Effect of 15d-PGJ2 on the expression of CD40 and RANTES induced by IFN-gamma and TNF-alpha on renal tubular epithelial cells (HK-2).
OBJECTIVE
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 J2 (15d-PGJ2) or 15d-PGJ2 + 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.


CONCLUSIONS
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.
Zhang
Ya Jie
YJ
Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Yang
Xiao
X
Kong
Qing Yu
QY
Zhang
Yun Fang
YF
Chen
Wei Ying
WY
Dong
Xiu Qing
XQ
Li
Xiao Yan
XY
Yu
Xue Qing
XQ
D019013:CD40 Antigens / Q000378:metabolism*; D002460:Cell Line; D018946:Chemokine CCL5 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
C477819:15-deoxyprostaglandin J2; D019013:CD40 Antigens; D018946:Chemokine CCL5; D004338:Drug Combinations; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015230:Prostaglandin D2