Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Lupus. 2010 Jun;19(7):830-6. doi: 10.1177/0961203309360540. Epub 2010 Feb 18.
Interferon-gamma is a potent Th1-type cytokine and a key molecule in the pathogenesis of autoimmune diseases including lupus nephritis. Retinoic acid-inducible gene-I is a putative RNA helicase that plays an important role in immune and inflammatory reactions. We previously demonstrated the increased expression of the retinoic acid-inducible gene-I protein in the kidney tissue of patients with lupus nephritis, and the presence of a significant amount of retinoic acid-inducible gene-I mRNA in the urinary sediment of patients with this inflammatory renal disease. In the present study, interferon-gamma was found to induce the expression of retinoic acid-inducible gene-I in human mesangial cells in culture. Knockdown of retinoic acid-inducible gene-I inhibited the interferon-gamma-induced upregulation of interferon regulatory factor 7, a transcriptional factor involved in immune and inflammatory reactions. These findings suggest that retinoic acid-inducible gene-I produced by mesangial cells may be involved in the pathogenesis of lupus nephritis.
干扰素-γ是一种强效的 Th1 型细胞因子，也是包括狼疮性肾炎在内的自身免疫性疾病发病机制中的关键分子。维甲酸诱导基因-I 是一种假定的 RNA 解旋酶，在免疫和炎症反应中发挥重要作用。我们之前已经证明，狼疮性肾炎患者的肾脏组织中维甲酸诱导基因-I 蛋白表达增加，并且这种炎症性肾病患者的尿沉渣中存在大量的维甲酸诱导基因-I mRNA。在本研究中，发现干扰素-γ可诱导人肾小球系膜细胞中维甲酸诱导基因-I 的表达。维甲酸诱导基因-I 的敲低抑制了干扰素-γ诱导的转录因子干扰素调节因子 7 的上调，该转录因子参与免疫和炎症反应。这些发现表明，肾小球系膜细胞产生的维甲酸诱导基因-I 可能参与了狼疮性肾炎的发病机制。
