title: Oxidative stress induced cytokine production in isolated rat pancreatic acinar cells: effects of small-molecule antioxidants.
abstract: Reactive oxygen species are considered important regulators in the pathogenesis and in the development of pancreatitis. The transcription factor nuclear factor kappaB (NF-kappaB) is activated by reactive oxygen species and regulates the gene expressions of inflammatory cytokines. The present study investigates (1) the susceptibility of isolated rat pancreatic acinar cells to oxidant attacks produced by adenosine diphosphate/ferrous iron, hypoxanthine/xanthine oxidase, and neutrophils primed with 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) and (2) the potential of small-molecule antioxidants (N-acetylcysteine, beta-carotene, rebamipide, allopurinol) and superoxide dismutase (SOD) to prevent such injury and oxidant-mediated NF-kappaB activation and inflammatory cytokine production in the cells. As a result, oxidative stress resulted in a time-dependent increase in lipid peroxide production in pancreatic acinar cells which was inhibited by small-molecule antioxidants and SOD. PMA-primed neutrophils induced NF-kappaB activation and increased the production of cytokines (IL-6, TNF-alpha) in the cells. This was in parallel with lipid peroxide production. Small-molecule antioxidants and SOD inhibited NF-kappaB activation and cytokine production in acinar cells caused by PMA-primed neutrophils. In conclusion, oxidative stress activates NF-kappaB, resulting in upregulation of inflammatory cytokines in pancreatic acinar cells. Small-molecule antioxidants might be clinically useful anti-inflammatory agents by inhibiting oxidant-induced cytokine production.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Jeong Yeon
authors.initials: JY
authors.lastname: Seo
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Jeong Taeg
authors.initials: JT
authors.lastname: Seo
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000244:Adenosine Diphosphate / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019271:Hypoxanthine / Q000008:administration & dosage; D058085:Iron Compounds / Q000008:administration & dosage; D008054:Lipid Peroxides / Q000096:biosynthesis; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D016207:Cytokines; D058085:Iron Compounds; D008054:Lipid Peroxides; D016328:NF-kappa B; D019271:Hypoxanthine; D000244:Adenosine Diphosphate; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate