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


CONCLUSIONS
These observations indicate that NAC can be used as a drug to prevent stone formation.
Tozawa
Keiichi
K
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan. toza@med.nagoya-cu.ac.jp
Yasui
Takahiro
T
Okada
Atsushi
A
Hirose
Masahito
M
Hamamoto
Shuzo
S
Itoh
Yasunori
Y
Kohri
Kenjiro
K
D000111:Acetylcysteine / Q000494:pharmacology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology* / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology*; D053495:Osteopontin / Q000096:biosynthesis*; D010070:Oxalates / Q000494:pharmacology*
D016328:NF-kappa B; D010070:Oxalates; D053495:Osteopontin; D000111:Acetylcysteine