Combination of Resolvin E1 and Lipoxin A4 Promotes the Resolution of Pulpitis
Objectives: To determine whether the combined administration of resolvin E1 (RvE1) and lipoxin A4 (LXA4) could promote resolution of pulpitis and to investigate the underlying mechanism. Methods: Preliminarily screening was first taken 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 expression of RelA, SIRT1, SIRT6, SIRT7 and pro-inflammatory factors. 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 the two other SPMs. Expression of RelA mRNA, p-p65 and Ac-p65 proteins, and pro-inflammatory factors relying on NF-κB transcription were up-regulated after LPS induction. Conversely, mRNA and protein levels of SIRT1, SIRT6, and SIRT7 were decreased. Double-immunofluorescence labelling showed that SIRT7 co-localized with p-p65 and Ac-p65 in the nucleus. Both RvE1 and LXA4 treatment downregulated NF-κB activation, more so in combination than alone. Inhibiting ChemR23 and ALX up-regulated expression of RelA mRNA, p-p65 and Ac-p65 proteins, and downstream pro-inflammatory factors, and reduced expression of 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 could promote pulpitis markedly to resolution. Conclusions: Combined administration of RvE1 and LXA4 could effectively inhibit NF-κB activation by up-regulating SIRT7 expression in DPFs, leading reduced production of pro-inflammatory factors, and promoting pulpitis resolution. This combination may be a promising strategy for treating pulpitis.
2022 IADR/APR General Session (Virtual) 2022 0125 Pulp Biology & Regeneration Research
Liu, Xiaochen
( School & Hospital of Stomatology, Tongji University
, Shanghai
, Shanghai
, China
; Shanghai Engineering Research Center of Tooth Restoration and Regeneration
, Shanghai
, Shanghai
, China
)
Zhang, Qi
( School & Hospital of Stomatology, Tongji University
, Shanghai
, Shanghai
, China
; Shanghai Engineering Research Center of Tooth Restoration and Regeneration
, Shanghai
, Shanghai
, China
)
the National Natural Science Foundation of China (grant numbers 81570966, 81870760 and 82170945)
The authors declare no conflict of interest.