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Mucosal Immunol. 2014 May;7(3):589-601. doi: 10.1038/mi.2013.78. Epub 2013 Oct 16.

Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice.

Author information

1
1] Univ Lille Nord de France, Lille, France [2] Inserm U995, Lille, France [3] UDSL, Lille, France [4] Hepato-Gastroenterology Department, CHU Lille, Lille, France.
2
1] Univ Lille Nord de France, Lille, France [2] Inserm U995, Lille, France [3] UDSL, Lille, France.
3
Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
4
1] INSERM, UMR892, Nantes, France [2] CNRS, UMR6299, Nantes, France [3] Université de Nantes, Nantes, France.
5
1] Univ Lille Nord de France, Lille, France [2] Inserm U995, Lille, France [3] UDSL, Lille, France [4] Clinical Bacteriology, College of Pharmacy, Lille, France.
6
Finlay Lab, Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
7
Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.

Abstract

The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10(-/-)) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor.

PMID:
24129165
PMCID:
PMC3998638
DOI:
10.1038/mi.2013.78
[Indexed for MEDLINE]
Free PMC Article

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