Santoro Amerigo, Majorana Alessandra, Bardellini Elena, Festa Silvana, Sapelli Pierluigi, Facchetti Fabio
Department of Odontostomatology, University of Brescia, Spedali Civili Brescia, Brescia, Italy.
J Pathol. 2003 Nov;201(3):466-72. doi: 10.1002/path.1423.
Lichen planus (LP) is a chronic inflammatory disorder involving cutaneous and mucosal surfaces, characterized by a T-cell-mediated immune response against epithelial cells, with persistent accumulation of T lymphocytes and epithelial cell damage. The mechanisms involved in this chronic inflammatory disease are largely unknown. A pivotal role in the pathogenesis of long-lasting inflammatory processes is played by the activation of nuclear factor kappa B (NF-kappaB), a primary transcription factor which upon translocation to the nucleus, binds to promoter regions of different genes encoding immune and pro-inflammatory mediators. Using immunohistochemistry, the present study analysed the expression of NF-kappaB in 25 cases of cutaneous LP (CLP) and 28 cases of oral LP (OLP) and correlated this with the recruitment of cytotoxic T-cells (expressing Tia-1 or perforin) in the inflammatory infiltrate. Nuclear NF-kappaB was expressed on basal and suprabasal keratinocytes in all cases of LP, while normal epithelium was consistently negative; OLP contained significantly higher numbers of NF-kappaB-positive keratinocytes than CLP (means: 89.32 versus 22.6; p<0.05). Furthermore, nuclear NF-kappaB expression by epithelial cells correlated with the amount of cytotoxic cell infiltration (p<0.02). These data suggest that increased NF-kappaB activity may represent the basis of maintenance of the inflammatory response. The differences observed between NF-kappaB expression on epithelial cells in OLP and CLP and their correlation with the degree of cytotoxic inflammatory infiltrate might explain the different clinical courses of the two variants of the disease, since OLP is typically more recalcitrant than CLP. As proposed for other chronic inflammatory disorders associated with increased NF-kappaB activity, the involvement of NF-kappaB in the pathogenesis of LP could be considered for selective therapeutic inhibitory targeting.
扁平苔藓（LP）是一种累及皮肤和黏膜表面的慢性炎症性疾病，其特征为针对上皮细胞的T细胞介导的免疫反应，伴有T淋巴细胞的持续积聚和上皮细胞损伤。这种慢性炎症性疾病所涉及的机制在很大程度上尚不清楚。核因子κB（NF-κB）的激活在持久炎症过程的发病机制中起关键作用，NF-κB是一种主要的转录因子，转位至细胞核后，会与编码免疫和促炎介质的不同基因的启动子区域结合。本研究采用免疫组织化学方法分析了25例皮肤扁平苔藓（CLP）和28例口腔扁平苔藓（OLP）中NF-κB的表达情况，并将其与炎症浸润中细胞毒性T细胞（表达Tia-1或穿孔素）的募集情况进行关联分析。在所有LP病例中，核NF-κB在基底和基底上层角质形成细胞中表达，而正常上皮始终为阴性；OLP中NF-κB阳性角质形成细胞的数量显著高于CLP（平均值：89.32对22.6；p<0.05）。此外，上皮细胞核NF-κB的表达与细胞毒性细胞浸润的数量相关（p<0.02）。这些数据表明，NF-κB活性增加可能是炎症反应持续存在的基础。OLP和CLP上皮细胞中NF-κB表达的差异及其与细胞毒性炎症浸润程度的相关性，可能解释了该疾病两种变体不同的临床病程，因为OLP通常比CLP更难治疗。正如针对其他与NF-κB活性增加相关的慢性炎症性疾病所提出的那样，NF-κB参与LP发病机制这一点可考虑用于选择性治疗性抑制靶点。
