Green Tea Polyphenol Epigallocatechin-3-gallate Suppresses Toll-like Receptor 4 Expression via Up-regulation of E3 Ubiquitin-protein Ligase RNF216

被引：54

作者：

Kumazoe, Motofumi ^{[1
]}

Nakamura, Yuki ^{[1
]}

Yamashita, Mai ^{[1
]}

Suzuki, Takashi ^{[1
]}

Takamatsu, Kanako ^{[1
]}

Huang, Yuhui ^{[1
]}

Bae, Jaehoon ^{[1
]}

Yamashita, Shuya ^{[1
]}

Murata, Motoki ^{[1
]}

Yamada, Shuhei ^{[1
]}

Shinoda, Yuki ^{[2
]}

Yamaguchi, Wataru ^{[2
]}

Toyoda, Yui ^{[2
]}

Tachibana, Hirofumi ^{[1
]}

机构：

[1] Kyushu Univ, Fac Agr, Dept Biosci & Biotechnol, Div Appl Biol Chem,Higashi Ku, 6-10-1 Hakozaki, Fukuoka 8128581, Japan

[2] Asahi Soft Drinks Co Ltd, Prod Res Dev Lab, Ibaraki 3020106, Japan

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2017年 / 292卷 / 10期

基金：

日本学术振兴会;

关键词：

67-KDA LAMININ RECEPTOR; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; ADIPOSE-TISSUE; MACROPHAGE ACCUMULATION; COMMON POLYMORPHISM; METABOLIC SYNDROME; RAT-LIVER; INFLAMMATION; OBESITY;

D O I：

10.1074/jbc.M116.755959

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha 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.

引用

页码：4077 / 4088

页数：12

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[1] Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity [J].