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Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice
Ece A Mutlu1, Phillip A Engen, Saul Soberanes
1Department of Medicine, Section of Gastroenterology and Nutrition Rush University Medical College, 1725 W Harrison Street, Chicago, IL 60612, USA. Ece_Mutlu@rush.edu
Background:
Exposure 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.
Methods:
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 4 kD dextran was measured at 48 hours.
Results:
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.
Conclusions:
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.
Insights
Particulate matter (PM) air pollution causes gut inflammation and cell death. Exposure to PM increases intestinal permeability and disrupts gut barrier function, potentially worsening inflammatory bowel diseases.
Area of Science:
- Gastroenterology
- Environmental Health
- Toxicology
Background:
- Particulate matter (PM) air pollution is a potential environmental trigger for gastrointestinal (GI) inflammatory conditions.
- PM can enter the GI tract through ingestion of contaminated air or secretions.
Purpose of the Study:
- To investigate the effects of urban PM on GI epithelial cells and intestinal tissue.
- To determine if PM exposure causes oxidative stress, cell death, and barrier dysfunction in the gut.
Main Methods:
- Caco-2 cells were used to measure PM-induced cell death and mitochondrial reactive oxygen species (ROS) generation.
- Mice were exposed to urban PM via gastric gavage, and intestinal tissues were analyzed for histology, gene expression, and permeability.
Main Results:
- PM exposure led to increased ROS generation, cell death, and disruption of tight junctions in Caco-2 cells.
- PM-exposed mice exhibited increased intestinal permeability, reduced tight junction protein ZO-1, elevated IL-6 mRNA, and increased apoptosis in the colon.
Conclusions:
- High-dose urban PM exposure induces oxidative stress, GI epithelial cell death, and inflammation in vitro and in vivo.
- These PM-induced gut alterations may contribute to the exacerbation of inflammatory gut disorders.
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