Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

Glucocorticoids have complex effects on human surfactant protein (SP) SP-A1 and SP-A2 gene expression that occur at both transcriptional and post-tran scriptional levels. In the lung adenocarcinoma cell line NCI-H441, dexameth asone causes a dose-dependent decrease in total SP-A mRNA levels and inhibi ts SP-A gene transcription. In this study, a deletional analysis of the SP- A1 promoter was performed in order to identify cis-acting elements that med iate dexamethasone responsiveness in NCI-H441 cells. The region -32/+63 rel ative to the start of SP-AI transcription mediated both basal promoter acti vity and dexamethasone repression of transcription. Removal of the region 18/+63 abolished dexamethasone responsiveness, indicating that sequences wi thin this region are necessary for the inhibitory effect. Furthermore, the region -32/+63 formed a sequence-specific DNA-protein complex with NCI-H441 nuclear extract. This DNA-protein complex was induced by dexamethasone exp osure and its formation was mediated partially by sequences within the regi on +26/+63.