Abstract
BackgroundExposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI) tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled particles.MethodsWe 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.ResultsPM 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.ConclusionsExposure 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.
Highlights
Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract
Particulate matter induces a dose-dependent reactive oxygen species (ROS) generation and cell death in colonic epithelial cells We previously reported that exposure of alveolar epithelial cells to PM10 collected from Düsseldorf, Germany induced the generation of ROS [51]
Consistent with our findings in lung epithelial cells, we observed that Caco-2 cells exposed to PM generated ROS from the mitochondria, which were required for the activation of NF-B and the development of apoptotic cell death in vitro
Summary
Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. As the bulk of PM enters the body by inhalation, investigators have used radiolabeled particles to examine the fate of inhaled particles in rodents [21] They found that the overwhelming majority of the particles (> 95%) are taken up by alveolar macrophages, brought to the oropharynx by mucociliary clearance and excreted in the feces [21]. PM may enter the GI tract directly through swallowed air or through the ingestion of foods such as vegetables and fruits coated with PM. These findings suggest that the steady state concentrations of PM in the GI tract may be similar to those encountered in the lung.
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