Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr) mice with renal injury

Kidney Int. 1997 Jan;51(1):79-86. doi: 10.1038/ki.1997.10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / physiopathology
  • Blotting, Southern
  • Cell Line, Transformed / immunology
  • Cell Line, Transformed / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epithelium / immunology
  • Epithelium / metabolism
  • Fluorescent Antibody Technique
  • Gene Expression / physiology
  • Interleukin-12 / analysis
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism*
  • Kidney Tubules / cytology*
  • Kidney Tubules / immunology*
  • Kidney Tubules / metabolism
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Polymerase Chain Reaction
  • Spleen / metabolism
  • Transcription, Genetic / physiology

Substances

  • Interleukin-12