Protease-activated receptor 2 has pivotal roles in cellular mechanisms involved in experimental periodontitis.
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.
Wong
David M
DM
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Tam
Vivian
V
Lam
Roselind
R
Walsh
Katrina A
KA
Tatarczuch
Liliana
L
Pagel
Charles N
CN
Reynolds
Eric C
EC
O'Brien-Simpson
Neil M
NM
Mackie
Eleanor J
EJ
Pike
Robert N
RN
D016301:Alveolar Bone Loss / Q000276:immunology / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology; D044464:Receptor, PAR-2 / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens / Q000096:biosynthesis / Q000276:immunology
D016207:Cytokines; D044464:Receptor, PAR-2; D018800:Thy-1 Antigens