Reactive oxygen species (ROS), generated by infiltrating neutrophils, are c
onsidered as an important regulator in the pathogenesis and deveolpment of
pancreatitis. A hallmark of the inflammatory response is the induction of c
ytokine gene expression, which may be regulated by oxidant-sensitive transc
ription factor, nuclear factor-kappa B (NF-kappa B), Present study aims to
investigate whether neutrophils primed by 4 beta-phorbol 12 beta-myristate
13 alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (L
PO), NF-kappa B activation and cytokine production in pancreatic acinar cel
ls, 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 T
NF-alpha were increased with the amounts of PMA-primed neutrophils added to
acinar cells while the productions of H2O2, LPO and cytokines increased wi
th time. PMA-primed neutrophils resulted in the activation of two species o
f NF-kappa B dimers (a p50/p65 heterodimer and a p50 homodimer), Both NAC a
nd SOD inhibited neutrophil-induced alterations in acinar cells. In conclus
ion, ROS, generated by neutrophils, activates NF-kappa B, resulting in upre
gulation of inflammatory cytokines in acinar cells. Antioxidants such as NA
C might be clinically useful antiinflammatory agents by inhibiting oxidant-
mediated activation of NF-kappa B and decreasing cytokine production.