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Microglia express functional 11β‐hydroxysteroid dehydrogenase type 1
Author(s) -
GottfriedBlackmore Andres,
Sierra Amanda,
Mcewen Bruce S.,
Ge Renshan,
Bulloch Karen
Publication year - 2010
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21007
Subject(s) - microglia , biology , proinflammatory cytokine , inflammation , glucocorticoid , corticosterone , neuroinflammation , cytokine , beta (programming language) , microbiology and biotechnology , receptor , glucocorticoid receptor , endocrinology , medicine , immunology , biochemistry , hormone , computer science , programming language
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 11β‐hydroxysteroid dehydrogenase (11βHSD) 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 11βHSD 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 11βHSD‐1, but not 11βHSD‐2, both in ex vivo FACS‐sorted adult cells and in vitro primary cultures. 11βHSD‐1 expression was increased in LPS‐activated microglia. Moreover, 11βHSD‐1 catalyzed the metabolic conversion of 11‐dehydro‐corticosterone into corticosterone (CORT), which potently reduced cytokine production in activated microglia. We propose that 11βHSD‐1 may provide microglia with an intrinsic mechanism to autoregulate and inhibit proinflammatory mediator production through CORT formation. © 2010 Wiley‐Liss, Inc.