Involvement of nuclear factor-xB in platelet-activating factor-mediated tumor necrosis factor-α expression
| Autor: | Hern-Ku Lee, Suhn Young Im, Tai You Ha, Su Ji Han, Hyun Mi Ko, Dong Geun Lee, Jung-Hwa Choi, Soon Bai Chun |
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| Rok vydání: | 1997 |
| Předmět: |
Lipopolysaccharides
medicine.medical_specialty Lipopolysaccharide Immunology Biology Cell Line Mice chemistry.chemical_compound In vivo Internal medicine Gene expression medicine Animals Immunology and Allergy Platelet Activating Factor Transcription factor Platelet-activating factor Tumor Necrosis Factor-alpha NF-kappa B Antagonist Proteins In vitro Mice Inbred C57BL Endocrinology Gene Expression Regulation chemistry Protein Biosynthesis Injections Intravenous Female lipids (amino acids peptides and proteins) Tumor necrosis factor alpha |
| Zdroj: | European Journal of Immunology. 27:2800-2804 |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | Tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) are important mediators of inflammatory reactions, and their release is controlled by a positive feedback network. However, the regulatory mechanisms underlying the interaction of these two molecules are unknown. Within 10 min of the injection of lipopolysaccharide (LPS) into C57BL/6 mice, effects inducible by PAF such as anaphylactic shock-like symptoms, disseminated intravascular coagulation, and hemorrhage in renal medullae were observed, and all these pathological changes were prevented by the PAF antagonist, BN 50739. The plasma level of PAF after LPS injection reached a peak at 5 min. TNF-alpha gene expression was evident 20 min after LPS injection and was maximal at 40 min, and the level of serum TNF-alpha reached a peak at 1 h. Pretreatment with BN 50739 inhibited LPS-induced TNF-alpha gene expression and protein synthesis in a dose-dependent manner. Injection of PAF or treatment of the macrophage cell line, J774A.1, with PAF activated the transcription factor, nuclear factor (NF)-kappa B, which is essential for inducible TNF-alpha transcription. The activation of NF-kappa B by PAF preceded the LPS-mediated TNF-alpha gene expression. Pretreatment with BN 50739 inhibited LPS-induced mobilization of NF-kappa B in a dose-dependent manner in vivo as well as in vitro. These data suggest that PAF, which is released immediately or shortly after LPS injection, induces the expression of TNF-alpha through the activation of NF-kappa B. |
| Databáze: | OpenAIRE |
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