Department of Oral pathology, the School of Stomatology, the Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Department of Maxillofacial surgery, the School of Stomatology, the Fourth Military Medical University, Xi'an, Shaanxi Province, China.
J Oral Pathol Med. 2017 Nov;46(10):1015-1022. doi: 10.1111/jop.12595. Epub 2017 Jul 2.
Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory oral mucosal disease of unknown etiology, and liquefaction degeneration in the basal keratinocytes is one of the specific histological changes. However, the understanding of liquefaction degeneration is still very limited, and how does it affect the prognosis of LP is largely unknown. Therefore, the objective of this study was to clarify the intrinsic change behind the liquefaction degeneration in lichen planus and to evaluate the effect of the OLP-typical cytokine, IFN-γ, on these changes.
Biopsies were collected from patients with OLP; immunochemistry staining was performed to analyze E-cadherin, vimentin, CK19, β1 integrin, nestin, STAT1, and STAT3 expression. Primary oral epithelial cells were cultured in vitro, and 20 ng/mL IFN-γ was applied to assay the effect on epithelial cells.
E-cadherin expression was decreased but vimentin expression was increased in the OLP epithelial cells that undergo liquefaction degeneration, showing the typical epithelial-mesenchymal transition (EMT) alteration. In vitro research showed that the OLP-typical cytokine, IFN-γ, possesses EMT-inducing ability, and the primary oral epithelial cells stimulated by IFN-γ acquired some properties of cancer stem cells, expressing more β1 integrin, α6 integrin, and nestin. In addition, the major downstream mediator of IFN-γ receptor, STAT1, was expressed more intensive and extensive with the malignant transition of OLP.
Liquefaction degeneration in oral lichen planus is an EMT phenomenon, the IFN-γ may be the main inducer, and IFN-γ signaling might be implicated in malignant transition of OLP.
口腔扁平苔藓(OLP)是一种病因不明的 T 细胞介导的慢性炎症性口腔黏膜疾病,基底角质形成细胞的液化变性是其特异性组织学改变之一。然而,对液化变性的认识仍然非常有限,它如何影响 LP 的预后也知之甚少。因此,本研究旨在阐明扁平苔藓液化变性背后的内在变化,并评估 OLP 典型细胞因子 IFN-γ对这些变化的影响。
收集 OLP 患者的活检组织;进行免疫组织化学染色,分析 E-钙黏蛋白、波形蛋白、CK19、β1 整合素、巢蛋白、STAT1 和 STAT3 的表达。体外培养原代口腔上皮细胞,应用 20ng/ml IFN-γ 检测其对上皮细胞的作用。
OLP 上皮细胞发生液化变性时,E-钙黏蛋白表达降低,波形蛋白表达增加,表现出典型的上皮-间充质转化(EMT)改变。体外研究表明,OLP 典型细胞因子 IFN-γ具有诱导 EMT 的能力,IFN-γ 刺激的原代口腔上皮细胞获得了一些癌症干细胞的特性,表达更多的β1 整合素、α6 整合素和巢蛋白。此外,IFN-γ 受体的主要下游介质 STAT1 在 OLP 恶性转化过程中表达更为密集和广泛。
口腔扁平苔藓的液化变性是一种 EMT 现象,IFN-γ 可能是主要诱导因子,IFN-γ 信号通路可能参与 OLP 的恶性转化。