Anti-inflammatory effect of PPARgamma in cultured human mesangial cells.
Our aim is to investigate whether peroxisome proliferator-activator receptor-gamma (PPARgamma) expression was altered in human mesangial cells under inflammatory stress and whether PPARgamma could retard the inflammatory responses. Based on cultured human mesangial cell lines (HMCLs), PPARgamma expressions at protein and mRNA levels were observed by Western blot analysis and reverse transcriptase polymerase chain reaction. Informatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Our results demonstrated that PPARgamma protein expression was dramatically increased in HMCLs stimulated by IL-1beta (10 ng/mL). The levels of IL-6 and TNF-alpha in HMCL supernatants, protein, and mRNA expressions of PPARgamma in IL-1beta challenge cells were significantly increased more than those in untreated cells. Importantly, PPARgamma agonists troglitazone, rosiglitazone, and 15-deoxy-delta(12, 14)-prosglandin J2 significantly decreased the up expression of TNF-alpha and IL-6 in HMCL supernatants stimulated by IL-1beta. Furthermore, troglitazone downregulated TNF-alpha and IL-6 mRNA expression from IL-1beta challenge HMCLs. Our data suggest that PPARgamma plays an important role in mesangial cells responding to inflammatory stress. PPARgamma may prove to be a pharmacological target in glomerulonephritis.
Xiong
Zuying
Z
Renal Division of First Hospital and Institute of Nephrology, Peking University, Beijing, China.
Huang
Haichang
H
Li
Jingzi
J
Guan
Youfei
Y
Wang
Haiyan
H
D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D047495:PPAR gamma / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D047495:PPAR gamma