title: Rosiglitazone, a PPAR-γ agonist, inhibits VEGF secretion by peripheral blood mononuclear cells and ROS production by human leukocytes.
abstract: OBJECTIVE
  To investigate the effects of rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the secretion of vascular endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMCs) and on the generation of reactive oxygen species (ROS) by leukocytes.
  
  
  METHODS
  PBMCs and leukocytes were obtained from venous blood samples collected from 20 healthy individuals. VEGF secretion was evaluated using a commercial ELISA kit, while ROS production was determined using a luminol-dependent chemiluminescence assay.
  
  
  RESULTS
  Rosiglitazone and calphostin C (a protein kinase C inhibitor) inhibited VEGF secretion by PBMCs by 63.7 and 62.3%, respectively. Both agents reduced ROS production in non-stimulated human leukocytes and down-regulated the enhanced generation of ROS in leukocytes that had been stimulated with the PKC activator phorbol 12,13-dibutyrate.
  
  
  CONCLUSIONS
  The results support the involvement of PKC as a direct, and/or NADPH-oxidase as an indirect, target for the action of rosiglitazone on VEGF secretion by PBMCs and ROS production in human leukocytes.
authors: Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Santa Efigênia, Belo Horizonte-MG, Brazil.
authors: R T
authors: RT
authors: Mattos
authors: A A
authors: AA
authors: Bosco
authors: J A
authors: JA
authors: Nogueira-Machado
mesh_terms: D000328:Adult; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D049449:Luminescence; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology; D047495:PPAR gamma / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D009281:Naphthalenes; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D000077154:Rosiglitazone; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C058819:calphostin C