Combination of resolvin E1 and lipoxin A4 promotes the resolution of pulpitis by inhibiting NF‐κB activation through upregulating sirtuin 7 in dental pulp fibroblasts

作者：Xiaochen Liu, Chunmeng Wang, Liping Pang, Liangliang Pan, Qi Zhang · 发表于：Cell Proliferation · 年份：2022 · DOI：10.1111/cpr.13227 · 被引用次数：30 · 研究领域：Sirtuins and Resveratrol in Medicine、Dental Erosion and Treatment、Endodontics and Root Canal Treatments

OBJECTIVES: To determine whether the combination of resolvin E1 (RvE1) and lipoxin A4 (LXA4) could promote resolution of pulpitis and to investigate the mechanism. MATERIALS AND METHODS: Preliminary screening was first conducted in four specialized pro-resolving mediators (SPMs). Real-time quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay and double-immunofluorescence labelling were employed to assess the expression of RelA, SIRT1, SIRT6, SIRT7 and pro-inflammatory factors. Dental pulp fibroblasts (DPFs) were transfected with siRNA to assess the biological role of SIRT7. A pulpitis model was utilized to evaluate the in vivo curative effect. RESULTS: Preliminary results showed that RvE1 and LXA4 reduced the expression of RelA more markedly than other two SPMs. Both RvE1 and LXA4 treatment downregulated nuclear factor kappa B (NF-κB) activation and increased the expression of SIRT1, SIRT6 and SIRT7, more so in combination than alone. Double-immunofluorescence labelling showed that SIRT7 co-localized with p-p65 and Ac-p65 in the nucleus. Inhibiting ChemR23 and ALX reversed the expression of RelA mRNA, p-p65 and Ac-p65 proteins, pro-inflammatory factors, SIRT1, SIRT6 and SIRT7. Silencing SIRT7 significantly increased p-p65 and Ac-p65 protein levels and decreased SIRT1 and SIRT6 expression. In vivo experiments showed that combined administration of RvE1 and LXA4 promoted pulpitis markedly to resolution. CONCLUSIONS: Combination of RvE1 and...