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 several cell types, including alveolar epithelial cells. Steroid hormones are important in gene regulation in alveolar epithelial cells. The effects of steroids on C3 production were examined using A549 human pulmonary alveolar epithelial cells. Treatment of A549 cells with the glucocorticoids dexamethasone, hydrocortisone, corticosterone, and 11-deoxycortisol increased C3 production, as measured by ELISA. The glucocorticoid receptor antagonist RU486 inhibited C3 synthesis by dexamethasone- and hydrocortisone-stimulated cells. Because the glucocorticoid receptor is a member of a superfamily of receptors, the effects of steroid members of the superfamily on C3 production were examined. The mineralocorticoid, aldosterone, increased C3 production. RU486 completely inhibited aldosterone's stimulatory effects on C3 production, whereas the mineralocorticoid receptor antagonist spironolactone partially inhibited aldosterone's effects. In contrast, testosterone, progesterone 17 alpha-hydroxyprogesterone, and estradiol did not alter C3 production by A549 cells. Northern analysis showed that C3 mRNA abundance in A549 cells increased following stimulation with dexamethasone, hydrocortisone, corticosterone, and aldosterone. Testosterone, progesterone, 17 alpha-hydroxyprogesterone, and estradiol did not alter C3 mRNA levels. Therefore, among the steroids tested, only glucocorticoids and aldosterone altered C3 production by A549 cells suggesting that these steroids may play a role in the regulation of C3 in the lung.
Zach
T L
TL
Department of Pediatrics, Creighton University, Omaha, NE 68198.
Herrman
V A
VA
Hill
L D
LD
Leuschen
M P
MP
D000450:Aldosterone / Q000494:pharmacology; D002460:Cell Line; D003176:Complement C3 / Q000096:biosynthesis*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology*
D003176:Complement C3; D005938:Glucocorticoids; D012333:RNA, Messenger; D013256:Steroids; D000450:Aldosterone