Kuldo, J. M. and Asgeirsdottir, S. A. and Zwiers, P. J. and Bellu, A. R. and Rots, M. G. and Schalk, J. A. C. and Ogawara, K. I. and Trautwein, C. and Banas, B. and Haisma, H. J. and Molema, G. and Kamps, J. A. A. M. (2013) Targeted adenovirus mediated inhibition of NF-kappa B-dependent inflammatory gene expression in endothelial cells in vitro and in vivo. JOURNAL OF CONTROLLED RELEASE, 166 (1). pp. 57-65. ISSN 0168-3659, 1873-4995
Full text not available from this repository. (Request a copy)Abstract
In chronic inflammatory diseases the endothelium expresses mediators responsible for harmful leukocyte infiltration. We investigated whether targeted delivery of a therapeutic transgene that inhibits nuclear factor kappa B signal transduction could silence the proinflammatory activation status of endothelial cells. For this, an adenovirus encoding dominant-negative I kappa B (dnI kappa B) as a therapeutic transgene was employed. Selectivity for the endothelial cells was achieved by introduction of antibodies specific for inflammatory endothelial adhesion molecules E-selectin or VCAM-1 chemically linked to the virus via polyethylene glycol. In vitro, the retargeted adenoviruses selectively infected cytokine-activated endothelial cells to express functional transgene. The comparison of transductional capacity of both retargeted viruses revealed that E-selectin based transgene delivery exerted superior pharmacological effects. Targeted delivery mediated dnI kappa B transgene expression in endothelial cells inhibited the induced expression of several inflammatory genes, including adhesion molecules, cytokines, and chemokines. In vivo, in mice suffering from glomerulonephritis, E-selectin-retargeted adenovirus selectively homed in the kidney to microvascular glomerular endothelium. Subsequent downregulation of endothelial adhesion molecule expression 2 days after induction of inflammation demonstrated the pharmacological potential of this gene therapy approach. The data justify further studies towards therapeutic virus design and optimization of treatment schedules to investigate their capacity to interfere with inflammatory disease progression. (C) 2012 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTI-GBM GLOMERULONEPHRITIS; LUPUS NEPHRITIS; DRUG-DELIVERY; DEXAMETHASONE; ACTIVATION; IMMUNOLIPOSOMES; NEPHROPATHY; APOPTOSIS; VECTORS; P38; Inflammation; Endothelium; NF-kappa B inhibition; Adenoviral gene therapy; E-selectin targeting |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 07:42 |
| Last Modified: | 24 Apr 2020 07:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17122 |
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