Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, Indianapolis, IN 46202-5186, United States.
Arch Oral Biol. 2012 May;57(5):495-502. doi: 10.1016/j.archoralbio.2011.10.013. Epub 2011 Nov 26.
Oral lichen planus (OLP) is a chronic inflammatory condition of the mucosa mediated by a complex signalling network between the keratinocytes and the sub-epithelial lymphocytes. Since OLP occurs in constantly renewing epithelium continuously exposed to commensals, we hypothesised that the epithelial cell microflora interactions may mediate the persistent inflammation. By virtue of their ability to respond to most oral commensal microorganisms, the toll like receptor-2 (TLR-2) and TLR-4 are the most widely investigated receptors in oral diseases. The overall objective of this study was to investigate the role of TLR-2 and TLR-4 in OLP.
Systemically healthy OLP and control subjects were recruited after obtaining the institutional review board approval. Expression of TLR-2 and TLR-4 proteins and transcripts in the tissue epithelium and in the epithelial cells isolated from saliva were determined by immunohistochemistry and quantitative real-time polymerase chain reaction respectively.
The tissue epithelium and the salivary epithelial cells expressed reduced TLR-2 and increased TLR-4 proteins and transcripts in OLP. The salivary epithelial cells from OLP subjects secreted elevated IL-12. However, upon stimulation with bacterial lipopolysaccharide the epithelial cells from OLP exhibited a mixed Th1 (IL-12) and Th2 (IL-4) response. Presence of dexamethasone significantly reduced inflammatory cytokines in the in vitro stimulated cultures of salivary epithelial cells from OLP subjects.
Collectively, our data support a critical role for the host-microbial interactions in the OLP pathogenesis. The potential use of exfoliated oral epithelial cells in saliva for functional analysis exponentially increases its value as biological specimen for clinical research.
口腔扁平苔藓(OLP)是一种由角质形成细胞和上皮下淋巴细胞之间复杂信号网络介导的慢性炎症性疾病。由于 OLP 发生在不断更新的上皮组织中,这些上皮组织持续暴露于共生菌中,我们假设上皮细胞微生物群相互作用可能介导持续的炎症。由于其能够对大多数口腔共生微生物做出反应,Toll 样受体 2(TLR-2)和 TLR-4 是口腔疾病中研究最广泛的受体。本研究的总体目的是研究 TLR-2 和 TLR-4 在 OLP 中的作用。
在获得机构审查委员会批准后,招募了系统性健康的 OLP 和对照受试者。通过免疫组织化学和定量实时聚合酶链反应分别确定组织上皮和从唾液中分离的上皮细胞中 TLR-2 和 TLR-4 蛋白和转录物的表达。
OLP 组织上皮和唾液上皮细胞表达减少的 TLR-2 和增加的 TLR-4 蛋白和转录物。OLP 受试者的唾液上皮细胞分泌升高的 IL-12。然而,在用细菌脂多糖刺激后,OLP 的上皮细胞表现出混合的 Th1(IL-12)和 Th2(IL-4)反应。地塞米松的存在显著降低了 OLP 受试者唾液上皮细胞体外刺激培养物中的炎症细胞因子。
总之,我们的数据支持宿主-微生物相互作用在 OLP 发病机制中的关键作用。脱落口腔上皮细胞在唾液中的功能分析的潜在用途极大地增加了其作为临床研究生物标本的价值。