Cigarette smoke extract modulates human β-defensin-2 and interleukin-8 expression in human gingival epithelial cells
Cigarette smoke extract modulates human β-defensin-2 and interleukin-8 expression in human gingival epithelial cells
复制标题
DOI：
10.1111/j.1600-0765.2008.01153.x
复制
发表时间：
2009-08-01
影响因子：
3.5
通讯作者：
Pichyangkul, S.
中科院分区：
文献类型：
--
作者：
Mahanonda, R.;Sa-Ard-Iam, N.;Pichyangkul, S.
背景与目的：人牙龈上皮细胞（HGECs）持续暴露于口腔细菌和其他有害物质。它们对刺激的反应在维持牙周内环境稳定中至关重要。本研究旨在探讨香烟烟雾提取物（CSE）对HGECs天然免疫功能的调节作用。材料与方法：采用逆转录-聚合酶链反应（RT-PCR）方法检测HGECs Toll样受体（TLR）的表达。CSE或尼古丁对抗菌肽人β-防御素-2（hBD-2）和促炎细胞因子白细胞介素（IL）-8在刺激的HGEC cultures的表达的影响进行了评估，通过RT-PCR和酶联免疫吸附试验。结果：HGECs表达TLRs 1，2，3，5，6，9，10的mRNA，和最低限度的TLR 4，但不是TLRs 7或8。用高度纯化的TLR 2、3或5配体刺激HGEC导致hBD-2和IL-8的表达。与单独使用任何一种试剂的刺激相比，在用牙龈卟啉单胞菌脂多糖（TLR 2配体）和肿瘤坏死因子-α联合刺激后的HGECs中观察到hBD-2和IL-8的增强。CSE暴露后，hBD-2的表达显着减少刺激HGEC文化，而IL-8的表达显着增加。这些影响也被观察到，但显着衰减，尼古丁treatment.Conclusion：人牙龈上皮细胞通过TLR信号转导在协调牙周组织的先天免疫反应中起着至关重要的作用。我们的研究结果代表了第一次证明，CSE可以通过抑制hBD-2和增强IL-8的产生来调节HGEC的功能，这可能是促进牙周病的一种可能的机制。
Background and Objective:Human gingival epithelial cells (HGECs) are continually exposed to oral bacteria and to other harmful agents. Their responses to stimuli are critical in maintaining periodontal homeostasis. The aim of this study was to investigate the modulating effect of cigarette smoke extract (CSE) on the innate immune responses of HGECs.Material and Methods:Toll-like receptor (TLR) expression of HGECs was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The effect of CSE or nicotine on the expression of the antimicrobial peptide human beta-defensin-2 (hBD-2) and the pro-inflammatory cytokine interleukin (IL)-8 in stimulated HGEC cultures was evaluated by RT-PCR and enzyme-linked immunosorbent assay.Results:The HGECs expressed mRNA of TLRs 1, 2, 3, 5, 6, 9, 10, and minimally of TLR4, but not of TLRs 7 or 8. Stimulation of HGECs with highly purified TLR2, 3 or 5 ligands led to expression of hBD-2 and of IL-8. Enhancement of hBD-2 and IL-8 was observed in HGECs after combined stimulation with Porphyromonas gingivalis lipopolysaccharide (TLR2 ligand) and tumour necrosis factor-alpha, compared with stimulation using either agent alone. After CSE exposure, hBD-2 expression was markedly reduced in stimulated HGEC cultures, whereas IL-8 expression was markedly increased. These effects were also observed, but were markedly attenuated, upon nicotine treatment.Conclusion:Human gingival epithelial cells play a critical role in orchestrating the innate immune responses of periodontal tissue via TLR signalling. Our results represent the first demonstration that CSE can modulate HGEC function by suppressing hBD-2 and enhancing IL-8 production, and this may be, in part, a possible mechanism which promotes periodontal disease.