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Suppression of NF-kappaB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells.

Authors
 Hyeyoung Kim  ;  Jeong Yeon Seo  ;  Kwan Ho Roh  ;  Joo Weon Lim  ;  Kyung Hwan Kim 
Citation
 Free Radical Biology and Medicine, Vol.29(7) : 674-683, 2000 
Journal Title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN
 0891-5849 
Issue Date
2000
MeSH
Acetylcysteine/pharmacology* ; Animals ; Antioxidants/pharmacology* ; Cells, Cultured ; Cytokines/analysis ; Cytokines/genetics* ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/immunology* ; Hydrogen Peroxide/metabolism ; Kinetics ; Lipid Peroxidation/drug effects* ; Male ; NF-kappa B/antagonists & inhibitors* ; Pancreas/drug effects ; Pancreas/immunology ; Pancreas/physiology* ; RNA, Messenger/genetics ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism ; Tetradecanoylphorbol Acetate/pharmacology ; Time Factors ; Transcription, Genetic/drug effects
Keywords
Reactive oxygen species ; NF-κB ; Cytokine ; Pancreatic acinar cells ; Neutrophils ; N-acetylcysteine ; Free radicals
Abstract
Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and development of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H(2)O(2) and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). Neutrophils generated ROS by stimulation with PMA, which was inhibited by NAC and SOD. In acinar cells, PMA-primed neutrophils increased the productions of H(2)O(2), LPO, and cytokines both time and dose dependently. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer) in acinar cells. Both NAC and SOD inhibited neutrophil-induced, oxidant-mediated alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-kappaB and decreasing cytokine production.
Full Text
https://www.sciencedirect.com/science/article/pii/S0891584900003683
DOI
10.1016/S0891-5849(00)00368-3
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171638
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