Cystic pancreatic neoplasms: an emerging problem.

Widespread usage of advanced abdominal imaging has resulted in an increased finding of cystic lesions in the pancreas in asymptomatic patients. Greater than 90% of cystic pancreatic lesions are of inflammatory origin, the well-known pancreatic pseudocysts. The critical issue confronting specialists is differentiating inflammatory lesions from neoplastic lesions.

Peptide YY reverses TNF-alpha induced transcription factor binding of interferon regulatory factor-1 and p53 in pancreatic acinar cells.

BACKGROUND: Cytokine activation in the pancreatitis induces local and systemic cellular damage. Transcription factors interferon regulatory factor-1 (IRF-1) and the tumor suppressor gene p53 collaborate to enhance p21 related cell cycle regulation during pathological disease progression. However, little is known about their role in the pancreas after cytokine challenge. Our laboratory has previously shown that TNF-alpha induces the binding of many transcription factors, including NF-kappa B, and treatment with the gut hormone, Peptide YY (PYY), ameliorates the effects. We hypothesized that TNF-alpha would induce IRF-1 and p53 protein binding in pancreatic acinar cells and that PYY would attenuate the effect. MATERIALS AND METHODS: Rat pancreatic acinar AR42J cells were treated with rat recombinant TNF-alpha (200 ng/ml). To verify that our model was inducing pancreatitis, alpha-amylase activity was measured in the cell culture supernatant by fluorescence spectroscopy. PYY [3-36] was added at 500 pM 30 min post-TNF treatment; cells were harvested at 2 h for extraction of nuclear protein. Transcription factor binding of IRF-1 and p53 were determined by protein/DNA array analysis using chemiluminescence detection, and relative spot densities were measured by densitometry. A two-fold increase or decrease in density was considered significant. RESULTS: Amylase enzyme activity was significantly (P < 0.05) elevated in the TNF-alpha-treated cells by 2 h. Protein/DNA array analysis revealed significant up-regulation of both IRF-1 and p53 protein in nuclear extracts. Induction by TNF-alpha increased IRF-1 protein binding 3.5-fold, while binding levels of p53 protein increased six-fold. The addition of PYY to TNF-treated cells reduced IRF-1 and p53 binding to control levels. CONCLUSIONS: We have shown for the first time that short-term exposure to TNF-alpha induces the binding activity of transcription factors IRF-1 and p53 in rat pancreatic acinar cells, and that addition of PYY reduces it. Regulation of transcription factor activity by PYY may have therapeutic potential in altering the progression of pancreatitis.