PKC δ mediates pro-inflammatory responses in a mouse model of caerulein-induced acute pancreatitis

Acute pancreatitis is an inflammatory disorder of the pancreas. Protein kinase C (PKC) delta plays an important role in mediating chemokine production in mouse pancreatic acinar cells. This study aims to investigate the role of PKC delta in the pathogenesis of acute pancreatitis and to explore the mechanisms through which PKC delta mediates pro-inflammatory signaling. Acute pancreatitis was induced in mice by ten hourly intraperitoneal injections of caerulein. PKC delta translocation inhibitor peptide (delta V1-1) at a dose of 1.0 mg/kg or Tat (carrier peptide) at a dose of 1.0 mg/kg was administered to mice either 1 h before or 1 h after the first caerulein injection. One hour after the last caerulein injection, the mice were killed and pancreas, lungs, and blood were collected. Prophylactic and therapeutic treatment with delta V1-1 attenuated caerulein-induced plasma amylase levels and pancreatic edema. Treatment with delta V1-1 decreased myeloperoxidase activity and monocyte chemotactic protein-1 levels in both pancreas and plasma. PKC delta mediated acute pancreatitis by activating pancreatic nuclear factor kappa B, activator protein-1, and mitogen-activated protein kinases. Moreover, blockade of PKC delta attenuated lung myeloperoxidase activity and edema. Histological examination of pancreatic and lung sections confirmed protection against acute pancreatitis. Treatment with Tat had no protective effect on acute pancreatitis. Blockade of PKC delta represents a promising prophylactic and/or therapeutic tool for the treatment of acute pancreatitis.