Upregulation of lymphoid and renal interferon-gamma mRNA in autoimmune MRL-Fas(lpr) mice with lupus nephritis.
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).
Fan
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Physiological Institute, University of Zürich-Irchel, Switzerland.
Wüthrich
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RP
D000818:Animals; D015152:Blotting, Northern; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics*; D007668:Kidney / Q000378:metabolism*; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D012194:RNA-Directed DNA Polymerase; D013154:Spleen / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D012333:RNA, Messenger; D007371:Interferon-gamma; D012194:RNA-Directed DNA Polymerase