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Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice.
Part Fibre Toxicol. 2011 Jun 09; 8:19.PF

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Section of Gastroenterology and Nutrition Rush University Medical College, 1725 W Harrison Street, Chicago, IL 60612, USA. Ece_Mutlu@rush.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21658250

Citation

Mutlu, Ece A., et al. "Particulate Matter Air Pollution Causes Oxidant-mediated Increase in Gut Permeability in Mice." Particle and Fibre Toxicology, vol. 8, 2011, p. 19.
Mutlu EA, Engen PA, Soberanes S, et al. Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice. Part Fibre Toxicol. 2011;8:19.
Mutlu, E. A., Engen, P. A., Soberanes, S., Urich, D., Forsyth, C. B., Nigdelioglu, R., Chiarella, S. E., Radigan, K. A., Gonzalez, A., Jakate, S., Keshavarzian, A., Budinger, G. R., & Mutlu, G. M. (2011). Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice. Particle and Fibre Toxicology, 8, 19. https://doi.org/10.1186/1743-8977-8-19
Mutlu EA, et al. Particulate Matter Air Pollution Causes Oxidant-mediated Increase in Gut Permeability in Mice. Part Fibre Toxicol. 2011 Jun 9;8:19. PubMed PMID: 21658250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice. AU - Mutlu,Ece A, AU - Engen,Phillip A, AU - Soberanes,Saul, AU - Urich,Daniela, AU - Forsyth,Christopher B, AU - Nigdelioglu,Recep, AU - Chiarella,Sergio E, AU - Radigan,Kathryn A, AU - Gonzalez,Angel, AU - Jakate,Shriram, AU - Keshavarzian,Ali, AU - Budinger,G R Scott, AU - Mutlu,Gökhan M, Y1 - 2011/06/09/ PY - 2011/04/12/received PY - 2011/06/09/accepted PY - 2011/6/11/entrez PY - 2011/6/11/pubmed PY - 2011/10/26/medline SP - 19 EP - 19 JF - Particle and fibre toxicology JO - Part Fibre Toxicol VL - 8 N2 - 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. SN - 1743-8977 UR - https://www.unboundmedicine.com/medline/citation/21658250/Particulate_matter_air_pollution_causes_oxidant_mediated_increase_in_gut_permeability_in_mice_ L2 - https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/1743-8977-8-19 DB - PRIME DP - Unbound Medicine ER -