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

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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Fan X,Oertli B,Wüthrich RP

doi

10.1038/ki.1997.10

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

79-86

issue

1

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)59841-4

journal_volume

51

pub_type

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