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Suppression of cerulein-induced cytokine expression by antioxidants in pancreatic acinar cells.

 Ji Hoon Yu  ;  Joo Weon Lim  ;  Wan Namkung  ;  Hyeyoung Kim  ;  Kyung Hwan Kim 
 LABORATORY INVESTIGATION, Vol.82(10) : 1359-1368, 2002 
Journal Title
Issue Date
Amylases/metabolism ; Animals ; Antioxidants/pharmacology* ; Cells, Cultured ; Ceruletide/pharmacology* ; Cytokines/genetics* ; Hydrogen Peroxide/metabolism ; Interleukin-1/genetics ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Male ; NF-kappa B/metabolism ; Pancreas/cytology ; Pancreas/drug effects ; Pancreas/immunology* ; Proline/analogs & derivatives* ; Proline/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Thiocarbamates/pharmacology
Reactive oxygen species (ROS) has been considered to be an important regulator in the development and pathogenesis of pancreatitis and an activator of the transcription factor, nuclear factor-kappaB (NF-kappaB), regulating inflammatory cytokine gene expression. NF-kappaB activation was demonstrated in cerulein pancreatitis, which rapidly induces an acute, edematous form of pancreatitis. This study aimed to investigate whether cerulein induced ROS generation, lipid peroxide and hydrogen peroxide production, NF-kappaB activation, and expression of cytokines (IL-1beta, IL-6) in pancreatic acinar cells. An additional aim was to establish whether these alterations were inhibited by antioxidants such as glutathione, superoxide dismutase, and catalase and an inhibitor of NF-kappaB activation, pyrrolidine dithiocarbamate (PDTC). To determine the possible interactions of the antioxidants and PDTC with cerulein-induced signaling, Ca2+ signal and amylase release were monitored in the pancreatic acinar cells treated with cerulein in the presence or absence of either the antioxidants or PDTC. The results showed that cerulein generated ROS and increased lipid peroxide and hydrogen peroxide production in the acinar cells, as determined by dichlorofluorescein diacetate dye. This resulted in NF-kappaB activation and the induction of cytokine gene expression in the cells. The cerulein-induced NF-kappaB activation was in parallel to IkappaBalpha degradation. Cerulein also induced Ca2+ signals and amylase release in acinar cells. Both antioxidants (glutathione, superoxide dismutase, catalase) and PDTC inhibited the cerulein-induced, oxidant-mediated alterations but did not affect the cerulein-evoked Ca2+ signals and amylase release in acinar cells. In conclusion, ROS, generated by cerulein, activates NF-kappaB, resulting in the up-regulation of inflammatory cytokine gene expression in acinar cells. NF-kappaB inhibition by scavenging ROS might alleviate the inflammatory response in pancreatic acinar cells by suppressing cytokine gene expression.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Gastroenterology (소화기병연구소) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Lim, Joo Weon(임주원)
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