Green tea polyphenol egcg upregulates tollip expression by suppressing ELF-1 expression

Motofumi Kumazoe, Mai Yamashita, Yuki Nakamura, Kanako Takamatsu, Jaehoon Bae, Shuya Yamashita, Shuhei Yamada, Hiroaki Onda, Takashi Nojiri, Kenji Kangawa, Hirofumi Tachibana

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

TLR signaling is critical to innate immune system regulation; however, aberrant TLR signaling is involved in several diseases, including insulin resistance, Alzheimer's disease, and tumor metastasis. Moreover, a recent study found that TLR-4 signaling pathway inhibition might be a target for the suppression of chronic inflammatory disorders. In this article, we show that the green tea polyphenol epigallocatechin-3-O-gallate (EGCG) increases the expression of Toll interacting protein, a strong inhibitor of TLR4 signaling, by suppressing the expression of E74-like ETS transcription factor 1 (Elf-1). A mechanistic study revealed that EGCG suppressed Elf-1 expression via protein phosphatase 2A/cyclic GMP (cGMP)-dependent mechanisms. We also confirmed that orally administered EGCG and a cGMP inducer upregulated Toll interacting protein expression, increased intracellular levels of cGMP in macrophages, and suppressed Elf-1 expression. These data support EGCG and a cGMP inducer as potential candidate suppressors of TLR4 signaling.

Original languageEnglish
Pages (from-to)3261-3269
Number of pages9
JournalJournal of Immunology
Volume199
Issue number9
DOIs
Publication statusPublished - Nov 1 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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