Xia Guangtao, Wu Sensen, Wang Xia, Fu Min
a Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People's Republic of China.
b Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, People's Republic of China.
Can J Physiol Pharmacol. 2018 Dec;96(12):1293-1300. doi: 10.1139/cjpp-2018-0467. Epub 2018 Oct 5.
Autoimmune hepatitis (AIH) is a chronic progressive autoimmune disease characterized by hepatic inflammation. This study aimed to investigate the effect of antagomir-155 on concanavalin A (ConA)-induced AIH, and its possible mechanisms. According to the results, the expression of miR-155 was raised in liver tissues after 48 h exposure to ConA. Treatment with antagomir-155 attenuated ConA-induced liver injury in mice by reducing serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels. In addition, antagomir-155 significantly alleviated the differentiation of Treg/Th17 cells in the livers of AIH mice, and suppressed Th17-cells-mediated production of pro-inflammatory cytokines IL-17A, IL-23, but not Treg-cells-mediated production of anti-inflammatory cytokine IL-10. Finally, the beneficial effect of antagomir-155 on ConA-induced AIH was abolished by administration of recombinant IL-17A. Our data demonstrated that antagomir-155 treatment could prevent AIH via regulating the differentiation of Treg and Th17 cells, suggesting that microRNA-155 may be an intriguing therapeutic target of AIH.
自身免疫性肝炎（AIH）是一种以肝脏炎症为特征的慢性进行性自身免疫性疾病。本研究旨在探讨抗 miR-155 对刀豆蛋白 A（ConA）诱导的 AIH 的影响及其可能机制。结果显示，ConA 处理 48 小时后肝脏组织中 miR-155 表达升高。抗 miR-155 治疗可降低血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶水平，减轻 ConA 诱导的小鼠肝损伤。此外，抗 miR-155 显著减轻 AIH 小鼠肝脏中 Treg/Th17 细胞的分化，并抑制 Th17 细胞介导的促炎细胞因子 IL-17A、IL-23 的产生，但不影响 Treg 细胞介导的抗炎细胞因子 IL-10 的产生。最后，给予重组 IL-17A 可消除抗 miR-155 对 ConA 诱导的 AIH 的有益作用。我们的数据表明，抗 miR-155 治疗可通过调节 Treg 和 Th17 细胞的分化预防 AIH，提示 microRNA-155 可能是 AIH 一个有吸引力的治疗靶点。
