A Nephrotoxic Mechanism of FK506 is Partially Related to TGF-β Production in Cultured Renal Proximal Tubular Cells in vitro

概要

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Recent studies in kidney transplant recipients have demonstrated a nephrotoxic adverse effect of the new macrolide immunosuppressant FK506. The mechanism of the nephrotoxicity of FK506 is unknown. FK506 enhances transforming growth factor-β (TGF-β) gene expression in rat kidney and liver. The present study was carried out to examine the direct effect of FK506 and TGF-β on an established porcine renal proximal tubular cell line (LLC-PK1) growth in vitro culture. The effect of FK506 on TGF-β production of the tubular cells was also evaluated. LLC-PK1 cell proliferation was assessed by the ^3H-thymidine incorporation. The results revealed that FK506 and TGF-β inhibited the proliferation of LLC-PK1 cells in a dose-dependent manner. FK506 decreased the growth rate of the cells to 95%±7% at 0.01 μM and 20%±3% at 10 μM. The growth rate of the cells at 5 ng/ml of TGF-β decreased almost maximally to 32%±2%. Significantly, FK506 could increased TGF-β production of LLC-PK1 cells. We formulated the hypothesis that FK506 associated renal toxicity are partially due to TGF-β overexpression which is induced by FK506.
北里大学の論文
1997-12-31