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Design of a chimeric promoter induced by pro‐inflammatory mediators in articular chondrocytes
Author(s) -
Meynier de Salinelles Véronique,
Berenbaum Francis,
Jacques Claire,
Salvat Colette,
Olivier Jean-Luc,
Béréziat Gilbert,
Raymondjean Michel,
Massaad Charbel
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02645-5
Subject(s) - transfection , response element , phospholipase a2 , chemistry , promoter , inflammation , microbiology and biotechnology , receptor , cytokine , chimeric gene , peroxisome proliferator activated receptor , recombinant dna , gene , biology , gene expression , immunology , enzyme , biochemistry
We have designed a chimeric promoter that can be stimulated by various pro‐inflammatory mediators and so drive the expression of therapeutic genes under inflammatory conditions. The promoter has two parts, the [−247/+20] fragment of the human type IIA secreted phospholipase A2 gene promoter, which is stimulated by the pro‐inflammatory cytokine interleukin‐1β (IL‐1β), and a double peroxisome proliferator‐activated receptor response element that is activated by some eicosanoids and by non‐steroidal anti‐inflammatory drugs (NSAIDs). Transfection experiments using rabbit articular chondrocytes in primary culture showed that this chimeric promoter produced a low basal activity and was induced by NSAIDs, WY‐14643, IL‐1β, and 15‐deoxy Δ 12,14 prostaglandin J2. The latter two compounds stimulated the promoter synergistically.

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