IgG4相关性唾液腺炎是近年来提出的自身免疫性疾病，受累唾液腺中IgG4阳性浆细胞浸润和纤维化是主要的病理特点，亦是腺体肿大和分泌功能障碍的重要原因。我们前期的工作显示，白介素-4（IL-4）是IgG4相关性唾液腺炎患者下颌下腺中升高最明显的细胞因子，但IL-4在唾液腺纤维化中的作用尚未阐明。本项目拟采用Real-time PCR、免疫印迹和免疫荧光等方法，在培养的大鼠和人下颌下腺成纤维细胞上观察IL-4对细胞增殖、肌成纤维细胞转化和胶原合成的影响；在培养的腺泡上皮细胞上检测IL-4对上皮向间充质转化的影响，从肌成纤维细胞转化和上皮间充质转化的角度明确IL-4的促纤维化作用。采用工具药和基因转染等方法，从受体、蛋白激酶、转录因子层面探讨IL-4调控纤维化的信号转导通路，为阐明IL-4在唾液腺纤维化中的作用及机制提供新见解，也为以IL-4及其受体为靶点治疗IgG4相关性唾液腺炎提供新思路。

IgG4-related sialadenitis is recently recognized as an autoimmune disease characterize by IgG4-positive plasma cell infiltration and storiform fibrosis which result in the enlarged glands and secretion dysfunction. Our preliminary work showed that interleukin-4 (IL-4) significantly elevated in the submandibular glands obtained from the patients with IgG4-related sialadenitis. However, the exact role of IL-4 in fibrosis of salivary gland has not been elucidated. In cultured rat and human submandibular fibroblasts, we will investigate the effects of IL-4 on cell proliferation, myofibroblast transformation and collagen production by use of Real-time PCR, Western blot, and immunofluorescent methods. Meanwhile, we will explore the effects IL-4 on epithelial to mesenchymal transition in the primary cultured rat submandibular epithelial cells and SMG-C6 cells. The signaling transduction mechanism involved in IL-4-modulated myofibroblast or epithelial-mesenchymal transition will be investigated from receptor, intracellular protein kinases, and transcription factor levels by using pharmacological inhibitors and gene transfection techniques. This study will clarify the key role and mechanism of IL-4 in the salivary gland fibrosis and provide new insight into the therapeutic strategy of IgG4-related sialadenitis by targeting IL-4 and its receptor.