Protease-Activated Receptor 2 Has Pivotal Roles in Cellular Mechanisms Involved in Experimental Periodontitis

• Published in: Infection and Immunity Vol. 78; no. 2; pp. 629 - 638
• Main Authors: Wong, David M, Tam, Vivian, Lam, Roselind, Walsh, Katrina A, Tatarczuch, Liliana, Pagel, Charles N, Reynolds, Eric C, O'Brien-Simpson, Neil M, Mackie, Eleanor J, Pike, Robert N
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.02.2010; American Society for Microbiology (ASM)
• Subjects: Alveolar Bone Loss - immunology; Alveolar Bone Loss - pathology; Animals; Biological and medical sciences; Bone resorption; CD4 antigen; CD8 antigen; CD90 antigen; Cytokines - immunology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; g-Interferon; Granulocyte-macrophage colony-stimulating factor; Helper cells; Host Response and Inflammation; Inflammation; Interleukin 2; Lymphocyte Activation - immunology; Lymphocytes T; Mast cells; Mast Cells - immunology; Mice; Mice, Knockout; Microbiology; Periodontitis; Periodontitis - immunology; Periodontitis - pathology; Porphyromonas gingivalis; Porphyromonas gingivalis - immunology; Receptor, PAR-2 - immunology; T-cell receptor; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology; Thy-1 Antigens - biosynthesis; Thy-1 Antigens - immunology; Tumor necrosis factor-a; Peptidases; Periodontal disease; Periodontitis; Enzyme; Stomatology; Hydrolases; Immunity; Mechanism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01019-09

The tissue destruction seen in chronic periodontitis is commonly accepted to involve extensive upregulation of the host inflammatory response. Protease-activated receptor 2 (PAR-2)-null mice infected with Porphyromonas gingivalis did not display periodontal bone resorption in contrast to wild-type-infected and PAR-1-null-infected mice. Histological examination of tissues confirmed the lowered bone resorption in PAR-2-null mice and identified a substantial decrease in mast cells infiltrating the periodontal tissues of these mice. T cells from P. gingivalis-infected or immunized PAR-2-null mice proliferated less in response to antigen than those from wild-type animals. CD90 (Thy1.2) expression on CD4⁺ and CD8⁺ T-cell-receptor β (TCRβ) T cells was significantly (P < 0.001) decreased in antigen-immunized PAR-2-null mice compared to sham-immunized PAR-2-null mice; this was not observed in wild-type controls. T cells from infected or antigen-immunized PAR-2-null mice had a significantly different Th1/inflammatory cytokine profile from wild-type cells: in particular, gamma interferon, interleukins (interleukin-2, -3, and -17), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha demonstrated lower expression than wild-type controls. The absence of PAR-2 therefore appears to substantially decrease T-cell activation and the Th1/inflammatory response. Regulation of such proinflammatory mechanisms in T cells and mast cells by PAR-2 suggests a pivotal role in the pathogenesis of the disease.