title: Activation of peroxisome proliferator-activated receptor-gamma by glitazones reduces the expression and release of monocyte chemoattractant protein-1 in human mesothelial cells.
abstract: Human peritoneal mesothelial cells (MC) play an important role in inflammatory processes of the peritoneal cavity by producing various cytokines and chemokines, such as monocyte chemoattractant protein-1 (MCP-1). The present study was designed to assess the effect of the peroxisome proliferator-activated receptor-gamma- (PPARγ-) activator rosiglitazone on the mesothelial MCP-1 expression and release. Primary cultures of MC were obtained from omental tissue. MCP-1 antigen concentrations were measured in the cell supernatant by ELISA and MCP-1 mRNA levels by real-time polymerase chain reaction. The presence of PPARγ on MC was assayed in a Western Blot analysis. MC constitutively express PPARγ. Activation of this receptor via rosiglitazone (0,1-10 μmol/L) resulted in significantly reduced amounts of mesothelial MCP-1 release as well as MCP-1 mRNA. The use of the PPARγ inhibitor GW-9662 could completely prevent the rosiglitazone effects. Rosiglitazone was also effective in reducing TNFα-induced enhanced secretion of MCP-1. Our findings indicate that glitazones are effective in reducing constitutive and TNFα-stimulated mesothelial MCP-1 mRNA expression and release.
authors.affiliation: Medizinische Poliklinik-Innenstadt, Klinikum der Universitaet Muenchen, Muenchen, Germany. matthias.sauter@med.uni-muenchen.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Sauter
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kastenmüller
authors.forename: Franziska
authors.initials: F
authors.lastname: Belling
authors.forename: Markus
authors.initials: M
authors.lastname: Wörnle
authors.forename: Roland
authors.initials: R
authors.lastname: Ladurner
authors.forename: Thomas
authors.initials: T
authors.lastname: Mussack
authors.forename: Thomas
authors.initials: T
authors.lastname: Sitter
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone