Green tea catechin, epigallocatechin gallate, suppresses signaling by the dsRNA innate immune receptor RIG-I

The Innate immune system constitutes the first line of defense against pathogen infections. The Retinoic acid-inducible gene I (RIG-I) receptor recognizes triphosphorylated ssRNAs and dsRNA to initiate downstream signaling of interferon response. However, unregulated activity of these receptors coul...

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Bibliographic Details
Published in:PloS one 2010-09, Vol.5 (9), p.e12878
Main Authors: Ranjith-Kumar, C T, Lai, Yvonne, Sarisky, Robert T, Cheng Kao, C
Format: Article
Language:English
Subjects:
Adapters
Adenosine triphosphatase
Analysis
Antioxidants - pharmacology
ATPases
Autoimmune diseases
B cells
Biochemistry
Biological response modifiers
Camellia sinensis - chemistry
Catechin
Catechin - analogs & derivatives
Catechin - pharmacology
Cell Biology/Cell Signaling
Cytokines
DEAD Box Protein 58
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - immunology
Dendritic cells
Double-stranded RNA
Down-Regulation - drug effects
Epigallocatechin gallate
Epigallocatechin-3-gallate
Green tea
Health aspects
HEK293 Cells
Humans
Immune response
Immune system
Immunity, Innate - drug effects
Immunology/Immunomodulation
Immunology/Innate Immunity
Infection
Influenza
Innate immunity
Interferon
Interleukin 6
Kinases
Ligands
Plant Extracts - pharmacology
Plasmids
Polyphenols
Protein structure
Proteins
Receptors
Receptors, Immunologic
Retinoic acid
Ribonucleic acid
RNA
RNA, Double-Stranded - genetics
RNA, Double-Stranded - immunology
Signal transduction
Signal Transduction - drug effects
Signaling
Standard deviation
Tea
Toll-like receptors
Transcription
Tretinoin
Tumor necrosis factor-TNF
Viral infections
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Summary:The Innate immune system constitutes the first line of defense against pathogen infections. The Retinoic acid-inducible gene I (RIG-I) receptor recognizes triphosphorylated ssRNAs and dsRNA to initiate downstream signaling of interferon response. However, unregulated activity of these receptors could lead to autoimmune diseases. We seek to identify small molecules that can specifically regulate RIG-I signaling. Epigallocatechin gallate (EGCG), a polyphenolic catechin present in green tea, was identified in a small molecule screen. It was found to bind RIG-I and inhibits its signaling at low micromolar concentrations in HEK293T cells. Furthermore, EGCG dose-dependently inhibited the ATPase activity of recombinant RIG-I but did not compete with RIG-I interaction with RNA or with ATP. EGCG did not inhibit signaling by Toll-like receptors 3, 4, 9 or constitutive signaling by the adapter protein IPS-1. Structure activity relationship analysis showed that EGCG, its epimer GCG and a digallate-containing compound, theaflavin 3,3' digallate (TFDG) were potent RIG-I inhibitors. EGCG also inhibited IL6 secretion and IFN- β mRNA synthesis in BEAS-2B cells, which harbors intact endogenous RIG-I signaling pathway. EGCG and its derivatives could have potential therapeutic use as a modulator of RIG-I mediated immune responses.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0012878