Cationic liposome-mediated efficient induction of type I interferons by a low dose of poly I:poly C in mouse cell lines.
Double-stranded polyriboinosinic acid:polyribocytidylic acid (poly I:poly C) is a powerful inducer of type I interferons (IFNs). However, the dose of poly I:poly C required for efficient IFN induction is so high as occasionally to be cytotoxic. In this work, we examined the IFN-inducibility of poly I:poly C complexed with several cationic reagents in mouse fibroblast L cells and found that Lipofectin and LipofectACE can induce the production of a substantial amount of type I IFNs (mostly beta-type) even at a two-order lower dose compared with poly I:poly C alone. Such effects of poly I:poly C were optimal at 0.1 microgram/ml for 2-10 microgram/ml of Lipofectin and LipofectACE. These conditions caused no significant cytotoxicity in the recipient cells. Furthermore, a short treatment (less than 10 min) with the complexes was sufficient for the maximum induction. This IFN induction method was applicable to other cell types and other species including human. Hence, our observations may pave the way for clinical application of the IFN inducer.
Okamoto
S
S
Departments of Drug Delivery Research Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
Watanabe
Y
Y
Takakura
Y
Y
Hashida
M
M
D000818:Animals; D002412:Cations / Q000494:pharmacology; D002460:Cell Line; D004337:Drug Carriers; D006801:Humans; D007369:Interferon Inducers / Q000008:administration & dosage / Q000494:pharmacology*; D007370:Interferon Type I / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis; D007739:L Cells; D008081:Liposomes; D051379:Mice; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002412:Cations; D004337:Drug Carriers; D007369:Interferon Inducers; D007370:Interferon Type I; D008081:Liposomes; D010714:Phosphatidylethanolamines; C020888:1,2-dielaidoylphosphatidylethanolamine; D016899:Interferon-beta; D011070:Poly I-C