【作者】 张理伟； 丛馨； 魏攀； 吴立玲； 俞光岩； 华红；

【Author】 Liwei Zhang;Xin Cong;Pan Wei;Liling Wu;Guangyan Yu;Hong Hua;Department of Oral Medicine, Peking University School and Hospital of Stomatology Department of Physiology and Pathophysiology, Peking University Health Science Center; Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology;

【机构】 北京大学口腔医学院口腔黏膜科； 生理与病理生理学系； 口腔颌面外科；

【摘要】 目的:舍格伦综合征(Sj?gren’s syndrome, SS)是一种主要累及泪腺和唾液腺的慢性自身免疫系统疾病,以外分泌腺灶性淋巴细胞浸润为主要特征。作为多因素共同参与的自身免疫疾病,SS的发病机制至今仍未明确。近年来,白介素(interleukin,IL)-17在SS发病中的作用受到越来越多的关注,其表达水平亦显著升高,但其致病机制尚不清楚。紧密连接是上皮细胞间重要的连接复合体之一,在唾液分泌过程中发挥重要作用。在SS动物模型中,唾液腺紧密连接分子的表达和分布发生显著改变。本研究旨在探索IL-17对SS患者唾液腺紧密连接分子表达和分布的影响。方法:以活检切除的黏液腺囊肿患者的唇腺为对照组,SS患者的唇腺为实验组,免疫荧光检测SS患者唇腺claudin-1,-3,-4,ZO-1等紧密连接分子的表达分布水平。同时,选取头颈部肿瘤行颈淋巴清扫术患者术中切除的下颌下腺组织,行组织块孵育,给予IL-17刺激,western blot及PCR检测IL-17刺激后紧密连接分子表达和分布水平。结果:与对照组相比,SS患者唇腺上皮细胞中,claudin-4及ZO-1在腺泡上皮细胞的顶侧膜分布减弱;claudin-1在顶侧膜分布减弱的同时,发生胞膜向胞浆重分布的现象;claudin-3的分布水平未见显著改变。IL-17作用于人下颌下腺上皮细胞后,claudin-4及ZO-1的表达水平显著降低,且在顶侧膜分布减弱,然而claudin-1及-3的表达和分布未见显著改变。结论:SS患者唇腺上皮细胞中,紧密连接分子的表达发生显著改变,IL-17可能参与了对紧密连接分子表达和分布的调控。更多还原

【Abstract】 Aim: Sj?gren’s syndrome(SS) is a chronic autoimmune disease characterized by lymphocytic infiltration in exocrine glands, especially in salivary and lacrimal glands. As a multifactorial autoimmune disease, the pathogenesis of SS still remains unclear. Recently, the pathogenic role of interleukin(IL)-17 in SS has attracted much attention. IL-17 was overexpressed in serum and local lesions of salivary glands of SS patients. Nevertheless, the pathological mechanisms of IL-17 in SS remains elusive. Tight junction(TJ) is a multifunctional protein complex localized in the apical region of lateral membrane, and plays a crucial role in saliva secretion. It has been reported that the integrity of tight junction was impaired in salivary glands of SS animal models. The present study was designed to explore the pathological role and mechanisms of IL-17 on salivary tight junction. Methods Labial glands from patients with salivary gland mucocele were used as control group, we detected the alteration of the expression and distribution of TJ proteins, claudin-1,-3,-4 and ZO-1 in labial glands of SS patients. In addition, submandibular glands isolated from head and neck cancer patients with radical neck dissection were incubated with IL-17, the expression and distribution of TJ proteins were detected, too. Results Compared with control group, the expression and distribution of claudin-4 and ZO-1 were significantly weakened in the apical membrane of SS labial acini; and redistribution from membrane to cytoplasm of claudin-1 was shown in SS labial acini. No significant difference was found for claudin-3. In vitro, IL-17 significantly altered the expression and distribution of claudin-4 and ZO-1 in cultured submandibular gland tissues, whereas no difference was found for claudin-1 and-3. Conclusion The expression of salivary TJ proteins were significantly altered in SS patients, IL-17 might play a crucial role on the regulation of salivary TJs.更多还原