title: Type 1 diabetes-associated TLR responsiveness of oral epithelial cells.
abstract: In type 1 diabetes (T1D), a Toll-like receptor (TLR)-hyper-inflammatory monocytic phenotype has been implicated as a mechanism of exacerbated tissue destruction. Other cells of the periodontium, including oral epithelial cells (OECs), express innate immune receptors, including TLRs. To delineate the TLR responses of OECs derived from T1D participants and to determine effects of the anti-inflammatory agent triclosan on the TLR-hyper-inflammatory phenotype, primary human OECs from individuals with T1D and diabetes-free individuals were stimulated with TLR ligands in the presence and/or absence of triclosan. The expression of pro-inflammatory cytokines and micro-RNAs (miRNAs) was evaluated. While the repertoire of TLRs expressed by OECs is similar to that expressed by macrophages (M), the relative amounts and ratios are significantly different. OECs demonstrate a TLR-response profile similar to that of M, yet attenuated. OECs have a unique response to P. gingivalis LPS, where miR146a and miR155 play a regulatory role in responsiveness. OECs from T1D participants are TLR-hyper-responsive, due to dysregulated induction of miR146a and miR155, which is abrogated by pre-treatment with triclosan. The aberrant TLR-activation of OECs in T1D has the potential to contribute to excessive soft- and hard-tissue destruction. Importantly, triclosan's anti-inflammatory property is effective in abrogating TLR-induced OEC hyperactivity.
authors: Department of Endodontics, College of Dentistry, University of Florida, Gainesville, USA.
authors: K G
authors: KG
authors: Neiva
authors: N L
authors: NL
authors: Calderon
authors: T R
authors: TR
authors: Alonso
authors: F
authors: F
authors: Panagakos
authors: S M
authors: SM
authors: Wallet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D018836:Inflammation Mediators / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D035683:MicroRNAs / Q000032:analysis; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology*; D010641:Phenotype; D016966:Porphyromonas gingivalis / Q000276:immunology; D051194:Toll-Like Receptor 1 / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis; D051216:Toll-Like Receptor 6 / Q000032:analysis; D051193:Toll-Like Receptors / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014260:Triclosan / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; D008024:Ligands; D008070:Lipopolysaccharides; D035683:MicroRNAs; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D053773:Transforming Growth Factor beta1; D014260:Triclosan
keywords: chemokines; cytokines; inflammation; periodontal disease; triclosan