Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France.
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000 Lille, France.
Sci Total Environ. 2022 Dec 1;850:158017. doi: 10.1016/j.scitotenv.2022.158017. Epub 2022 Aug 13.
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.
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.
环境因素在炎症性肠病（IBD）发病机制中的关键作用已得到认可。铝被怀疑是 IBD 的一个风险因素。然而，将铝暴露与疾病发展联系起来的机制尚不清楚。我们研究了铝转运和亚细胞定位对人结肠易感性铝诱导炎症的作用。
从克罗恩病（CD）或对照患者和 Caco-2 细胞中分离出人结肠活检，并孵育铝。评估铝对细胞因子分泌和转运体表达的影响。在 Caco-2 细胞中使用转运抑制剂和在人结肠活检中评估转运体的遗传多态性来研究铝动力学参数的作用。
研究表明，铝暴露会诱导 CD 患者而非健康患者结肠细胞因子的分泌。在 Caco-2 细胞中，铝内化与炎症状态相关。在人结肠中，分析 ABCB1 和 SLC26A3 转运体的遗传多态性和表达表明，其活性降低与铝诱导的炎症有关。
我们假设解毒反应的改变会导致肠道内稳态失调，并导致 IBD 的表达。我们的研究强调了基因/环境相互作用对铝不良健康影响的复杂性，突出了易受影响的人群或患者亚群。更好地理解基因表达或 SNP 与外源性化学物动力学参数之间的相关性将使医学模式向更个性化的疾病管理和治疗转变。
