title: 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.
authors.affiliation: Department of Clinical Dentistry-Center for Clinical Dental Research, University of Bergen, Bergen, Norway;
authors.forename: Manal
authors.initials: M
authors.lastname: Mustafa
authors.forename: Ahmed
authors.initials: A
authors.lastname: Zarrough
authors.forename: Anne Isine
authors.initials: AI
authors.lastname: Bolstad
authors.forename: Henning
authors.initials: H
authors.lastname: Lygre
authors.forename: Kamal
authors.initials: K
authors.lastname: Mustafa
authors.forename: Hatice
authors.initials: H
authors.lastname: Hasturk
authors.forename: Charles
authors.initials: C
authors.lastname: Serhan
authors.forename: Alpdogan
authors.initials: A
authors.lastname: Kantarci
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D044045:Lipoxins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D044045:Lipoxins; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D015232:Dinoprostone
keywords: inflammation; regeneration; resolution