Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice

We measured PM-induced cell death and mitochondrial ROS generation in Caco-2 cells stably expressing oxidant sensitive GFP localized to mitochondria in the absence or presence of an antioxidant. C57BL/6 mice were exposed to a very high dose of urban PM from Washington, DC (200 μg/mouse) or saline via gastric gavage and small bowel and colonic tissue were harvested for histologic evaluation, and RNA isolation up to 48 hours. Permeability to 4kD dextran was measured at 48 hours.PM induced mitochondrial ROS generation and cell death in Caco-2 cells. PM also caused oxidant-dependent NF-κB activation, disruption of tight junctions and increased permeability of Caco-2 monolayers. Mice exposed to PM had increased intestinal permeability compared with PBS treated mice. In the small bowel, colocalization of the tight junction protein, ZO-1 was lower in the PM treated animals. In the small bowel and colon, PM exposed mice had higher levels of IL-6 mRNA and reduced levels of ZO-1 mRNA. Increased apoptosis was observed in the colon of PM exposed mice.Exposure to high doses of urban PM causes oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut in vitro and in vivo. These PM-induced changes may contribute to exacerbations of inflammatory disorders of the gut.In human populations, investigators have associated PM exposure with an increasing number of adverse health outcomes including all-cause mortality, cardiovascular mortality, accelerated atherosclerosis in postmenopausal women, loss of lung function in healthy adults, impaired lung development in children, exacerbations of obstructive lung disease, pneumonia and increased risk of venous thromboembolism [1-11]. Recently, Kaplan et al reported that individuals younger than 23 years were more likely to be diagnosed with Crohn's disease if they lived in regions with higher NO2 concentrations [12], a marker of traffic related pollution that correlates