Rationally Designed Two-Photon Ratiometric Elastase Probe for Investigating Inflammatory Bowel Disease

Area of Science:

• Biochemistry
• Molecular Biology
• Medical Imaging

Background:

• Elastase, a serine protease, is crucial for digestion and immunity.
• Neutrophil elastase is implicated in inflammatory bowel disease (IBD).
• Existing methods lack precise tools for real-time elastase activity monitoring in vivo.

Purpose of the Study:

• To develop and utilize a novel fluorescent probe for detecting intracellular elastase activity.
• To investigate elastase level dynamics in mouse organs under IBD conditions.
• To elucidate the role of neutrophil migration in IBD-associated elastase changes.

Main Methods:

• Rational design and synthesis of a two-photon ratiometric fluorescent elastase probe.
• In vivo imaging of elastase activity in various mouse organs.
• Comparison of elastase levels in healthy, IBD-induced, and immune-deficient mice.

Main Results:

• The probe successfully detected intracellular elastase activity linked to inflammation.
• Healthy mice showed higher elastase in the liver and duodenum; IBD induced changes in liver, duodenum, colon, and lung.
• Downregulation in the liver suggests neutrophil migration to upregulated organs like the duodenum.

Conclusions:

• The developed probe is effective for mapping neutrophil migration and visualizing inflammation.
• Elastase level changes in IBD are influenced by neutrophil migration and local production.
• The liver plays a key role in immune response during inflammation-induced elastase changes.