Original Report: Laboratory Investigation

Effect of 15d-PGJ₂ on the Expression of CD40 and RANTES Induced by IFN- and TNF- on Renal Tubular Epithelial Cells (HK-2)
Ya Jie Zhang, Xiao Yang, Qing Yu Kong, Yun Fang Zhang, Wei Ying Chen, Xiu Qing Dong, Xiao Yan Li, Xue Qing Yu

Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China

Address of Corresponding Author

Am J Nephrol 2006;26:356-362 (DOI: 10.1159/000094735)

  Key Words

• Peroxisome proliferator-activated receptor-
• Inflammation
• Renal tubular epithelial cells
• CD40
• RANTES

  Abstract

Background/Aims: Recent evidence shows that peroxisome proliferator-activated receptor- (PPAR-) ameliorates a variety of inflammatory conditions. CD40 is a co-stimulatory molecule and its ligation induces production of different proinflammatory cytokines including RANTES (regulated upon activation, normal T cell expressed), which are considered as important factors in the initiation and maintenance of inflammatory response. The aim of this study was to investigate the effect of PPAR- on CD40 and RANTES production on cultured human renal proximal tubular epithelial (HK-2) cells. Methods: HK-2 cells were maintained under defined in vitro conditions and treated with either PPAR- agonist 15-deoxy-12,14-prostaglandin J₂ (15d-PGJ₂) or 15d-PGJ₂ + PPAR- antagonist GW9662, and then stimulated with a combination of tumor necrosis factor- (TNF-) and interferon- (IFN-). The CD40 and RANTES levels were investigated. Results: HK-2 cells expressed low levels of CD40 and RANTES. Activation of HK-2 cells by combined treatment of TNF- and IFN- results in strong synergistic effects on the expression of CD40 and the secretion of RANTES. 15d-PGJ₂ significantly decreased CD40 and RANTES expression and GW9662 partly abrogated the inhibition of 15d-PGJ₂ on CD40 and RANTES. Conclusion: 15d-PGJ₂ significantly decreased CD40 and RANTES expression in HK-2 cells, which were partially mediated by PPAR--dependent pathways. These results point to PPAR- as a remarkable new target in the prevention of tubular inflammatory injury associated with renal disease.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Dr. Xiao Yang, MD, PhD, Department of Nephrology
First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong 510080 (PR China)
Tel. +86 20 8733 5811, Fax +86 20 8776 9673
E-Mail yangxiao_999@yahoo.com.cn

  Article Information

Received: May 15, 2006
Accepted: June 21, 2006
Published online: July 24, 2006
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 1, Number of References : 32