Silencing of TNF-alpha receptors coordinately suppresses TNF-alpha expression through NF-kappaB activation blockade in THP-1 macrophage.
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-kappaB activation to a higher extent. It was further observed that NF-kappaB 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-kappaB activation.
Verma
Nandini
N
Institute of Genomics and Integrative Biology, Delhi, India.
Chaudhury
Indrajit
I
Kumar
Deepak
D
Das
Rakha H
RH
D000873:Anthracenes / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000873:Anthracenes; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone