PPARγ inhibits inflammatory reaction in oxidative stress induced human diploid fibloblast

The ageing of an inevitable life function is an unavoidable regressive physical process. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor family. PPARγ plays an important role in regulating several metabolic pathways. Recently, PPARγ has been implicated in inflammatory responses and age-related diseases. The aim of this study was to determine the anti-inflammatory reaction of PPARγ in an induced ageing progress. The late passage of human diploid fibroblasts (HDF), an in vitro ageing model, reveals the biological index materials of ageing. Aged cells showed decreased PPARγ expression and elevated levels of intracellular adhesion molecule-1 (ICAM-1), an inflammatory molecule. To induce the aged cell phenotype, the middle stage of HDF cells (PD31) were induced stress induced premature senescence (SIPS) with 200μMH₂O ₂ for 2 h. SIPS-HDF cells showed high levels of ICAM-1, extracellular signal regulated kinase (ERK1/2) activity and matrix metallomatrix protease (MMP-2, -9) activity, and low levels of PPARγ expression. A reconstitution of SIPS HDF cells with Ad/PPARγ resulted in the downregulation of ICAM-1, ERK1/2, MMP-2 and -9, and normalized growth of SIPS-HDF cells. Moreover, PPARγ in aged HDF cells reduced pro-inflammatory molecules and eliminated the formation of reactive oxygen species (ROS) through the ERK1/2 pathway. These results strongly suggest that PPARγ plays a key role in age-related inflammation and may have clinical applications as a molecular target in the treatment of age-related inflammation.