George T N, Miakotina O L, Goss K L, Snyder J M
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
Am J Physiol. 1998 Apr;274(4):L560-6. doi: 10.1152/ajplung.1998.274.4.L560.
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 (10(-6) 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 10(-6) 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.
表面活性蛋白（SPs）是肺表面活性物质正常功能所必需的，肺表面活性物质是一种脂蛋白物质，可防止呼气末肺泡塌陷。我们研究了皮质醇和全反式视黄酸（RA）对H441细胞（一种人肺腺癌细胞系）中SP-A和SP-B基因表达的影响。10^(-6) M的皮质醇可显著抑制SP-A mRNA水平，使其降至对照水平的60-70%，并使SP-B mRNA水平增加五到六倍。单独使用RA（10^(-6) M）对SP-A mRNA水平无影响，并适度降低了皮质醇的抑制作用。单独使用RA以及皮质醇与RA的组合均显著增加了SP-B mRNA水平。RA对SP-A基因转录速率或SP-A mRNA稳定性无影响。单独使用皮质醇以及皮质醇与RA的组合均显著抑制SP-A基因转录速率，但对SP-A mRNA半衰期无影响。10^(-6) M的RA对SP-B基因转录速率无影响，但延长了SP-B mRNA半衰期。单独使用皮质醇以及皮质醇与RA的组合均导致SP-B基因转录速率显著增加，同时也导致SP-B mRNA稳定性显著增加。我们得出结论，RA对SP-A基因表达无影响，且通过影响SP-B mRNA稳定性而非SP-B基因转录速率来增加SP-B mRNA水平。此外，RA与皮质醇组合的作用通常与单独使用皮质醇的作用相似。
