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[摘要]：Persistently elevated level of TNF-alpha has been implicated in several inflammatory disorders, however, its autocrine production through TNF-alpha receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-alpha expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-alpha induced NF-kappa B activation to a higher extent. It was further observed that NF-kappa B inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-alpha expression. All these results suggest that TNF-alpha expression is regulated by synergistic signaling of TNF receptors through downstream NF-kappa B activation. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
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