Korean J Nephrol.  2004 Nov;23(6):859-866.

Peroxisome Proliferator-Activated Receptor gamma Agonists Inhibit the Expression of Monocyte Chemoattractant Protein-1 in Human Mesangial Cells

• Kim YS
• Kim YO
• Yoon SA
• Yang CW
• Kim YS
• Chang YS
• Bang BK

Abstract

BACKGROUND
PPAR gamma is a member of the nuclear hormone receptor superfamily of transcription factors. PPAR gamma plays an important role in the control of inflammation as well as numerous cellular processes including glucose homeostasis, cell proliferation, cell differentiation, and extracellular matrix remodelling. MCP-1 is an important mediator for monocyte/macrophage infiltration in various inflammatory renal diseases. The aim of this study was to investigate whether PPAR gamma agonists (ciglitazone, 15d-PGJ2) regulate IL-1beta-induced MCP-1 expression in cultured human mesangial cells. METHODS: Human Mesangial cells were pre-incubated with ciglitazone (1, 5, 10 microM) or 15d-PGJ2 (0.01, 0.1, 1 microM) for 30 min and then treated with IL-1beta (250 pg/mL). MCP-1 concentration in the conditioned medium was mesured by ELISA. NF-kappa B DNA binding activity in the nuclear extract was mesured by electrophoretic mobility shift assay, and I kappa B alpha expression in the cytoplasmic extract was mesured by Western blot analysis. RESULTS: Both ciglitazone and 15d-PGJ2 significantly inhibited IL-1beta-induced MCP-1 production in mesangial cells in a time-dependent manner. The inhibition was maintained from 12 hr to 72 hr. However, they did not regulate IL-1beta-induced IkB alpha degradation and NF-kappa B binding activity. CONCLUSION: PPAR gamma agonists (ciglitazone, 15d-PGJ2) inhibit IL-1beta-induced MCP-1 expression in mesangial cells. Our data provide new insight into the therapeutic potential of PPAR gamma agonists in the inflammatory renal diseases.

Keyword

Mesangial cell; MCP-1; PPAR gamma

MeSH Terms

Blotting, Western
Cell Differentiation
Cell Proliferation
Chemokine CCL2*
Culture Media, Conditioned
Cytoplasm
DNA
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix
Glucose
Homeostasis
Humans*
I-kappa B Proteins
Inflammation
Mesangial Cells*
Monocytes*
NF-kappa B
Peroxisomes*
PPAR gamma*
Transcription Factors
Chemokine CCL2
Culture Media, Conditioned
DNA
Glucose
I-kappa B Proteins
NF-kappa B
PPAR gamma
Transcription Factors