Green tea polyphenol epigallocatechin-3-gallate suppresses toll-like receptor 4 expression via up-regulation of E3 ubiquitin-protein ligase RNF216

Motofumi Kumazoe, Yuki Nakamura, Mai Yamashita, Takashi Suzuki, Kanako Takamatsu, Yuhui Huang, Jaehoon Bae, Shuya Yamashita, Motoki Murata, Shuhei Yamada, Yuki Shinoda, Wataru Yamaguchi, Yui Toyoda, Hirofumi Tachibana

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Toll-like receptor 4 (TLR4) plays an essential role in innate immunity through inflammatory cytokine induction. Recent studies demonstrated that the abnormal activation of TLR4 has a pivotal role in obesity-induced inflammation, which is associated with several diseases, including hyperinsulinemia, hypertriglyceridemia, and cardiovascular disease. Here we demonstrate that (-)-epigallocatechin-3-O-gallate, a natural agonist of the 67-kDa laminin receptor (67LR), suppressed TLR4 expression through E3 ubiquitin-protein ring finger protein 216 (RNF216) up-regulation. Our data indicate cyclic GMP mediates 67LR agonist-dependent RNF216 up-regulation. Moreover, we show that the highly absorbent 67LR agonist (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3″Me) significantly attenuated TLR4 expression in the adipose tissue. EGCG3″Me completely inhibited the high-fat/high-sucrose (HF/HS)-induced up-regulation of tumor necrosis factor α in adipose tissue and serum monocyte chemoattractant protein-1 increase. Furthermore, this agonist intake prevented HF/HS-induced hyperinsulinemia and hypertriglyceridemia. Taken together, 67LR presents an attractive target for the relief of obesity-induced inflammation.

Original languageEnglish
Pages (from-to)4077-4088
Number of pages12
JournalJournal of Biological Chemistry
Volume292
Issue number10
DOIs
Publication statusPublished - Mar 10 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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