Green Tea Polyphenol Epigallocatechin-3-gallate Suppresses Toll-like Receptor 4 Expression via Up-regulation of E3 Ubiquitin-protein Ligase RNF216.
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.
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Motofumi
M
Kumazoe
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Yuki
Y
Nakamura
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Mai
M
Yamashita
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Takashi
T
Suzuki
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Kanako
K
Takamatsu
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Yuhui
Y
Huang
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Jaehoon
J
Bae
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Shuya
S
Yamashita
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Motoki
M
Murata
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and.
Shuhei
S
Yamada
the Products Research & Development Laboratory, Asahi Soft Drinks Co., Ltd., Ibaraki 302-0106, Japan.
Yuki
Y
Shinoda
the Products Research & Development Laboratory, Asahi Soft Drinks Co., Ltd., Ibaraki 302-0106, Japan.
Wataru
W
Yamaguchi
the Products Research & Development Laboratory, Asahi Soft Drinks Co., Ltd., Ibaraki 302-0106, Japan.
Yui
Y
Toyoda
From the Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581 and tatibana@agr.kyushu-u.ac.jp.
Hirofumi
H
Tachibana
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006946:Hyperinsulinism / Q000378:metabolism / Q000517:prevention & control; D015228:Hypertriglyceridemia / Q000378:metabolism / Q000517:prevention & control; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000517:prevention & control; D017474:Receptors, Laminin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D008070:Lipopolysaccharides; D016328:NF-kappa B; D017474:Receptors, Laminin; D013662:Tea; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; C000603313:RNF216 protein, mouse; D044767:Ubiquitin-Protein Ligases
67-kDa laminin receptor; E3 ubiquitin ligase; EGCG; RNF216; Toll-like receptor 4 (TLR4); cyclic GMP (cGMP); hypertriglyceridemia; inflammation; obesity