title: Autoantibodies to beta1-adrenoceptors in human chronic periodontitis induce overexpression of fibroblast CD40 and trigger prostaglandin E2 generation.
abstract: OBJECTIVE
  Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate beta(1)-adrenoceptors (beta(1)-AR) of human gingival fibroblasts were studied to provide evidence of altered humoral immune response in chronic periodontal disease.
  
  
  METHODS
  Flow cytometry and enzyme-linked immunosorbent assay using cell culture-adherent gingival fibroblasts and/or their purified membranes and/or a synthetic peptide corresponding to the second extracellular loop of human beta(1)-AR were used to detect serum antibodies. The effects of antibodies from chronic periodontal disease patients on PGE(2) generation and CD40 expression were also tested.
  
  
  RESULTS
  Circulating immunoglobulin G (IgG) from chronic periodontal disease patients (but not from normal individuals) interacted with the fibroblast surface, activating beta(1)-AR. Atenolol or CGP 20712 (beta 1-AR antagonists) and beta(1) synthetic peptide inhibited the interaction of IgG with beta(1)-AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist-like activity associated with specific beta(1)-AR activation, increasing PGE(2) generation and CD40 overexpression. The corresponding affinity-purified anti-beta(1)-AR peptide IgG mimicked these effects. Both effects were prevented by inhibition of cyclo-oxygenase.
  
  
  CONCLUSIONS
  This article supports the participation of humoral immune alterations in chronic periodontal disease resulting in postsynaptic functional deregulation. Overproduction of proinflammatory mediators (PGE(2) and CD40 expression) is induced as a consequence of antibody-beta(1)-AR interaction. The PGE(2)-CD40-IgG axis may play a part in the pathophysiological mechanisms underlying the inflammatory process in chronic periodontal disease.
authors.affiliation: Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Sterin-Borda
authors.forename: C
authors.initials: C
authors.lastname: Furlan
authors.forename: E
authors.initials: E
authors.lastname: Borda
mesh_terms: D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology*; D018441:Biofilms; D019013:CD40 Antigens / Q000096:biosynthesis*; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000276:immunology* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005881:Gingiva / Q000166:cytology / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry / Q000276:immunology; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D001323:Autoantibodies; D019013:CD40 Antigens; D016861:Cyclooxygenase Inhibitors; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1; D015232:Dinoprostone; D007213:Indomethacin