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

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 TNFα 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.

• Authors: Ahmed Bettaieb, Yannan Xi, Ellen Hosein, Nicole Coggins, Santana Bachaalany, Florian Wiede, Salvador Perez, Stephen M Griffey, Juan Sastre, Tony Tiganis, Fawaz G Haj
• Journal: Cell communication and signaling : CCS (Cell Commun Signal) Vol. 12 Pg. 13 (Mar 10 2014) ISSN: 1478-811X [Electronic] England
• PMID: 24606867 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• NF-kappa B
• RNA, Messenger
• STAT3 Transcription Factor
• Tumor Necrosis Factor-alpha
• Ceruletide
• Lipase
• Protein Tyrosine Phosphatase, Non-Receptor Type 2
• Amylases

Topics

• Amylases (blood)
• Animals
• Ceruletide (toxicity)
• Interleukin-6 (blood)
• Lipase (blood)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NF-kappa B (metabolism)
• Pancreatitis, Acute Necrotizing (chemically induced, metabolism)
• Phosphorylation
• Protein Tyrosine Phosphatase, Non-Receptor Type 2 (deficiency, genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• STAT3 Transcription Factor (metabolism)
• Tumor Necrosis Factor-alpha (blood)