Pancreatic T cell protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis

Ahmed Bettaieb, Yannan Xi, Ellen Hosein, Nicole Coggins, Santana Bachaalany, Florian Wiede, Salvador Perez, Stephen M Griffey, Juan Sastre, Tony Tiganis, Fawaz Haj

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: Acute pancreatitis (AP) is a common clinical problem whose incidence has been progressively increasing in recent years. Onset of the disease is trigged by intra-acinar cell activation of digestive enzyme zymogens that induce autodigestion, release of pro-inflammatory cytokines and acinar cell injury. T-cell protein tyrosine phosphatase (TCPTP) is implicated in inflammatory signaling but its significance in AP remains unclear. Results: In this study we assessed the role of pancreatic TCPTP in cerulein-induced AP. TCPTP expression was increased at the protein and messenger RNA levels in the early phase of AP in mice and rats. To directly determine whether TCPTP may have a causal role in AP we generated mice with pancreatic TCPTP deletion (panc-TCPTP KO) by crossing TCPTP floxed mice with Pdx1-Cre transgenic mice. Amylase and lipase levels were lower in cerulein-treated panc-TCPTP KO mice compared with controls. In addition, pancreatic mRNA and serum concentrations of the inflammatory cytokines TNF and IL-6 were lower in panc-TCPTP KO mice. At the molecular level, panc-TCPTP KO mice exhibited enhanced cerulein-induced STAT3 Tyr705 phosphorylation accompanied by a decreased cerulein-induced NF-κB inflammatory response, and decreased ER stress and cell death. Conclusion: These findings revealed a novel role for pancreatic TCPTP in the progression of cerulein-induced AP.

Original languageEnglish (US)
Article number13
JournalCell Communication and Signaling
Volume12
Issue number1
DOIs
StatePublished - Mar 10 2014

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Keywords

  • Acute pancreatitis
  • Inflammation
  • Knockout mice
  • STAT3
  • TCPTP

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biochemistry
  • Medicine(all)

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