一般注記Purpose: Caries-related immune response is first recognized by dental pulp fibroblast cells and is tightly regulated to avert pulpitis. Nucleotide-binding oligomerization domain (NOD) 1 signaling, which is essential for initiating the innate immune response to bacterial infection, is subject to many regulatory mechanisms. However, little is known about post transcriptional regulation of NOD1 dependent responses in dental pulp fibroblast cells. NOD1 recognizes D-glutamyl-meso-diaminopimelic acid (iE-DAP). RIP2 is associated with NOD1 and play critical roles in the immune system. Matrix metalloproteinases (MMPs) such as MMP-1, 2, 3, and 14 were also shown to be expressed in inflamed dental pulp tissue. MMP-3 can degrade the extracellular matrix (ECM) and activate other MMPs. MMP-3 is considered to be involved in wound healing, inflammation, and tumor initiation. Dental pulp destruction may be regulated, in part, by matrix metalloproteinase-3 (MMP-3), and other MMPs activated by MMP-3 have been shown to regulate the degradation and regeneration of dental pulp tissue. In the present study, we investigated that MMP-3 was produced in response to iE-DAP and cell signaling in human pulp fibroblasts (HPFs).Methods: HPFs were incubated in serum-free α-MEM containing iE-DAP (10 g/mL) for 24 h with or without the RIP inhibitor, 0.5, 1, 5, 10, 15, 20 nM Gefitinib. The production of MMP-3 and expression of RIP2 were evaluated by RIP2 and MMP-3 antibodies using western blot analysis. HPFs were incubated in serum-free α-MEM containing iE-DAP (10 g/mL) for 24 h with or without the JNK inhibitor, AS601245 or SP600125. The production of MMP-3 and activation of JNK by iE-DAP were evaluated by the phosphorylation of JNK and MMP-3 antibodies using western blot analysis.Results: iE-DAP enhanced the production of MMP-3 in a dose dependent manner in HPFs. RIP2 inhibitor suppressed the production of MMP-3 on iE-DAP stimulated HPFs. We demonstrated that MMP-3 was produced from HPFs in response to iE-DAP in a JNK-dependent manner.Conclusion: These results suggest that iE-DAP/NOD1 induced the production of MMP-3 in HPFs through a signaling cascade involving RIP2-mediated phosphorylation of JNK.
2017年度
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）