Baculovirus transduction of chondrocytes elicits interferon-alpha/beta and suppresses transgene expression
| Autor: | Takayuki Abe, Yoshiharu Matsuura, Yen-Lin Chen, Shiaw-Min Hwang, Huang-Chi Chen, Yu-Chen Hu, Hsiao-Chiao Shiah, Hsiao-Ping Lee, Ching-Kuang Chuang |
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| Rok vydání: | 2009 |
| Předmět: |
Transcriptional Activation
viruses media_common.quotation_subject Transgene medicine.medical_treatment Genetic Vectors Biology Gene delivery Transduction (genetics) Chondrocytes Interferon Transduction Genetic Drug Discovery Genetics medicine Animals Transgenes Internalization Promoter Regions Genetic Molecular Biology Genetics (clinical) Cells Cultured media_common Tissue Engineering Interferon-alpha Interferon-beta Chondrogenesis Molecular biology Rats Cytokine Molecular Medicine Cytokines Tumor necrosis factor alpha Rabbits Baculoviridae medicine.drug |
| Zdroj: | The journal of gene medicine. 11(4) |
| ISSN: | 1521-2254 |
| Popis: | Background Baculovirus is an effective vector for gene delivery into primary chondrocytes and repeated baculovirus transduction (i.e. supertransduction) appears to be promising for prolonging transgene expression, but how supertransduction may influence baculovirus-mediated gene delivery is unknown. Methods We first investigated whether prior baculovirus transduction suppressed the ensuing transgene expression mediated by the supertransduced baculovirus, and then examined whether baculovirus triggered the expression of various cytokines. Whether interferon-α and -β (IFN-α/β) suppressed the transgene expression as well as the pivotal step responsible for the attenuated transgene expression were examined. Results Baculovirus transduction of chondrocytes elicited an immediate yet transient expression of IFN-α/β, which repressed the transgene expression in a dose-dependent manner. The attenuation was observed for transgene expression driven by different promoters and resulted neither from internalization or nuclear import of baculovirus. Moreover, the attenuation was alleviated if supertransduction was performed when IFN-α/β responses diminished. Baculovirus transduction also triggered the expression of tumor necrosis factor-α and interleukin (IL)-6, but not IL-1β. Despite the induction of these responses, supertransduction of chondrocytes with a baculovirus expressing bone morphogenetic protein-2 successfully enhanced the chondrogenic differentiation and matrix synthesis. Conclusions Baculovirus transduction of primary chondrocytes elicits antiviral effects that suppress transgene expression. Nonetheless, baculovirus supertransduction comprises a feasible approach to extend transgene expression for cartilage engineering. Copyright © 2009 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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