Journal
LIFE SCIENCES
Volume 86, Issue 17-18, Pages 654-660Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2010.02.017
Keywords
Catechin; Dental pulp fibroblast; Inflammation; Signal pathway
Funding
- Japan Society for the Promotion of Science [20592228, 20592229, 20791386]
- Grants-in-Aid for Scientific Research [22791838, 20592228, 20791386, 20592229] Funding Source: KAKEN
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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 NH2-terminal kinase (SAP/JNK), NF-kappa B 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. (C) 2010 Elsevier Inc. All rights reserved.
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