Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas.

Abstract

OBJECTIVES:

Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP).

METHODS:

Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin α 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE).

RESULTS:

Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels.

CONCLUSIONS:

Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas.

• Authors: Thomas Pausch, Sarah Adolph, Klaus Felix, Andrea S Bauer, Frank Bergmann, Jens Werner, Werner Hartwig
• Journal: Pancreas (Pancreas) 2018 May/Jun Vol. 47 Issue 5 Pg. 561-567 ISSN: 1536-4828 [Electronic] United States
• PMID: 29683978 (Publication Type: Journal Article)

Chemical References

• Cytokines
• alpha-Defensins
• human neutrophil peptide 1

Topics

• Carcinoma, Pancreatic Ductal (genetics, metabolism)
• Cell Line
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics, metabolism)
• Cytokines (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Pancreas (metabolism, pathology)
• Pancreatic Neoplasms (genetics, metabolism)
• Pancreatitis, Chronic (genetics, metabolism)
• alpha-Defensins (genetics, metabolism)