Autoantibodies to beta1-adrenoceptors in human chronic periodontitis induce overexpression of fibroblast CD40 and trigger prostaglandin E2 generation.
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.
Sterin-Borda
L
L
Pharmacology Unit, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
Furlan
C
C
Borda
E
E
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
D001323:Autoantibodies; D019013:CD40 Antigens; D016861:Cyclooxygenase Inhibitors; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1; D015232:Dinoprostone; D007213:Indomethacin