Tl. Zach et al., EFFECT OF STEROIDS ON THE SYNTHESIS OF COMPLEMENT C3 IN A HUMAN ALVEOLAR EPITHELIAL-CELL LINE, Experimental lung research, 19(5), 1993, pp. 603-616
The third component of complement, C3, is produced in the lung by seve
ral cell types, including alveolar epithelial cells. Steroid hormones
are important in gene regulation in alveolar epithelial cells. The eff
ects of steroids on C3 production were examined using A549 human pulmo
nary alveolar epithelial cells. Treatment of A549 cells with the gluco
corticoids dexamethasone, hydrocortisone, corticosterone, and 11-deoxy
cortisol increased C3 production, as measured by ELISA. The glucocorti
coid receptor antagonist RU486 inhibited C3 synthesis by dexamethasone
- and hydrocortisone-stimulated cells. Because the glucocorticoid rece
ptor is a member of a superfamily of receptors, the effects of steroid
members of the superfamily on C3 production were examined. The minera
locorticoid, aldosterone, increased C3 production. RU486 completely in
hibited aldosterone's stimulatory effects on C3 production, whereas th
e mineralocorticoid receptor antagonist spironolactone partially inhib
ited aldosterone's effects. In contrast, testosterone, progesterone 17
alpha-hydroxyprogesterone, and estradiol did not alter C3 production b
y A549 cells. Northern analysis showed that C3 mRNA abundance in A549
cells increased following stimulation with dexamethasone, hydrocortiso
ne, corticosterone, and aldosterone. Testosterone, progesterone, 17alp
ha-hydroxyprogesterone, and estradiol did not alter C3 mRNA levels. Th
erefore, among the steroids tested, only glucocorticoids and aldostero
ne altered C3 production by A549 cells suggesting that these steroids
may play a role in the regulation of C3 in the lung.