SELECTIVE INHIBITION OF COLLAGEN GENE EXPRESSION IN FIBROBLASTS BY AN INTERFERON-gamma TRANSGENE

Because interferon-gamma (IFN-gamma) selectively inhibits collagen gene expression, we hypothesized that expression of IFN-gamma cDNA in fibroblasts might be a useful strategy to inhibit the development of fibrosis. A replication-deficient E1, E3 adenovirus vector encoding murine IFN-gamma (AdCMVmIF...

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Bibliographic Details
Published in:Experimental lung research 1999, Vol.25 (3), p.199-215
Main Authors: Jaffe, H A, Gao, Z, Mori, Y, Li, L, Varga, J
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenovirus
Collagen
Fibroblast
Fibrosis
Interferon-gamma
Transgene
Animals
Biological and medical sciences
Biotechnology
Blotting, Northern
Cells, Cultured
Collagen - genetics
Collagen - metabolism
Defective Viruses
Fibroblasts - metabolism
Fibroblasts - virology
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene therapy
Gene Transfer Techniques
Genetic Vectors
Health. Pharmaceutical industry
Industrial applications and implications. Economical aspects
Interferon-gamma - genetics
Interferon-gamma - physiology
L-Lactate Dehydrogenase - metabolism
Medical sciences
Mice
Plasmids - genetics
Pneumology
Recombinant Fusion Proteins - genetics
Respiratory system : syndromes and miscellaneous diseases
RNA, Messenger - metabolism
Suppression, Genetic
Transgenes - physiology
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Summary:Because interferon-gamma (IFN-gamma) selectively inhibits collagen gene expression, we hypothesized that expression of IFN-gamma cDNA in fibroblasts might be a useful strategy to inhibit the development of fibrosis. A replication-deficient E1, E3 adenovirus vector encoding murine IFN-gamma (AdCMVmIFNgamma) was constructed. Infection of murine fibroblasts with AdCMVmIFNgamma in vitro was well tolerated. The results showed that INF-gamma mRNA was expressed in infected cells, and as much as 17.7 ng of mIFN-gamma/106 cells was secreted into culture supernatants. Steady-state levels of alpha1 (I) procollagen mRNA were decreased by 90% in infected cells compared to uninfected cells. The inhibition of collagen mRNA expression was partially abrogated with a neutralizing anti-mIFN-gamma antibody. Secretion of total collagen by AdCMVmIFNgamma-infected fibroblasts was decreased by 60% compared to uninfected cells. Induction cells. Induction of cytokine responsive gene-2 expression in AdCMVmIFNgamma infected cells demonstrated that suppression of collagen production was a selective response. The results suggest a novel strategy of cytokine gene transfer and expression for the treatment of fibrotic lung diseases.
ISSN:0190-2148
1521-0499
DOI:10.1080/019021499270268