Li Huidan, Sun Xiaoxuan, Zhang Jie, Sun Yue, Huo Rongfen, Li Haichuan, Zhai Tianhang, Shen Baihua, Zhang Miaojia, Li Ningli
Shanghai Institute of Immunology & Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Rheumatology, the First Affiliated Hospital of Nanjing Medical University Nanjing, China.
Int Immunopharmacol. 2016 Jan;30:27-35. doi: 10.1016/j.intimp.2015.11.023. Epub 2015 Nov 26.
Paeoniflorin (PF), an active compound extracted from Paeony root, has been used in therapy of autoimmune diseases with effective clinical efficiency and higher safety. Sjogren's syndrome (SS) is a chronic, systemic, immune-mediated inflammatory disease. In this study, we demonstrated that novel pro-inflammatory factor Cyr61/CCN1 was up-regulated in epithelial cells of salivary glands of primary SS patients and submandibular gland autoantigen-induced experimental SS mice. Blocking Cyr61 expression with special monoclonal antibody improved saliva secretion by ameliorating inflammatory infiltration and cytokines production in vivo. Furthermore, we showed that PF could alleviate inflammation by down-regulating Cyr61 expression in experimental SS mice. In conclusion, our new findings revealed for the first time that Cyr61 involves the pathogenesis of primary SS and PF alleviates SS-like symptoms associated with inhibiting Cyr61 expression, providing new insights into the potential molecular mechanism of PF in primary SS treatment.
芍药苷（PF）是从芍药根中提取的一种活性化合物，已被用于自身免疫性疾病的治疗，临床疗效显著且安全性较高。干燥综合征（SS）是一种慢性、全身性、免疫介导的炎症性疾病。在本研究中，我们证明新型促炎因子Cyr61/CCN1在原发性SS患者唾液腺上皮细胞和下颌下腺自身抗原诱导的实验性SS小鼠中上调。用特异性单克隆抗体阻断Cyr61表达可通过改善体内炎症浸润和细胞因子产生来促进唾液分泌。此外，我们表明PF可通过下调实验性SS小鼠中的Cyr61表达来减轻炎症。总之，我们的新发现首次揭示Cyr61参与原发性SS的发病机制，PF通过抑制Cyr61表达减轻SS样症状，为PF治疗原发性SS的潜在分子机制提供了新见解。
