Original Article
Acta Pharmacologica Sinica (2009) 30: 107–112; doi: 10.1038/aps.2008.15; published online 22nd December 2008
PPAR-
agonists inhibit TGF-
1-induced chemokine expression in human tubular epithelial cells
Wei-ming Wang1, Hui-di Zhang1, Yuan-meng Jin1, Bing-bing Zhu1 and Nan Chen1
1Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China
Correspondence: Prof Nan Chen, E-mail: chen-nan@medmail.com.cn
Received 20 August 2008; Accepted 12 November 2008; Published online 22 December 2008.
Abstract
Aim:
Peroxisome proliferator-activated receptor-
(PPAR-
) has a wide range of biological functions, including anti-inflammation. In this study, we investigated the inhibitory effects of PPAR-
on transforming growth factor
1 (TGF-
1)-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-
1. Expression of MCP-1 and IL-8 was measured using real-time PCR and ELISA.
Results:
Treatment with 5 ng/mL TGF-
1 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
mol/L and TGL at 2.5
mol/L exhibited inhibitory effects on TGF-
1-induced MCP-1 expression. Additionally, 15d-PGJ2 at 2.5 and 5
mol/L and TGL at 2.5
mol/L inhibited TGF-
1-induced expression of IL-8.
Conclusion:
PPAR-
agonists (15d-PGJ2 and TGL) could inhibit the TGF-
1-induced expression of chemokines in HK-2 cells. Our results suggest that PPAR-
agonists have the potential to be used as a treatment regimen to reduce inflammation in renal tubulointerstitial disease.
Keywords:
peroxisome proliferator-activated receptor-
, 15d-PGJ2, troglitazone, transforming growth factor
1, tubular epithelial cell, chemokine, monocyte chemoattractant protein-1, interleukin-8
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