Autoantibodies to β1-adrenoceptors in human chronic periodontitis induce overexpression of fibroblast CD40 and trigger PGE2 generation

Abstract

Background and Objective: Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate b1 -adrenoceptors (b1 -AR) of human gingival fibroblasts were studied to provide evidence of altered humoral immune response in chronic periodontal 2disease. Material and 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 b1-AR were used to detect serum antibodies. The effects of antibodies from chronic periodontal disease patients on PGE2 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, 3activating b1-AR. Atenolol or CGP 20712 and b1 synthetic peptide inhibited the 4interaction of IgG with b1-AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist-like activity associated with specific b1-AR activation, increasing PGE2 generation and CD40 overexpression. The corresponding affinity-purified anti-b1 -AR peptide IgG mimicked these effects. Both effects were prevented by inhibition of cyclo-oxygenase. Conclusion: This article supports the participation of humoral immune alterations in chronic periodontal disease resulting in postsynaptic functional deregulation. Overproduction of proinflammatory mediators (PGE2 and CD40 expression) is induced as a consequence of antibody–b1 -AR interaction. The PGE2–CD40–IgG 5axis may play a part in the pathophysiological mechanisms underlying the inflammatory process in chronic periodontal disease.