HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs
Cell Death Discovery
Nature Publishing Group UK
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Huang, P., Li, Y., Xu, C., Melino, G., Shao, C., & Shi, Y. (2020). HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs. Cell Death Discovery, 6 (1)https://doi.org/10.1038/s41420-020-0262-7
Funder: the National Key R&D Program of China [2018YFA0107500], National Natural Science Foundation of China [81530043, 81930085 and 31771260], the Scientific Innovation Project of the Chinese Academy of Sciences [XDA16020403], the Social Development Project of Jiangsu Province [BE2016671], and the State Key Laboratory of Radiation Medicine and Protection, Soochow University [GZN1201804 and GZN1201903].
Abstract: 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.
Article, /631/532/2074, /631/250/127, article
External DOI: https://doi.org/10.1038/s41420-020-0262-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/321345