Late generation lentiviral vectors: evaluation of inflammatory potential in human airway epithelial cells.
Lentiviruses (LVs) are considered one of the most promising tools for gene transfer, however, their potential to induce pro-inflammatory cytokines on delivery into the respiratory tissue remains to be established. Here we tested a third-generation vesicular stomatitis virus (VSV)-G pseudotyped LV vector in the two respiratory epithelial cell lines A549 and CFT1-C2. We observed that the VSV-G LV vector does not induce (a) activation of the nuclear factor (NF)-kappaB, which intervenes in transcription of pro-inflammatory genes; (b) expression of ICAM-1; and (c) transcription of a panel of cytokines, with the exception of a mild and transient (24h) increase of IFN-gamma mRNA. In contrast, an adenovirus-derived vector strongly activated NF-kappaB and different transcripts such as those of ICAM-1, IL-8, RANTES, IP-10, TNF-alpha, IL-6, IL-1 beta. In conclusion, this third-generation VSV-G pseudotyped LV vector does not elicit major pro-inflammatory signals in human airway epithelial cells and appears to be better suited for gene delivery strategies.
Copreni
Elena
E
Institute for the Experimental Treatment of Cystic Fibrosis, H.S. Raffaele, Via Olgettina, 20132 Milano, Italy.
Nicolis
Elena
E
Tamanini
Anna
A
Bezzerri
Valentino
V
Castellani
Stefano
S
Palmieri
Lucia
L
Giri
Maria Grazia
MG
Vella
Antonio
A
Colombatti
Marco
M
Rizzotti
Paolo
P
Conese
Massimo
M
Cabrini
Giulio
G
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology*; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000096:biosynthesis; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1