Effect of 15d-PGJ2 on the expression of CD40 and RANTES induced by IFN-γ and TNF-α on renal tubular epithelial cells (HK-2)

作者：Zhang, Ya Jie; Yang, Xiao^*; Kong, Qing Yu; Zhang, Yun Fang; Chen, Wei Ying; Dong, Xiu Qing; Li, Xiao Yan; Yu, Xue Qing

来源：American Journal of Nephrology, 2006, 26(4): 356-362.

DOI：10.1159/000094735

• peroxisome proliferator-activated receptor-gamma
• inflammation
• renal tubular epithelial cells
• CD40
• RANTES

Background/Aims: Recent evidence shows that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) 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-gamma 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-gamma agonist 15-deoxy-12,14-prostaglandin J(2) (15d-PGJ(2)) or 15d-PGJ(2) + PPAR-gamma antagonist GW9662, and then stimulated with a combination of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). 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-alpha and IFN-gamma 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-gamma-dependent pathways. These results point to PPAR-gamma as a remarkable new target in the prevention of tubular inflammatory injury associated with renal disease.

• 出版日期2006
• 单位中山大学