Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice

Ahmed Bettaieb, Shinichiro Koike, Samah Chahed, Santana Bachaalany, Stephen M Griffey, Juan Sastre, Fawaz Haj

Research output: Contribution to journalArticle

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Abstract

Acute pancreatitis (AP) is a common and devastating gastrointestinal disorder that causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP, we used pancreas PTP1B knockout (panc-PTP1B KO) mice and determined the effects of pancreatic PTP1B deficiency on cerulein- and arginine-induced acute pancreatitis. We report that PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein-treated panc-PTP1B KO mice compared with controls. Moreover, cerulein- and arginine-induced serum amylase and lipase were significantly higher in panc-PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B, IL-6, and tumor necrosis factor-α were increased in panc-PTP1B KO mice compared with controls. Furthermore, panc-PTP1B KO mice exhibited enhanced cerulein- and arginine-induced NF-κB inflammatory response accompanied with increased mitogen-activated protein kinases activation and elevated endoplasmic reticulum stress. Notably, these effects were recapitulated in acinar cells treated with a pharmacological inhibitor of PTP1B. These findings reveal a novel role for pancreatic PTP1B in cerulein- and arginine-induced acute pancreatitis.

Original languageEnglish (US)
Pages (from-to)2043-2054
Number of pages12
JournalAmerican Journal of Pathology
Volume186
Issue number8
DOIs
StatePublished - Aug 1 2016

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Pancreatitis
Ceruletide
Pancreas
Knockout Mice
Arginine
Inflammation
Endoplasmic Reticulum Stress
Acinar Cells
Amylases
Mitogen-Activated Protein Kinases
Serum
Lipase
Interleukin-6
Tumor Necrosis Factor-alpha
Pharmacology
Cytokines
Morbidity
Messenger RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice. / Bettaieb, Ahmed; Koike, Shinichiro; Chahed, Samah; Bachaalany, Santana; Griffey, Stephen M; Sastre, Juan; Haj, Fawaz.

In: American Journal of Pathology, Vol. 186, No. 8, 01.08.2016, p. 2043-2054.

Research output: Contribution to journalArticle

Bettaieb, Ahmed ; Koike, Shinichiro ; Chahed, Samah ; Bachaalany, Santana ; Griffey, Stephen M ; Sastre, Juan ; Haj, Fawaz. / Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice. In: American Journal of Pathology. 2016 ; Vol. 186, No. 8. pp. 2043-2054.
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