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 Citations (Scopus)

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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Non-Receptor Type 2 Protein Tyrosine Phosphatase
Ceruletide
Pancreatitis
Acinar Cells
Cytokines
Messenger RNA
Enzyme Precursors
Phosphorylation
Enzyme Activation
Cell death
Amylases
Lipase

Keywords

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

ASJC Scopus subject areas

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

Cite this

Pancreatic T cell protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis. / Bettaieb, Ahmed; Xi, Yannan; Hosein, Ellen; Coggins, Nicole; Bachaalany, Santana; Wiede, Florian; Perez, Salvador; Griffey, Stephen M; Sastre, Juan; Tiganis, Tony; Haj, Fawaz.

In: Cell Communication and Signaling, Vol. 12, No. 1, 13, 10.03.2014.

Research output: Contribution to journalArticle

Bettaieb, A, Xi, Y, Hosein, E, Coggins, N, Bachaalany, S, Wiede, F, Perez, S, Griffey, SM, Sastre, J, Tiganis, T & Haj, F 2014, 'Pancreatic T cell protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis', Cell Communication and Signaling, vol. 12, no. 1, 13. https://doi.org/10.1186/1478-811X-12-13
Bettaieb, Ahmed ; Xi, Yannan ; Hosein, Ellen ; Coggins, Nicole ; Bachaalany, Santana ; Wiede, Florian ; Perez, Salvador ; Griffey, Stephen M ; Sastre, Juan ; Tiganis, Tony ; Haj, Fawaz. / Pancreatic T cell protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis. In: Cell Communication and Signaling. 2014 ; Vol. 12, No. 1.
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AU - Bachaalany, Santana

AU - Wiede, Florian

AU - Perez, Salvador

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AB - 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.

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