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 ĸB (NF-ĸB) is involved in protein-overload stimulated renal inflammatory pathomechanisms. The aim of this study was to investigate albumin-induced NF-ĸB expression as well as NF-ĸB activity upon long long term exposure to albumin in human proximal tubular cells as only acute albumin-induced NF-ĸB activity has been reported so far.Methods: To investigate the hypothesis, that NF-ĸB 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 µg/ml). The NF-ĸB and TNF-α specific mRNA expression was detected by RT-PCR. NF-ĸB specific protein expression was analysed by Western blot. Reporter gene assays were performed to determine the NF-ĸB specific activity.Results: Albumin-exposure induced an increase in NF-ĸB specific mRNA expression, NF-ĸB 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-α specific mRNA expression as biological, inflammatory parameter associated with the albumin-induced NF-ĸB activity was detectable.Conclusion: We suggest, that albumin-exposure induces an increase in NF-ĸB and TNF-α specific mRNA expression, NF-ĸB specific protein expression and protein activity in renal proximal tubule cells in culture, which is at least in part PKC and tyrosine kinase dependent.

© 2002 S. Karger AG, Basel
2002
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