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NADPH oxidase mediates interleukin-6 expression in cerulein-stimulated pancreatic acinar cells

Authors
 Ji Hoon Yu  ;  Joo Weon Lim  ;  Kyung Hwan Kim  ;  Hyeyoung Kim 
Citation
 INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, Vol.37(7) : 1458-1469, 2005 
Journal Title
 INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY 
ISSN
 1357-2725 
Issue Date
2005
MeSH
Animals ; Cell Line, Tumor ; Ceruletide/toxicity* ; Electrophoretic Mobility Shift Assay ; Enzyme Activation ; Interleukin-6/biosynthesis* ; NADPH Oxidases/antagonists & inhibitors ; NADPH Oxidases/metabolism* ; NF-kappa B/metabolism* ; Onium Compounds/pharmacology ; Pancreas/enzymology ; Pancreas/metabolism* ; Protein Subunits/antagonists & inhibitors ; Protein Subunits/metabolism ; Rats ; Reactive Oxygen Species/metabolism*
Keywords
NADPH oxidase ; NF-κB ; IL-6 ; Pancreatic acinar cells ; Cerulein
Abstract
NADPH oxidase produces a large amount of reactive oxygen species (ROS) mainly in phagocytic cells. ROS are involved in NF-κB activation, cytokine expression and thus, pathogenesis of pancreatitis. However, the source of ROS in pancreatic acinar cells has not been clarified. Cerulein rapidly induces acute and edematous form of pancreatitis. We investigated whether pancreatic acinar cells contain NADPH oxidase, and whether NADPH oxidase mediates interleukin-6 (IL-6) in pancreatic acinar AR42J cells stimulated with cerulein. Expression of NADPH oxidase subunits and NADPH oxidase activity were determined in the cells by immunofluorescence staining and lucigenin luminescence, respectively. Oxidant-sensitive nuclear transcription factor NF-κB activation was monitored by electrophoretic mobility shift assay. IL-6 expression was determined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbant assay. NADPH oxidase inhibitor diphenylene iodonium (DPI), antioxidant rebamipide, and antisense oligonucleotides (AS ODNs) for NADPH oxidase subunits p22phox and p47phox were used to determine the involvement of NADPH oxidase in NF-κB activation and IL-6 expression in AR42J cells. As a result, pancreatic acinar AR42J cells constitutively express NADPH oxidase subunits p67phox and p47phox in the cytosol and Nox1 and p22phox in the membrane. Cerulein-stimulated NADPH oxidase activity and induced NF-κB activation and IL-6 expression in AR42J cells. Treatment of DPI or rebamipide and transfection of AS ODNs for NADPH oxidase subunits suppressed cerulein-induced NF-κB activation and IL-6 expression compared to S ODNs. In conclusion, NADPH oxidase may mediate the expression of inflammatory cytokines by stimulating NF-κB activation in pancreatic acinar cells during the course of pancreatitis.
Full Text
http://www.sciencedirect.com/science/article/pii/S1357272505000385
DOI
10.1016/j.biocel.2005.02.004
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Kim, Hye Young(김혜영)
Yu, Ji Hoon(유지훈)
Lim, Joo Weon(임주원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114806
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