Fatty acid ethyl ester (FAEE) associated acute pancreatitis: An ex-vivo study using human pancreatic acini.
Acute pancreatitis
Alcohol
Apoptosis
Co-localization
Cytokines
Fatty acid ethyl esters
Journal
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
ISSN: 1424-3911
Titre abrégé: Pancreatology
Pays: Switzerland
ID NLM: 100966936
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
06
05
2020
revised:
09
09
2020
accepted:
08
10
2020
pubmed:
21
10
2020
medline:
6
10
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Fatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model. Experiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS. We observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset. Our data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS.
Sections du résumé
BACKGROUND & AIM
OBJECTIVE
Fatty acid ethyl esters (FAEEs), are produced by non-oxidative alcohol metabolism and can cause acinar cell damage and subsequent acute pancreatitis in rodent models. Even though experimental studies have elucidated the FAEE mediated early intra-acinar events, these mechanisms have not been well studied in humans. In the present study, we evaluate the early intra-acinar events and inflammatory response in human pancreatic acinar tissues and cells in an ex-vivo model.
METHODS
METHODS
Experiments were conducted using normal human pancreatic tissues exposed to FAEE. Subcellular fractionation was performed on tissue homogenates and trypsin and cathepsin B activities were estimated in these fractions. Acinar cell injury was evaluated by histology and immunohistochemistry. Cytokine release from exposed acinar cells was evaluated by performing Immuno-fluorescence. Serum was collected from patients with AP within the first 72 h of symptom onset for cytokine estimation using FACS.
RESULTS
RESULTS
We observed significant trypsin activation and acinar cell injury in FAEE treated tissue. Cathepsin B was redistributed from lysosomal to zymogen compartment at 30 min of FAEE exposure. IHC results indicated the presence of apoptosis in pancreatic tissue at 1 & 2hrs of FAEE exposure. We also observed a time dependent increase in secretion of cytokines IL-6, IL-8, TNF-α from FAEE treated acinar tissue. There was also a significant elevation in plasma cytokines in patents with alcohol associated AP within 72 h of symptom onset.
CONCLUSION
CONCLUSIONS
Our data suggest that alcohol metabolites can cause acute acinar cell damage and subsequent cytokine release which could eventually culminant in SIRS.
Identifiants
pubmed: 33077383
pii: S1424-3903(20)30778-X
doi: 10.1016/j.pan.2020.10.027
pii:
doi:
Substances chimiques
Esters
0
Fatty Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1620-1630Informations de copyright
Copyright © 2020. Published by Elsevier B.V.