P. gingivalis, a gram (-) anaerobe, has been recognized widely as the predominant pathogenic organism in adult periodontitis. P. gingivalis successfully colonizes the hard and soft tissues of the mouth (teeth and mucosa) and can invade and replicate in human gingival epithelial cells. Fimbriae are a major adherence-mediating determinant of P. gingivalis and also participate in the invasion process. The overall objectives of this study are the identification of the gingival epithelial cell receptor(s) for P. gingivalis fimbriae, and the determination of the epithelial cell downstream signaling events induced by P. gingivalis fimbriae-receptor binding. Our preliminary work has identified integrins as potential epithelial cell receptors for P. gingivalis fimbriae. The role of integrins as the cognate receptor for P. gingivalis fmbriae and in the subsequent signal transduction events will be main subject of this proposal. Fimbriae-receptor interactions will be investigated by antibody and peptide inhibition assays, electron microscopy and anti-sense RNA technology. The events that occur downstream of fimbriae-receptor binding will be examined by studying potentially interacting cell signaling and structural proteins. The tyrosine phosphorylation and trans- and colocalization of these proteins will be investigated by immunoprecipitation, fluorescence microscopy, and microinjection techniques. We expect this study will provide novel and crucial insights into understanding of the pathogenesis of periodontal diseases and also help advance the current treatment regimes designed to prevent or delay the disease process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DE014168-04
Application #
6775709
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Hardwick, Kevin S
Project Start
2001-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
4
Fiscal Year
2004
Total Cost
$128,493
Indirect Cost
Name
University of Washington
Department
Dentistry
Type
Schools of Dentistry
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Yilmaz, Ozlem; Verbeke, Philippe; Lamont, Richard J et al. (2006) Intercellular spreading of Porphyromonas gingivalis infection in primary gingival epithelial cells. Infect Immun 74:703-10
Zhang, Yi; Wang, Tiansong; Chen, Weibin et al. (2005) Differential protein expression by Porphyromonas gingivalis in response to secreted epithelial cell components. Proteomics 5:198-211
Park, Yoonsuk; Yilmaz, Ozlem; Jung, Il-Young et al. (2004) Identification of Porphyromonas gingivalis genes specifically expressed in human gingival epithelial cells by using differential display reverse transcription-PCR. Infect Immun 72:3752-8
Yilmaz, Ozlem; Jungas, Thomas; Verbeke, Philippe et al. (2004) Activation of the phosphatidylinositol 3-kinase/Akt pathway contributes to survival of primary epithelial cells infected with the periodontal pathogen Porphyromonas gingivalis. Infect Immun 72:3743-51
Yilmaz, Ozlem; Young, Patrick A; Lamont, Richard J et al. (2003) Gingival epithelial cell signalling and cytoskeletal responses to Porphyromonas gingivalis invasion. Microbiology 149:2417-26
Yilmaz, Ozlem; Watanabe, Kiyoko; Lamont, Richard J (2002) Involvement of integrins in fimbriae-mediated binding and invasion by Porphyromonas gingivalis. Cell Microbiol 4:305-14