Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr) mice with renal injury
Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr) mice with renal injury
复制标题
DOI：
10.1038/ki.1997.10
复制
发表时间：
1997-01-01
影响因子：
19.6
通讯作者：
Wuthrich, RP
中科院分区：
文献类型：
--
作者：
Fan, XH;Oertli, B;Wuthrich, RP
吞噬细胞源性白细胞介素 12 (IL-12) 是一种关键细胞因子，可在各种炎症和感染性疾病中诱导有效 Th1 型免疫反应的发展。为了确定 IL-12 在自身免疫性肾损伤发病机制中的重要性，我们检查了 MRL-Fas(lpr) 狼疮肾炎模型中肾脏产生的这种异二聚体细胞因子。与正常小鼠相比，MRL-Fas(lpr)肾脏中编码IL-12 p35和p40亚基的RT-PCR产物显着增加。免疫荧光染色显示IL-12 p75异二聚体在分离的浸润单核细胞以及MRL-Fas(lpr)中的近端肾小管上皮细胞上表达，但在正常小鼠肾脏中表达较少。 IL-12 表达的增强与肾内 IFN-γ 转录的增加相关。 p35 和 p40 转录物以及可溶性 IL-12 p75 蛋白也由培养的 TEC 产生。此外，在 TEC 上检测到膜结合的 IL-12。我们得出的结论是，MRL-Fas(lpr) 狼疮肾炎中 IL-12 的产生显着上调。除了单核细胞外，TEC 是 IL-12 的重要来源，因此可以参与自身免疫性肾损伤中 Th1 型免疫反应的发展。
Phagocyte-derived interleukin-12 (IL-12) is a key cytokine that induces the development of an effective Th1 type immune response in various inflammatory and infectious disorders. To determine the importance of IL-12 in the pathogenesis of autoimmune renal injury we examined the renal production of this heterodimeric cytokine in the MRL-Fas(lpr) lupus nephritis model. Compared with normal mice, RT-PCR products encoding both the p35 and p40 subunits of IL-12 were markedly increased in the kidney of MRL-Fas(lpr). Immunofluorescence staining demonstrated expression of the IL-12 p75 heterodimer on isolated infiltrating mononuclear cells and also on proximal tubular epithelial cells in MRL-Fas(lpr) but less in normal mice kidneys. The enhanced expression of IL-12 correlated with an increased intrarenal transcription of IFN-gamma. The p35 and p40 transcripts and soluble IL-12 p75 protein were also produced by cultured TEC. In addition, membrane bound IL-12 was detected on TEC. We conclude that IL-12 production is significantly up-regulated in MRL-Fas(lpr) lupus nephritis. In addition to mononuclear cells, TEC are an important source of IL-12 and could thereby participate in the development of a Th1 type immune response in autoimmune renal injury.