title: Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress.
abstract: OBJECTIVE
  Hypertension is associated with increased plasma inflammatory markers such as cytokines and increased vascular cyclooxygenase-2 (COX-2) expression. The ability of peroxisome proliferator-activated receptor-γ (PPARγ) agonists to reduce oxidative stress seems to contribute to their anti-inflammatory properties. This study analyzes the effect of pioglitazone, a PPARγ agonist, on interleukin-1β-induced COX-2 expression and the role of reactive oxygen species (ROS) on this effect.
  
  
  RESULTS
  Vascular smooth muscle cells from hypertensive rats stimulated with interleukin-1β (10 ng/ml, 24 h) were used. Interleukin-1β increased: 1) COX-2 protein and mRNA levels; 2) protein and mRNA levels of the NADPH oxidase subunit NOX-1, NADPH oxidase activity and ROS production; and 3) phosphorylation of inhibitor of nuclear factor kappa B (IκB) kinase (IKK) nuclear expression of the p65 nuclear factor kappa B (NF-κB) subunit and cell proliferation, all of which were reduced by apocynin (30 μmol/l). Interleukin-1β-induced COX-2 expression was reduced by apocynin, tempol (10 μmol/l), catalase (1000 U/ml) and lactacystin (5 μmol/l). Moreover, H2O2 (50 μmol/l, 90 min) induced COX-2 expression, which was reduced by lactacystin. Pioglitazone (10 μmol/l) reduced the effects of interleukin-1β on: 1) COX-2 protein and mRNA levels; 2) NOX-1 protein and mRNA levels, NADPH oxidase activity and ROS production; and 3) p-IKK, p65 expressions and cell proliferation. Pioglitazone also reduced the H2O2-induced COX-2 expression and increased Cu/Zn and Mn-superoxide dismutase protein expression. PPARγ small interfering RNA (5 nmol/l) further increased interleukin-1β-induced COX-2 and NOX-1 mRNA levels. In addition, pioglitazone increased the interleukin-1β-induced PPARγ mRNA levels.
  
  
  CONCLUSIONS
  PPARγ activation with pioglitazone reduces interleukin-1β-induced COX-2 expression by interference with the redox-sensitive transcription factor NF-κB.
authors.affiliation: Departamento de Bioquímica, Fisiología y Genética Molecular, Universidad Rey Juan Carlos, Alcorcón, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Martín
authors.forename: José V
authors.initials: JV
authors.lastname: Pérez-Girón
authors.forename: Raquel
authors.initials: R
authors.lastname: Hernanz
authors.forename: Roberto
authors.initials: R
authors.lastname: Palacios
authors.forename: Ana M
authors.initials: AM
authors.lastname: Briones
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuño
authors.forename: Guillermo
authors.initials: G
authors.lastname: Zalba
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.forename: María J
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D051546:Cyclooxygenase 2; D000077205:Pioglitazone