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

First Author  Fan X Year  1997
Journal  Kidney Int Volume  51
Issue  1 Pages  79-86
PubMed ID  8995720 Mgi Jnum  J:38057
Mgi Id  MGI:85449 Doi  10.1038/ki.1997.10
Citation  Fan X, et al. (1997) Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr) mice with renal injury. Kidney Int 51(1):79-86
abstractText  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.
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