title: The role of hyperglycemia in mechanisms of exacerbated inflammatory responses within the oral cavity.
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.
authors: Department of Periodontology, University of Florida, College of Dentistry, Gainesville, FL 32610, USA. jamieamir@me.com
authors: Jamie
authors: J
authors: Amir
authors: Matthew
authors: M
authors: Waite
authors: Jeffrey
authors: J
authors: Tobler
authors: Dana L
authors: DL
authors: Catalfamo
authors: Theofilos
authors: T
authors: Koutouzis
authors: Joseph
authors: J
authors: Katz
authors: Shannon M
authors: SM
authors: Wallet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D020239:Receptor Cross-Talk / Q000276:immunology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
chemical_list: D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4