The Effect of Adenosine in the Phenotype of Gingival Fibroblast

Abstract

The oral microenvironment is the first site exposed to external factors such as food, liquids, allergens, microbes or even micro injuries from masticatory forces. The gingival mucosa has the specific ability to heal from micro injuries such as minor cuts without significant scar tissue formation when compared to skin. Although the gingival mucosa shows fascinating behaviors, it is still prone to inflammatory diseases, such as periodontitis. Periodontitis is an aging-associated and infection-driven inflammatory disease affecting almost half of the American adult population that leads to structural deterioration of the gingival mucosa, and ultimately to alveolar bone loss. Substantial variation in the clinical presentation of periodontitis is recognized, based on age of onset, extent, and severity (staging/grading). The specific biological mechanisms underlying phenotypic variations in the clinical presentation of periodontitis are poorly understood. Different cell types exist within the gingival tissue, including stromal gingival fibroblasts, which are a very heterogeneous population of cells that can assume diverse phenotypes. Our research was focused on the role of gingival fibroblasts in periodontitis. Previous work in our lab has identified adenosine signaling as a key pathway able to control inflammatory cytokine secretion of gingival fibroblasts. Adenosine signaling is a key metabolic pathway that regulates mucosal inflammation and tissue homeostasis. In this project, we combined data from human correlative studies and in vitro analysis of immunofluorescence to demonstrate the effect of adenosine in the inflammatory response of gingival fibroblasts, typified by the expression of CXCL1 chemokine. The selection of this chemokine is due to its ability to mediate neutrophil adhesion (a crucial event during inflammation) and attraction of additional immune cells to propagate inflammation. Thus, the overall goal of this project is to unveil the effect of adenosine in the inflammatory phenotype of gingival fibroblasts.