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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hsiang, C. H. Glass, C. K. Sengchanthalangsy, L. L. Pascual, G. Ghosh, G. Straus, D. S. Welch, J. S. Ricote, M. Li, M. |
| Description | Author Affiliation: Straus DS ( Biomedical Sciences Division, University of California, Riverside, CA 92521, USA.); |
| Abstract | Prostaglandin J(2) (PGJ(2)) and its metabolites Delta(12)-PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) are naturally occurring derivatives of prostaglandin D(2) that have been suggested to exert antiinflammatory effects in vivo. 15d-PGJ(2) is a high-affinity ligand for the peroxisome proliferator-activated receptor gamma (PPARgamma) and has been demonstrated to inhibit the induction of inflammatory response genes, including inducible NO synthase and tumor necrosis factor alpha, in a PPARgamma-dependent manner. We report here that 15d-PGJ(2) potently inhibits NF-kappaB-dependent transcription by two additional PPARgamma-independent mechanisms. Several lines of evidence suggest that 15d-PGJ(2) directly inhibits NF-kappaB-dependent gene expression through covalent modifications of critical cysteine residues in IkappaB kinase and the DNA-binding domains of NF-kappaB subunits. These mechanisms act in combination to inhibit transactivation of the NF-kappaB target gene cyclooxygenase 2. Direct inhibition of NF-kappaB signaling by 15d-PGJ(2) may contribute to negative regulation of prostaglandin biosynthesis and inflammation, suggesting additional approaches to the development of antiinflammatory drugs. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 9 |
| Volume Number | 97 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2000-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Isoenzymes Genetics NF-kappa B Metabolism Nitric Oxide Synthase Prostaglandin D2 Analogs & Derivatives Prostaglandin-Endoperoxide Synthases Receptors, Cytoplasmic And Nuclear Physiology Signal Transduction Drug Effects Transcription Factors Animals Cell Line Cyclooxygenase 2 Cyclopentanes Pharmacology Glutathione Transferase HeLa Cells Membrane Proteins Nitric Oxide Synthase Type II Prostaglandins A Recombinant Fusion Proteins Tetradecanoylphorbol Acetate Transfection Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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