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

Abstract

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated disorders affecting the skin and gut, respectively, and share underlying mechanisms involving immune dysregulation and microbiota alterations. Imiquimod (IMQ), a compound commonly used to induce psoriasis-like skin inflammation in mice and exacerbate dextran sulfate sodium (DSS)-induced colitis. Accumulated research findings indicate that IMQ-induced reactive oxygen species (ROS) play a crucial role in biological functions and inflammation. In this study, we investigate the role of ROS in the pathogenesis of intestinal colitis and assess its potential as a therapeutic target by exposing mice to IMQ and establishing a novel disease model. Our results demonstrate that IMQ directly induces colitis-like inflammation in the intestines by depleting the mucus layer, reducing mucin 2 production, and increasing intestinal permeability. This induced model exhibits key features of inflammatory bowel disease, including pathological tissue characteristics. IMQ disrupts intestinal tight junctions and weakens barrier function, primarily through the ROS/extracellular signal-regulated kinase pathway. Moreover, antioxidant pretreatment alleviates colitis-like symptoms and restores intestinal barrier integrity. This IMQ-induced colitis model provides new insights into the molecular mechanisms underlying IBD and suggests its utility as a translational platform for assessing the therapeutic potential of redox-modulating interventions.