Identification of switching factor that determinates life and death of human dental pulp cells

Anandamide （AEA）触发细胞凋亡。本研究旨在探讨其受体在ane诱导的人牙髓细胞（HPC）凋亡及其信号通路中的作用。AEA明显诱导HPC细胞凋亡。CB2拮抗剂和VR1拮抗剂均能抑制aea诱导的细胞死亡。细胞外信号调节激酶（ERKs）抑制剂显著阻止HPC细胞死亡。ERK抑制剂和CB2拮抗剂抑制aea调节的核因子κB （NF-κB）活化。此外，NF-κB亚单位（p50和p65）的特异性siRNA抑制aea诱导的HPC细胞死亡。因此，aea诱导的髓细胞凋亡受NF-κ b依赖性和非依赖性通路的调控。P物质（SP）诱导促炎细胞因子的表达，如白细胞介素(IL)-6，这与牙髓炎症有关。为了确定sp诱导IL-6的信号通路，我们检测了人牙髓细胞（sf -10）培养物中丝裂原活化蛋白激酶（MAPKs）的活性。SP在5 min内诱导p38 MAPK磷酸化；这种激活持续长达40分钟，并且独立于SP刺激PF-10细胞后诱导的细胞外信号相关激酶（ERK-1和ERK-2）的激活。电泳迁移率转移实验（EMSA）表明，p38 MAPK不参与sp诱导的核因子κB （NF-κB）的活化。然而，p38 MAPK介导sp诱导IL-6的产生，如使用该激酶的特异性抑制剂所示。我们的研究结果表明，p38 MAPK的激活对于牙髓组织中不依赖NF-κ b的神经源性炎症调节因子很重要。

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.