Bilirubin effect on endothelial adhesion molecules expression is mediated by the NF-kappaB signaling pathway
| Autor: | Graciela Luján, Mazzone, Igino, Rigato, J Donald, Ostrow, Claudio, Tiribelli |
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| Přispěvatelé: | Mazzone, G. L., Rigato, I., Ostrow, Jd, Tiribelli, Claudio |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
drug effects
Analysis of Variance Animals Atherosclerosi Proline prevention /&/ control Bilirubin Active Transport Cell Nucleus drug effects Analysis of Variance Animals Atherosclerosis metabolism/pharmacology Blotting Western CREB-Binding Protein metabolism Cell Adhesion Molecules metabolism Cell Line Mice NF-kappa B antagonists /&/ inhibitors/metabolism Phosphorylation Proline analogs /&/ derivatives/pharmacology Reverse Transcriptase Polymerase Chain Reaction Signal Transduction drug effects Thiocarbamates pharmacology Tumor Necrosis Factor-alpha pharmacology Blotting Western Active Transport Cell Nucleus metabolism Cell Adhesion Molecule Cell Line antagonists /&/ inhibitors/metabolism Mice Thiocarbamates Animals Phosphorylation Cell Nucleu Analysis of Variance drug effects Thiocarbamate Blotting Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha NF-kappa B Bilirubin Atherosclerosis metabolism/pharmacology CREB-Binding Protein drug effects prevention /&/ control analogs /&/ derivatives/pharmacology Western metabolism Cell Adhesion Molecules Signal Transduction |
| Popis: | We have recently demonstrated that unconjugated bilirubin (UCB) limits the overexpression of adhesion molecules and inhibits the PMN endothelial adhesion induced by the pro-inflammatory cytokine TNFalpha. To understand the molecular events involved we investigated whether the inhibitory effect is determined by a direct influence of UCB on different nuclear pathways. Co-treatment of cells with UCB, TNFalpha, and pyrridoline dithiocarbamate (PDTC), a NF-kappaB inhibitor, additively enhanced the inhibitory effect of UCB. UCB prevented the nuclear translocation of NF-kappaB induced by TNFalpha. The failure of UCB to alter TNFalpha-induced phosphorylation of cAMP-response element-binding protein (CREB) suggested that the CREB pathway is not involved in the UCB inhibition and that UCB blunting effect on the overexpression of adhesion molecules occurs via inhibition of the NF-kappaB transduction pathway. Collectively these data may contribute to explain the protective effect of bilirubin against development of atherosclerosis. |
| Databáze: | OpenAIRE |
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