Surfactant protein B (SP-B) plays a vital role in the pulmonary function of neonates; infants with inherited SP-B deficiency follow a course of progressive and fatal pulmonary failure unless they undergo lung transplantation. In previous studies, we have shown that all-trans retinoic acid (RA), a ligand of the steroid hormone receptor family, increases SP-B mRNA levels in H441 human lung adenocarcinoma cells and in cultured human fetal lung explants. In order to determine the temporal nature of the RA effect on SP-B mRNA, H441 cells were incubated with 10-6M all-trans RA for 1, 2, 4, 8, 12 or 24 hours. The stimulatory effect of all-trans RA on SP-B mRNA levels was observed as early as after 4 hours of exposure to the hormone. We also found that other retinoids, including 9-cis retinoic acid, 13-cis retinoic acid and retinol, do not affect SP-B mRNA levels in the H441 cell line. Glucocorticoids have been shown to increase SP-B mRNA levels in H441 cells and in cultured human fetal lung tissue. We hypothesized that the combination of glucocorticoids and all-trans RA regulates SP-B gene expression in a manner different from the effect of either agent alone. In initial experiments, H441 cells were treated in serum-free medium for 24 hours with cortisol (10-10M to 10-6M) added alone. SP-B mRNA levels were increased compared to control levels in a dose-dependent manner from 1.8 times over control levels in 10-9M cortisol to 4.7 times over control levels in 10-6M cortisol; there was no effect of 10-10M cortisol. H441 cells were then exposed to varying concentrations of cortisol (10-10 M to 10-6M) in the presence of all-trans RA (10-6M). SP-B mRNA levels were further stimulated to 2.8 times control levels in 10-9M cortisol and to 7 times control levels in 10-6M cortisol. At each concentration of cortisol, 10-9M to 10-6M, there was an average 40% increase in the stimulatory effect of cortisol on the level of SP-B mRNA with the addition of 10-6M all-trans RA. These data are suggestive that there is an additive effect of all-trans retinoic acid on cortisol-stimulated surfactant protein B gene expression in human lung epithelial cells.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
George, T., Snyder, J. RETINOIC ACID AND GLUCOCORTICOIDS REGULATE SURFACTANT PROTEIN B GENE EXPRESSION IN HUMAN LUNG EPITHELIAL CELLS. • 337. Pediatr Res 39 (Suppl 4), 59 (1996). https://doi.org/10.1203/00006450-199604001-00357
Issue Date:
DOI: https://doi.org/10.1203/00006450-199604001-00357