Pioglitazone, a PPARgamma ligand, suppresses NFkappaB activation through inhibition of IkappaB kinase activation in cerulein-treated AR42J cells.
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.
Wan
Hongyu
H
Department of Gastroenterology, Affiliated Ruijin Hospital of Shanghai Jiaotong University, 197 Ruijin Er Road, Shanghai 200025, China.
Yuan
Yaozong
Y
Qian
Aihua
A
Sun
Yan
Y
Qiao
Minmin
M
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
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