Human dental pulp cells (HDPCs) play an important role in pulpitis. Semaphorin3A (Sema3A), which is an axon guidance molecule, is a member of the secretory semaphorin family. Recently, Sema3A has been reported to be an osteoprotective factor and to be involved in the immune response. However, the role of Sema3A in dental pulp inflammation remains unknown. The aim of this study was to reveal the existence of Sema3A in human dental pulp tissue and the effect of Sema3A which is released from tumor necrosis factor (TNF)‐α‐stimulated HDPCs on production of proinflammatory cytokines, such as interleukin (IL)‐6 and CXC chemokine ligand 10 (CXCL10), from HDPCs stimulated with TNF‐α. Sema3A was detected in inflamed pulp as compared to normal pulp. HDPCs expressed Neuropilin‐1(Nrp1) which is Sema3A receptor. TNF‐α increased the levels of IL‐6 and CXCL10 in HDPCs in time‐dependent manner. Sema3A inhibited production of these two cytokines from TNF‐α‐stimulated HDPCs. TNF‐α induced soluble Sema3A production from HDPCs. Moreover, antibody‐based neutralization of Sema3A further promoted production of IL‐6 and CXCL10 from TNF‐α‐stimulated HDPCs. Sema3A inhibited nuclear factor (NF)‐κB P65 phosphorylation and inhibitor κBα degradation in TNF‐α‐stimulated HDPCs. These results indicated that Sema3A is induced in human dental pulp, and TNF‐α acts on HDPCs to produce Sema3A, which partially inhibits the increase in IL‐6 and CXCL10 production induced by TNF‐α, and that the inhibition leads to suppression of NF‐κB activation. Therefore, it is suggested that Sema3A may regulate inflammation in dental pulp and be novel antiinflammatory target molecule for pulpitis.

中文翻译：

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从人牙髓细胞释放的信号素 3A 通过抑制核因子-κB 激活抑制肿瘤坏死因子-α 诱导的白细胞介素 6 和 CXC 趋化因子配体 10 产生的增加。

人类牙髓细胞 (HDPC) 在牙髓炎中起重要作用。Semaphorin3A (Sema3A) 是一种轴突导向分子，是分泌型信号素家族的成员。最近，据报道 Sema3A 是一种骨保护因子并参与免疫反应。然而，Sema3A 在牙髓炎症中的作用仍然未知。本研究的目的是揭示人牙髓组织中 Sema3A 的存在以及从肿瘤坏死因子 (TNF)-α 刺激的 HDPC 释放的 Sema3A 对促炎细胞因子的产生的影响，如白细胞介素 (IL)- 6 和 CXC 趋化因子配体 10 (CXCL10)，来自用 TNF-α 刺激的 HDPC。与正常牙髓相比，在发炎牙髓中检测到 Sema3A。HDPC 表达 Neuropilin-1（Nrp1），它是 Sema3A 受体。TNF-α 以时间依赖性方式增加 HDPC 中 IL-6 和 CXCL10 的水平。Sema3A 抑制 TNF-α 刺激的 HDPC 产生这两种细胞因子。TNF-α 诱导 HDPC 产生可溶性 Sema3A。此外，基于抗体的 Sema3A 中和进一步促进了 TNF-α 刺激的 HDPC 产生 IL-6 和 CXCL10。Sema3A 抑制 TNF-α 刺激的 HDPC 中的核因子 (NF)-κB P65 磷酸化和抑制剂 κBα 降解。这些结果表明Sema3A在人牙髓中被诱导，TNF-α作用于HDPCs产生Sema3A，部分抑制TNF-α诱导的IL-6和CXCL10产生的增加，并且抑制导致NF的抑制-κB 激活。因此，提示Sema3A可能调节牙髓炎症，是牙髓炎的新型抗炎靶分子。