NF-kappaB and cytokines in pancreatic acinar cells.
Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment 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-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 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). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced 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 clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.
Kim
H
H
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea. kim626@yumc.yonsei.ac.kr
Seo
J Y
JY
Kim
K H
KH
D000208:Acute Disease; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010195:Pancreatitis / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D016328:NF-kappa B