VACCINE

Mucosal Immunology • May 2014
Aluminum enhances inflammation
and decreases mucosal healing in
experimental colitis in mice
Author information
Pineton de Chambrun G1, Body-Malapel M2,
Frey-Wagner I3, Djouina M2, Deknuydt F4, Atrott K3,
Esquerre N2, Altare F4, Neut C5, Arrieta MC6, Kanneganti TD7,
Rogler G3, Colombel JF1, Cortot A1, Desreumaux P1, Vignal C2
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. 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. INSERM, UMR892, Nantes, France [2] CNRS, UMR6299, Nantes, France [3]
Université de Nantes, Nantes, France
5. 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
“Deleterious effects of aluminum on
intestinal inflammation and mucosal repair
strongly suggest that aluminum might be an
environmental Inflammatory Bowel Disease risk factor.”
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.
http://www.ncbi.nlm.nih.gov/pubmed/24129165