title: Pioglitazone, a PPARgamma ligand, suppresses NFkappaB activation through inhibition of IkappaB kinase activation in cerulein-treated AR42J cells.
abstract: OBJECTIVE
  NFkappaB plays a major role in the immune and inflammation responses of pancreatitis. Recently, there is increasing evidence that the expression and activity of PPARgamma may participate in the activity of NFkappaB. Therefore, we investigated a putative relationship of the two transcription factors in cerulein-treated pancreatic acinar AR42J cells.
  
  
  METHODS
  AR42J were stimulated by cerulein with or without the presence of a PPARgamma activator pioglitazone or a PPARgamma antagonist GW9662.
  
  
  RESULTS
  Treatment of AR42J cells with pioglitazone attenuated cerulein induced p50 and p65 NFkappaB dimer activity in the nucleus as measured by transcription factor assay. Cytosolic expression of IkappaBalpha protein was reduced by cerulein, basal signalling was not influenced by the PPARgamma inhibitor GW9662 and pioglitazone. Adversely, the inhibitory effect of pioglitazone on NFkappaB activity induced by cerulein was almost reversed by GW9662.
  
  
  CONCLUSIONS
  These findings provide evidence for the involvement of the nuclear hormone receptors PPARgamma in the activity of NFkappaB in cerulein-treated AR42J cells.
authors.affiliation: Department of Gastroenterology, Affiliated Ruijin Hospital of Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wan
authors.forename: Yaozong
authors.initials: Y
authors.lastname: Yuan
authors.forename: Aihua
authors.initials: A
authors.lastname: Qian
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Minmin
authors.initials: M
authors.lastname: Qiao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002108:Ceruletide / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D047468:Immunoprecipitation; D008024:Ligands; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052002:NF-kappa B p50 Subunit / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis; D047495:PPAR gamma / Q000187:drug effects*; D010766:Phosphorylation; D000077205:Pioglitazone; D051381:Rats; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics
chemical_list: D007004:Hypoglycemic Agents; D008024:Ligands; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D047495:PPAR gamma; D053246:Receptor Activator of Nuclear Factor-kappa B; D045162:Thiazolidinediones; D051996:Transcription Factor RelA; D002108:Ceruletide; D051550:I-kappa B Kinase; D000077205:Pioglitazone