EFFECT OF STEROIDS ON THE SYNTHESIS OF COMPLEMENT C3 IN A HUMAN ALVEOLAR EPITHELIAL-CELL LINE

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.