Protease-activated receptor 2 has pivotal roles in cellular mechanisms involved in experimental periodontitis

Infect Immun. 2010 Feb;78(2):629-38. doi: 10.1128/IAI.01019-09. Epub 2009 Nov 23.

Abstract

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 beta (TCRbeta) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss / immunology
  • Alveolar Bone Loss / pathology
  • Animals
  • Cytokines / immunology
  • Flow Cytometry
  • Lymphocyte Activation / immunology
  • Mast Cells / immunology
  • Mice
  • Mice, Knockout
  • Periodontitis / immunology*
  • Periodontitis / pathology
  • Porphyromonas gingivalis / immunology
  • Receptor, PAR-2 / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • Thy-1 Antigens / biosynthesis
  • Thy-1 Antigens / immunology

Substances

  • Cytokines
  • Receptor, PAR-2
  • Thy-1 Antigens