Resolvin D1 protects periodontal ligament

Abstract

Resolution agonists are endogenous mediators that drive inflammation to homeostasis. We earlier demonstrated in vivo activity of resolvins and lipoxins on regenerative periodontal wound healing. The goal of this study was to determine the impact of resolvin D1 (RvD1) on the function of human periodontal ligament (PDL) fibroblasts, which are critical for wound healing during regeneration of the soft and hard tissues around teeth. Primary cells were cultured from biopsies obtained from three individuals free of periodontal diseases. Peripheral blood mononuclear cells were isolated by density gradient centrifugation from whole blood of healthy volunteers. PGE2, leukotriene B4 (LTB4), and lipoxin A4 (LXA4) in culture supernatants were measured by ELISA. The direct impact of RvD1 on PDL fibroblast proliferation was measured and wound closure was analyzed in vitro using a fibroblast culture "scratch assay." PDL fibroblast function in response to RvD1 was further characterized by basic FGF production by ELISA. IL-1β and TNF-α enhanced the production of PGE2. Treatment of PDL cells and monocytes with 0.1-10 ng/ml RvD1 (0.27-27 M) reduced cytokine induced production of PGE2 and upregulated LXA4 production by both PDL cells and monocytes. RvD1 significantly enhanced PDL fibroblast proliferation and wound closure as well as basic FGF release. The results demonstrate that anti-inflammatory and proresolution actions of RvD1 with upregulation of arachidonic acid-derived endogenous resolution pathways (LXA4) and suggest resolution pathway synergy establishing a novel mechanism for the proresolution activity of the ω-3 docosahexaenoic acid-derived resolution agonist RvD1.

Higher Intakes of Fruits and Vegetables, β-Carotene, Vitamin C, α-Tocopherol, EPA, and DHA Are Positively Associated with Periodontal Healing after Nonsurgical Periodontal Therapy in Nonsmokers but Not in Smokers

“…In a recent clinical trial, patients undergoing SRP taking a supplement with 300 mg/d of EPA + DHA had a lower mean PD, compared with those taking placebo (31). In vitro, resolvin D1, a downstream metabolite of DHA, has been shown to optimize healing of periodontal biopsies through downregulation of inflammatory mediators (50). Therefore, the consumption of fish or the use of v-3 FAs in conjunction with SRP should be further investigated.…”

LXA4 actions direct fibroblast function and wound closure

“…showed that the treatment of human periodontal ligament cells (PDL; a fibroblast-like cell) with RvD1, reduces cytokine induced production of the pro-inflammatory mediator prostaglandin E 2 , and up-regulates LXA 4 production. In addition, RvD1 significantly enhanced PDL proliferation, wound closure and fibroblast growth factor (FGF) release [36]. In another study, using a rat model of dorsal skin wound, Spite et al .…”

Activation of autophagy in macrophages by pro-resolving lipid mediators

“…7,8 At least 2 series of resolvins have been recognized: D-series resolvins are oxygenation products of docosahexaenoic acid (DHA) and E-series are synthetized from eicosapentaenoic acid (EPA). Resolvin D1 (RvD1) is among the best studied SPMs, promoting resolution after lung or kidney damage, 9,10 in periodontal diseases 11 and in allergic airways responses. 12 Moreover, RvD1 increases efferocytosis 13 by promoting an antiinflammatory/pro-resolving "M2-like" macrophage phenotype.…”