The Journal of pharmacology and experimental therapeutics, 2003-05, Vol.305 (2), p.573-580
2003
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Details
- Autor(en) / Beteiligte
- Titel
- Rac1 and superoxide are required for the expression of cell adhesion molecules induced by tumor necrosis factor-alpha in endothelial cells
- Ist Teil von
- The Journal of pharmacology and experimental therapeutics, 2003-05, Vol.305 (2), p.573-580
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2003
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Oxidative signals play an important role in the regulation of endothelial cell adhesion molecule expression. Small GTP-binding protein Rac1 is activated by various proinflammatory substances and regulates superoxide generation in endothelial cells. In the present study, we demonstrate that adenoviral-mediated expression of dominant negative N17Rac1 (Ad.N17Rac1) suppresses tumor necrosis factor-alpha (TNF-alpha)-induced vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin gene expression in a dose-dependent manner. Ad.N17Rac1 did not inhibit TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) binding activity or inhibitor of NF-kappaB-alpha degradation. In contrast, Ad.N17Rac1 inhibited TNF-alpha-induced NF-kappaB-driven HIV(kappaB)(4)-CAT and p288VCAM-Luc promoter activity, suggesting that N17Rac1 inhibits TNF-alpha-induced VCAM-1, E-selectin, and ICAM-1 through suppressing NF-kappaB-mediated transactivation. In addition, expression of superoxide dismutase by adenovirus suppressed TNF-alpha-induced VCAM-1, E-selectin, and ICAM-1 mRNA accumulation. However, adenoviral-mediated expression of catalase only partially inhibited TNF-alpha-induced E-selectin gene expression and had no effect on VCAM-1 and ICAM-1 gene expression. These data suggest that Rac1 and superoxide play crucial roles in the regulation of expression of cell adhesion molecules in endothelial cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-3565eISSN: 1521-0103DOI: 10.1124/jpet.102.047894Titel-ID: cdi_pubmed_primary_12606638
- Format
- –
- Schlagworte
- Adenoviridae - genetics, Blotting, Northern, Catalase - biosynthesis, Cell Adhesion Molecules - biosynthesis, Cell Adhesion Molecules - genetics, Cell Nucleus - metabolism, Cells, Cultured, Cytokines - biosynthesis, E-Selectin - biosynthesis, E-Selectin - genetics, Electrophoretic Mobility Shift Assay, Endothelium, Vascular - cytology, Endothelium, Vascular - drug effects, Endothelium, Vascular - metabolism, Enzyme-Linked Immunosorbent Assay, Genes, Reporter - genetics, Humans, Hydrogen Peroxide - metabolism, Intercellular Adhesion Molecule-1 - biosynthesis, Intercellular Adhesion Molecule-1 - genetics, NF-kappa B - metabolism, Plasmids - genetics, rac1 GTP-Binding Protein - genetics, rac1 GTP-Binding Protein - metabolism, Reactive Oxygen Species - metabolism, RNA, Messenger - biosynthesis, Signal Transduction - drug effects, Stimulation, Chemical, Superoxide Dismutase - biosynthesis, Superoxides - metabolism, Transfection, Tumor Necrosis Factor-alpha - pharmacology, Up-Regulation - drug effects, Vascular Cell Adhesion Molecule-1 - biosynthesis, Vascular Cell Adhesion Molecule-1 - genetics