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 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. 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. Copyright (c) 2006 S. Karger AG, Basel.
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 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. 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. Copyright (c) 2006 S. Karger AG, Basel.
Authors: R Hontecillas; W T Horne; M Climent; A J Guri; C Evans; Y Zhang; B W Sobral; J Bassaganya-Riera Journal: Mucosal Immunol Date: 2010-11-10 Impact factor: 7.313