title: Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.
abstract: This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Huaixiu
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Medical Engineering, The Second Artillery General Hospital of PLA, Beijing, China.
authors.forename: Minguang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Shisen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Stomatology, Navy General Hospital, Beijing, China.
authors.forename: Songshan
authors.initials: S
authors.lastname: Lin
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D010513:Periodontal Ligament / Q000166:cytology / Q000276:immunology / Q000473:pathology; D010518:Periodontitis / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D010646:Phentolamine / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000276:immunology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D016207:Cytokines; D008070:Lipopolysaccharides; D018340:Receptors, Adrenergic, alpha-1; D014446:Tyrosine 3-Monooxygenase; D010646:Phentolamine