Microglia express functional 11β‐hydroxysteroid dehydrogenase type 1
Abstract
Glucocorticoids are potent regulators of inflammation exerting permissive, stimulatory, and suppressive effects. Glucocorticoid access to intracellular receptors is regulated by the activity of two distinct enzymes known as 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) Type 1 and Type 2, which catalyze the activation or deactivation of glucocorticoids. Although expression of these enzymes in major organ systems and their roles in the metabolic effects of glucocorticoids have been described, their role in the inflammatory response has only recently started to be addressed. In this report, we have studied the expression and activity of 11 beta HSD Type 1 and Type 2 in microglia cells. Microglia, the brain's resident macrophages, initiate and orchestrate CNS inflammatory responses. Importantly, activated microglia are implicated in most neurodegenerative conditions, making them key subjects of study. We found that microglia expressed 11 beta HSD-1, but not 11 beta HSD-2, both in ex vivo FACS-sorted adult cells and in vitro primary cultures. 11 beta HSD-1 expression was increased in LPS-activated microglia. Moreover, 11 beta HSD-1 catalyzed the metabolic conversion of 11-dehydro-corticosterone into corticosterone (CORT), which potently reduced cytokine production in activated microglia. We propose that 11 beta HSD-1 may provide microglia with an intrinsic mechanism to autoregulate and inhibit proinflammatory mediator production through CORT formation.
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11β-HSD type 1 generates bioactive glucocorticoids from inactive 11-keto derivatives while type 2 catalyzes the opposite reaction; type 1 is widely expressed by neurons and glial cells, whereas type 2 expression is more restricted.
“Briefly, 11β-HSD type 1 generates the bioactive form (cortisol or corticosterone) from inactive 11-keto derivatives while 11β-HSD type 2 catalyzes the opposite reaction. Interestingly, 11-keto derivatives do not bind to CBG in plasma nor are expelled by the efflux pumps of the BBB. As a result, 11-keto-GCs reach the CNS more readily than the bioactive form. 11β-HSD type 1 is widely expressed by”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [69]
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- Authors
- Gottfried‐Blackmore, A., Sierra, A., Mcewen, B. S., Ge, R., & Bulloch, K.
- Affiliations
- Rockefeller University (US)
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2010-05-05
- Volume
- 58
- Issue
- 10
- Pages
- 1257-1266
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2131276581
- Cited by
- 27
- References
- 52
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2014: 1 · 2013: 4 · 2012: 5
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Woodin Dendritics, LLC (NIMH 5R01MH41256, NIA 5PO1AG16765)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- microglia, 11β-hydroxysteroid dehydrogenase type 1, glucocorticoids, corticosterone, 11-dehydrocorticosterone, lipopolysaccharide stimulation, neuroinflammation, cytokine production, neurodegeneration, glucocorticoid metabolism
- MeSH terms
- Animals, Brain, Cells, Cultured, Corticosterone, Glucocorticoids, Lipopolysaccharides, Mice, Transgenic, Cytokines, Microglia, 11-beta-Hydroxysteroid Dehydrogenase Type 1, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Green Fluorescent Proteins, Mice
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