PPAR-gamma agonists inhibit TGF-beta1-induced chemokine expression in human tubular epithelial cells.
OBJECTIVE
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has a wide range of biological functions, including anti-inflammation. In this study, we investigated the inhibitory effects of PPAR-gamma on transforming growth factor beta1 (TGF-beta1)-induced interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) expression in renal tubular epithelial cells (HK-2).


METHODS
HK-2 cells were pretreated with 15d-PGJ2 or troglitazone (TGL) and then treated with TGF-beta1. Expression of MCP-1 and IL-8 was measured using real-time PCR and ELISA.


RESULTS
Treatment with 5 ng/mL TGF-beta1 for 24 h increased both MCP-1 and IL-8 mRNA and protein levels in HK-2 cells. Both 15d-PGJ2 at 2.5 and 5 micromol/L and TGL at 2.5 micromol/L exhibited inhibitory effects on TGF-beta1-induced MCP-1 expression. Additionally, 15d-PGJ2 at 2.5 and 5 micromol/L and TGL at 2.5 micromol/L inhibited TGF-beta1-induced expression of IL-8.


CONCLUSIONS
PPAR-gamma agonists (15d-PGJ2 and TGL) could inhibit the TGF-beta1-induced expression of chemokines in HK-2 cells. Our results suggest that PPAR-gamma agonists have the potential to be used as a treatment regimen to reduce inflammation in renal tubulointerstitial disease.
Wang
Wei-ming
WM
Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
Zhang
Hui-di
HD
Jin
Yuan-meng
YM
Zhu
Bing-bing
BB
Chen
Nan
N
D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000276:immunology*; D047495:PPAR gamma / Q000819:agonists* / Q000276:immunology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000494:pharmacology*; D000077288:Troglitazone
C477819:15-deoxyprostaglandin J2; D018932:Chemokine CCL2; D002839:Chromans; D007004:Hypoglycemic Agents; D016209:Interleukin-8; D047495:PPAR gamma; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D000077288:Troglitazone; D015230:Prostaglandin D2