2002
DOI: 10.1172/jci14536
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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 16 publications
(12 citation statements)
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References 32 publications
(28 reference statements)
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“…This however, has not been investigated so far; similar studies focused rather on effective transgene expression under arthritic conditions. 12,[28][29][30] In this study, we demonstrate for the first time that disease-regulated mIL-4 expression by the IL-1E/IL-6P promoter provides not only therapeutically efficacious protein levels under arthritic conditions, but also sufficiently low activity under naive conditions. Minimizing the undesired effects of biologicals, in this case the potent proinflammatory and chemotactic properties of IL-4, requires promoters with low basal activity under naive conditions.…”
Section: Discussionmentioning
confidence: 66%
“…This however, has not been investigated so far; similar studies focused rather on effective transgene expression under arthritic conditions. 12,[28][29][30] In this study, we demonstrate for the first time that disease-regulated mIL-4 expression by the IL-1E/IL-6P promoter provides not only therapeutically efficacious protein levels under arthritic conditions, but also sufficiently low activity under naive conditions. Minimizing the undesired effects of biologicals, in this case the potent proinflammatory and chemotactic properties of IL-4, requires promoters with low basal activity under naive conditions.…”
Section: Discussionmentioning
confidence: 66%
“…17,18 We compared the expression characteristics of this two-component system with the IL-1/IL-6 hybrid promoter construct. The C3-Tat/Hiv twocomponent system in RAW cells showed the same high background activity and LPS induction comparable to the conventional CMV promoter ( Figure 7).…”
Section: Resultsmentioning
confidence: 99%
“…It must be emphasized that the basal transgene levels and the fold induction using the C3-Tat/HIV two-component system were far better in adenoviral-transfected HepG2 cells and in primary rat synovial fibroblasts. 16,18 A major difference was the 24-h serum (0.5% FBS) starvation used in these studies whereas we performed our experiments A disease-inducible promoter responsive in arthritis FAJ van de Loo et al in 5% FCS. Different batches of fetal calf serum may contain varying amounts of growth factors, cytokines (IL-6) or traces of endotoxin, and the C3-Tat/HIV twocomponent promoter system is extremely responsive to stimulation.…”
Section: Discussionmentioning
confidence: 99%
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“…In both studies, a single adenoviral vector was designed which encoded either hIL-1Ra 174 or hIL-10. 175 In mouse CIA Ad (10 7 PFU) harbouring the construct C3-Tat/HIV-hIL-1Ra were injected i.a. followed by disease induction 3 days later.…”
Section: Targeting Immune Cellsmentioning
confidence: 99%