Aims: 

The study focused on the involvement of oxidative stress in the underlying mechanisms mediating chemokine production in pancreatic acinar cells during mild and severe acute pancreatitis (AP).

Methods: 

AP was induced in rats by either bile-pancreatic duct obstruction (BPDO) (mild AP) or retrograde infusion of 3.5% sodium taurocholate (NaTc) into the bile-pancreatic duct (severe AP). N-Acetylcysteine (NAC) was used as an antioxidant treatment. Glutathione (GSH) levels and myeloperoxidase (MPO) activity were analyzed in pancreatic tissue. mRNA expression of the chemokines monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant (CINC) as well as the phosphorylation of p38-MAPK and the activation of the NF-kB and STAT-3 transcription factors were analyzed in isolated acinar cells.

Results: 

GSH depletion and MPO activity, as a result of AP, were higher in NaTc-induced AP. NAC only prevented the depletion of GSH and reduced MPO activity in pancreas of rats with BPDO-induced AP. Acinar overexpression of MCP-1 and CINC and activation p38-MAPK, NF-kB and STAT-3 were found in both models of AP. NAC treatment repressed the acinar chemokine expression and inhibited the signalling pathways in mild but not in severe AP.

Conclusions: 

Oxidative stress plays a key role in the expression of chemokines in acinar cells during acute pancreatitis mediated by MAPK, NF-kB and STAT-3 activation.