Design of a chimeric promoter induced by pro-inflammatory mediators in articular chondrocytes.
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-1beta (IL-1beta), 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-1beta, and 15-deoxy Delta12,14 prostaglandin J2. The latter two compounds stimulated the promoter synergistically.
Meynier de Salinelles
Véronique
V
UMR Physiologie et Physiopathologie, Université Pierre et Marie Curie, 7 quai Saint Bernard, 75252, Cedex 05, Paris, France.
Berenbaum
Francis
F
Jacques
Claire
C
Salvat
Colette
C
Olivier
Jean-Luc
JL
Béréziat
Gilbert
G
Raymondjean
Michel
M
Massaad
Charbel
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002358:Cartilage, Articular / Q000166:cytology*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D004274:DNA, Recombinant / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015777:Eicosanoids / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D054501:Group II Phospholipases A2; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D010741:Phospholipases A / Q000235:genetics; D054467:Phospholipases A2; D011401:Promoter Regions, Genetic; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004274:DNA, Recombinant; D015777:Eicosanoids; D005938:Glucocorticoids; D018836:Inflammation Mediators; D007375:Interleukin-1; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003907:Dexamethasone; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2