Department of Endodontics, College of Dentistry, University of Florida, Gainesville, USA.
J Dent Res. 2014 Feb;93(2):169-74. doi: 10.1177/0022034513516345. Epub 2013 Dec 13.
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.
在 1 型糖尿病 (T1D) 中，Toll 样受体 (TLR)-炎症性单核细胞表型被认为是加剧组织破坏的一种机制。牙周组织的其他细胞，包括口腔上皮细胞 (OEC)，表达先天免疫受体，包括 TLR。为了描绘源自 T1D 参与者的 OEC 的 TLR 反应，并确定抗炎剂三氯生对 TLR-炎症表型的影响，从 T1D 参与者和无糖尿病个体中分离出原代人 OEC，并用 TLR 配体在存在和/或不存在三氯生的情况下进行刺激。评估促炎细胞因子和 micro-RNAs (miRNAs) 的表达。虽然 OECs 表达的 TLR 谱与巨噬细胞 (M) 表达的 TLR 谱相似，但相对数量和比例有很大差异。OEC 表现出与 M 相似但减弱的 TLR 反应谱。OEC 对 P. gingivalis LPS 有独特的反应，其中 miR146a 和 miR155 在反应性中起调节作用。由于 miR146a 和 miR155 的失调诱导，T1D 参与者的 OEC 对 TLR 反应过度，三氯生预处理可消除这种过度反应。T1D 中 OEC 的异常 TLR 激活有可能导致过度的软组织和硬组织破坏。重要的是，三氯生的抗炎特性可有效阻断 TLR 诱导的 OEC 过度活跃。
