A549 cells increased 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 combination 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 cells, as assessed by Western blotting. We speculate that IFN-gamma and glucocorticoids may be important in the local regulation of C3 synthesis in the lung.