RGD Reference Report - IL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat. - Rat Genome Database

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IL-1 up-regulates osteopontin expression in experimental crescentic glomerulonephritis in the rat.

Authors: Yu, XQ  Fan, JM  Nikolic-Paterson, DJ  Yang, N  Mu, W  Pichler, R  Johnson, RJ  Atkins, RC  Lan, HY 
Citation: Yu XQ, etal., Am J Pathol. 1999 Mar;154(3):833-41.
RGD ID: 6909131
Pubmed: PMID:10079261   (View Abstract at PubMed)
PMCID: PMC1866418   (View Article at PubMed Central)
DOI: DOI:10.1016/S0002-9440(10)65330-8   (Journal Full-text)

Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to promote macrophage infiltration in rat anti-glomerular basement membrane (GBM) glomerulonephritis. The present study investigated the role of interleukin-1 (IL-1) in the up-regulation of renal OPN expression in this disease model. Accelerated anti-GBM glomerulonephritis was induced in groups of six rats. Animals were treated by a constant infusion of the IL-1 receptor antagonist or saline (control) over days -1 to 14 (induction phase) or days 7 to 21 (established disease). In normal rat kidney, OPN was expressed in a few tubules (<5%) and absent from glomeruli. During the development of rat anti-GBM disease (days 7 to 21), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli (>5 cells per glomerular cross-section) and tubular epithelial cells (50-75% OPN-positive). Up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histological damage including glomerular crescentic formation and tubulointerstitial fibrosis. In contrast, IL-1 receptor antagonist treatment of either the induction phase of disease or established disease significantly reduced OPN mRNA and protein expression in glomeruli (/75-85%, P < 0.001) and tubules (/45-60%, P < 0.001). The reduction in OPN expression was associated with significant inhibition of macrophage accumulation and progressive renal injury. In vitro, the addition of IL-1 to the normal rat tubular epithelial cell line NRK52E up-regulated OPN mRNA and protein levels, an effect that was dose-dependent and inhibited by the addition of IL-1 receptor antagonist, thus demonstrating that IL-1 can act directly to up-regulate renal OPN expression. In conclusion, this study provides in vivo and in vitro evidence that IL-1 up-regulates OPN expression in experimental kidney disease and support for the argument that inhibition of OPN expression is one mechanism by which IL-1 receptor antagonist treatment suppresses macrophage-mediated renal injury.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1RNHumanIgA glomerulonephritis  IDA rat model treated with human proteinRGD 
Il1rnRatIgA glomerulonephritis  ISOIL1RN (Homo sapiens)rat model treated with human proteinRGD 
Il1rnMouseIgA glomerulonephritis  ISOIL1RN (Homo sapiens)rat model treated with human proteinRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Mus musculus)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Homo sapiens)
IL1RN  (interleukin 1 receptor antagonist)


Additional Information