Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction...

Area of Science:

• Immunology
• Gastroenterology
• Molecular Biology

Background:

• Intestinal barrier dysfunction is a key factor in inflammatory bowel disease (IBD) pathogenesis.
• The Aryl hydrocarbon receptor (AhR) plays a role in maintaining intestinal mucosal homeostasis.

Purpose of the Study:

• To investigate the role of AhR activation in maintaining intestinal barrier function.
• To explore the therapeutic potential of AhR agonists in IBD models.

Main Methods:

• Dextran sulphate sodium (DSS)-induced colitis model in C57BL/6 mice treated with FICZ.
• In vitro studies using Caco-2 cells treated with TNF-α/IFN-γ and FICZ.
• Analysis of tight junction (TJ) protein expression, MLC phosphorylation, MLCK expression, and NF-κB signaling pathway.

Main Results:

• FICZ-induced AhR activation attenuated DSS-induced decreases in TJ protein expression.
• FICZ inhibited increases in MLC phosphorylation and MLCK expression in DSS-induced colitis.
• In vitro, AhR activation prevented TNF-α/IFN-γ-induced decreases in TER and TJ disruption, and inhibited MLCK/MLC phosphorylation via NF-κB suppression.

Conclusions:

• AhR activation by FICZ preserves intestinal barrier integrity.
• AhR signaling modulates key pathways involved in intestinal inflammation and barrier function.
• AhR-activating factors show promise as therapeutic agents for IBD.