2002
DOI: 10.1172/jci0214536
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Abstract: The treatment of chronic inflammatory diseases is complicated by their unpredictable, relapsing clinical course. Here, we describe a new strategy in which an inflammation-regulated therapeutic transgene is introduced into the joints to prevent recurrence of arthritis. To this end, we designed a recombinant adenoviral vector containing a two-component, inflammation-inducible promoter controlling the expression of human IL-10 (hIL-10) cDNA. When tested in vitro, this system had a low-level basal activity and was… Show more

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Cited by 39 publications
(18 citation statements)
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“…A recombinant adenovirus vector expressing human IL‐10 under the control of this two‐component, inflammation‐inducible promoter revealed a low level basal activity in transduced primary synovial fibroblasts in vitro. However, the expression was activated by up to five orders of magnitude by various inflammatory stimuli, including TNFα, IL‐1β, IL‐6 and LPS . In vivo , when applied into joints of rats suffering from LPS‐induced arthritis, IL‐10 expression was induced with disease recurrence and thereby effectively prevented the influx of inflammatory cells and the associated swelling of the joints .…”
Section: Discussionmentioning
confidence: 99%
“…A recombinant adenovirus vector expressing human IL‐10 under the control of this two‐component, inflammation‐inducible promoter revealed a low level basal activity in transduced primary synovial fibroblasts in vitro. However, the expression was activated by up to five orders of magnitude by various inflammatory stimuli, including TNFα, IL‐1β, IL‐6 and LPS . In vivo , when applied into joints of rats suffering from LPS‐induced arthritis, IL‐10 expression was induced with disease recurrence and thereby effectively prevented the influx of inflammatory cells and the associated swelling of the joints .…”
Section: Discussionmentioning
confidence: 99%
“…Certain inducible promoters have also shown value, and these may prove useful in the future to permit regulated transgene expression, something that could improve both the safety and efficacy of gene therapy. 10 …”
Section: Arthritis Gene Therapy: the Basicsmentioning
confidence: 99%
“…This then transactivates the HIV long terminal repeat, which is used to drive expression of the therapeutic gene of interest. This has shown utility in animal models of rheumatoid arthritis (RA), with transgene expression increased 4–5 orders of magnitude in response to inflammatory stimuli (25, 26). An IL‐1/IL‐6 hybrid promoter has also shown promise in preliminary experiments (27).…”
Section: Strategiesmentioning
confidence: 99%