Resolvin D1 protects periodontal ligament

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. PGE(2), leukotriene B-4 (LTB4), and lipoxin A(4) (LXA(4)) 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-1 beta and TNF-alpha enhanced the production of PGE(2). Treatment of PDL cells and monocytes with 0.1-10 ng/ml RvD1 (0.27-27 M) reduced cytokine induced production of PGE(2) and upregulated LXA(4) 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 (LXA(4)) and suggest resolution pathway synergy establishing a novel mechanism for the proresolution activity of the omega-3 docosahexaenoic acid-derived resolution agonist RvD1.