Late generation lentiviral vectors: Evaluation of inflammatory potential in human airway epithelial cells

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• 作者：Elena Copreni ; Elena Nicolis ; Anna Tamanini ; Valentino Bezzerri ; Stefano Castellani ; Lucia Palmieri ; Maria Grazia Giri ; Antonio Vella ; Marco Colombatti ; Paolo Rizzotti ; Massimo Conese ; Giulio Cabrini
• 关键词：Lentivirus ; Adenovirus ; Gene therapy ; Cystic fibrosis ; Lung ; Cytokines
• 刊名：Virus Research
• 出版年：2009
• 出版时间：September 2009
• 年：2009
• 卷：144
• 期：1-2
• 页码：8-17
• 全文大小：1831 K

文摘

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)-κB, 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 (24 h) increase of IFN-γ mRNA. In contrast, an adenovirus-derived vector strongly activated NF-κB and different transcripts such as those of ICAM-1, IL-8, RANTES, IP-10, TNF-α, IL-6, IL-1β. 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.