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.
Copyright 2002 S. Karger AG, Basel