Acta Pharmacologica Sinica (2009) 30: 107-112; doi: 10.1038/aps.2008.15; published online 22nd December 2008

PPAR-γ agonists inhibit TGF-β1-induced chemokine expression in human tubular epithelial cells

Wei-ming WANG, Hui-di ZHANG, Yuan-meng JIN, Bing-bing ZHU, Nan CHEN*

Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China


Aim: Peroxisome proliferator-activated receptor-γ (PPAR-γ) has a wide range of biological functions, including anti-inflammation.  In this study, we investigated the inhibitory effects of PPAR-γ on transforming growth factor β1 (TGF-β1)-induced interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) expression in renal tubular epithelial cells (HK-2).

Methods: HK-2 cells were pretreated with 15d-PGJ2 or troglitazone (TGL) and then treated with TGF-β1.  Expression of MCP-1 and IL-8 was measured using real-time PCR and ELISA.

Results: Treatment with 5 ng/mL TGF-β1 for 24 h increased both MCP-1 and IL-8 mRNA and protein levels in HK-2 cells.  Both 15d-PGJ2 at 2.5 and 5 μmol/L and TGL at 2.5 μmol/L exhibited inhibitory effects on TGF-β1-induced MCP-1 expression.  Additionally, 15d-PGJ2 at 2.5 and 5 μmol/L and TGL at 2.5 μmol/L inhibited TGF-β1-induced expression of IL-8. 

Conclusion: PPAR-γ agonists (15d-PGJ2 and TGL) could inhibit the TGF-β1-induced expression of chemokines in HK-2 cells.  Our results suggest that PPAR-γ agonists have the potential to be used as a treatment regimen to reduce inflammation in renal tubulointerstitial disease.

Keywords: peroxisome proliferator-activated receptor-γ; 15d-PGJ2; troglitazone; transforming growth factor β1; tubular epithelial cell; chemokine; monocyte chemoattractant protein-1; interleukin-8