解析素 E1 通过依赖 Chemerin 受体 23 抑制牙髓成纤维细胞活化来缓解牙髓炎。

Resolvin E1 Ameliorates Pulpitis by Suppressing Dental Pulp Fibroblast Activation in a Chemerin Receptor 23-dependent Manner.

机构信息

Department of Endodontics, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.

出版信息

J Endod. 2019 Sep;45(9):1126-1134.e1. doi: 10.1016/j.joen.2019.05.005. Epub 2019 Jul 26.

DOI:10.1016/j.joen.2019.05.005

PMID:31353056

Abstract

INTRODUCTION

Timely resolution of pulp inflammation is a prerequisite for the healing of inflamed dental pulp. Stromal cells, particularly fibroblasts, play a critical role in the inflammation resolution process. Resolvin E1 (RvE1) is a lipid-derived endogenous proresolution molecule that mediates this resolution process. In the present study, we investigated the effects of RvE1 on dental fibroblasts during the pathogenesis of pulpitis.

METHODS

The pulp tissues in maxillary incisors of male Sprague-Dawley rats (N = 50) were exposed to the oral environment for 0, 9, 24, and 48 hours, after which they were treated with RvE1 or its vehicle. The inflammatory changes after 24 hours were assessed using hematoxylin-eosin staining, immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction. Chemerin receptor 23 (ChemR23) expression in rat pulp tissues and human dental fibroblasts was detected by immunofluorescence, Western blot analysis, and quantitative polymerase chain reaction. Finally, small interfering RNA-based knockdown studies were performed to evaluate the effects of RvE1 inhibition on proinflammatory genes and nuclear factor kappa B signaling of human dental pulp fibroblasts.

RESULTS

Early treatment (within 24 hours after pulp exposure) with RvE1 promoted a decline in the number of inflammatory cells and gene expression of proinflammatory cytokines. Moreover, it reduced ChemR23 expression in the fibroblastlike cells of inflamed pulp tissues. In vitro, ChemR23 was widely expressed in human dental fibroblasts. RvE1 significantly suppressed cytokine production by fibroblasts, with down-regulation of the nuclear translocation of nuclear factor kappa B p65 in these cells. Knockdown of ChemR23 almost abolished the anti-inflammatory effect of RvE1.

CONCLUSIONS

RvE1 can suppress the activation of dental pulp fibroblasts in a ChemR23-dependent manner and inhibit inflammation in the relevant early stages of pulpitis.

摘要

简介

牙髓炎症的及时解决是牙髓炎症愈合的前提。基质细胞，尤其是成纤维细胞，在炎症消退过程中起着至关重要的作用。内源性消退介质 E1（RvE1）是一种脂质衍生的内源性前炎症消退分子，可介导此消退过程。在本研究中，我们研究了 RvE1 在牙髓炎发病过程中对牙髓成纤维细胞的影响。

方法

雄性 Sprague-Dawley 大鼠（N = 50）上颌切牙牙髓组织暴露于口腔环境中 0、9、24 和 48 小时后，用 RvE1 或其载体处理。24 小时后通过苏木精-伊红染色、免疫组织化学、酶联免疫吸附测定和定量聚合酶链反应评估炎症变化。通过免疫荧光、Western blot 分析和定量聚合酶链反应检测大鼠牙髓组织和人牙髓成纤维细胞中趋化因子受体 23（ChemR23）的表达。最后，通过小干扰 RNA 敲低研究评估 RvE1 抑制对人牙髓成纤维细胞促炎基因和核因子 kappa B 信号的影响。

结果

RvE1 的早期治疗（牙髓暴露后 24 小时内）可减少炎症细胞数量和促炎细胞因子的基因表达。此外，它还降低了炎性牙髓组织中成纤维样细胞中 ChemR23 的表达。体外，ChemR23 在人牙髓成纤维细胞中广泛表达。RvE1 可显著抑制成纤维细胞细胞因子的产生，并下调这些细胞中核因子 kappa B p65 的核转位。ChemR23 的敲低几乎消除了 RvE1 的抗炎作用。