Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Regulation of adenovirus-mediated elafin transgene expression by bacteriallipopolysaccharide
Autore:
Simpson, AJ; Cunningham, GA; Porteous, DJ; Haslett, C; Sallenave, JM;
Indirizzi:
Univ Edinburgh, Sch Med, Rayne Lab,MRC,Ctr Inflammat Res, Resp Med Unit, Edinburgh EH8 9AG, Midlothian, Scotland Univ Edinburgh Edinburgh MidlothianScotland EH8 9AG Midlothian, Scotland Univ Edinburgh, Western Gen Hosp, Med Genet Sect, Mol Med Ctr, Edinburgh EH9 2XU, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH9 2XU Midlothian, Scotland
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 11, volume: 12, anno: 2001,
pagine: 1395 - 1406
SICI:
1043-0342(200107)12:11<1395:ROAETE>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELASTASE-SPECIFIC INHIBITOR; LEUKOCYTE PROTEINASE-INHIBITOR; MONOCYTE-DERIVED MACROPHAGES; ALVEOLAR EPITHELIAL-CELLS; GENE-THERAPY; IN-VIVO; ANTIBACTERIAL ACTIVITY; NEUTROPHIL DEFENSINS; PROTEASE INHIBITORS; RESPIRATORY-TRACT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Sallenave, JM Univ Edinburgh, Sch Med, Rayne Lab,MRC,Ctr Inflammat Res, Resp Med Unit, Edinburgh EH8 9AG, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH8 9AG otland
Citazione:
A.J. Simpson et al., "Regulation of adenovirus-mediated elafin transgene expression by bacteriallipopolysaccharide", HUM GENE TH, 12(11), 2001, pp. 1395-1406

Abstract

Lipopolysaccharide (LPS) is a mediator of inflammatory lung injury. Selective augmentation of host defense molecules such as elafin (an elastase inhibitor with antimicrobial activity) at the onset of pulmonary inflammation is an attractive potential therapeutic strategy. The aim of this study was to determine whether elafin expression could be induced by LPS administered after transfection with adenovirus (Ad) encoding human elafin downstream ofthe murine cytomegalovirus (CMV) promoter (known to be potentially responsive to LPS). In addition, we aimed to determine the effect of local elafin augmentation on neutrophil migration to the lung. LPS significantly up-regulated elafin expression from pulmonary epithelial cells transfected with Ad-elafin in vitro. In murine airways expression of human elafin was achievedusing doses low enough (3 x 10(7) plaque forming units) to circumvent overt vector-induced inflammation. LPS significantly up-regulated human elafin secretion in murine airways treated with Ad-elafin [117 ng/ml in bronchoalveolar lavage fluid (BALF) after LPS administration, 5.9 ng/ml after PBS, p < 0.01)]. Over-expression of elafin significantly augmented LPS-mediated neutrophil migration into the airways in vivo (1.30 x 10(6) neutrophils in BALF after Ad-elafin/LPS treatment, 0.54 x 10(6) after Ad-lacZ/LPS (p < 0.05), 0.63 x 10(6) after PBS/LPS (p < 0.05)) and significantly enhanced human neutrophil migration in vitro. These data suggest novel functions for elafinin neutrophil migration, and that judicious selection of promoters may allow single, low-dose adenoviral administration to effect inflammation-specific expression of potentially therapeutic transgenes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 13:26:46