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

Cell Physiol Biochem. 2002;12(4):187-96. doi: 10.1159/000066278.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzoquinones
  • Cattle
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Indoles / pharmacology
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / drug effects*
  • Kidney Tubules, Proximal / metabolism*
  • Lactams, Macrocyclic
  • Maleimides / pharmacology
  • Models, Biological
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism*
  • Quinones / pharmacology
  • RNA, Messenger / metabolism
  • Rifabutin / analogs & derivatives
  • Serum Albumin, Bovine / pharmacology*
  • Species Specificity
  • Tumor Necrosis Factor-alpha / metabolism


  • Benzoquinones
  • Enzyme Inhibitors
  • Indoles
  • Lactams, Macrocyclic
  • Maleimides
  • NF-kappa B
  • Quinones
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Rifabutin
  • Serum Albumin, Bovine
  • herbimycin
  • bisindolylmaleimide I