Hamedi M, Bergmeier L A, Hagi-Pavli E, Vartoukian S R, Fortune F
Centre Clinical and Diagnostic Oral Sciences, Institute of dentistry, Bart's and The London School of Medicine and Dentistry, London, UK.
Scand J Immunol. 2014 Nov;80(5):369-76. doi: 10.1111/sji.12211.
Behçet's disease (BD) is a chronic, multisystemic, recurrent vasculitis disease of unknown aetiology. Proinflammatory cytokines are a key feature of the disease, but the triggers for their induction are not well understood and/or controversial. Suppressor of cytokine signalling (SOCS) proteins which negatively regulate the JAK-STAT signalling pathway of cytokine induction may be dysregulated in BD. The expression of SOCS1 and 3 mRNA and protein was studied in peripheral blood mononuclear cells (PBMCs) and neutrophils of patients with BD and compared with healthy controls (HCs) and patients with recurrent aphthous stomatitis (RAS) using RT-PCR, Western blot and immunohistochemistry. SOCS1 and 3 mRNA was also measured in buccal mucosal cells (BMC) of patients with BD and HCs. SOCS1 and 3 mRNA was significantly upregulated in PBMCs of patients with BD compared with HCs (P = 0.0149; P = 0.0007). In addition, there were subtle differences between expression in active and symptom-free BD (quiescent BD). SOCS1 and SOCS 3 were also significantly upregulated in BMC from oral ulcers of BD compared with HCs (both at P = 0.0001). A differential expression of both SOCS1 and 3 was observed between PBMCs and neutrophils in patients with BD. Immunohistochemical analysis revealed differential expression of SOCS proteins in the buccal mucosa with an increased expression at the ulcer surface of ulcers than in the non-ulcerated tissue. These observations suggest a dysregulation of the expression of these important regulators not only between patients with BD and healthy controls but also between mucosal and systemic tissues, which may reflect the nature of the aetiopathology of the disease.
白塞病(BD)是一种病因不明的慢性、多系统、复发性血管炎疾病。促炎细胞因子是该疾病的一个关键特征,但其诱导触发因素尚未完全明确和/或存在争议。细胞因子信号转导抑制因子(SOCS)蛋白可负向调节细胞因子诱导的JAK-STAT信号通路,在BD中可能失调。本研究采用逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹法和免疫组织化学方法,检测BD患者外周血单个核细胞(PBMCs)和中性粒细胞中SOCS1和3 mRNA及蛋白的表达,并与健康对照(HCs)和复发性阿弗他口炎(RAS)患者进行比较。同时,还检测了BD患者和HCs颊黏膜细胞(BMC)中SOCS1和3 mRNA的表达。与HCs相比,BD患者PBMCs中SOCS1和3 mRNA显著上调(P = 0.0149;P = 0.0007)。此外,活动期BD和无症状BD(静止期BD)的表达存在细微差异。与HCs相比,BD患者口腔溃疡处BMC中SOCS1和SOCS 3也显著上调(均为P = 0.0001)。BD患者PBMCs和中性粒细胞中SOCS1和3均存在差异表达。免疫组织化学分析显示,颊黏膜中SOCS蛋白存在差异表达,溃疡表面的表达高于未溃疡组织。这些观察结果表明,这些重要调节因子的表达不仅在BD患者和健康对照之间失调,而且在黏膜组织和全身组织之间也失调,这可能反映了该疾病发病机制的本质。