Role of nuclear factor-kappaB in the antiviral action of interferon and interferon-regulated gene expression.
Interferons (IFNs) play critical roles in host defense by modulating the expression of various genes via tyrosine phosphorylation of STAT transcription factors. IFN-alpha/beta activates another important transcription factor, nuclear factor-kappaB (NF-kappaB), but its role in IFN-mediated activity is poorly understood. Sensitivity to the antiviral and gene-inducing effects of IFN was examined in normal fibroblasts and in NF-kappaB knockout fibroblasts from p50- and p65-null mice. Antiviral assays demonstrated that NF-kappaB knockout fibroblasts were sensitized to the antiviral action of IFN. Moreover, analysis of IFN-stimulated gene expression by real-time PCR demonstrated selective effects of NF-kappaB on gene expression. Our results demonstrate that a subset of IFN-stimulated genes is regulated through an NF-kappaB-dependent pathway and that NF-kappaB may regulate the sensitivity of cells to IFN-mediated antiviral activity.
Pfeffer
Lawrence M
LM
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38103, USA. lpfeffer@utmem.edu
Kim
Jong-Gwan
JG
Pfeffer
Susan R
SR
Carrigan
Dennis J
DJ
Baker
Darren P
DP
Wei
Lai
L
Homayouni
Ramin
R
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051381:Rats; D011994:Recombinant Proteins; D051996:Transcription Factor RelA
D000998:Antiviral Agents; D017931:DNA Primers; D007370:Interferon Type I; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011994:Recombinant Proteins; D051996:Transcription Factor RelA