Transcriptional regulation of human pulmonary surfactant proteins SP-B and SP-C by glucocorticoids.
Expression of the pulmonary surfactant-associated proteins SP-B and SP-C is under both developmental and hormonal regulation. We used human fetal lung to investigate developmental changes and the mechanism of glucocorticoid stimulation of SP-B and SP-C gene expression. There were similar approximately 3-fold increases in SP-B cytoplasmic mRNA content and transcription rate comparing lung samples of 24 wk versus 16 wk gestation. During 5 days of lung explant culture without hormones, the transcription rate increased for SP-B and decreased for SP-C, paralleling changes in mRNA content. Treatment with 100 nM dexamethasone maximally increased transcription of the SP-B gene (approximately 3-fold) and SP-C gene (approximately 11-fold) after 2 and 8 h, respectively, similar to changes in mRNA content. In dose-response studies, the maximal increase in transcription rate occurred at approximately 10 nM dexamethasone for SP-B and at > or = 100 nM for SP-C. Induction of SP-B mRNA content and transcription rate were not affected by prior cycloheximide exposure, whereas induction of SP-C mRNA was decreased by as little as 1 h exposure to inhibitor. We conclude that glucocorticoids, acting directly in type II cells, regulate the SP-B and SP-C genes primarily at the level of transcription. Induction of SP-C, but not SP-B, requires ongoing protein synthesis which likely reflects involvement of a labile transcription factor. The difference in glucocorticoid sensitivity may indicate that the two surfactant protein genes contain glucocorticoid response elements with different affinities for receptor.
Ballard
P L
PL
Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia 19104, USA.
Ertsey
R
R
Gonzales
L W
LW
Gonzales
J
J
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured / Q000166:cytology / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011510:Proteolipids / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011500:Protein Synthesis Inhibitors; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003907:Dexamethasone; D003513:Cycloheximide