Comparison of the effects of betamethasone and dexamethasone on surfactant protein a mRNA expression in human lung cells

Objective: While prenatal administration of synthetic corticosteroids stimulates both fetal lung development and expression of pulmonary surfactant, the specific effects may depend on the corticosteroid formulation used. We compared the dose-dependent effects of various concentrations of two synthetic corticosteroids, betamethasone and dexamethasone, on steady state levels of surfactant protein A (SP-A) mRNA in human lung cells. Methods: Cultured human NCI-H441 bronchoalveolar epithelial cells were exposed to varying concentrations of betamethasone or dexamethasone (10^-7 to 10^-12 M) for 48 h alone or in combination with dibutyryl cAMP (1 mM), which augments surfactant protein gene expression. RNA was harvested and SP-A mRNA levels were quantified by real-time quantitative reverse transcriptase polymerase chain reaction analysis. Results were compared using the Kruskal-Wallis test. Results: A dose-dependent modification in SP-A mRNA levels was demonstrated with both dexamethasone and betamethasone. Cells treated with cAMP expressed higher levels of SP-A mRNA than untreated cells. A biphasic curve in the SP-A mRNA response to corticosteroids was elicited only in the presence of cAMP: at lower concentrations (10^-10 through 10^-12 M), SP-A mRNA levels were upregulated, whereas at higher concentrations (10^-7 and 10^-8 M), SP-A mRNA levels were reduced. Dexamethasone was more effective than betamethasone in inducing these changes. Conclusions: Our results support a biphasic effect on SP-A mRNA levels after exposure to corticosteroids in combination with cAMP. At higher corticosteroid concentrations, betamethasone is less inhibitory than dexamethasone on SP-A mRNA.