RGD Reference Report - Corticosteroids worsen proteinuria and increase intraglomerular signaling by NF-kB in a model of membranous glomerulonephritis. - Rat Genome Database

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Corticosteroids worsen proteinuria and increase intraglomerular signaling by NF-kB in a model of membranous glomerulonephritis.

Authors: Mudge, SJ  Paizis, K  Auwardt, RB  Levidiotis, V  Fraser, SA  Power, DA 
Citation: Mudge SJ, etal., Nephron Exp Nephrol. 2010;116(2):e23-31. Epub 2010 Jun 29.
RGD ID: 7175342
Pubmed: PMID:20588061   (View Abstract at PubMed)
DOI: DOI:10.1159/000317128   (Journal Full-text)

BACKGROUND/AIMS: Passive Heymann nephritis (PHN) is a model of human membranous glomerulonephritis characterized by heavy proteinuria. We have recently demonstrated activation of NF-kappaB by podocytes in this model. In this study, therefore, we have determined whether dexamethasone (DEX) and pyrrolidine dithiocarbamate (PDTC), therapies that inhibit NF-kappaB, influence proteinuria. METHODS: Twenty-one days after induction of PHN, rats were divided into three groups: group 1 received saline, group 2 received DEX for 7 days, and group 3 received PDTC for 7 days. The effects of these drugs on activation of NF-kappaB and proteinuria were then determined. RESULTS: DEX administration was associated with a very significant increase in proteinuria, whereas PDTC produced a slight decrease. Within the glomerulus, both agents were associated with increased levels of IL-1beta mRNA and protein, compared with untreated rats, and there was increased nuclear localization of p50 in both of the treated groups. Neither agent, therefore, inhibited NF-kappaB activation within the glomerulus. Both agents produced a decrease in the systemic anti-sheep Ig immune response, and there was reduced interstitial alphabeta T-cell infiltration compared with controls. CONCLUSION: These data suggest that agents predicted to inhibit NF-kappaB might have opposing effects in membranous glomerulonephritis. The use of steroids to treat membranous glomerulonephritis, therefore, might produce unpredictable results, depending on whether suppression of the systemic immune response or inflammatory events within the kidney is more important in a particular patient.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
membranous glomerulonephritis  ISOIl1b (Rattus norvegicus)7175342; 7175342 RGD 
membranous glomerulonephritis  IDA 7175342 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1b  (interleukin 1 beta)

Genes (Mus musculus)
Il1b  (interleukin 1 beta)

Genes (Homo sapiens)
IL1B  (interleukin 1 beta)


Additional Information