Type 1 Diabetes–associated TLR Responsiveness of Oral Epithelial Cells. (February 2014)

• Record Type: Journal Article
• Authors: Neiva, K.G.; Calderon, N.L.; Alonso, T.R.; Panagakos, F.; Wallet, S.M.
• Is Part Of: Journal of dental research. Volume 93:Number 2(2014:Feb.)
• Page Start: 169
• Page End: 174
• Publication Date: 2014-02
• Subjects: triclosan -- inflammation -- cytokines -- chemokines -- periodontal disease; Dentistry -- Periodicals; Dentistry -- Social aspects -- Periodicals; Dentistry -- Periodicals; Research -- Periodicals; 617.6005
• DOI: 10.1177/0022034513516345
• Languages: English
• ISSNs: 0022-0345

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 (Mϕ), the relative amounts and ratios are significantly different. OECs demonstrate a TLR-response profile similar to that of Mϕ, 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.