NF-kappaB activation in renal tubular epithelial cells by oxalate stimulation

Int J Urol. 2008 Oct;15(10):924-8. doi: 10.1111/j.1442-2042.2008.02131.x. Epub 2008 Aug 20.

Abstract

Objectives: The transcription factor nuclear factor-kappaB (NF-kappaB) is involved in inflammatory and immune responses through the induction of various cytokines and growth factors. Recently, the coordinated action of NF-kappaB and activator protein-1 was reported in osteopontin (OPN) expression. In the present study, we demonstrated that oxalate induces OPN expression by activating NF-kappaB in renal tubular cells. Furthermore, we investigated the inhibitory effect of N-acetyl-L-cysteine (NAC) on NF-kappaB activation in the human renal tubular cell line.

Methods: All of the experiments were carried out using human kidney-2 cells, which are human proximal tubular epithelial cells immortalized by transduction with the human papillomavirus 16E6/E7 gene. The time-dependent extraction of total protein was performed after the uptake of 0.5 mM oxalate by the cells. The NF-kappaB activation and OPN expression were examined by western blotting and immunocytochemistry.

Results: As a result of oxalate stimulation, the amount of p65 subunit in the nucleus increased significantly (P < 0.05), and NAC significantly inhibited the translocation of p65 into the nucleus (P < 0.05).

Conclusion: These observations indicate that NAC can be used as a drug to prevent stone formation.

MeSH terms

  • Acetylcysteine / pharmacology
  • Cells, Cultured
  • Epithelial Cells / drug effects*
  • Epithelial Cells / physiology*
  • Humans
  • Kidney Tubules / cytology*
  • Kidney Tubules / physiology*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / drug effects*
  • NF-kappa B / physiology*
  • Osteopontin / biosynthesis*
  • Oxalates / pharmacology*

Substances

  • NF-kappa B
  • Oxalates
  • Osteopontin
  • Acetylcysteine