期刊
SCIENCE OF THE TOTAL ENVIRONMENT
卷 850, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.scitotenv.2022.158017
关键词
Xenobiotics; Transporters; MDR1; Polymorphisms
资金
- Hauts de France Region
- Ministere de l'Enseignement Superieur et de la Recherche (CPER Climibio)
- European Fund for Regional Economic Development
- Lille University Hospital
This study found that aluminum exposure induced cytokine secretion in the colon of CD patients but not healthy individuals. Aluminum internalization in Caco-2 cells was correlated with inflammatory status. Analysis of genetic polymorphisms and transporter expression in human colon showed that decreased activity of ABCB1 and SLC26A3 transporters was involved in aluminum-induced inflammation.
Background & aim: The key role of environmental factors in the pathogenesis of Inflammatory Bowel Diseases (IBD) is recognized. Aluminum is suspected to be a risk factor for IBD. However, mechanisms linking aluminum exposure to disease development are unknown. We examined the role of aluminum transport and subcellular localisation on human colon susceptibility to aluminum-induced inflammation.Methods: Human colon biopsies isolated from Crohn's disease (CD) or control patients and Caco-2 cells were incubated with aluminum. The effects of aluminum were evaluated on cytokine secretion and transporter expression. The role of aluminum kinetics parameters was studied in Caco-2 using transport inhibitors and in human colon biopsies by assessing genetic polymorphisms of transporters.Results: Aluminum exposure was shown to induce cytokine secretion in colon of CD but not healthy patients. In Caco-2 cells, aluminum internalisation was correlated with inflammatory status. In human colon, analysis of genetic polymorphisms and expression of ABCB1 and SLC26A3 transporters showed that their decreased activity was involved in aluminum-induced inflammation.Conclusions: We hypothesize that alteration in detoxifying response would lead to a deregulation of intestinal homeo-stasis and to the expression of IBD. Our study emphasizes the complexity of gene/environment interaction for alumi-num adverse health effect, highlighting at risk populations or subtypes of patients. A better understanding of correlations between gene expression or SNP and xenobiotic kinetics parameters would shift the medical paradigm to more personalized disease management and treatment.
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