Differential Response of Surfactant Protein-A Genetic Variants to Dexamethasone Treatment

ABSTRACT

PURPOSE: Surfactant protein A(SP-A) is involved in surfactant physiology and structure, and plays a major role in innate host defense and inflammatory processes in the lung. Steroid therapy is widely used for mothers who threaten to deliver prematurely and also used commonly in the management of preterm infants with chronic lung disease. Two SP-A genes(SP-A1, SP-A2) and several alleles have been characterized for each SP-A gene in human. Preliminary evidence indicates that differences may exist among alleles in response to Dexamethasone(Dexa) and that the SP-A 3'UTR plays a role in this process. We studied whether 3'UTR-mediated differences exist among the most frequently found SP-A alleles in response to Dexa. METHODS: Constructs containing the 3'UTR from eight different SP-A alleles were made using luciferase as a the reporter gene. These constructs were driven by the SV40 promotor and were transfected along with a transfection control vector in H441 cells that express SP-A. The activity of the reporter gene in the presence or absence of Dexa(100 nM) treatment was measured. All the experiments for the eight SP-A alleles studied, were performed in triplicate and repeated five times. The results were normalized to the transfection control. RESULTS: Expression of alleles of 6A3, 6A, 1A were significantly decreased in response to Dexa. CONCLUSION: Three UTR mediated differences exist among human SP-A variants both in the basal expression and in response to Dexa. These genotype-dependent differences may point to a need for a careful consideration of individual use of steroid treatment in the prematurely born infant.