title: Free cationic liposomes inhibit the inflammatory response to cationic lipid-DNA complex injected intravenously and enhance its transfection efficiency.
abstract: In this report, we show that intravenous (i.v.) injection into mice of a complex made of the cationic lipid diC14-amidine and the luciferase reporter plasmid (pCMV-luc) results in efficient gene expression in several organs but elicits an inflammatory response characterized by a release of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) into the serum of treated animals. A single preinjection of free diC14-amidine liposomes improves the i.v. transfection efficiency of the diC14-amidine/protamine/pCMV-luc complex as much as 40 times. This improvement is correlated with the ability of free liposomes to inhibit TNF-alpha but not IFN-gamma production resulting from complex injection. TNF-alpha-rich serum obtained from mice injected with diC14-amidine/protamine/pCMV-luc complex inhibits luciferase expression in transfected mouse lung endothelial (MLE) cells cultured in vitro, whereas IFN-gamma has no effect. This inhibitory effect can be partly abolished by treating the mouse serum with a specific anti-TNF-alpha antibody. These data point out that cationic lipids are potent inhibitors of the inflammatory response to the CpG motifs in plasmid DNA. This property is shown to enhance the in vivo transfection efficiency.
authors.affiliation: Center of Structural Biology and Bioinformatics, Université Libre de Bruxelles, Campus Plaine CP 206/2, B-1050 Brussels, Belgium. aelouaha@ben.ulb.ac.be
authors.forename: Abdelatif
authors.initials: A
authors.lastname: Elouahabi
authors.forename: Veronique
authors.initials: V
authors.lastname: Flamand
authors.forename: Sibel
authors.initials: S
authors.lastname: Ozkan
authors.forename: Frederic
authors.initials: F
authors.lastname: Paulart
authors.forename: Michel
authors.initials: M
authors.lastname: Vandenbranden
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Ruysschaert
mesh_terms: D000818:Animals; D002412:Cations; D004247:DNA / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage; D008055:Lipids / Q000008:administration & dosage*; D008081:Liposomes; D051379:Mice; D014162:Transfection / Q000592:standards*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000096:biosynthesis
chemical_list: D002412:Cations; D008055:Lipids; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA