Epithelial tissues function as the first line of defense between the host and the outside environment, which includes pathogenic and non-pathogenic bacteria. In the oral cavity, epithelial tissues are constantly exposed to a variety of bacteria, but most individuals maintain a healthy homeostasis. However, little is known about how this homeostatic relationship is orchestrated. Preliminary data utilizing RNA interference via siRNA suggest that compensatory mechanisms exist among Pattern Recognition Receptors (PRRs). Additionally, when a PRR is activated, the expression of other PRRs increases. These data strongly suggest that epithelial cells have novel mechanisms to balance expression of PRRs in response to bacteria. The hypothesis to be tested in this proposal is that PRRs balance their responses in epithelial innate immunity upon exposure to oral bacteria depending on the characteristics and pathogenicity of the bacteria. The goal of this work is to understand cross- communication between epithelial receptors as well as the specific signaling pathways that are involved in the PRR cross-communication in epithelial innate immunity. This proposal will investigate how various epithelial cell receptors compensate for the activation or absence of one another in inducing appropriate epithelial innate immune responses. In addition, this proposal will examine if activation of PRRs differentially regulate the NF?B and MAPK signaling pathways, thus tailoring epithelial innate immune responses to individual bacterium. Since bacteria have multiple Microbial-Associated Molecular Patterns and epithelial cells express multiple PRRs, it is reasonable to expect that there is cross-communication and balancing between these PRRs in epithelial responses to various bacteria in order to induce appropriate innate immune responses. The proposed studies will lead to a better understanding of the way oral epithelia produce appropriate innate immune responses to pathogenic and non-pathogenic bacteria, guiding a way to new therapeutic targets to prevent and treat oral diseases, such as periodontal disease.

Public Health Relevance

The specific aims to be studied include investigation of how various epithelial cell receptors compensate for the activation or absence of one another in inducing appropriate epithelial innate immune responses. This proposal will also investigate if activation of pattern-recognition receptors differentially regulate the NF?B and MAPK signaling pathways, thus tailoring epithelial innate immune responses to individual bacterium. The proposed studies will lead to a better understanding of the way oral epithelia produce appropriate innate immune responses to pathogenic and non- pathogenic bacteria, guiding a way to new therapeutic targets to prevent and treat oral diseases, such as periodontal disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE019632-01
Application #
7631989
Study Section
Special Emphasis Panel (ZRG1-MOSS-B (02))
Program Officer
Lunsford, Dwayne
Project Start
2009-08-01
Project End
2014-04-30
Budget Start
2009-08-01
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$351,000
Indirect Cost
Name
University of Washington
Department
Dentistry
Type
Schools of Dentistry
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Drury, Jeanie L; Chung, Whasun Oh (2015) DNA methylation differentially regulates cytokine secretion in gingival epithelia in response to bacterial challenges. Pathog Dis 73:1-6
Promsong, Aornrutai; Chung, Whasun Oh; Satthakarn, Surada et al. (2015) Ellagic acid modulates the expression of oral innate immune mediators: potential role in mucosal protection. J Oral Pathol Med 44:214-21
Satthakarn, S; Chung, W O; Promsong, A et al. (2015) Houttuynia cordata modulates oral innate immune mediators: potential role of herbal plant on oral health. Oral Dis 21:512-8
Gil, Sucheol; Coldwell, Susan; Drury, Jeanie L et al. (2015) Genotype-specific regulation of oral innate immunity by T2R38 taste receptor. Mol Immunol 68:663-70
Kretschmar, S; Yin, L; Roberts, F et al. (2012) Protease inhibitor levels in periodontal health and disease. J Periodontal Res 47:228-35
Yin, L; Chung, W O (2011) Epigenetic regulation of human ?-defensin 2 and CC chemokine ligand 20 expression in gingival epithelial cells in response to oral bacteria. Mucosal Immunol 4:409-19