Gene/environment interaction in the susceptibility of Crohn's disease patients to aluminum.
MDR1
Polymorphisms
SLC26A3
Transporters
Xenobiotics
Journal
The Science of the total environment
ISSN: 1879-1026
Titre abrégé: Sci Total Environ
Pays: Netherlands
ID NLM: 0330500
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
received:
29
03
2022
revised:
09
08
2022
accepted:
09
08
2022
pubmed:
17
8
2022
medline:
7
10
2022
entrez:
16
8
2022
Statut:
ppublish
Résumé
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. 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. 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. We hypothesize that alteration in detoxifying response would lead to a deregulation of intestinal homeostasis and to the expression of IBD. Our study emphasizes the complexity of gene/environment interaction for aluminum 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.
Sections du résumé
BACKGROUND & AIM
OBJECTIVE
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
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
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
CONCLUSIONS
We hypothesize that alteration in detoxifying response would lead to a deregulation of intestinal homeostasis and to the expression of IBD. Our study emphasizes the complexity of gene/environment interaction for aluminum 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.
Identifiants
pubmed: 35973536
pii: S0048-9697(22)05116-6
doi: 10.1016/j.scitotenv.2022.158017
pii:
doi:
Substances chimiques
Cytokines
0
Xenobiotics
0
Aluminum
CPD4NFA903
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
158017Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Olivier Tillement reports a relationship with MexBrain that includes: board membership, employment, equity or stocks, and funding grants.