Targeting of the receptor for advanced glycation end products regulates neutrophil infiltration and extravascular recruitment in mice acute pancreatitis.

Abstract

Infiltration of leukocytes and pancreatic acinar cell damaging are good indicators of extreme Acute Pancreatitis (AP). The signaling pathways for inflammation and tissue damage of the pancreas not been elucidated yet. In this study, we evaluated the role of targeting of the Receptor for Advanced Glycation End products (RAGE) signaling in AP. Moreover, we investigated the role of signaling RAGE in AP. C57BL/6 mice were injected with a RAGE inhibitor (anti-RAGE) (500 μg/kg) before induction of taurocholate into the pancreatic duct to induce pancreatitis. Treatment anti-RAGE decreased blood amylase concentration, neutrophil recruitment in the pancreas, hemorrhage and edema formation in pancreatitis decreased by taurocholate. Additionally, anti-RAGE administration decreased the MPO activity in the pancreas and lung induced by taurocholate. Intraperitoneal (IP) injection of anti-RAGE significantly decreased concentrations of CXCL2 and IL-6 in the pancreas and plasma respectively in response to challenges of taurocholate. Finally, RAGE inhibition did not have a direct impact on secretagogue-induced trypsinogen activation in pancreatic acinar cells in vitro. Thus, these findings show new signaling pathways in AP and suggest that RAGE targeting may be an efficient way to improve extreme AP.