Antimicrobial peptide human neutrophil peptide 1 as a potential link between chronic Inflammation and ductal adenocarcinoma of the pancreas

• Verfasst von: Pausch, Thomas [VerfasserIn]
• Verfasst von: Adolph, Sarah Anna Julia [VerfasserIn]
• Verfasst von: Felix, Klaus M. [VerfasserIn]
• Verfasst von: Bauer, Andrea [VerfasserIn]
• Verfasst von: Bergmann, Frank [VerfasserIn]
• Verfasst von: Werner, Jens [VerfasserIn]
• Verfasst von: Hartwig, Werner [VerfasserIn]
• Titel: Antimicrobial peptide human neutrophil peptide 1 as a potential link between chronic Inflammation and ductal adenocarcinoma of the pancreas
• Verf.angabe: Thomas Pausch, Sarah Adolph, Klaus Felix, Andrea S. Bauer, Frank Bergmann, Jens Werner, Werner Hartwig
• E-Jahr: 2018
• Jahr: [2018]
• Umfang: 7 S.
• Fussnoten: Gesehen am 11.02.2020
• Titel Quelle: Enthalten in: Pancreas
• Ort Quelle: Philadelphia, Pa. : Lippincott Williams & Wilkins, 1986
• Jahr Quelle: 2018
• Band/Heft Quelle: 47(2018), 5, Seite 561-567
• ISSN Quelle: 1536-4828
• DOI: doi:10.1097/MPA.0000000000001054
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1689795506

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.