Colitis Alters Oxysterol Metabolism and is Affected by 4β-Hydroxycholesterol Administration
Colitis Alters Oxysterol Metabolism and is Affected by 4β-Hydroxycholesterol Administration
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DOI：
10.1093/ecco-jcc/jjy157
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发表时间：
2019-02-01
影响因子：
8
通讯作者：
Muccioli, Giulio G.
中科院分区：
文献类型：
--
作者：
Guillemot-Legris, Owein;Mutemberezi, Valentin;Muccioli, Giulio G.
背景和目的：炎症性肠病（IBD）是一种具有挑战性的健康问题，其病因复杂，涉及遗传和环境参数。尽管我们对IBD的病理生理学的了解有所提高，但仍有许多有待探索的地方。在这种情况下，生物活性脂类，更具体地说是氧甾醇，即胆固醇的氧合衍生物，代表了一个有趣的研究途径。事实上，氧甾醇或其受体参与炎症和免疫调节。因此，我们开始研究IBD中的催产素。方法：我们使用高效液相色谱/质谱和分子生物学工具来定量几种小鼠结肠炎（急性和慢性）模型以及克罗恩病和溃疡性结肠炎患者的结肠活检中的氧甾醇水平及其代谢酶的表达。结果：我们发现，在急性和慢性IBD小鼠模型以及人类IBD中，氧甾体都发生了改变。两种被量化的氧甾醇，4 -羟基胆固醇和25-羟基胆固醇，在我们所有的模型中都持续改变，因此可能对这一背景感兴趣。因此，我们给结肠炎小鼠注射了这些药物。虽然25-羟基胆固醇没有影响，但4 -羟基胆固醇加重了结肠炎症。结论：我们的研究解决了氧化甾醇在结肠炎中的潜在参与，并明确指出了这些生物活性脂质的积极作用和临床相关性。
Background and Aims: Inflammatory bowel diseases [IBD] represent a challenging health issue with a complex aetiology involving genetic and environmental parameters. Although our understanding of the pathophysiology of IBD has improved, much remains to be explored. In this context, bioactive lipids, more specifically oxysterols, i.e. oxygenated derivatives of cholesterol, represent an interesting avenue to investigate. Indeed, oxysterols or their receptors are involved in inflammation and immune regulation. Therefore, we set out to study the oxysterome in IBD.Methods: We used both high-performance liquid chromatograph/mass spectroscopy and molecular biology tools to quantify oxysterol levels and the expression of their metabolic enzymes in several models of murine colitis [both acute and chronic], as well as in colon biopsies from patients with Crohn's disease and ulcerative colitis.Results: We found that the oxysterome is altered in IBD, in both acute and chronic murine models as well as in human IBD. Two of the oxysterols quantified, 4 beta-hydroxycholesterol and 25-hydroxycholesterol, were consistently altered in all our models and therefore could be of interest in this context. Hence, we administered them to mice with colitis. While 25-hydroxycholesterol had no effect, 4 beta-hydroxycholesterol worsened colon inflammation.Conclusions: Our study addresses the potential involvement of oxysterols in colitis and clearly points towards an active role as well as a clinical relevance for these bioactive lipids.