Prostaglandins regulate surfactant protein A (SP-A) gene expression in human fetal lung in vitro

Acarregui, Michael J., Snyder, Jeanne M., Mitchell, Murray D. and Mendelson, Carole R. (1990) Prostaglandins regulate surfactant protein A (SP-A) gene expression in human fetal lung in vitro. Endocrinology, 127 3: 1105-1113. doi:10.1210/endo-127-3-1105


Author Acarregui, Michael J.
Snyder, Jeanne M.
Mitchell, Murray D.
Mendelson, Carole R.
Title Prostaglandins regulate surfactant protein A (SP-A) gene expression in human fetal lung in vitro
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 1990-09
Sub-type Article (original research)
DOI 10.1210/endo-127-3-1105
Volume 127
Issue 3
Start page 1105
End page 1113
Total pages 9
Place of publication Bethesda, MA, U.S.A.
Publisher Endocrine Society
Language eng
Subject 1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
0601 Biochemistry and Cell Biology
Formatted abstract
We previously have observed that dexamethasone has a biphasic effect on surfactant protein A (SP-A) mRNA levels in human fetal lung in vitro. At concentrations of 10-10-10-9 M, dexamethasone increases the levels of SP-A mRNA, whereas, at concentrations > 10-8 M, the steroid is markedly inhibited. In studies to define the molecular mechanisms for these effects, we observed that dexamethasone causes a dose-dependent stimulation of SP-A gene transcription, but paradoxically causes a dose-dependent inhibition of SP-A mRNA stability. In light of the well-characterized inhibitory effect of glucocorticoids on prostaglandin (PG) synthesis in a number of tissues, it was our objective in the present study to investigate the role of PGs on SP-A gene expression in human fetal lung in vitro and to determine whether the action of dexamethasone (>10-8 M) to reduce SP-A mRNA levels could be mediated by its effect to inhibit PG synthesis. We found that dexamethasone (10-7 M) caused a marked decrease in the secreted levels of the PGE2 and PGF(2α), the prostacyclin metabolite, 6-keto-PGF(1α), and the thromboxane A2 metabolite, thromboxane B2. Indomethacin, which also caused a pronounced reduction in the levels of these secreted prostanoids, had a marked effect to reduce SP-A mRNA levels in human fetal lung in vitro. The inhibitory effects of indomethacin were associated with an 73% reduction in cAMP formation by the fetal lung in culture, and were prevented by simultaneous incubation with dibutyryl cAMP or with PGE2. PGE2 markedly increased cAMP formation by the human fetal lung tissue incubated in the absence or presence of indomethacin. Inhibitory effects of dexamethasone and indomethacin also were observed on two morphological indices of lung differentiation, alveolar lumenal volume density, and lamellar body volume density. PGE2 significantly increased lumenal volume density of the human fetal lung explants. The finding that the inhibitory action of dexamethasone (10-7 M) on SP-A mRNA levels could not be prevented by simultaneous incubation with either PGE2 or dibutyryl cAMP and that dexamethasone had no apparent effect on cAMP formation by the fetal lung in vitro is suggestive that the action of dexamethasone (≥10-8 M) to reduce SP-A mRNA levels is mediated at least in part by actions alternative to its inhibitory effects on PG synthesis. Our findings are further suggestive that increased PGE2 synthesis by human fetal lung in vitro may promote increased cAMP formation with a consequent induction of type II cell differentiation and SP-A gene expression.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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Created: Thu, 26 Aug 2010, 12:45:09 EST