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- Title
Silencing of TNF-α receptors coordinately suppresses TNF-α expression through NF-κB activation blockade in THP-1 macrophage
- Authors
Verma, Nandini; Chaudhury, Indrajit; Kumar, Deepak; Das, Rakha H.
- Abstract
Abstract: Persistently elevated level of TNF-α has been implicated in several inflammatory disorders, however, its autocrine production through TNF-α receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-α expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-α induced NF-κB activation to a higher extent. It was further observed that NF-κB inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-α expression. All these results suggest that TNF-α expression is regulated by synergistic signaling of TNF receptors through downstream NF-κB activation.
- Subjects
TUMOR necrosis factors; GENE silencing; CELL receptors; SUPPRESSOR cells; MACROPHAGES; CELL lines; CELLULAR signal transduction; SMALL interfering RNA
- Publication
FEBS Letters, 2009, Vol 583, Issue 17, p2968
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2009.08.007