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A Novel Role for NF‐kB p50 and p65 Proteins in Interferon Signaling and Antiviral Activity
Author(s) -
Wei Lai,
Homayouni Ramin,
Pfeffer Lawrence
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1079
Subject(s) - p50 , chromatin immunoprecipitation , transcription factor , nf κb , interferon , biology , signal transduction , gene , nfkb1 , irf1 , interferon regulatory factors , microbiology and biotechnology , gene expression , cytokine , promoter , immunology , genetics
Interferons (IFNs) are antiviral cytokines that selectively regulate gene expression through several signaling pathways including NF‐κB. To investigate the specific role of NF‐κB in interferon signaling, we performed gene expression profiling after IFN treatments of embryonic fibroblasts derived from mice with targeted deletion in NF‐κB p50 and p65 genes. Interestingly, a subset of genes, involved in antiviral and immunomodulatory activities, were induced higher by IFN in NF‐κB knockout cells. Chromatin immunoprecipitation (ChIP) experiments demonstrated that binding of p50‐p50 and p65‐p50 NF‐κB dimers to the promoter of these genes occurred prior to the binding of Irf1 transcription factor, suggesting that IFN induction of these genes is suppressed through NF‐κB. Indeed, NF‐κB suppressed both antiviral and immunomodulatory actions of IFN against influenza virus. Our results suggest that modulating NF‐κB activity may provide a new avenue for enhancing the effectiveness of cytokine therapy.