Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Bruxelles, Belgium.
Service de Chirurgie Digestive, CHU UCL Namur, Université catholique de Louvain, Bruxelles, Belgium.
J Crohns Colitis. 2019 Feb 1;13(2):218-229. doi: 10.1093/ecco-jcc/jjy157.
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.
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.
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, 4β-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, 4β-hydroxycholesterol worsened colon inflammation.
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.
炎症性肠病（IBD）是一个具有挑战性的健康问题，其发病机制复杂，涉及遗传和环境因素。尽管我们对 IBD 的病理生理学有了更多的了解，但仍有许多问题需要探索。在这种情况下，生物活性脂质，特别是氧化固醇，即胆固醇的含氧衍生物，是一个很有前途的研究方向。事实上，氧化固醇或其受体参与了炎症和免疫调节。因此，我们着手研究 IBD 中的氧化固醇组。
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模型[急性和慢性]以及克罗恩病和溃疡性结肠炎患者的结肠活检中的氧化固醇水平及其代谢酶的表达。
我们发现，氧化固醇组在 IBD 中发生了改变，无论是在急性和慢性的小鼠模型中，还是在人类 IBD 中。我们定量的两种氧化固醇，4β-羟基胆固醇和 25-羟基胆固醇，在我们所有的模型中都发生了持续的改变，因此在这种情况下可能具有研究价值。因此，我们给患有结肠炎的小鼠施用了这两种氧化固醇。虽然 25-羟基胆固醇没有效果，但 4β-羟基胆固醇使结肠炎症恶化。
我们的研究探讨了氧化固醇在结肠炎中的潜在作用，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。
