Upregulation of lymphoid and renal interferon-gamma mRNA in autoimmune MRL-Fas(lpr) mice with lupus nephritis

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Gene Expression Regulation / immunology
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics*
  • Kidney / metabolism*
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / metabolism
  • Lymph Nodes / metabolism
  • Lymphoid Tissue / metabolism*
  • Mice
  • Mice, Inbred MRL lpr
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis*
  • RNA-Directed DNA Polymerase
  • Spleen / metabolism
  • Up-Regulation / genetics
  • Up-Regulation / immunology*


  • RNA, Messenger
  • Interferon-gamma
  • RNA-Directed DNA Polymerase