Fan X, Oertli B, Wüthrich R P
Physiological Institute, University of Zürich-Irchel, Switzerland.
Kidney Int. 1997 Jan;51(1):79-86. doi: 10.1038/ki.1997.10.
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.
吞噬细胞衍生的白细胞介素-12（IL-12）是一种关键细胞因子，在各种炎症和感染性疾病中诱导有效的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，我们在MRL-Fas(lpr)狼疮性肾炎模型中检测了这种异二聚体细胞因子的肾脏产生情况。与正常小鼠相比，编码IL-12 p35和p40亚基的RT-PCR产物在MRL-Fas(lpr)小鼠肾脏中显著增加。免疫荧光染色显示，IL-12 p75异二聚体在MRL-Fas(lpr)小鼠分离的浸润单核细胞以及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表达增强与肾内干扰素-γ转录增加相关。培养的肾小管上皮细胞（TEC）也产生p35和p40转录本以及可溶性IL-12 p75蛋白。此外，在TEC上检测到膜结合的IL-12。我们得出结论，在MRL-Fas(lpr)狼疮性肾炎中IL-12的产生显著上调。除单核细胞外，TEC是IL-12的重要来源，因此可能参与自身免疫性肾损伤中Th1型免疫反应的发展。
