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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 12/2020

01-12-2020 | Cytokines | Original Article

Characterizing caspase-1 involvement during esophageal disease progression

Authors: Gillian Barber, Akanksha Anand, Katarzyna Oficjalska, James J. Phelan, Aisling B. Heeran, Ewelina Flis, Niamh E. Clarke, Jenny A. Watson, Julia Strangmann, Brian Flood, Hazel O’Neill, Dermot O’Toole, Finbar MacCarthy, Narayanasamy Ravi, John V. Reynolds, Elaine W. Kay, Michael Quante, Jacintha O’Sullivan, Emma M. Creagh

Published in: Cancer Immunology, Immunotherapy | Issue 12/2020

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Abstract

Barrett’s esophagus (BE) is an inflammatory condition and a neoplastic precursor to esophageal adenocarcinoma (EAC). Inflammasome signaling, which contributes to acute and chronic inflammation, results in caspase-1 activation leading to the secretion of IL-1β and IL-18, and inflammatory cell death (pyroptosis). This study aimed to characterize caspase-1 expression, and its functional importance, during disease progression to BE and EAC. Three models of disease progression (Normal–BE–EAC) were employed to profile caspase-1 expression: (1) a human esophageal cell line model; (2) a murine model of BE; and (3) resected tissue from BE-associated EAC patients. BE patient biopsies and murine BE organoids were cultured ex vivo in the presence of a caspase-1 inhibitor, to determine the importance of caspase-1 for inflammatory cytokine and chemokine secretion.
Epithelial caspase-1 expression levels were significantly enhanced in BE (p < 0.01). In contrast, stromal caspase-1 levels correlated with histological inflammation scores during disease progression (p < 0.05). Elevated secretion of IL-1β from BE explanted tissue, compared to adjacent normal tissue (p < 0.01), confirmed enhanced activity of caspase-1 in BE tissue. Caspase-1 inhibition in LPS-stimulated murine BE organoids caused a significant reduction in IL-1β (p < 0.01) and CXCL1 (p < 0.05) secretion, confirming the importance of caspase-1 in the production of cytokines and chemokines associated with disease progression from BE to EAC. Targeting caspase-1 activity in BE patients should therefore be tested as a novel strategy to prevent inflammatory complications associated with disease progression.
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Metadata
Title
Characterizing caspase-1 involvement during esophageal disease progression
Authors
Gillian Barber
Akanksha Anand
Katarzyna Oficjalska
James J. Phelan
Aisling B. Heeran
Ewelina Flis
Niamh E. Clarke
Jenny A. Watson
Julia Strangmann
Brian Flood
Hazel O’Neill
Dermot O’Toole
Finbar MacCarthy
Narayanasamy Ravi
John V. Reynolds
Elaine W. Kay
Michael Quante
Jacintha O’Sullivan
Emma M. Creagh
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 12/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02650-4

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