The effect of promoter strength in adenoviral vectors in hyperplastic synovium

To compare the activity of the CytoMegaloVirus promoter (CMV) and the Major Late promoter (MLP) in synoviocytes in vitro and in vivo. To determine the phenotype of infected cells and the induction of inflammation. To investigate the effects of the cytomegalovirus (CMV) or major late (MLP) promoter o...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and experimental rheumatology 2000-09, Vol.18 (5), p.547-552
Main Authors: GOOSSENS, P. H, SCHOUTEN, G. J, HEEMSKERK, B, T HART, B. A, BOUT, A, KLUIN, P. M, BREEDVELD, F. C, VALERIO, D, HUIZINGA, T. W. J
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Animals
Antigens, CD - metabolism
Antigens, Differentiation, Myelomonocytic - metabolism
Arthritis - chemically induced
Arthritis - genetics
Arthritis - pathology
Biological and medical sciences
Cells, Cultured
Collagen
Cytomegalovirus - genetics
Diseases of the osteoarticular system
Female
Gene Expression
Genes, Reporter
Genetic Vectors
Hyperplasia
Immunohistochemistry
Inflammatory joint diseases
Lac Operon - genetics
Macaca mulatta
Male
Medical sciences
Promoter Regions, Genetic - physiology
Reference Values
Synovial Membrane - pathology
Synovial Membrane - physiopathology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:To compare the activity of the CytoMegaloVirus promoter (CMV) and the Major Late promoter (MLP) in synoviocytes in vitro and in vivo. To determine the phenotype of infected cells and the induction of inflammation. To investigate the effects of the cytomegalovirus (CMV) or major late (MLP) promoter on adenovirus-mediated reporter gene transduction of synoviocytes in vitro and in vivo. After infection with adenoviral vectors harboring CMV- and MLP-driven luciferase and lacZ genes, gene expression was examined in cultured synoviocytes and in the synovium of rhesus monkeys with collagen-induced arthritis. Immunohistochemical staining for the macrophage-marker CD68 and lacZ expression was performed. Inflammation was scored in the synovial membrane of injected and non-injected joints. CMV-driven reporter gene expression was found to be 6 to 10 times higher than MLP-driven gene expression in both cultured synoviocytes and monkey synovium. Both CD68 positive and CD68 negative cells were lacZ positive. Inflammation in joints injected with CMV-driven adenoviral vectors was not higher than that in MLP-driven adenoviral vectors- or non-injected joints. These experiments show that the CMV promoter induces higher gene expression in synoviocytes than the MLP promoter. Both fibroblast-like and macrophage-like synoviocytes can be infected with adenoviral vectors. No deleterious effects of the CMV-promoter driven adenoviral vectors were observed.
ISSN:0392-856X
1593-098X