TLR4 Signaling Inhibitory Pathway Induced by Green Tea Polyphenol Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor

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.

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

“…A previous study also showed that TLR4-activated NF-κB and MAPK signalling pathways were suppressed by the up-regulation of Tollip [26]. Moreover, down-regulation of Tollip leads to abrogation of the suppressive effect of EGCG on TLR4-triggered inflammatory responses [18]. These results indicated that Tollip plays a pivotal role in the negative regulation of TLR4 signalling.…”

Section: Discussionmentioning

confidence: 71%

“…Previous studies have shown that EGCG has a potential anti-inflammatory effect [18, 19] and reduces MMP-9 expression through a cell surface receptor, 67-kDa laminin receptor (67LR) [20]. Recently, it has been confirmed that 67LR is involved in the suppressive effect of EGCG on TLR4 expression in macrophages.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Epigallocatechin-3-Gallate Inhibits Matrix Metalloproteinase-9 and Monocyte Chemotactic Protein-1 Expression Through the 67-κDa Laminin Receptor and the TLR4/MAPK/NF-κB Signalling Pathway in Lipopolysaccharide-Induced Macrophages

Fan

et al. 2017

Cell Physiol Biochem

Background/Aims: Epigallocatechin-3-gallate (EGCG), a major catechin found in green tea, has been shown to prevent cardiovascular diseases. Previously, Matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1) and toll-like receptor 4 (TLR4) were confirmed to play an important role in atherosclerosis and plaque instability. Both TLR4 and its negative regulator, Toll-interacting protein (Tollip), could be mediated by EGCG. The present study aimed to examine the effect of physiological concentration of EGCG (1 µM) on the expression of MMP-9 and MCP-1 in lipopolysaccharide (LPS)-induced macrophages and the potential mechanisms underlying its actions. Methods: The RAW264.7 cell line was used. Western blot was used to determine MCP-1, TLR4, Tollip, Mitogen-activated protein kinase (MAPK) and Nuclear factor-κB (NF-κB) protein expression. MMP-9 activity was assayed by gelatine zymography. The mRNA expression of MMP-9 and MCP-1 was measured by realtime polymerase chain reaction (RT-PCR). Results: EGCG (1 µM) significantly suppressed the expression of MMP-9 and MCP-1 and inhibited MAPK and NF-κB in LPS-induced macrophages but was blocked by Tollip silencing. The expression of LPS-induced MMP-9 and MCP-1 and the phosphorylation of the ERK1/2, P38 and NF-κB pathway proteins decreased after TLR4 siRNA treatment. Furthermore, EGCG mediated TLR4 and Tollip expression through binding to 67-kDa laminin receptor (67LR). Conclusion: The results of our study suggested that EGCG (1 µM) suppresses the TLR4/MAPK/NF-κB signalling pathway, decreases the expression of the plaque instability-mediating cytokines MMP-9 and MCP-1, and might prove to be effective in stabilizing atherosclerotic plaque.

Journal of Biological Chemistry

“…However, little is known about the repression of these mediators of TLR4 at the protein level. We previously reported on the inhibitory effect of EGCG on TLR4 signaling by the EGCG receptor in a 67LR-dependent manner (34). However, little is known on the upstream mechanism.…”

Section: Discussionmentioning

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

Self Cite

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).