IL-1β-Mediated Immunometabolic Adaptation in Corneal Epithelial Cells

Area of Science:

• Ocular surface disease
• Immunology
• Mitochondrial biology

Background:

• Corneal epithelium is vulnerable to stressors causing inflammation.
• Interleukin-1 beta (IL-1β) is a key inflammatory mediator in the tear film.
• The impact of IL-1β on corneal epithelial cell (CEC) mitochondrial function is not well understood.

Purpose of the Study:

• To investigate the effects of IL-1β on mitochondrial function in human CECs.
• To assess how varying concentrations and durations of IL-1β exposure impact CECs.

Main Methods:

• Human CECs were cultured with IL-1β (50 or 100 ng/mL) for 24 or 72 hours.
• Assessed reactive oxygen species (ROS), inflammatory cytokines, mitochondrial potential, ultrastructure, mitophagy, and metabolite composition.
• Examined lipid droplets using microscopy.

Main Results:

• Short-term IL-1β increased IL-8, ROS, and decreased mitochondrial membrane potential.
• Long-term IL-1β elevated IL-8, IL-6, ROS, and paradoxically increased mitochondrial membrane potential and spare respiratory capacity.
• Metabolomics revealed upregulation of the pentose phosphate pathway, TCA cycle, and altered lipid metabolism.

Conclusions:

• Prolonged IL-1β exposure induces metabolic rewiring in CECs, enhancing spare respiratory capacity.
• Corneal epithelial cells demonstrate an adaptive response to chronic inflammation.
• Findings have implications for understanding immune responses and cellular stress in ocular epithelia.