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

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-κB (NF-κB). Present study aims to investigate whether neutrophils primed by 4β-phorbol 12β-myristate 13α-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-κB 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 H2O2, LPO, and cytokines both time and dose dependently. PMA-primed neutrophils resulted in the activation of two species of NF-κB 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-κB, 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-κB and decreasing cytokine production.