Fine Particulate Matter (PM2.5) Disrupts Intestinal Barrier Function by Inducing Oxidative Stress and PI3K/AKT-Mediated Inflammation in Caco-2 Cells.

Fine particulate matter (PM2.5) is an environmental factor that triggers gastrointestinal diseases. However, the effects of PM2.5 on intestinal function are not fully understood. This study established an environmental exposure cell model to explore PM2.5-induced intestinal permeability alteration and its mechanisms. Intestinal barrier permeability was evaluated via trans-epithelial electrical resistance (TEER) measurement and FITC-dextran paracellular penetration analysis, followed by detection of intercellular junction protein β-catenin and its coding gene CTNNB1. Expression of inflammatory cytokines (TNF-α, IL-6) and phosphorylation of PI3K and AKT were assessed using quantitative real-time polymerase chain reaction and Western blot, respectively. Reactive oxygen species (ROS) and malondialdehyde were measured using commercial kits to observe cellular oxidative stress. The results showed that PM2.5 impaired the intestinal barrier, as indicated by reduced TEER, increased FITC-dextran penetration, down-regulated expression of β-catenin and CTNNB1. Additionally, compared with the control, inflammatory cytokines and oxidative stress markers were significantly elevated after PM2.5 exposure. The ratio of p-PI3K/PI3K and p-AKT/AKT was also up-regulated in PM2.5-exposed Caco-2 cells. Pretreatment with PI3K inhibitor LY294002 and ROS scavenger NAC modulated β-catenin expression, reduced inflammation/ROS, and alleviated the hyperpermeability of Caco-2 cells. Thus, our results reveal that PM2.5 induces PI3K/AKT-mediated inflammation and ROS generation in Caco-2 cells, leading to intestinal barrier impairment.