Epigallocatechin-3-gallate inhibits TF and TNF-α expression induced by the anti-β2GPI/β2GPI complex in human THP-1 cells

Wang,Ting; Zhou,Hong; Xie,Hongxiang; Mu,Yuan; Xu,Ya; Liu,Jingjing; Zhang,Xiaolei

doi:10.3892/ijmm.2014.1635

Epigallocatechin-3-gallate inhibits TF and TNF-α expression induced by the anti-β2GPI/β2GPI complex in human THP-1 cells

Authors:
- Ting Wang
- Hong Zhou
- Hongxiang Xie
- Yuan Mu
- Ya Xu
- Jingjing Liu
- Xiaolei Zhang
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Affiliations: Department of Clinical Laboratory and Hematology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
Published online on: January 27, 2014 https://doi.org/10.3892/ijmm.2014.1635
Pages: 994-1002

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Abstract

Epigallocatechin-3-gallate (EGCG) is the major polyphenolic component of green tea. The aim of the current study was to investigate the inhibitory effects of EGCG on anti-β2-glycoprotein I (β2GPI)/β2GPI-induced tissue factor (TF) and tumor necrosis factor-α (TNF-α) expression in the human acute monocytic leukemia cell line, THP-1, as well as the underlying mechanisms. Human THP-1 cells cultured in vitro were treated with lipopolysaccharide (LPS, 500 ng/ml) or with the anti-β2GPI (10 µg/ml)/β2GPI (100 µg/ml) complex following pre-treatment with or without EGCG (0-50 µg/ml). The expression levels of TF, TNF-α and Toll-like receptor 4 (TLR4) were measured, and the activation of mitogen-activated protein kinases (MAPKs) including p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), and the nuclear factor-κB (NF-κB) signaling pathway was determined by western blot analysis. The results revealed that the anti-β2GPI/β2GPI complex activated the THP-1 cells, resulting in the enhanced expression of the coagulation cytokine, TF, as well as that of the pro-inflammatory cytokine, TNF-α; these levels were almost comparable to those induced by LPS. Pre-treatment with EGCG decreased the TF and TNF-α levels in the THP-1 cells treated with the anti-β2GPI/β2GPI complex in a dose-dependent manner and counteracted the upregulation of TLR4 expression (mRNA and protein) which was induced by the anti-β2GPI/β2GPI complex or LPS. Furthermore, EGCG suppressed the phosphorylation of p38, ERK1/2 and JNK and blocked the activation of the NF-κB signaling pathway induced by the anti-β2GPI/β2GPI complex or LPS. In conclusion, our results indicate that EGCG decreases the anti-β2GPI/β2GPI-induced TF and TNF-α expression in THP-1 cells possibly through the inhibition of the intracellular signal transduction pathway of TLRs-MAPKs-NF-κB axis and may serve as a preventive and therapeutic agent for antiphospholipid syndrome (APS).

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