Ld. Hill et al., C3 SYNTHESIS BY A549 ALVEOLAR EPITHELIAL-CELLS IS INCREASED BY INTERFERON-GAMMA AND DEXAMETHASONE, Immunology, 79(2), 1993, pp. 236-240
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.