| Project/Area Number |
17591998
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Conservative dentistry
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| Research Institution | Kagoshima University |
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Principal Investigator |
TOKUBA Masayuki Kagoshima University, Medical and Dental Hospital, Assistant Professor, 医学部・歯学部附属病院, 講師 (20253891)
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| Co-Investigator(Kenkyū-buntansha) |
TORII Mitsuo Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院医歯学総合研究科, 教授 (30116066)
NAGAOKA Shigetaka Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院医歯学総合研究科, 助教授 (10155913)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | VR-1 / PAR-2 / substance P / IL-6 / ERK MAPK / p38 MAPK / AP-1 / Sp-1 / アナンダマイド / MTTアッセイ / フローサイトメトリー / 細胞死 / アポトーシス / CB2 / MAPキナーゼ |
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| Research Abstract |
Anandamide (AEA) triggers apoptosis. Here, we aim to investigate the role of its receptors on ANE-induced apoptosis and its signaling pathway in human dental pulp cells (HPC). AEA clearly induced apoptosis on HPC. Both CB2 antagonist and VR1 antagonist inhibited AEA-induced cell death. An inhibitor of extracellular signal-regulated kinases (ERKs) significantly prevented HPC cell death. ERK inhibitors and CB2 antagonist inhibited AEA-regulated nuclear factor-kappa B (NF-κB) activation. Furthermore, specific siRNA for NF-κB suunits (p50 and p65) inhibited AEA-induced HPC cell death. In this regard, AEA-induced pulp apoptosis was regulated by NF-κB-dependent and-independent pathways.
Substance P (SP) induces the expression of proinflammatory cytokines, such as interleukin (IL)-6, which are implicated in pulp inflammation. To determine the signal pathway of SP-induced IL-6, we examined the activities of the mitogen-activated protein kinases (MAPKs) in human dental pulp cell (PF-10) cultures. SP induced the phosphorylation of p38 MAPK within 5 min; this activation persisted for up to 40 min and was independent of the activation of extracellular signal-related kinases (ERK-1 and ERK-2), which was induced after SP stimulation of PF-10 cells. As shown by electrophoresic mobility shift assay (EMSA), p38 MAPK was not involved in SP-induced activation of nuclear factor-kappa B (NF-κB). However, p38 MAPK mediated SP-induced IL-6 production, as shown by the use of specific inhibitors of this kinase. Our results suggest that the activation of p38 MAPK is important for NF-κB-independent regulator of neurogenic inflammation in dental pulp tissues.
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