Steroid hormone receptor expression and function in microglia

GLIA - Tập 56 Số 6 - Trang 659-674 - 2008
Amanda Sierra1,2, Andres Gottfried‐Blackmore1,2, Teresa A. Milner3,2, Bruce S. McEwen2, Karen Bulloch4
1AS and ACG are equal contributors to this study.
2Laboratory of Neuroendocrinology, Rockefeller University, New York, New York
3Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York
4Laboratory of Cell Physiology and Immunology, Rockefeller University, New York, New York

Tóm tắt

AbstractSteroid hormones such as glucocorticoids and estrogens are well‐known regulators of peripheral immune responses and also show anti‐inflammatory properties in the brain. However, the expression of steroid hormone receptors in microglia, the pivotal immune cell that coordinates the brain inflammatory response, is still controversial. Here we use real time RT‐PCR to show that microglia, isolated from adult fms‐EGFP mice by FACS, express glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and estrogen receptor alpha (ERα). GR was the most abundant steroid hormone receptor transcript in microglia. The presence of GR and ERα immunoreactivity was further confirmed in vivo at the ultrastructural level. To understand the role of steroid hormone receptors during the inflammation process, we evaluated the expression of steroid hormone receptors after inflammatory challenge and found a significant down‐regulation of GR, MR, and ERα in microglia. Finally, we tested the immunomodulatory properties of estrogens and glucocorticoids. Estradiol benzoate did not have any significant impact on the inflammatory profile of ex vivo sorted microglia, either in resting conditions or after challenge. Furthermore, corticosterone was a more consistent anti‐inflammatory agent than 17β‐estradiol in vitro. Our results support the hypothesis that adult microglia are a direct target of steroid hormones and that glucocorticoids, through the predominant expression of GR and MR, are the primary steroid hormone regulators of microglial inflammatory activity. The down‐regulation of steroid hormone receptors after LPS challenge may serve as a prerequisite to suppressing the anti‐inflammatory actions of endogenous steroid hormones on the immune system, and contribute to a sustained activation of microglia. © 2008 Wiley‐Liss, Inc.

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