Characterizing caspase-1 involvement during esophageal disease progression

Area of Science:

• Gastroenterology
• Inflammation research
• Cancer biology

Background:

• Barrett's esophagus (BE) is a precancerous condition linked to chronic inflammation.
• Inflammasome signaling, including caspase-1 activation, drives inflammation and cell death.
• Caspase-1 plays a role in secreting inflammatory cytokines like IL-1β and IL-18.

Purpose of the Study:

• To investigate caspase-1 expression and its functional role in the progression from normal esophagus to BE and esophageal adenocarcinoma (EAC).
• To assess the impact of caspase-1 inhibition on inflammatory mediator secretion in BE models.

Main Methods:

• Utilized three models: human esophageal cell lines, a murine BE model, and patient-derived tissues.
• Analyzed caspase-1 expression in epithelial and stromal compartments.
• Cultured BE patient biopsies and murine BE organoids ex vivo with a caspase-1 inhibitor to measure cytokine and chemokine secretion.

Main Results:

• Epithelial caspase-1 expression was significantly increased in BE.
• Stromal caspase-1 levels correlated with inflammation severity.
• Caspase-1 inhibition in BE organoids reduced IL-1β and CXCL1 secretion.

Conclusions:

• Caspase-1 activity is enhanced in BE and contributes to the secretion of inflammatory mediators.
• Targeting caspase-1 may represent a novel therapeutic strategy to prevent progression from BE to EAC.