C3 synthesis by A549 alveolar epithelial cells is increased by interferon-γ and dexamethasone

The third component of complement, C3, is produced in the lung by several cell types including alveolar epithelial cells. Since interferon-γ (IFN-γ) and dexamethasone regulate C3 gene expression in non-pulmonary cells, and because IFN-γ and dexamethasone interact to regulate the functional activity of alveolar epithelial cells, we investigated the effects of IFN-γ and dexamethasone on C3 production by A549 human alveolar epithelial cells. Treatment of A549 cells with IFN-γ 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-γ for 3 days and was 3.4-fold greater than control. Dexamethasone (0.1 μM) stimulation of A549 cells increased C3 production 6.7-fold over controls on day 3. Treatment of A549 cells with IFN-γ plus dexamethasone resulted in an 11- to 13-fold increase in C3 synthesis. C3 mRNA levels were increased in A549 cells treated with IFN-γ and dexamethasone individually and in combination suggesting that IFN-γ and dexamethasone increase C3 synthesis by a pre-translational mechanism. IFN-γ 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-γ and glucocorticoids may be important in the local regulation of C3 synthesis in the lung.