title: Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice.
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.
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Pineton de Chambrun
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] Inserm U995, Lille, France [3] UDSL, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Body-Malapel
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Frey-Wagner
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] Inserm U995, Lille, France [3] UDSL, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Djouina
authors.affiliation: 1] INSERM, UMR892, Nantes, France [2] CNRS, UMR6299, Nantes, France [3] Université de Nantes, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Deknuydt
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Atrott
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] Inserm U995, Lille, France [3] UDSL, Lille, France.
authors.forename: N
authors.initials: N
authors.lastname: Esquerre
authors.affiliation: 1] INSERM, UMR892, Nantes, France [2] CNRS, UMR6299, Nantes, France [3] Université de Nantes, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Altare
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Neut
authors.affiliation: Finlay Lab, Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: M C
authors.initials: MC
authors.lastname: Arrieta
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: T-D
authors.initials: TD
authors.lastname: Kanneganti
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Rogler
authors.affiliation: 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.
authors.forename: J-F
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Cortot
authors.affiliation: 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.
authors.forename: P
authors.initials: P
authors.lastname: Desreumaux
authors.affiliation: 1] Univ Lille Nord de France, Lille, France [2] Inserm U995, Lille, France [3] UDSL, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Vignal
mesh_terms: D000535:Aluminum / Q000009:adverse effects / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006099:Granuloma; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010710:Phosphates / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D017607:Aluminum Compounds; D016207:Cytokines; D018836:Inflammation Mediators; D010710:Phosphates; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid; D000535:Aluminum; C012714:aluminum phosphate