Pancreatic protein tyrosine phosphatase 1B deficiency exacerbates acute pancreatitis in mice

Abstract

Acute pancreatitis (AP) is one of the most common gastrointestinal disorders and causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP we utilized pancreas PTP1B knockout (panc‐PTP1B KO) mice to determine the effects of pancreatic PTP1B deficiency on cerulein‐ and arginine‐induced pancreatitis. PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein‐treated panc‐PTP1B KO mice compared with controls. Moreover, cerulein‐ and arginine‐induced serum amylase and lipase were higher in panc‐PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL‐1β, IL‐6 and TNFα were increased in panc‐PTP1B KO mice. Moreover, panc‐PTP1B KO mice exhibited enhanced cerulein‐ and arginine‐induced NF‐κB inflammatory response accompanied by increased MAPKs activation and elevated ER stress. These findings revealed a novel role for pancreatic PTP1B in cerulein‐ and arginine‐induced acute pancreatitis.