Premium
Silencing of TNF‐α receptors coordinately suppresses TNF‐α expression through NF‐κB activation blockade in THP‐1 macrophage
Author(s) -
Verma Nandini,
Chaudhury Indrajit,
Kumar Deepak,
Das Rakha H.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.08.007
Subject(s) - autocrine signalling , gene silencing , tumor necrosis factor alpha , receptor , nf κb , thp1 cell line , chemistry , microbiology and biotechnology , signal transduction , downregulation and upregulation , biology , cell culture , immunology , biochemistry , genetics , gene
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.