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Autoantibodies to β 1 ‐adrenoceptors in human chronic periodontitis induce overexpression of fibroblast CD40 and trigger prostaglandin E 2 generation
Author(s) -
SterinBorda L.,
Furlan C.,
Borda E.
Publication year - 2009
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2008.01139.x
Subject(s) - autoantibody , proinflammatory cytokine , immune system , antibody , pathogenesis , cd40 , immunology , chronic periodontitis , immunoglobulin g , periodontitis , chemistry , endocrinology , biology , medicine , inflammation , biochemistry , in vitro , cytotoxic t cell
Background and Objective: Autoimmune mechanisms may contribute to the pathogenesis of periodontal disease. Autoantibodies with the potential to bind and activate β 1 ‐adrenoceptors (β 1 ‐AR) of human gingival fibroblasts were studied to provide evidence of altered humoral immune response in chronic periodontal disease. 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 β 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 β 1 ‐AR. Atenolol or CGP 20712 (beta 1‐AR antagonists) and β 1 synthetic peptide inhibited the interaction of IgG with β 1 ‐AR. Immunoglobulin G from chronic periodontal disease patients also displayed agonist‐like activity associated with specific β 1 ‐AR activation, increasing PGE 2 generation and CD40 overexpression. The corresponding affinity‐purified anti‐β 1 ‐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 (PGE 2 and CD40 expression) is induced as a consequence of antibody–β 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.