Green tea polyphenol epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor on lipopolysaccharide-stimulated dendritic cells

et al. 2016

Cell Physiol Biochem

Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer) and MMPs (matrix metalloproteinases) by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG) has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR) has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. Results: We showed that EGCG (10-50µmol/L) significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Conclusion: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages

et al. 2016

Cell Physiol Biochem

“…In macrophages, 67LR was shown to be involved in the inhibitory effect of EGCG on the LPS-induced TLR4 signaling and peptidoglycan-induced TLR2 signaling pathway [13,14]. It was also shown to be involved in the inhibitory effect of EGCG on the TLR4 signaling pathway in dendritic cells [15]. Recently, it has been demonstrated that 67LR as a cell-surface EGCG receptor mediates the anti-inflammatory action of EGCG in endotoxin-stimulated human cerebral microvascular endothelial cells (hCMECs) [16].…”

Section: Introductionmentioning

confidence: 99%

Green Tea Polyphenol Epigallocatechin-3-Gallate Inhibits TNF-a-Induced Production of Monocyte Chemoattractant Protein-1 in Human Umbilical Vein Endothelial Cells

Gao

et al. 2014

Cell Physiol Biochem

Aims: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, displays a variety of pharmacological properties and recently received attention as a prospective dietary intervention in cardiovascular diseases (CVD). This study was conducted to test the hypothesis that EGCG was able to inhibit tumor necrosis factor-a (TNF-a)-induced production of monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) and investigated the underlying molecular mechanisms. Methods: The inhibitory effect of EGCG on TNF-a-induced expression of MCP-1 was measured using ELISA and RT-qPCR. The effect of EGCG on TNF-a-induced nuclear factor-kappa B (NF-κB) activation was investigated by western blot and luciferase assays. Monocyte adhesion assay was detected by microscope. Results: EGCG significantly suppressed the TNF-a-induced protein and mRNA expression of MCP-1. Investigation of the mechanism suggested that EGCG suppressed the TNF-a-mediated NF-κB activation. In addition, the 67-kD laminin receptor (67LR) was involved in EGCG-mediated suppression of MCP-1 generation. Furthermore, EGCG potently inhibited monocyte adhesion to activated HUVECs. Conclusion: EGCG suppresses TNF-a-induced MCP-1 expression in HUVECs. This effect was mediated by 67LR and was via the inhibition of NF-κB activation. Our results demonstrated that EGCG might be a possible medicine for CVD prevention and treatment.

Journal of Biological Chemistry

“…Consistent with NFB activation, lipid infusion stimulated TNF-␣, IL-6, and MCP-1 mRNA expression in adipose tissue of wildtype mice, but not in TLR4 Ϫ/Ϫ mice (9 -13). Several studies have shown that the natural 67LR agonist EGCG has an inhibitory effect on TLR4-dependent inflammation (14,15). Therefore, to determine the effect of EGCG on TLR4 expression in macrophages, peritoneal macrophages were treated with the indicated concentrations of EGCG.…”

Section: Lr Agonist Strongly Suppressed Tlr4 Expression Through Rnf216mentioning

confidence: 99%

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

Kumazoe

Nakamura

Yamashita

et al. 2017

Edited by Jeffrey E. PessinToll-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 ( Obesity and related metabolic disorders continue to spread worldwide at an alarming rate, which is mainly in response to changes in dietary habits, particularly the adoption of Western diets, which include an excessive intake of high-fat/high-sucrose (HF/HS) 3 foods (1-3).