title: 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).
abstract: 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.
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
authors.forename: Ya Jie
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Qing Yu
authors.initials: QY
authors.lastname: Kong
authors.forename: Yun Fang
authors.initials: YF
authors.lastname: Zhang
authors.forename: Wei Ying
authors.initials: WY
authors.lastname: Chen
authors.forename: Xiu Qing
authors.initials: XQ
authors.lastname: Dong
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Xue Qing
authors.initials: XQ
authors.lastname: Yu
mesh_terms: 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*
chemical_list: C477819:15-deoxyprostaglandin J2; D019013:CD40 Antigens; D018946:Chemokine CCL5; D004338:Drug Combinations; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015230:Prostaglandin D2