茶儿茶素通过 Toll 样受体 2 配体刺激的牙髓细胞中的丝裂原活化蛋白激酶通路减少炎症反应。

Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells.

机构信息

Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.

出版信息

Life Sci. 2010 Apr 24;86(17-18):654-60. doi: 10.1016/j.lfs.2010.02.017. Epub 2010 Feb 20.

DOI:10.1016/j.lfs.2010.02.017

PMID:20176036

Abstract

AIMS

In this study, we evaluated whether catechins could inhibit the expression of pro-inflammatory mediators induced by dental caries-related bacteria, Streptococci, or pathogen-associated molecular patterns (PAMPs) stimulation in human dental pulp fibroblasts (HDPF). We further determined the mechanisms of the anti-inflammatory activity of catechins.

MAIN METHODS

Streptococci or PAMP-stimulated HDPF were treated with catechin, and then the expression and production of pro-inflammatory mediators were determined by RT-PCR and ELISA. Furthermore, the signal transduction pathways activated with toll-like receptor (TLR)2 ligand were assessed by Immunoblot and ELISA using blocking assay with specific inhibitors.

KEY FINDINGS

Increased expressions of pro-inflammatory mediators are found in inflamed dental pulp, especially in HDPF. We recently reported that dental pulpal innate immune responses may mainly result from the predominantly-expressed TLR2 signaling. Catechins, polyphenolic compounds in green tea, exert protective and healing effects through multiple mechanisms, including antioxidative and anti-inflammatory effects. However, there are no reports concerning the effects of catechins on dental pulp. In this study, we demonstrated that the up-regulated expressions of IL-8 or PGE(2) in Streptococci or PAMP-stimulated HDPF were inhibited by catechins, (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG). In TLR2 ligand-stimulated HDPF, specific inhibitors of extracellular signal regulated kinase (ERK)1/2, p38, c-jun NH(2)-terminal kinase (SAP/JNK), NF-kappaB or catechins markedly reduced the level of pro-inflammatory mediators and the phosphorylation of these signal transduction molecules was suppressed by catechins.

SIGNIFICANCE

These findings suggest that catechins might be useful therapeutically as an anti-inflammatory modulator of dental pulpal inflammation.

摘要

目的

本研究旨在评估儿茶素是否能抑制与龋齿相关的细菌链球菌或病原体相关分子模式（PAMP）刺激人牙髓成纤维细胞（HDPF）后促炎介质的表达。我们进一步确定了儿茶素抗炎活性的机制。

主要方法

用儿茶素处理链球菌或 PAMP 刺激的 HDPF，然后通过 RT-PCR 和 ELISA 测定促炎介质的表达和产生。此外，用 TLR2 配体激活的信号转导通路通过免疫印迹和 ELISA 进行评估，并用特异性抑制剂进行阻断试验。

主要发现

在炎症牙髓中发现促炎介质表达增加，尤其是在 HDPF 中。我们最近报道牙髓固有免疫反应可能主要来自于主要表达的 TLR2 信号。儿茶素是绿茶中的多酚化合物，通过多种机制发挥保护和愈合作用，包括抗氧化和抗炎作用。然而，目前还没有关于儿茶素对牙髓影响的报道。在这项研究中，我们表明儿茶素、（-）-表儿茶素没食子酸酯（ECG）和（-）-表没食子儿茶素没食子酸酯（EGCG）可抑制链球菌或 PAMP 刺激的 HDPF 中 IL-8 或 PGE（2）的上调表达。在 TLR2 配体刺激的 HDPF 中，ERK1/2、p38、c-jun NH2-末端激酶（SAP/JNK）、NF-κB 的特异性抑制剂或儿茶素明显降低了促炎介质的水平，并抑制了这些信号转导分子的磷酸化。