Salem A, Al-Samadi A, Stegajev V, Stark H, Häyrinen-Immonen R, Ainola M, Hietanen J, Konttinen Y T
Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Oral Pathology, University of Helsinki, Helsinki, Finland.
Oral Dis. 2015 Apr;21(3):378-85. doi: 10.1111/odi.12290. Epub 2014 Oct 8.
Oral lichen planus (OLP) is an autoimmune disease characterized by a band-like T-cell infiltrate below the apoptotic epithelial cells and degenerated basement membrane. We tested the hypothesis that the high-affinity histamine H4 receptors (H4 Rs) are downregulated in OLP by high histamine concentrations and proinflammatory T-cell cytokines.
Immunohistochemistry and immunofluorescence staining, image analysis and quantitative real-time polymerase chain reaction of tissue samples and cytokine-stimulated cultured SCC-25 and primary human oral keratinocytes.
H4 R immunoreactivity was weak in OLP and characterized by mast cell (MC) hyperplasia and degranulation. In contrast to controls, H4 R immunostaining and MC counts were negatively correlated in OLP (P = 0.003). H4 R agonist at nanomolar levels led to a rapid internalization of H4 Rs, whereas high histamine concentration and interferon-γ decreased HRH4 -gene transcripts.
Healthy oral epithelial cells are equipped with H4 R, which displays a uniform staining pattern in a MC-independent fashion. In contrast, in OLP, increased numbers of activated MCs associate with increasing loss of epithelial H4 R. Cell culture experiments suggest a rapid H4 R stimulation-dependent receptor internalization and a slow cytokine-driven decrease in H4 R synthesis. H4 R may be involved in the maintenance of healthy oral mucosa. In OLP, this maintenance might be impaired by MC degranulation and inflammatory cytokines.
口腔扁平苔藓（OLP）是一种自身免疫性疾病，其特征为凋亡上皮细胞和变性基底膜下方出现带状T细胞浸润。我们检验了以下假设：在OLP中，高亲和力组胺H4受体（H4Rs）因高组胺浓度和促炎T细胞细胞因子而下调。
对组织样本以及细胞因子刺激培养的SCC-25和原代人口腔角质形成细胞进行免疫组织化学和免疫荧光染色、图像分析以及定量实时聚合酶链反应。
H4R免疫反应性在OLP中较弱，其特征为肥大细胞（MC）增生和脱颗粒。与对照组相比，OLP中H4R免疫染色与MC计数呈负相关（P = 0.003）。纳摩尔水平的H4R激动剂导致H4Rs迅速内化，而高组胺浓度和干扰素-γ降低了HRH4基因转录本。
健康的口腔上皮细胞配备有H4R，其以与MC无关的方式呈现均匀的染色模式。相比之下，在OLP中，活化MC数量增加与上皮H4R丢失增加相关。细胞培养实验表明，H4R刺激依赖的受体内化迅速，而细胞因子驱动的H4R合成减少缓慢。H4R可能参与健康口腔黏膜的维持。在OLP中，这种维持可能因MC脱颗粒和炎性细胞因子而受损。
