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Cell Physiol Biochem. 2002;12(4):187-96.

Albumin induces NF-kappaB expression in human proximal tubule-derived cells (IHKE-1).

Author information

1
Institute of Physiology, University of Wuerzburg, Germany. karina.drumm@mail.uni-wuerzburg.de

Abstract

BACKGROUND:

Chronic renal diseases with enhanced glomerular protein filtration are accompanied by tubulointerstitial inflammation and progression to renal function deterioration. Filtered proteins, like albumin, seem to be a pathogenic factor per se in the progression of renal diseases. There is evidence that the nuclear factor kappaB (NF-kappaB) is involved in protein-overload stimulated renal inflammatory pathomechanisms. The aim of this study was to investigate albumin-induced NF-kappaB expression as well as NF-kappaB activity upon long long term exposure to albumin in human proximal tubular cells as only acute albumin-induced NF-kappaB activity has been reported so far.

METHODS:

To investigate the hypothesis, that NF-kappaB may be involved in protein-induced renal inflammatory pathomechanisms, we exposed human renal proximal tubule-derived cells (IHKE-1) to bovine serum albumin (BSA: 50 and 500 microg/ml). The NF-kappaB and TNF-alpha specific mRNA expression was detected by RT-PCR. NF-kappaB specific protein expression was analysed by Western blot. Reporter gene assays were performed to determine the NF-kappaB specific activity.

RESULTS:

Albumin-exposure induced an increase in NF-kappaB specific mRNA expression, NF-kappaB protein expression and activity. These effects are decreased by the protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM) and the tyrosine kinase inhibitor herbimycin A. An albumin-induced increase in TNF-alpha specific mRNA expression as biological, inflammatory parameter associated with the albumin-induced NF-kappaB activity was detectable.

CONCLUSION:

We suggest, that albumin-exposure induces an increase in NF-kappaB and TNF-alpha specific mRNA expression, NF-kappaB specific protein expression and protein activity in renal proximal tubule cells in culture, which is at least in part PKC and tyrosine kinase dependent.

PMID:
12297724
DOI:
10.1159/000066278
[Indexed for MEDLINE]

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