Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells.
Desmosterol: A natural product derived from macroalgae modulates inflammatory response and oxidative stress pathways in intestinal epithelial cells.
复制标题
DOI：
10.3389/fimmu.2022.1101643
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
胆固醇及其生物合成中间体的血清水平是评估人类和动物代谢相关疾病的关键指标。然而，这些中间体对基因功能和调控的分子作用仍然难以捉摸。在这里，我们表明，链甾醇（DES）是最丰富的中间参与胆固醇生物合成，是高度富集在红/褐藻。它在调节回肠上皮细胞（IPI-2 I）中参与氧化应激和炎症反应过程的核心基因中发挥关键作用。我们观察到从红藻中提取的DES不影响IPI-2 I细胞的生长或存活。转录组学测量显示，DES处理显著下调了参与氧化过程和胆固醇稳态途径的基因。与这一观点一致，细胞活性氧（ROS）水平显着降低DES治疗的反应。相比之下，关键炎性基因包括IL-6、TNF-α和IFN-γ在RNA-seq分析中显著上调，如通过qRT-PCR进一步证实的。由于DES是核受体RORγ的特异性激动剂，我们还发现DES在mRNA和蛋白水平上引起RORγ的表达增加，这表明它是DES给药的潜在介质。总之，这些结果强调了DES可能通过RORγ在炎症和氧化过程中的重要生理作用，并且可能有助于未来的抗氧化治疗和免疫治疗。
The serum level of cholesterol and its biosynthetic intermediates are critical indicators to access metabolism-related disorders in humans and animals. However, the molecular actions of these intermediates on gene functions and regulation remained elusive. Here, we show that desmosterol (DES) is the most abundant intermediate involved in cholesterol biosynthesis and is highly enriched in red/brown algae. It exerts a pivotal role in modulating core genes involved in oxidative stress and inflammatory response processes in the ileum epithelial cells (IPI-2I). We observed that the DES extracted from red algae did not affect IPI-2I cell growth or survival. A transcriptomic measurement revealed that the genes enrolled in the oxidative process and cholesterol homeostasis pathway were significantly down-regulated by DES treatment. Consistent with this notion, cellular reactive oxygen species (ROS) levels were markedly decreased in response to DES treatment. In contrast, key inflammatory genes including IL-6, TNF-α, and IFN-γ were remarkably upregulated in the RNA-seq analysis, as further confirmed by qRT-PCR. Given that DES is a specific agonist of nuclear receptor RORγ, we also found that DES caused the elevated expression of RORγ at mRNA and protein levels, suggesting it is a potential mediator under DES administration. Together, these results underscore the vital physiological actions of DES in inflammatory and oxidative processes possibly via RORγ, and may be helpful in anti-oxidation treatment and immunotherapy in the future.
登录
查看更多内容
DOI：
10.1038/nri3793
发表时间：
2015-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Tall AR;Yvan-Charvet L
通讯作者：
Yvan-Charvet L
抑制 DNA 甲基化通过 LRP1-PI3K/AKT 途径减少氧化应激诱导的线粒体依赖性细胞凋亡，从而减轻顺铂引起的听力损失
影响因子：
14.5
作者：
He, Yingzi;Zheng, Zhiwei;Liu, Chang;Li, Wen;Zhao, Liping;Nie, Guohui;Li, Huawei
通讯作者：
Li, Huawei
影响因子：
32.4
作者：
Omenetti, Sara;Bussi, Claudio;Stockinger, Brigitta
通讯作者：
Stockinger, Brigitta
影响因子：
1.8
作者：
Sánchez-Machado, DI;López-Hernández, J;López-Cervantes, J
通讯作者：
López-Cervantes, J
影响因子：
4.1
作者：
Sion, B;Grizard, G;Boucher, D
通讯作者：
Boucher, D