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Cerulein-induced pancreatitis is similar to human edematous pancreatitis, characterized by the dysregulation of digestive enzyme production, edema formation, and an infiltration of inflammatory cells into the pancreas. We previously showed that the Janus kinase 2 (JAK2)/STAT3 pathway mediates inflammatory signaling in cerulein-stimulated pancreatic acinar cells. PPAR-gamma has been implicated in the regulation of inflammatory responses in several cells. In the present study, we investigated the role of PPAR-gamma in cerulein-induced activation of JAK2/STAT3 in pancreatic acinar cells. Treatment with cerulein induced the activation of JAK2/STAT3 and PPAR-gamma expression in AR42J cells. Cerulein-induced PPAR-gamma expression was inhibited by AG490, a JAK2/STAT3 inhibitor, in AR42J cells. An immunoprecipitation analysis showed that PPAR-gamma binds to STAT3 in cerulein-stimulated AR42J cells. Down-regulation of PPAR-gamma by siRNA increased STAT3 phosphorylation in AR42J cells stimulated with cerulein. These results show that PPAR-gamma inactivates STAT3 by directly interacting with STAT3 in cerulein-stimulated pancreatic acinar cells. Overexpression of PPAR-gamma may be beneficial for preventing pancreatitis by suppressing the activation of STAT3 in pancreatic acinar cells.
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참고문헌 (18)
참고문헌 신청
Granger J / 2005 / Acute pancreatitis: models, markers, and mediators / Shock 24(Suppl 1):45~51
Hofbauer B / 1998 / Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats / Am J Physiol 275:G352~G362
Qi QR / 2014 / Regulation and function of signal transducer and activator of transcription 3 / World J Biol Chem 5:231~239
Yu JH / 2008 / SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by regulating JAK2/STAT3signaling in pancreas / Int J Biochem Cell Biol 40:677~688
Kliewer SA / 1995 / A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation / Cell 83:813~819
Hofbauer B / 1998 / Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats / Am J Physiol 275:G352~G362
Qi QR / 2014 / Regulation and function of signal transducer and activator of transcription 3 / World J Biol Chem 5:231~239
Yu JH / 2008 / SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by regulating JAK2/STAT3signaling in pancreas / Int J Biochem Cell Biol 40:677~688
Kliewer SA / 1995 / A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation / Cell 83:813~819
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