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Titolo:
Adenovirus-mediated expression of interleukin-1 receptor antagonist in swine cells in vitro and in vivo
Autore:
Morrison, DF; Murtaugh, MP;
Indirizzi:
Univ Minnesota, Dept Vet Pathobiol, St Paul, MN 55108 USA Univ Minnesota St Paul MN USA 55108 Vet Pathobiol, St Paul, MN 55108 USA
Titolo Testata:
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
fascicolo: 1, volume: 78, anno: 2001,
pagine: 71 - 81
SICI:
0165-2427(20010110)78:1<71:AEOIRA>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE-TRANSFER; INFLAMMATORY RESPONSE; RECOMBINANT ADENOVIRUS; ALVEOLAR MACROPHAGES; NONHUMAN-PRIMATES; CFTR GENE; IL-1; VECTOR; LUNG; PLEUROPNEUMONIA;
Keywords:
adenovirus; gene delivery; pig; cytokine; interleukin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Murtaugh, MP Univ Minnesota, Dept Vet Pathobiol, 1971 Commonwealth Ave, StPaul, MN 55108 USA Univ Minnesota 1971 Commonwealth Ave St Paul MN USA 55108 USA
Citazione:
D.F. Morrison e M.P. Murtaugh, "Adenovirus-mediated expression of interleukin-1 receptor antagonist in swine cells in vitro and in vivo", VET IMMUNOL, 78(1), 2001, pp. 71-81

Abstract

Adenovirus-mediated gene delivery of anticytokines is a powerful tool for modulating the cytokine environment under conditions of respiratory disease. In order to determine the feasibility of cytokine modulation in the context of respiratory disease in swine, nonreplicating E1- and E3-deficient adenovirus constructs expressing a model protein, beta -galactosidase, and an anticytokine, the IL-1 receptor antagonist (IL-1Ra), were evaluated for in vitro expression in porcine PK15 cells, and in vivo following endotracheal instillation into the lungs. beta -Galactosidase and IL-1Ra were readily expressed in vitro in swine cells. Endotracheal administration of lacZ-containing adenovirus demonstrated that endothelial and epithelial cells in the alveolar spaces and bronchi of the middle and lower lobes were the principalsites of infection and expression, whereas beta -galactosidase staining was not observed in the upper lobe. Endotracheal administration of IL-1Ra recombinant adenovirus resulted in sustained expression of IL-1Ra into the alveolar spaces, where it was recovered in a concentration of 660 pg/ml in 500ml of lavage fluid, equivalent to 330 ng IL-1Ra, in the lungs 7 days aftertreatment. Moreover, in vivo instillation of nonreplicating adenovirus didnot induce an inflammatory response in the 1-week time frame of the study period. Lung weight as a percent of body weight, serum zinc, serum amyloid A, leukocyte differentials, neutrophil activity, and TNF levels all were the same between untreated pigs and pigs treated with either recombinant adenovirus. The results indicate that the delivery of IL-1Ra to swine lungs vianonreplicating, recombinant adenovirus may be an effective method for in vivo modulation of IL-1 activity and investigation of cytokine involvement in respiratory disease pathogenesis. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 08:17:49