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PLoS One. 2010 Sep 22;5(9):e12878. doi: 10.1371/journal.pone.0012878.

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

Author information

1
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, USA. ctrkumar@indiana.edu

Abstract

BACKGROUND:

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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.

CONCLUSIONS/SIGNIFICANCE:

EGCG and its derivatives could have potential therapeutic use as a modulator of RIG-I mediated immune responses.

PMID:
20877565
PMCID:
PMC2943919
DOI:
10.1371/journal.pone.0012878
[Indexed for MEDLINE]
Free PMC Article

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