Lipid Peroxidation, NF-κB Activation and Cytokine Production in Neutrophil-Stimulated Pancreatic Acinar Cells

Lipid Peroxidation, NF-κB Activation and Cytokine Production in Neutrophil-Stimulated Pancreatic Acinar Cells

<P> Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. The present study aims to investigate whether neutrophils primed by 4β-phorbol 12β-myristate 13α-acetate (PMA) affect the productions H<SUB>2</SUB>O<SUB>2</SUB> and lipid peroxide (LPO), NF-κB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by an antioxidant, N-acetylcysteine (NAC) and superoxide dismutase (SOD). H<SUB>2</SUB>O<SUB>2</SUB> (ferrithiocyanate method), LPO (as thiobarbiturate reactive substances), and cytokines (IL-1β, IL-6, TNF-α; enzyme-linked immunosorbent assay) and NF-κB activation (electrophoretic mobility shift assay) were analyzed in acinar cells treated with or without PMA-primed neutrophils in the absence or presence of NAC (10 mM) or SOD (300 U/ml). As a result, the productions of H2O2, LPO and TNF-α were increased with the ratio of PMA-primed neutrophils to acinar cells while the productions of LPO, IL-1β, IL-6 and TNF-α were increased with time. PMA-primed neutrophils resulted in the activation of NF-κB. Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-κB, resulting in upregulation of inflammatary cytokines in acinar cells. Antioxidants might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-κB and decreasing cytokine production.