PPARgamma 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. PPARgamma plays an important role in regulating several metabolic pathways. Recently, PPARgamma has been implicated in inflammatory responses and age-related diseases. The aim of this study was to determine the anti-inflammatory reaction of PPARgamma 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 PPARgamma 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 200 microM H(2)O(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 PPARgamma expression. A reconstitution of SIPS HDF cells with Ad/PPARgamma resulted in the downregulation of ICAM-1, ERK1/2, MMP-2 and -9, and normalized growth of SIPS-HDF cells. Moreover, PPARgamma 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 PPARgamma plays a key role in age-related inflammation and may have clinical applications as a molecular target in the treatment of age-related inflammation.
Lee
Young-Hee
YH
Department of Oral Biochemistry and Institute of Oral Bioscience, BK21 program, School of Dentistry, Chonbuk National University, Korea.
Lee
Nan-Hee
NH
Bhattarai
Govinda
G
Yun
Ji-Soo
JS
Kim
Tae-Il
TI
Jhee
Eun-Chung
EC
Yi
Ho-Keun
HK
D000375:Aging / Q000276:immunology*; D002478:Cells, Cultured; D004171:Diploidy; D015536:Down-Regulation; D005347:Fibroblasts / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology*
D047495:PPAR gamma; D018799:Intercellular Adhesion Molecule-1