Periodontal tissue destruction involves a complex series of events including colonization of the tooth surface and gingival sulcus by a diverse array of bacteria. This is thought to be followed by penetration of the sulcular epithelium and the elicitation of a host-response in the underlying connective tissue. A prominent bacterium in periodontal infections is P. gingivalis. Considerable efforts has been spent examine the effect of P. gingivalis and its virulence factors in vitro and on it's capacity to colonize epithelium. However, surprisingly little is known about the in vivo response to P. gingivalis in connective tissue and to specific P. gingivalis factors that are thought to modulate the host response, fimbriae and LPS. The goal of this proposal is to focus on these two specific P. gingivalis components. We will test the hypothesis that fimbriae and LPS play a cental role in activating the innate host response and in mediating PO. gingivalis induced tissue destruction. This will be accomplished by quantitative analysis of the inflammatory response, soft tissue necrosis, osteoclast activity and survival of bacteria in vivo. Mechanistic studies will be undertaken by blocking the function of fimbriae or LPS in vivo, and then determining if this causes a significant change in the host response. Most importantly, we will determine if the host-response to P. gingivalis and P. gingivalis fimbriae and/or LPS is exaggerated in diabetic mice compared to non-diabetic littermates. These analysis will focus on the difference diabetics and normals with respect to induced neutrophil/monocyte chemotaxis and osteoclastogenesis (representing primary outcome variables) and cytokine/chemokine induction, lymphocyte recruitment, soft tissue necrosis, and bacterial survival and connective tissue (representing secondary outcome variables.)

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Program Projects (P01)
Project #
5P01DE013191-04
Application #
6744856
Study Section
Special Emphasis Panel (ZDE1)
Project Start
2003-04-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2003
Total Cost
$179,669
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
Janket, S; Meurman, J H; Baird, A E et al. (2010) Salivary immunoglobulins and prevalent coronary artery disease. J Dent Res 89:389-94
Qvarnstrom, M; Janket, S; Jones, J A et al. (2008) Salivary lysozyme and prevalent hypertension. J Dent Res 87:480-4
Janket, Sok-Ja; Jones, Judith; Rich, Sharron et al. (2007) The effects of xerogenic medications on oral mucosa among the Veterans Dental Study participants. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:223-30
Miyamoto, Takanari; Yumoto, Hiromichi; Takahashi, Yusuke et al. (2006) Pathogen-accelerated atherosclerosis occurs early after exposure and can be prevented via immunization. Infect Immun 74:1376-80
Takahashi, Yusuke; Davey, Michael; Yumoto, Hiromichi et al. (2006) Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells. Cell Microbiol 8:738-57
Zhou, Qingde; Desta, Tesfahun; Fenton, Matthew et al. (2005) Cytokine profiling of macrophages exposed to Porphyromonas gingivalis, its lipopolysaccharide, or its FimA protein. Infect Immun 73:935-43
Gyurko, R; Shoji, H; Battaglino, R A et al. (2005) Inducible nitric oxide synthase mediates bone development and P. gingivalis-induced alveolar bone loss. Bone 36:472-9
Gibson 3rd, Frank C; Savelli, Juan; Van Dyke, Thomas E et al. (2005) Gingipain-specific IgG in the sera of patients with periodontal disease is necessary for opsonophagocytosis of Porphyromonas gingivalis. J Periodontol 76:1629-36
Chou, Hsin-Hua; Yumoto, Hiromichi; Davey, Michael et al. (2005) Porphyromonas gingivalis fimbria-dependent activation of inflammatory genes in human aortic endothelial cells. Infect Immun 73:5367-78
Graves, D T; Naguib, G; Lu, H et al. (2005) Inflammation is more persistent in type 1 diabetic mice. J Dent Res 84:324-8

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