MECHANISMS BEHIND CX2CL1-DRIVEN MONOCYTE RECRUITMENT DURING PERIODONTITIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Periodontal disease results from chronic inflammation which is induced and maintained by the recruitment of circulating leukocytes into the gingival tissues. This research proposal is designed to investigate the mechanism by which circulating monocytes are captured by the local vasculature, the first step in the process of transmigration into gingival tissue. While many different immune system cells, chemokines, and cytokines are implicated in periodontal inflammation we choose to focus our study on CX3CL1, a chemokine associated with monocyte capture during periodontitis. Our hypothesis is that CX3CL1 promotes periodontitis by regulating the molecular migration machinery required to recruit monocyte exit from the circulation to enter the underlying gingival tissue. In Aim I. we will investigate CX3CL1 regulation of the molecular machinery needed for adhesion and transmigration. In Aim II. we will link CX3CL1 signaling to the regulation of ROCK, a serine/threonine kinase with potent effects on monocyte adhesion and transendothelial migration. The overall goal of this research project is to take advantage of an easy-to-manipulate cell culture model system to define key regulatory mechanisms in CX3CL1-driven monocyte recruitment, which will be the foundation for developing an in vivo periodontitis experimental model.