Recently, our group developed ultrasound (US)-responsive and mannose-modified gene carriers (Man-PEG(2000) bubble lipoplexes), and successfully obtained a high level of gene expression in mannose receptor-expressing cells following gene transfection using Man-PEG(2000) bubble lipoplexes and US exposure. We also reported that large amounts of plasmid DNA (pDNA) were transferred into the cytoplasm of the targeted cells in the gene transfection using this method. In the present study, we investigated the involvement of transcriptional processes on enhanced gene expression obtained by unmodified and Man-PEG(2000) bubble lipoplexes with US exposure. The transcriptional process related to activator protein-1 (AP-1) and nuclear factor-kappa B (NF kappa B) was activated by US exposure, and was founded to be involved in enhanced gene expression obtained by gene transfection using unmodified and Man-PEG(2000) bubble lipoplexes with US exposure. On the other hand, activation of AP-1 and NF kappa B pathways followed by US exposure was hardly involved in the inflammatory responses in the gene transfection using this method. These findings suggest that activation of AP-1 and NF kappa B followed by US exposure is involved in the enhanced gene expression using unmodified and Man-PEG(2000) bubble lipoplexes with US exposure, and the selection of pDNAs activated by US exposure is important in this gene transfection method. (C) 2011 Elsevier B.V. All rights reserved.