Korean J Physiol Pharmacol.  1999 Oct;3(5):521-528.

Lipid peroxidation, NF-kappaB activation and cytokine production in neutrophil-stimulated pancreatic acinar cells

• Kim H
• Seo JY
• Cho SH
• Kim KH

Abstract

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 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) affect the productions H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by an antioxidant, N-acetylcysteine (NAC) and superoxide dismutase (SOD). H2O2 (ferrithiocyanate method), LPO (as thiobarbiturate reactive substances), and cytokines (IL-1beta, IL-6, TNF-alpha enzyme-linked immunosorbent assay) and NF-kappaB 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-alpha were increased with the ratio of PMA-primed neutrophils to acinar cells while the productions of LPO, IL-1beta, IL-6 and TNF-alpha were increased with time. PMA-primed neutrophils resulted in the activation of NF-kappaB. Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatary cytokines in acinar cells. Antioxidants might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-kappaB and decreasing cytokine production.

Keyword

Lipid peroxide; NF-kappaB; Cytokine; Pancreatic acinar cell; Neutrophil

MeSH Terms

Acetylcysteine
Acinar Cells*
Anti-Inflammatory Agents
Antioxidants
Cytokines
Interleukin-6
Lipid Peroxidation*
Neutrophils
NF-kappa B*
Pancreatitis
Reactive Oxygen Species
Superoxide Dismutase
Tumor Necrosis Factor-alpha
Up-Regulation
Acetylcysteine
Anti-Inflammatory Agents
Antioxidants
Cytokines
Interleukin-6
NF-kappa B
Reactive Oxygen Species
Superoxide Dismutase
Tumor Necrosis Factor-alpha