Inflammation-induced recombinant protein expression in vivo using promoters from acute-phase protein genes

Varley, A. W., Coulthard, M. G., Meidell, R. S., Gerard, R. D. and Munford, R. S. (1995) Inflammation-induced recombinant protein expression in vivo using promoters from acute-phase protein genes. Proceedings of the National Academy of Sciences of the United States of America, 92 12: 5346-5350. doi:10.1073/pnas.92.12.5346


Author Varley, A. W.
Coulthard, M. G.
Meidell, R. S.
Gerard, R. D.
Munford, R. S.
Title Inflammation-induced recombinant protein expression in vivo using promoters from acute-phase protein genes
Formatted title
Inflammation-induced recombinant protein expression in vivo using promoters from acute-phase protein genes
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 1995-06-06
Sub-type Article (original research)
DOI 10.1073/pnas.92.12.5346
Open Access Status Not Open Access
Volume 92
Issue 12
Start page 5346
End page 5350
Total pages 5
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted abstract
We report that promoters for two murine acute-phase protein (APP) genes, complement factor 3 (C3) and serum amyloid A3 (SAA3), can increase recombinant protein expression in response to inflammatory stimuli in vivo. To deliver APP promoter-luciferase reporter gene constructs to the liver, where most endogenous APP synthesis occurs, we introduced them into a nonreplicating adenovirus vector and injected the purified viruses intravenously into mice. When compared with the low levels of basal luciferase expression observed prior to inflammatory challenge, markedly increased expression from the C3 promoter was detected in liver in response to both lipopolysaccharide (LPS) and turpentine, and lower-level inducible expression was also found in lung. In contrast, expression from the SAA3 promoter was found only in liver and was much more responsive to LPS than to turpentine. After LPS challenge, hepatic luciferase expression increased rapidly and in proportion to the LPS dose. Use of cytokine-inducible promoters in gene transfer vectors may make it possible to produce antiinflammatory proteins in vivo in direct relationship to the intensity and duration of an individual's inflammatory response. By providing endogenously controlled production of recombinant antiinflammatory proteins, this approach might limit the severity of the inflammatory response without interfering with the beneficial components of host defense and immunity.
Keyword Adenovirus vector
Gene therapy
Lipopolysaccharide
Sepsis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Thu, 02 Jun 2011, 10:07:33 EST by Melanie Thomas on behalf of Paediatrics & Child Health - RBWH