| Autor: |
Przybyszewska M; Cell Biology Department, Maria Skłodowska-Curie Memorial Institute of Oncology and Cancer Centre, Warsaw, Poland. magip@coi.waw.pl, Miłoszewska J, Rzońca S, Trembacz H, Pyśniak K, Kotlarz A, Swoboda P, Zalewska M, Małecki M |
| Jazyk: |
angličtina |
| Zdroj: |
Archivum immunologiae et therapiae experimentalis [Arch Immunol Ther Exp (Warsz)] 2011 Aug; Vol. 59 (4), pp. 315-26. Date of Electronic Publication: 2011 Jun 03. |
| DOI: |
10.1007/s00005-011-0133-2 |
| Abstrakt: |
Post-radiation inflammatory reaction leads to an irreversible pulmonary fibrosis which may cause lethal respiratory insufficiency. Pathological inflammatory and fibrotic changes might be attenuated by inhibiting tumour necrosis factor (TNF)-α activity using TNF-α soluble receptors. Thus, an experimental antifibrotic gene therapy with the plasmid vector encoding a mouse soluble receptor I for TNF-α (psTNFR-I) was assessed. Soluble TNFR-I encoding gene was cloned into pcDNA3.1 plasmid. The ability of psTNFR-I expressing vector to transfect cells, and its biological activity in vitro and in vivo were examined by PCR, RT-PCR, MTT assay and ELISA. The C57Bl/6J mice received single intramuscular injection of psTNFR-I, conjugated with polyetylenimine (PEI) 25 kDa, equally divided to both hind legs, 3 days before irradiation (20 Gy, Co60), and either a single injection or ten injections once a week after irradiation. The data proved the effectiveness of psTNFR-I product to neutralise TNF-α activity in vitro. The in vivo plasmid incorporation and maintenance was confirmed. Measurements of plasma soluble TNFR-I levels showed that the in vivo gene transfer was effective. PEI was found to enhance transfection efficiency in vivo. The psTNFR-I/PEI complexes caused no toxicity in the transfected mice. C57Bl/6J mice that received prolonged psTNFR-I/PEI injections developed lethal fibrotic syndrome and died 8 weeks later than the mice treated with a double plasmid injection and the control mice treated with a control plasmid. Sequential administration of soluble TNFR-I by a nonviral, intramuscular gene transduction in the early and late post-radiation inflammatory phase prolonged survival of irradiated mice and attenuated the symptoms of lung fibrosis. The psTNFR-I gene transduction may provide a safe and simple method to partially neutralise TNF-α activity and prevent radiation-induced lung injury. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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