15-Deoxy-Δ 12,14 -prostaglandin J 2 inhibits multiple steps in the NF-κB signaling pathway
| Autor: | Chin Hui Hsiang, Daniel S. Straus, Gourisankar Ghosh, Lei Lei Sengchanthalangsy, Christopher K. Glass, Mercedes Ricote, Mei Li, Gabriel Pascual, John S. Welch |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Recombinant Fusion Proteins
Nitric Oxide Synthase Type II Receptors Cytoplasmic and Nuclear Cyclopentanes IκB kinase Transfection Cell Line chemistry.chemical_compound Transactivation Animals Humans Prostaglandin a Transcription factor Cyclopentenone prostaglandins Glutathione Transferase Prostaglandins A Multidisciplinary biology Prostaglandin D2 NF-kappa B Membrane Proteins Biological Sciences Molecular biology Cell biology Isoenzymes chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Tetradecanoylphorbol Acetate lipids (amino acids peptides and proteins) Cyclooxygenase Nitric Oxide Synthase Signal transduction HeLa Cells Signal Transduction Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 97:4844-4849 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.97.9.4844 |
| Popis: | Prostaglandin J 2 (PGJ 2 ) and its metabolites Δ 12 -PGJ 2 and 15-deoxy-Δ 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 γ (PPARγ) and has been demonstrated to inhibit the induction of inflammatory response genes, including inducible NO synthase and tumor necrosis factor α, in a PPARγ-dependent manner. We report here that 15d-PGJ 2 potently inhibits NF-κB-dependent transcription by two additional PPARγ-independent mechanisms. Several lines of evidence suggest that 15d-PGJ 2 directly inhibits NF-κB-dependent gene expression through covalent modifications of critical cysteine residues in IκB kinase and the DNA-binding domains of NF-κB subunits. These mechanisms act in combination to inhibit transactivation of the NF-κB target gene cyclooxygenase 2. Direct inhibition of NF-κB signaling by 15d-PGJ 2 may contribute to negative regulation of prostaglandin biosynthesis and inflammation, suggesting additional approaches to the development of antiinflammatory drugs. |
| Databáze: | OpenAIRE |
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