HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs.,Cell Death Discovery

当前位置： X-MOL 学术 › Cell Death Discov. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs.
Cell Death Discovery ( IF 6.1 ) Pub Date : 2020-04-20 , DOI: 10.1038/s41420-020-0262-7
Peiqing Huang ₁ , Yinghong Li ₁ , Chenchang Xu ₁ , Gerry Melino _{2,

3} , Changshun Shao ₁ , Yufang Shi _{1,

4,

5}

Affiliation

Inflammatory factors such as IFNγ and TNFα could endow mesenchymal stem cells (MSCs) a potent immunomodulatory property, a process called licensing, but the mechanisms are not fully understood. We here found that glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to the active cortisol and thereby regulates tissue glucocorticoid (GC) levels, was greatly upregulated by IFNγ and TNFα in human umbilical cord-derived MSCs (UC-MSCs) in a synergistic manner. While IFNγ alone was not able to induce HSD11B1, it could increase the activity of NF-kB and thus augment the upregulation of HSD11B1 by TNFα. Interestingly, the upregulation of HSD11B1 by IFNγ and TNFα also required glucocorticoid receptor. Furthermore, HSD11B1 was shown to be required for the expression of TNF-stimulated gene 6 (TSG-6), an important anti-inflammatory effector molecule of MSCs. Therefore, the inflammatory factors IFNγ and TNFα can promote GC metabolism and thereby drive the expression of anti-inflammatory factor TSG-6 in human UC-MSCs, forming a potential negative feedback loop. These findings help to understand the relationship between inflammation and GC metabolism.

中文翻译：

HSD11B1被IFNγ和TNFα协同上调，并介导人UC-MSC中TSG-6的表达。

诸如IFNγ和TNFα的炎性因子可能赋予间充质干细胞（MSC）强大的免疫调节特性，这一过程称为许可过程，但其机理尚不完全清楚。我们在这里发现，将糖皮质激素激活酶11β-羟基类固醇脱氢酶1型（HSD11B1）将非活性可的松转化为活性皮质醇，从而调节组织糖皮质激素（GC）的水平，在人脐带间充质干细胞中被IFNγ和TNFα上调。（UC-MSC）以协同方式。尽管单独的IFNγ不能诱导HSD11B1，但它可以增加NF-kB的活性，从而增强TNFα对HSD11B1的上调。有趣的是，IFNγ和TNFα对HSD11B1的上调也需要糖皮质激素受体。此外，已显示HSD11B1是表达TNF刺激的基因6（TSG-6）所必需的，该基因是MSC的重要抗炎效应分子。因此，炎性因子IFNγ和TNFα可以促进GC代谢，从而驱动人UC-MSC中抗炎因子TSG-6的表达，形成潜在的负反馈回路。这些发现有助于了解炎症与GC代谢之间的关系。

更新日期：2020-04-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文