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Departments of 1 Pediatrics and 2 Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242
The surfactant
proteins (SPs) are required for the normal function of pulmonary
surfactant, a lipoprotein substance that prevents alveolar collapse at
end expiration. We characterized the effects of cortisol and all
trans-retinoic acid (RA) on SP-A and
SP-B gene expression in H441 cells, a human pulmonary adenocarcinoma cell line. Cortisol, at 10
6
M, caused a significant inhibition of SP-A mRNA to levels that were
60-70% of controls and a five- to sixfold increase in the levels
of SP-B mRNA. RA alone (106
M) had no effect on SP-A mRNA levels and modestly reduced the inhibitory effect of cortisol. RA alone and the combination of cortisol
and RA both significantly increased SP-B mRNA levels. RA had no effect
on the rate of SP-A gene transcription or on SP-A mRNA stability.
Cortisol alone and the combination of cortisol and RA significantly
inhibited the rate of SP-A gene transcription but had no effect on SP-A
mRNA half-life. RA at 106 M
had no effect on the rate of SP-B gene transcription but prolonged SP-B
mRNA half-life. Cortisol alone and the combination of cortisol and RA
caused a significant increase in the rate of SP-B gene transcription
and also caused a significant increase in SP-B mRNA stability. We
conclude that RA has no effect on SP-A gene expression and increases
SP-B mRNA levels by an effect on SP-B mRNA stability and not on the
rate of SP-B gene transcription. In addition, the effects of the
combination of RA and cortisol were generally similar to those of
cortisol alone.
H441 cell line; pulmonary surfactant; lung; surfactant protein A mRNA; surfactant protein B mRNA
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