Porphyromonas gingivalis (Pg) is a keystone periodontal pathogen. Controlling chronic inflammation elicited by periodontal pathogens is thought central to mitigating soft and hard tissue destruction that characterizes periodontal disease (PD). Clinical treatment of patients with moderate to severe PD typically requires highly invasive approaches. Thus, development of non-invasive measures to therapeutically regulate pathogen-driven inflammation and limit oral bone loss are sought to augment current PD clinical treatment modalities. Recent studies have identified that one group of nuclear hormone receptors, peroxisome proliferator-activated receptors (PPARs), as potential molecules of therapeutic value as PPARs have been shown to control expression of genes involved in inflammation. Although some supportive data exists regarding the role played by PPARs in pathogen- induced inflammation, there is a significant gap in our knowledge in the context of PD-associated bacterial infection-elicited inflammation, and oral bone loss. Based on our preliminary data, and the gap in knowledge regarding specific PPAR exploitation as a therapeutic target for controlling Pg infection-elicited inflammation and oral bone loss, we propose that that PPARs control the expression of key inflammatory elements that contribute inflammation and oral bone loss elicited by the defined periodontal pathogen Pg. Our approach, will utilize an in vitro screen employing human tissue resident macrophages and epithelial cells to identify a PPAR agonist or antagonist that most significantly reduces cellular inflammatory response to Pg challenge. This PPAR-targeting molecule will then be tested in an animal model to define its therapeutic value in reducing Pg oral infection- elicited inflammation and oral bone loss.
As bacterial-induced chronic inflammation drives the soft and hard tissue damage associated with periodontal disease, novel approaches to control inflammation are sought to augment current periodontal therapy. We speculate that peroxisome proliferator-activated receptor (PPAR) modulation controls inflammation and oral bone loss elicited by periodontal pathogens such as Porphyromonas gingivalis. We will employ human cells and mouse modeling, to define specific PPAR candidate modulator(s) as novel therapeutics targeting P. gingivalis-elicited inflammation and oral bone loss.
| Papadopoulos, G; Shaik-Dasthagirisaheb, Y B; Huang, N et al. (2017) Immunologic environment influences macrophage response to Porphyromonas gingivalis. Mol Oral Microbiol 32:250-261 |
| Shaik-Dasthagirisaheb, Yazdani B; Mekasha, Samrawit; He, Xianbao et al. (2016) Signaling events in pathogen-induced macrophage foam cell formation. Pathog Dis 74: |
