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Peptide YY attenuates STAT1 and STAT3 activation induced by TNF-alpha in acinar cell line AR42J

Kristine Robinson1, Linda Vona-Davis, Dale Riggs

  • 1Department of Surgery, West Virginia University, Morgantown, WV 26506, USA.

Journal of the American College of Surgeons
|May 2, 2006
PubMed
Abstract

Insights

Tumor necrosis factor-alpha (TNF-alpha) activates STAT1 and STAT3 in pancreatic cells, increasing inflammation. Peptide YY (PYY) inhibits this activation, reducing inflammatory markers and offering potential pancreatitis therapeutic strategies.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Gastroenterology

Background:

  • Signal transducers and activators of transcription (STAT) proteins, specifically STAT1 and STAT3, are implicated in inflammatory diseases.
  • The role of STAT1 and STAT3 in pancreatic inflammation is not well understood.
  • Peptide YY (PYY) is a gastrointestinal hormone known to reduce pancreatitis and modulate inflammatory transcription factors like NF-kappaB and Smad3/4.

Purpose of the Study:

  • To investigate the effect of tumor necrosis factor-alpha (TNF-alpha) on STAT1 and STAT3 activation in pancreatic acinar cells.
  • To determine if Peptide YY (PYY) can attenuate TNF-alpha-induced STAT1 and STAT3 activation and subsequent inflammatory responses.
  • To explore the potential of targeting STAT proteins and PYY for pancreatitis treatment.

Main Methods:

  • Rat pancreatic acinar cells were stimulated with TNF-alpha and subsequently treated with PYY.
  • Amylase secretion and cytokine production (IL-1beta, IL-4, IL-6, IL-10, TNF-alpha) were measured.
  • STAT1 and STAT3 transcription factor binding activity was assessed using protein/DNA arrays, electrophoretic mobility shift assays (EMSA), and ELISA.

Main Results:

  • TNF-alpha significantly increased amylase production and the release of multiple inflammatory cytokines.
  • PYY treatment reversed the TNF-alpha-induced increase in amylase secretion and cytokine production.
  • TNF-alpha markedly upregulated STAT1 and STAT3 activation, while PYY significantly downregulated their DNA binding activity, confirmed by multiple assays.

Conclusions:

  • TNF-alpha activates STAT1 and STAT3 in pancreatic acinar cells, contributing to inflammatory cytokine production.
  • PYY effectively attenuates the protein/DNA binding activity of STAT1 and STAT3, suggesting a role in mitigating pancreatitis.
  • Further research into STAT proteins and PYY may reveal novel therapeutic avenues for managing pancreatitis.

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