Antimicrobial peptide human neutrophil peptide 1 as a potential link between chronic Inflammation and ductal adenocarcinoma of the pancreas
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 pancreatit...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[2018]
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| In: |
Pancreas
Year: 2018, Volume: 47, Issue: 5, Pages: 561-567 |
| ISSN: | 1536-4828 |
| DOI: | 10.1097/MPA.0000000000001054 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1097/MPA.0000000000001054 Verlag, Volltext: https://journals.lww.com/pancreasjournal/fulltext/2018/05000/Antimicrobial_Peptide_Human_Neutrophil_Peptide_1.8.aspx 
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| Author Notes: | Thomas Pausch, Sarah Adolph, Klaus Felix, Andrea S. Bauer, Frank Bergmann, Jens Werner, Werner Hartwig |
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| 520 | |a 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. | ||
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