DOI

https://doi.org/10.25772/X213-BG58

Defense Date

2021

Document Type

Thesis

Degree Name

Master of Science

Department

Biochemistry

First Advisor

Daniel Miller

Abstract

Periodontal disease is a polymicrobial disease affecting 10-15% of the population. Periodontal disease affects the quality of life by reducing mastication and potentially causing tooth loss. Periodontal disease is also linked to more severe, systemic diseases such as cardiovascular disease and rheumatoid arthritis. Development of the diseased state occurs when the plaque biofilm shifts from healthy to dysbiotic. The shift to a dysbiotic biome brings with it a shift in bacterial presence, specifically an increase in gram-negative bacteria, such as T. denticola. T. denticola is a gram-negative, anaerobic spirochete whose relationship with oral epithelial cells is poorly understood. Preliminary data shows an increase in interleukin-36�� (IL-36��) gene expression when human immortalized gingival keratinocytes are infected with T. denticola 35405. In this study, we look at IL-36�� cytokine production in gingival keratinocytes infected with T. denticola and begin to uncover the mechanism through which IL-36�� signaling is conducted.

Initially, we established IL-36�� gene expression is increased with an increasing multiplicity of infection when HIGK cells are infected with T. denticola 35405, with expression being highest at MOI 200. Upon establishing IL-36�� expression in response to 35405, we established that IL-36�� is also upregulated in response to multiple T. denticola strains. In order to begin to investigate the signaling mechanism of IL-36��, a time point for which the highest IL-36�� expression occurred needed to be established. After establishment of this time point, we began looking for signaling receptors known to activate an innate immune response in response to T. denticola. We found TLR2 to be upregulated during IL-36�� increased expression. Suppression of TLR2 using siRNA limited IL-36�� expression, establishing it plays a role in IL-36�� signaling. Further research into signaling molecules downstream of TLR2 will help to better understand how T. denticola induces an inflammatory response and further our understanding of the role IL-36�� plays in periodontal tissue destruction.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-10-2021

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