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Am J Physiol Lung Cell Mol Physiol 284: L738-L748, 2003. First published January 10, 2003; doi:10.1152/ajplung.00375.2002
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Vol. 284, Issue 5, L738-L748, May 2003

Human SP-A 3'-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone

Guirong Wang1, Xiaoxuan Guo1, and Joanna Floros1,2

Departments of 1 Cellular and Molecular Physiology and 2 Pediatrics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

Human surfactant protein A (SP-A) is encoded by two genes (SP-A1, SP-A2), and each is identified with several alleles. SP-A is involved in normal lung function, innate immunity, inflammatory processes, and is regulated by glucocorticoids. We investigated the role of 3'-untranslated region (UTR) of 10 SP-A variants on gene expression using transient transfection of 3'-UTR constructs in the human lung adenocarcinoma cell line NCI-H441. We found: 1) both basal mRNA and protein levels of the reporter gene of SP-A 3'-UTR constructs are significantly (P < 0.01) reduced compared with controls (vector pGL3 and surfactant protein B pGL3) and that differences exist among alleles; and 2) after dexamethasone (Dex) treatment (100 nM for 16 h), mRNA was reduced (31-51%). Seven alleles showed a significant decrease (P < 0.05) in mRNA, and three did not. Reporter activity was also decreased, from 17% (1A1) to 38% (1A), with six alleles showing a significant decrease. The data indicate that the 3'-UTR of SP-As play a differential role in SP-A basal expression and in response to Dex. Therefore, a careful consideration of individual use of steroid treatment may be considered.

allele; gene regulation; surfactant protein A; 3'-untranslated region


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