Fan X, Wüthrich R P
Physiological Institute, University of Zürich-Irchel, Switzerland.
Inflammation. 1997 Feb;21(1):105-12. doi: 10.1023/a:1027399027170.
MRL-Fas(lpr) mice develop an aggressive form of autoimmunity, characterized by immune complex-mediated glomerulonephritis and massive expansion of lymphoid tissues. Increased MHC class II expression by macrophages and renal parenchymal cells is a prominent feature of MRL-Fas(lpr) mice. Since interferon-gamma (IFN-gamma) is the major and the most potent inducer of MHC class II molecules it could play a pathogenic role in the disease process in MRL-Fas(lpr). We have analyzed IFN-gamma expression in normal and nephritic MRL-Fas(lpr) mice by examining renal and lymphoid IFN-gamma-specific mRNA production, using reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting. We detect abundant IFN-gamma mRNA expression in the kidney of nephritic MRL-Fas(lpr) by RT-PCR, whereas normal mice display absent or only very weak expression of this cytokine. By RT-PCR, IFN-gamma mRNA is detectable in normal spleen, but is overexpressed in the enlarged spleen and lymph nodes of MRL-Fas(lpr). Northern blotting using total RNA from tissues confirms abundant IFN-gamma expression in spleen and lymph node of MRL-Fas(lpr). We conclude that enhanced renal IFN-gamma mRNA expression is a prominent feature of MRL-Fas(lpr) lupus nephritis. Increased IFN-gamma produced by infiltrating T cells could lead to increased MHC class II expression by renal parenchymal cells, thereby promoting the nephritic process by augmentation of antigen presentation in the kidney of autoimmune MRL-Fas(lpr).
MRL-Fas(lpr)小鼠会发展出一种侵袭性自身免疫形式,其特征为免疫复合物介导的肾小球肾炎和淋巴组织的大量增生。巨噬细胞和肾实质细胞中MHC II类分子表达增加是MRL-Fas(lpr)小鼠的一个显著特征。由于干扰素-γ(IFN-γ)是MHC II类分子的主要且最有效的诱导剂,它可能在MRL-Fas(lpr)的疾病进程中发挥致病作用。我们通过使用逆转录-聚合酶链反应(RT-PCR)和Northern印迹法检测肾脏和淋巴组织中IFN-γ特异性mRNA的产生,分析了正常和患肾炎的MRL-Fas(lpr)小鼠中IFN-γ的表达情况。通过RT-PCR我们检测到患肾炎的MRL-Fas(lpr)小鼠肾脏中有丰富的IFN-γ mRNA表达,而正常小鼠中该细胞因子表达缺失或仅非常微弱。通过RT-PCR,在正常脾脏中可检测到IFN-γ mRNA,但在MRL-Fas(lpr)增大的脾脏和淋巴结中其表达过度。使用组织总RNA进行的Northern印迹证实了MRL-Fas(lpr)脾脏和淋巴结中有丰富的IFN-γ表达。我们得出结论,肾脏中IFN-γ mRNA表达增强是MRL-Fas(lpr)狼疮性肾炎的一个显著特征。浸润的T细胞产生的IFN-γ增加可能导致肾实质细胞中MHC II类分子表达增加,从而通过增强自身免疫性MRL-Fas(lpr)小鼠肾脏中的抗原呈递来促进肾炎进程。