歯髄炎発症における自然免疫機構の役割と緑茶カテキンの歯髄炎抑制効果の検討

Pulpitis, dental pulpal inflammation, is mainly associated with the dental caries-related pathogen invaded into dentinal tubules. Many types of cytokines and inflammatory mediators are induced for the initiation and progression of pulpitis. Among these cytokines and mediators, interleukin (IL)-6, IL-8, monocyte-chemoattractant protein (MCP)-1, interferon-γ-inducible protein (IP)-10, prostaglandin (PG)E2, are produced by inflamed human dental pulp fibroblasts (HDPFs). Generally, the initial sensing of microbial pathogens is mediated by pattern recognition receptors (PRRs) for pathogen-associated molecular patterns (PAMPs). PRRs, such as toll-like receptor (TLR) and nucleotide-binding oligomerization domein (NOD), are essential for the mammalian innate immune response. TLR2, TLR3, TLR4 and TLR5 expressions have been determined in HDPFs and thier specific agonists can induce TLR-mediated inflammatory signals. Moreover, NOD1 and NOD2 expression are determined in dental pulp tissue and HDPFs. NOD2 is specifically responsible for cooperative effects with TLR2 agonists in HDPFs. Since dental pulpal inflammation is characterized as the immune response triggered by the invasion of caries-related bacteria into dentinal tubules, pathogen recognition by multiple PRRs engagement including TLR&NOD might constitute a key event for the onset of resulting exacerbated pulpal inflammatory response. Catechin, the polyphenolic compounds in green tea, reduces risks of oxidative stress, atheroslerosis, cancer and cardiovascular diseases therefore associated with many important health benefits. Especially, epicatechin-3-gallate (ECG) and epigallocatechin-3-gallate (EGCG) are representative types of green tea catechin and shows strong bioactivity. We demonstrated that ECG and EGCG can inhibit some inflammatory cytokines production in HDPFs stimulated with PAMPs such as Pam3CSK4 (TLR2 specific ligand), LPS (TLR4 specific ligand) and MDP (NOD2 specific ligand). Moreover, ECG and EGCG inhibit the phosphorylations of mitogen-activated protein kinase (MAPK) and the activation of nucler factor (NF)-κB. Recently, it has been shown that the biological activities of EGCG are mediated through the binding to the cell-surface 67-kDa laminin receptor (67LR). However, there are no reports about the expression of 67LR on HDPFs. Anti-inflammatory effect of catechin is important for the development of new therapeutic strategies and treatments for dental pulpal inflammation.