In vitro and in vivo effects of glucocorticoids on gene transfer to skeletal muscle

As a pharmacological approach to potentially improve gene transfer efficien cy into skeletal muscle cells, glucocorticoids were shown here to allow eff icient transfection of cultured and mouse human myoblasts, human pulmonary A549 cells, but not dog myoblasts, independently of the transfection protoc ol, the reporter gene and the transcription promoter employed. Transduction with adenovirus was also increased by dexamethasone. Pretreatment of cells 48 h prior to transfection was most effective and was shown to be concentr ation-dependent. This effect is mediated by binding to the glucocorticoid r eceptor, but not by glucocorticoid responsive elements present in the vecto rs. The acute dexamethasone effect could be due to increased plasmid entry into the cells as suggested by Southern blot, whereas the sustained increas e of luciferase activity in dexamethasone-treated cultures may be related t o intracellular mechanisms following cell entry. In mice in vivo, a similar increase of luciferase activity upon glucocorticoid treatment was found. ( C) 1999 Federation of European Biochemical Societies.