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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)
Ist Teil von
American journal of nephrology, 2006-09, Vol.26 (4), p.356-362
Ort / Verlag
Basel, Switzerland: Karger
Erscheinungsjahr
2006
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Background/Aims: Recent evidence shows that peroxisome proliferator-activated receptor-γ (PPAR-γ) 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-γ 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-γ agonist 15-deoxy-12,14-prostaglandin J2 (15d-PGJ2) or 15d-PGJ2 + PPAR-γ antagonist GW9662, and then stimulated with a combination of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). 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-α and IFN-γ 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-γ-dependent pathways. These results point to PPAR-γ as a remarkable new target in the prevention of tubular inflammatory injury associated with renal disease.