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Potential role of NADPH oxidase-mediated activation of Jak2/Stat3 and mitogen-activated protein kinases and expression of TGF-β1 in the pathophysiology of acute pancreatitis.

 Kyung Don Ju  ;  Joo Weon Lim  ;  Kyung Hwan Kim  ;  Hyeyoung Kim 
 INFLAMMATION RESEARCH, Vol.60(8) : 791-800, 2011 
Journal Title
Issue Date
Animals ; Cell Line ; Ceruletide/pharmacology ; Enzyme Activation* ; Enzyme Inhibitors/metabolism ; Humans ; Janus Kinase 2/metabolism* ; Mitogen-Activated Protein Kinases/metabolism* ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism* ; Pancreas, Exocrine/cytology ; Pancreas, Exocrine/drug effects ; Pancreas, Exocrine/metabolism ; Pancreatitis/physiopathology* ; Rats ; Reactive Oxygen Species/metabolism ; STAT3 Transcription Factor/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Tyrphostins/metabolism
Cerulein ;  NADPH oxidase ;  Jak2/Stat3 ;  TGF-β1  ; Pancreatic acinar cells 
OBJECTIVE: NADPH oxidase is potentially associated with acute pancreatitis by producing reactive oxygen species (ROS). We investigated whether NADPH oxidase mediates the activation of Janus kinase (Jak)2/signal transducers and activators of transcription (Stat)3 and mitogen-activated protein kinases (MAPKs) to induce the expression of transforming growth factor-β1 (TGF-β1) in cerulein-stimulated pancreatic acinar cells. TREATMENT: AR42J cells were treated with an NADPH oxidase inhibitor diphenyleneiodonium (DPI) or a Jak2 inhibitor AG490. Other cells were transfected with antisense or sense oligonucleotides (AS or S ODNs) for NADPH oxidase subunit p22(phox) or p47(phox). METHODS: TGF-β1 was determined by enzyme-linked immonosorbent assay. STAT3-DNA binding activity was measured by electrophoretic mobility shift assay. Levels of MAPKs as well as total and phospho-specific forms of Jak1/Stat3 were assessed by Western blot analysis. RESULTS: Cerulein induced increases in TGF-β1, Stat3-DNA binding activity and the activation of MAPKs in AR42J cells. AG490 suppressed these cerulein-induced changes, similar to inhibition by DPI. Cerulein-induced activation of Jak2/Stat3 and increases in MAPKs and TGF-β1 levels were inhibited in the cells transfected with AS ODN for p22(phox) and p47(phox) compared to S ODN controls. CONCLUSION: Inhibition of NADPH oxidase may be beneficial for prevention and treatment of pancreatitis by suppressing Jak2/Stat3 and MAPKs and expression of TGF-β1 in pancreatic acinar cells.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
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