Department of Pediatric Dentistry, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Department of Periodontology, Stomatological Hospital, Southern Medical University, Guangzhou, China.
J Oral Pathol Med. 2018 Feb;47(2):166-172. doi: 10.1111/jop.12655. Epub 2017 Nov 17.
We recently reported that the CC chemokine ligand 2 (CCL2)-CC receptor 2 (CCR2) axis was involved in the pathogenesis of oral lichen planus (OLP). However, the exact mechanism for the high expression of CCL2 in OLP specimens is not clear. Therefore, this study was designed to investigate the potential role of the toll-like receptor 4 (TLR-4) pathway in overproduction of CCL2 in OLP lesions.
Immunohistochemical staining and real-time RT-PCR were used to detect TLR-4, CCL2, and CCR2 expression in OLP lesions. Then, gingival epithelial cells from OLP lesions were established and treated with Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). CCL2 expression in epithelial cells was determined by Western blotting and real-time RT-PCR. In some experiments, TAK-242, a specific inhibitor of TLR-4, was used to block the TLR-4 pathway before cells were stimulated with LPS.
We found that TLR-4 was significantly increased in the epithelium of OLP specimens, compared with controls. Moreover, LPS can induce the over production of CCL2 in epithelial cells of OLP, in vitro. TAK-242 effectively eliminated the increase in CCL2 expression induced by LPS by blocking the TLR-4/NF-κB pathway. In addition, we again confirmed that expression of CCL2 and CCR2 was increased in OLP specimens.
Increased TLR-4 expression contributes to the upregulated expression of CCL2 in the epithelium of OLP lesions, which suggests that oral bacteria participate in the pathogenesis of OLP via the TLR-4 pathway.
我们最近报道称，CC 趋化因子配体 2（CCL2）-CC 受体 2（CCR2）轴参与了口腔扁平苔藓（OLP）的发病机制。然而，OLP 标本中 CCL2 高表达的确切机制尚不清楚。因此，本研究旨在探讨 Toll 样受体 4（TLR-4）通路在 OLP 病变中 CCL2 过度产生中的潜在作用。
采用免疫组织化学染色和实时 RT-PCR 检测 OLP 病变中 TLR-4、CCL2 和 CCR2 的表达。然后，建立 OLP 病变的牙龈上皮细胞，并用牙龈卟啉单胞菌（P. gingivalis）脂多糖（LPS）处理。通过 Western blot 和实时 RT-PCR 检测上皮细胞中 CCL2 的表达。在一些实验中，在 LPS 刺激细胞之前，使用 TLR-4 的特异性抑制剂 TAK-242 阻断 TLR-4 通路。
我们发现，与对照组相比，TLR-4 在 OLP 标本的上皮细胞中显著增加。此外，LPS 可在体外诱导 OLP 上皮细胞中 CCL2 的过度产生。TAK-242 通过阻断 TLR-4/NF-κB 通路有效消除了 LPS 诱导的 CCL2 表达增加。此外，我们再次证实 CCL2 和 CCR2 的表达在 OLP 标本中增加。
TLR-4 表达增加导致 OLP 病变上皮细胞中 CCL2 的表达上调，这表明口腔细菌通过 TLR-4 通路参与 OLP 的发病机制。
