caa a22 4500 445885769 CHVBK 20180317145559.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00011-011-0335-4 doi (NATIONALLICENCE)springer-10.1007/s00011-011-0335-4 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 [Elektronische Daten] [Kyung Ju, Joo Lim, Kyung Kim, Hyeyoung Kim] 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 p22phox or p47phox. 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 p22phox and p47phox 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. Springer Basel AG, 2011 Cerulein nationallicence NADPH oxidase nationallicence Jak2/Stat3 nationallicence TGF-β1 nationallicence Pancreatic acinar cells nationallicence Ju Kyung Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 120-752, Seoul, Korea aut Lim Joo Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, 120-749, Seoul, Korea aut Kim Kyung Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 120-752, Seoul, Korea aut Kim Hyeyoung Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, 120-749, Seoul, Korea aut Inflammation Research SP Birkhäuser Verlag Basel 60/8(2011-08-01), 791-800 1023-3830 60:8<791 2011 60 11 https://doi.org/10.1007/s00011-011-0335-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0335-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ju Kyung Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 120-752, Seoul, Korea aut NATIONALLICENCE 700 1- Lim Joo Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, 120-749, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Kyung Department of Pharmacology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 120-752, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Hyeyoung Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, 120-749, Seoul, Korea aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/8(2011-08-01), 791-800 1023-3830 60:8<791 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer