Targeted disruption of LIG-1 gene results in psoriasiform epidermal hyperplasia |
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Authors: | Suzuki Yutaka Miura Hiroyuki Tanemura Atsushi Kobayashi Kinji Kondoh Gen Sano Shigetoshi Ozawa Kentaro Inui Shigeki Nakata Aya Takagi Tsutomu Tohyama Masaya Yoshikawa Kunihiko Itami Satoshi |
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Institution: | UMR Physiologie et Physiopathologie, Université Pierre et Marie Curie, 7 quai Saint Bernard, 75252, Cedex 05, Paris, France. |
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Abstract: | 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. |
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