SP-A 3 '-UTR is involved in the glucocorticoid inhibition of human SP-A gene expression

The Synthetic glucocorticoid dexamethasone has a major inhibitory effect on human surfactant protein Al (SP-AI) and SP-A2 gene expression that occurs at both the transcriptional and posttranscriptional levels. Toward the iden tification of cis-acting elements that may be involved in the dexamethasone regulation of SP-A mRNA stability, chimeric chloramphenicol acetyltransfer ase (CAT) constructs that contained various portions of SP-A1 or SP-A2 cDNA in place of the native CAT S'-untranslated region (UTR) were transiently t ransfected into the lung adenocarcinoma cell line NCI-H441. CAT activity wa s reduced in NCI-H441 cells by exposure to 100 nM dexamethasone only for th e chimeric CAT constructs that contained the SP-A 3'-UTR. Moreover, the inh ibitory response seen with dexamethasone was greater for the 3'-UTR derived from the SP-AI allele 6A(3) than with the 3'-UTR derived from either the S P-A1 allele 6A(2) or SP-A2 allele 1A(0), indicating differential regulation between SP-A genes and/or alleles.