Date on Master's Thesis/Doctoral Dissertation
Oral Biology, MS
Committee Co-Chair (if applicable)
Gingipains; Fibronectin; Extracellular Matrix; Protease activated receptors
Periodontitis is a chronic inflammatory disease that is characterized by severe tissue destruction of the gingiva and other tooth supporting structures; if left untreated, tooth loss and disintegration of the alveolar bone occurs. This chronic inflammatory state has been linked to other systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and Alzheimer’s disease. Porphyromonas gingivalis is the major pathogenic microbe in periodontitis. The main virulence factors of P. gingivalis are the Arg-aa and Lys-aa gingipains, which are proteolytic enzymes implicated in a plethora of activities that allow P. gingivalis to subvert the human immune system in the oral cavity and cause host tissue destruction. Here, we report that Arg-aa gingipains, RgpB and HRgpA stimulate fibroblasts to express fibronectin, a glycoprotein associated with tissue injury and repair, through the transcription of its gene promoter in a dose and time dependent fashion. Interestingly, when using a protease activated receptor 2 antagonists, gingipain induced fibronectin promoter activity was attenuated. Furthermore, gingipains stimulate fibroblasts to produce a pro-inflammatory matrix triggering production of IL-6 and IL-8 by monocytes that correlated with fibronectin-EDA expression. Taken together, our data suggests Arg-gingipains act on host fibroblasts to produce fibronectin which, stimulates immune cell activation. Taken together, these data suggest that gingipains promote and environment that disrupts host homeostasis.
Marschall, Jeffrey S., "Porphyromonas gingivalis gingipains induce a pro-inflammatory extracellular microenvironment : the role of PAR-2 and fibronectin." (2016). Electronic Theses and Dissertations. Paper 2453.
Biological Phenomena, Cell Phenomena, and Immunity Commons, Medical Immunology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons, Oral Biology and Oral Pathology Commons, Periodontics and Periodontology Commons