Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr) mice with renal injury.
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.
Fan
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X
Physiological Institute, University of Zürich-Irchel, Switzerland.
Oertli
B
B
Wüthrich
R P
RP
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000503:physiopathology; D015139:Blotting, Southern; D002461:Cell Line, Transformed / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D018664:Interleukin-12 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008181:Lupus Nephritis / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D018664:Interleukin-12