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 induce s 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 r enal production of this heterodimeric cytokine in the MRL-Fas(lpr) lup us nephritis model. Compared with normal mice, RT-PCR products encodin g both the p35 and p40 subunits of IL-12 were markedly increased in th e kidney of MRL-Fas(lpr). Immunofluorescence staining demonstrated exp ression of the IL-12 p75 heterodimer on isolated infiltrating mononucl ear cells and also on proximal tubular epithelial cells in MRL-Fas(lpr ) but less in normal mice kidneys. The enhanced expression of IL-12 co rrelated with an increased intrarenal transcription of IFN-gamma. The p35 and p40 transcripts and soluble IL-12 p75 protein were also produc ed by cultured TEC. In addition, membrane bound IL-12 was detected on TEC. We conclude that IL-12 production is significantly up-regulated i n 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.