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 language | English (US) |
|---|---|
| Article number | 13 |
| Journal | Cell Communication and Signaling |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - 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)
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 journal › Article
}
TY - JOUR
T1 - Pancreatic T cell protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis
AU - Bettaieb, Ahmed
AU - Xi, Yannan
AU - Hosein, Ellen
AU - Coggins, Nicole
AU - Bachaalany, Santana
AU - Wiede, Florian
AU - Perez, Salvador
AU - Griffey, Stephen M
AU - Sastre, Juan
AU - Tiganis, Tony
AU - Haj, Fawaz
PY - 2014/3/10
Y1 - 2014/3/10
N2 - 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.
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.
KW - Acute pancreatitis
KW - Inflammation
KW - Knockout mice
KW - STAT3
KW - TCPTP
UR - http://www.scopus.com/inward/record.url?scp=84898441655&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898441655&partnerID=8YFLogxK
U2 - 10.1186/1478-811X-12-13
DO - 10.1186/1478-811X-12-13
M3 - Article
C2 - 24606867
AN - SCOPUS:84898441655
VL - 12
JO - Cell Communication and Signaling
JF - Cell Communication and Signaling
SN - 1478-811X
IS - 1
M1 - 13
ER -