共查询到20条相似文献,搜索用时 15 毫秒
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Proteinase inhibitor 9 (PI-9) inhibits caspase-1 (interleukin (IL)-1beta-converting enzyme) and granzyme B, thereby regulating production of the pro-inflammatory cytokine IL-1beta and susceptibility to granzyme B-induced apoptosis. We show that cellular PI-9 mRNA and protein are induced by IL-1beta, lipopolysaccharide, and 12-O-tetradecanoylphorbol-13-acetate. We identified functional imperfect nuclear factor-kappaB (NF-kappaB) sites at -135 and -88 and a consensus activator protein-1 (AP-1) site at -308 in the PI-9 promoter region. Using transient transfections in HepG2 cells to assay PI-9 promoter mutations, we find that mutational ablation of the AP-1 site or of either NF-kappaB site reduces IL-1beta-induced expression of PI-9 by approximately 60%. Mutational ablation of the two NF-kappaB sites and of the AP-1 site nearly abolishes both basal and IL-1beta-induced expression of PI-9. Nuclear extracts from IL-1beta-treated HepG2 cells exhibited strong, IL-1beta-inducible binding to the NF-kappaB sites and to the AP-1 site. Electrophoretic mobility shift assays show that after IL-1beta treatment c-Jun/c-Fos and JunD bind to the AP-1 site, whereas the p50/p65 heterodimer binds to the two NF-kappaB sites. Estrogens induce PI-9, but induction of PI-9 by estrogens and IL-1beta is not synergistic. In transiently transfected, estrogen receptor-positive HepG2ER7 cells, estrogens do not interfere with IL-1beta induction, whereas IL-1beta exhibits dose-dependent repression of estrogen-inducible PI-9 expression. Our surprising finding that the pro-inflammatory cytokine IL-1beta strongly induces PI-9 suggests a novel mechanism for regulating inflammation and apoptosis through a negative feedback loop controlling expression of the anti-inflammatory and anti-apoptotic protein, PI-9. 相似文献
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Chandrasekar B Mummidi S Valente AJ Patel DN Bailey SR Freeman GL Hatano M Tokuhisa T Jensen LE 《The Journal of biological chemistry》2005,280(28):26263-26277
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Analysis of the AP-1 sites in the IL-2 promoter. 总被引:18,自引:0,他引:18
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Ma W Gee K Lim W Chambers K Angel JB Kozlowski M Kumar A 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(1):318-330
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Chandrasekar B Mummidi S Mahimainathan L Patel DN Bailey SR Imam SZ Greene WC Valente AJ 《The Journal of biological chemistry》2006,281(22):15099-15109
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