The role of hyperglycemia in mechanisms of exacerbated inflammatory responses within the oral cavity |
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| Authors: | Amir Jamie Waite Matthew Tobler Jeffrey Catalfamo Dana L Koutouzis Theofilos Katz Joseph Wallet Shannon M |
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| Institution: | aDepartment of Periodontology, University of Florida, College of Dentistry, P.O. Box 100434, Gainesville, FL 32610, USA;bDepartment of Oral Biology, University of Florida, College of Dentistry, P.O. Box 100434, Gainesville, FL 32610, USA;cDepartment of Oral and Maxillofacial Diagnostic Sciences, University of Florida, College of Dentistry, P.O. Box 100434, Gainesville, FL 32610, USA |
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| Abstract: | Immune modulating factors are necessary for pathogen clearance, but also contribute to host tissues damage, as those seen in periodontal diseases. Many of these responses can be exacerbated by host conditions including type 2 diabetes T2D], where toll-like receptor 4 TLR4] and the receptor for advanced glycated end products RAGE] play a significant role. Here we investigate causality associated with the increase in inflammatory markers observed in periodontally diseased patients with T2D using multi-variant correlation analysis. Inflammation associated with periodontal diseases, characterized by elevated pro-inflammatory cytokines, innate immune receptor expression, and cellular infiltrate was exacerbated in patients with T2D. In addition, a feed forward loop regulated by poor glycemic control was associated with a loss of mucosal barrier integrity and accumulation of innate immune receptor ligands resulting in an exacerbation of ongoing inflammation, where RAGE and TLR4 cooperated to induce responses in oral epithelial cells, which were exacerbated by hyperglycemia. |
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| Keywords: | Type 2 diabetes Periodontal disease Toll-like receptor 4 Receptor for advanced glycated end products Lipopolysaccharide N-carboxyl (methyl-lysine) Oral epithelial cells Microbial translocation |
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