Suppressive effects of iron on TGF-β1 production by renal proximal tubular epithelial cells

Background: TGF-beta(1), which is one of the profibrogenic cytokines, is considered essential for both the tubulointerstitial fibrosis found in chronic kidney diseases and the repair of tissue damage in acute renal injury. Iron plays an important part in inflammatory damage since it supplies cytotoxic hydroxyl radicals. The aim of the present study was to examine the direct effects of iron on TGF-beta(1) production and the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, by human renal proximal tubular epithelial cells (RPTEC). Methods: Using human RPTEC, TGF-beta(1) expression was studied by immunohistochemical staining, ELISA and RNase protection assays. 8-OHdG expression was evaluated by immunohistochemical staining. Results: Ferric iron suppressed both TGF-beta(1) secretion and mRNA expression, and enhanced 8-OHdG expression in RPTEC in a dose-dependent manner. Desferrioxamine, an iron chelator, eliminated the suppressive effect of ferric citrate on TGF-beta(1) production. Conclusions: The results suggest that iron may delay the repair of kidney injury during the acute inflammatory phase via a reduction in TGF-beta(1) production by RPTEC. Iron chelation may therefore be a useful strategy in the treatment of inflammatory kidney diseases. Copyright (C) 2005 S. Karger AG, Basel.