title: 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.
  
  
  CONCLUSIONS
  These findings revealed a novel role for pancreatic TCPTP in the progression of cerulein-induced AP.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.forename: Yannan
authors.initials: Y
authors.lastname: Xi
authors.forename: Ellen
authors.initials: E
authors.lastname: Hosein
authors.forename: Nicole
authors.initials: N
authors.lastname: Coggins
authors.forename: Santana
authors.initials: S
authors.lastname: Bachaalany
authors.forename: Florian
authors.initials: F
authors.lastname: Wiede
authors.forename: Salvador
authors.initials: S
authors.lastname: Perez
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Griffey
authors.forename: Juan
authors.initials: J
authors.lastname: Sastre
authors.forename: Tony
authors.initials: T
authors.lastname: Tiganis
authors.affiliation: Department of Nutrition, University of California Davis, One Shields Ave, 3135 Meyer Hall, Davis, CA 95616, USA. fghaj@ucdavis.edu.
authors.forename: Fawaz G
authors.initials: FG
authors.lastname: Haj
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D015850:Interleukin-6 / Q000097:blood; D008049:Lipase / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism*; D010766:Phosphorylation; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide; D008049:Lipase; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D000681:Amylases