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1 Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA
2 Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA; Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA
* To whom correspondence should be addressed. E-mail: jfloros{at}psu.edu.
Human SP-A is encoded by two genes (SP-A1, SP-A2) and each 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'-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 to controls (vector pGL3 and SP-B pGL3); and differences exist among alleles. 2) After Dexamethasone (Dex) treatment (100 nM for 16 hr) mRNA was reduced (31% to 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.
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