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

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.