Silencing of TNF-α receptors coordinately suppresses TNF-α expression through NF-κB activation blockade in THP-1 macrophage

Nandini Verma, Indrajit Chaudhury, Deepak Kumar, Rakha H. Das

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2968-2974
Number of pages7
JournalFEBS Letters
Volume583
Issue number17
DOIs
StatePublished - Sep 3 2009

Keywords

  • DNAzyme
  • NF-κB
  • TNF-R1
  • TNF-R2
  • TNF-α
  • siRNA

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