Inhibition of nonviral cationic liposome-mediated gene transfer into primary human respiratory cells by interferon-gamma.
The effect of interferon (IFN) gamma on cationic liposome-mediated gene transfer into primary respiratory epithelial cells was investigated. Treatment of primary respiratory epithelial cells with IFN-gamma resulted in a dose-dependent increase in the intermediate filament cytokeratin 13 and a decrease in cellular proliferation, indicating that respiratory cells underwent squamous differentiation. IFN-gamma pretreatment resulted in a dramatic inhibition of transfection efficiency mediated by a cationic liposome (DOTAP). Incubation of squamous nasal cells with DOTAP/DNA complexes for various periods at 4 degrees C and evaluation of luciferase levels suggested that IFN-gamma pretreatment inhibits complex binding to the cells. In primary nasal and bronchial cells cytofluorimetric analysis demonstrated that IFN-gamma reduces binding of FITC-labeled complexes. The data indicate that differentiation of respiratory epithelial cells to a squamous phenotype, which may occur in chronic respiratory diseases such as cystic fibrosis, induces a refractory condition to gene transfer by nonviral cationic liposomes.
Institute for Experimental Treatment of Cystic Fibrosis, San Raffaele Scientific Institute, Via Olgettina 58, Milan 20132, Italy.
Giovanna
G
Sersale
Daniela
D
Carpani
Valeria
V
Casotti
Alessandra
A
Livraghi
Salvatore
S
Carrabino
Maurizio
M
Di Cicco
Baroukh M
BM
Assael
Annamaria
A
Giunta
Massimo
M
Conese
D002411:Cation Exchange Resins; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008081:Liposomes; D008156:Luciferases / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology; D014162:Transfection
D002411:Cation Exchange Resins; D016207:Cytokines; D008081:Liposomes; D007371:Interferon-gamma; D008156:Luciferases