Resolving E1 regulates inflammatory cellinfiltration and cytokine production in diabeticperiodontitis

Abstract

Background and Aim: Diabetic periodontitis involves a complexinflammatory process where periodontitis and diabetes aggravate theseverity of the other. We hypothesized that Resolvin E1 (RvE1), apro-resolution mediator of inflammation, decreases inflammatory cellinfiltrate and pro-inflammatory cytokine expression in diabeticperiodontitis through active ligand-receptor activation.Methods: The db/db mouse (leptin receptor mutation) was crossbredwith ERV1 transgenic mice (overexpresses receptor for RvE1) to gener-ate double-mutant mice (db/db-ERV1).Wild-type (WT) and transgenicmice overexpressing ERV1 only were used as controls. Experimentalperiodontitis was induced with 7-0 silk ligatures tied around the maxillarysecond molars. Half of the animals received 10 mM RvE1 daily for7 days. Gingival expression of IL-17+and IL-2+cells was evaluated byimmunohistochemistry. Peripheral blood serum samples were tested forIL-17A, IL-17F, CCL20, IL-6, and IL-10 by multiplex immunoassay.Results: Diabetic mice exhibited significantly more bone loss, withincreased levels of IL-6, IL-17, CCL20, and IL-10 at baseline comparedto the WT animals (p < 0.001). db/db-ERV1 mice were protected fromthe increased inflammatory phenotype and periodontal disease(p < 0.001 compared to db/db mice). Experimental periodontitis led toa significant increase in cytokine levels in all groups; however, it wassignificantly lower in the db/db-ERV1 mice compared to the diabeticand WT groups (p < 0.05). RvE1 treatment prevented experimentalperiodontitis-induced cytokine production in all groups; with a moresignificant impact on the db/db ERV1 group. Periodontitis increasedthe percentage of IL-17+cells in tissues in all groups; RvE1 treatmentprevented this increase in ERV1, db/db, and db/ERV1 mice anddecreased IL-2+cells in db/db and db/db ERV1 mice (p < 0.05).Conclusions: RvE1 resolves inflammation and restores periodontalhomeostasis through receptor-mediated activity and prevents excessinflammation induced by periodontitis in diabetic mice