Imiquimod-induced colitis: A novel ROS/ERK-driven model of intestinal inflammation and barrier dysfunction.

Area of Science:

• Gastroenterology and Immunology
• Molecular Biology and Pathology

Background:

• Psoriasis and Inflammatory Bowel Disease (IBD) are chronic immune-mediated conditions sharing common pathogenic pathways.
• Imiquimod (IMQ) is known to induce skin inflammation and exacerbate gut inflammation, with reactive oxygen species (ROS) implicated.
• The precise role of ROS in IMQ-induced intestinal inflammation and its therapeutic potential remain to be fully elucidated.

Purpose of the Study:

• To investigate the role of ROS in the pathogenesis of IMQ-induced intestinal colitis.
• To establish a novel mouse model of colitis using IMQ.
• To assess the therapeutic potential of targeting ROS in IBD.

Main Methods:

• Mice were exposed to Imiquimod (IMQ) to induce colitis.
• Assessment of intestinal barrier function, including mucus layer integrity, mucin 2 production, and tight junction disruption.
• Investigation of the ROS/extracellular signal-regulated kinase (ERK) pathway.
• Evaluation of antioxidant pretreatment effects on colitis symptoms and barrier function.

Main Results:

• IMQ directly induced colitis-like inflammation by depleting the mucus layer and reducing mucin 2, increasing intestinal permeability.
• IMQ disrupted intestinal tight junctions and weakened barrier function via the ROS/ERK pathway.
• Antioxidant pretreatment significantly alleviated colitis symptoms and restored intestinal barrier integrity.

Conclusions:

• IMQ induces intestinal inflammation and barrier dysfunction through ROS-dependent mechanisms, establishing a relevant IBD model.
• The ROS/ERK pathway is critical in IMQ-induced gut pathology.
• This IMQ-induced colitis model serves as a valuable platform for evaluating redox-modulating therapies for IBD.