The Effect of Aerosol Polyethylenimine/Interferon-γ Plasmid Complexes on Expression of Inflammatory Cytokines in Mouse Lung

Abstract

The expression of inflammatory cytokines in lung tissue plays an important role in immune function of the lung. In this study, we tested whether aerosol delivery of the gene of interferon-γ (IFNγ) could affect inflammatory cytokine expression in mouse lung. Murine IFNγ-expressing plasmids (pcDNA-IFNγ) complexed with polyethylenimine (PEI) (PEI/pcDNA-IFNγ) were constructed, and their transfection efficiency was assessed in vivo using real-time quantitative RT-PCR and enzyme-linked immunosorbent assay. After aerosol administration of the plasmid complexes and confirmation of the IFNγ plasmid location in lung tissue, we measured mRNA levels of the inflammatory cytokines interleukin-1 (IL-1), IL-6, IL-10, tumor necrosis factor-α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on days 1 to 7 in mouse lung tissues using real-time RT-PCR. IFNγ mRNA expression in mouse lung was significantly increased 24 hr after a single aerosol administration of PEI/pcDNA-IFNγ and gradually decreased over the next 5 days, whereas the mRNA expressions of IL-1, IL-6, and GM-CSF were markedly decreased, but not those of IL-10 and TNF-α. PEI/IFNγ gene therapy delivered by aerosol has immune-regulating potential by suppressing lung cytokine mRNA expression, and therefore may alleviate lung disease.