Glucocorticoids and Central Nervous System Inflammation

Dinkel, Klaus; Ogle, William O.; Sapolsky, Robert M.

doi:10.1080/13550280290100914

Cited by 31 publications

(24 citation statements)

References 213 publications

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“…Glucocorticoids have well-known immunosuppressive properties in the peripheral immune system which make them clinically useful for the treatment of autoimmune diseases, chronic inflammation, or to avoid transplant rejection (Dinkel et al, 2002). The rapid increase of glucocorticoid circulating levels after systemic inflammatory challenge has been interpreted as a protective, antiinflammatory response (Nadeau and Rivest, 2003;Nakano et al, 1987); in agreement, adrenalectomy results in a 40-fold increase in the lethal effects of LPS (Koniaris et al, 2001).…”

Section: Glucocorticoid Receptors In Microgliasupporting

confidence: 54%

Steroid hormone receptor expression and function in microglia

Sierra

Gottfried-Blackmore

Milner

et al. 2008

Glia

347

238

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Steroid 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 (ERa). GR was the most abundant steroid hormone receptor transcript in microglia. The presence of GR and ERa 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 ERa 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 17b-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 antiinflammatory actions of endogenous steroid hormones on the immune system, and contribute to a sustained activation of microglia. V V C

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Section: Glucocorticoid Receptors In Microgliasupporting

confidence: 54%

Steroid hormone receptor expression and function in microglia

Sierra

Gottfried-Blackmore

Milner

et al. 2008

Glia

347

238

View full text Add to dashboard Cite

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“…In a previous study, we found that tropical House Sparrows invest more in immune defense (Martin et al, in revision a) and rely on diVerent immune cell populations (lymphocytes) than their temperate counterparts when mounting PHA responses (Martin et al, in revision b). Thus, the immunological insensitivity to CORT we found in this experiment could be a consequence of the same challenge inducing diVerent types of immune activity in each population and only one of these types of defense being sensitive to CORT (Dinkel et al, 2002;Sapolsky et al, 2000). Indeed, had we measured a diVerent aspect of immune defense, we might have obtained a diVerent result altogether (Schmid-Hempel and Ebert, 2003).…”

Section: How Could Latitudinal Diverences In Cort and Its Evects On Imentioning

confidence: 71%

“…Indeed, had we measured a diVerent aspect of immune defense, we might have obtained a diVerent result altogether (Schmid-Hempel and Ebert, 2003). Other immune defenses, like antibody production and acute phase (fever) responses, may not be aVected by CORT in the same way as cutaneous immune function induced by PHA (Dinkel et al, 2002;Sapolsky et al, 2000).…”

Section: How Could Latitudinal Diverences In Cort and Its Evects On Imentioning

confidence: 99%

“…Historically, high levels of CORT were touted as obligatorily immunosuppressive (reviewed in McEwen et al, 1997), but more recent studies have shown that this relationship is actually more complex. The eVects of CORT on immune function depend on the type of immune activity measured and how long CORT is allowed to take eVect Dinkel et al, 2002;Sapolsky et al, 2000). SpeciWcally, over the short term, cutaneous immune function, the type we studied, tends to be stimulated by CORT.…”

Section: Introductionmentioning

confidence: 99%

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Corticosterone suppresses cutaneous immune function in temperate but not tropical House Sparrows, Passer domesticus

Martin

Gilliam

Han

et al. 2005

General and Comparative Endocrinology

152

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“…Since protein malnutrition can increase lipopolysaccharide-induced NFκB activation and proinflammatory cytokines in liver [32], we investigated whether PEM increases hippocampal NFκB activation in response to global ischemia. A second objective of the study was to address the possibility that PEM alters serum glucose or glucocorticoid levels since these physiological variables modify ischemic brain injury [33,34].…”

Section: Introductionmentioning

confidence: 99%

Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

Nazarali

Paterson

2008

The Journal of Nutritional Biochemistry

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Protein-energy malnutrition (PEM) exacerbates functional impairment caused by brain ischemia. This is correlated with reactive gliosis, which suggests an increased inflammatory response. The objective of the current study was to investigate if PEM increases hippocampal activation of nuclear factor κB (NFκB), a transcription factor that amplifies the inflammatory response involved in ischemic brain injury. Mongolian gerbils (11-12 weeks old) were randomly assigned to control diet (12.5% protein) or protein-deficient diet (2%) for 4 weeks. The 2% protein group had a 15% decrease in voluntary food intake (P<.001; unpaired t test), resulting in PEM. Body weight after 4 weeks was 20% lower in the PEM group (P<.001). Gerbils were then exposed to sham surgery or global ischemia induced by 5-min bilateral common carotid artery occlusion. PEM independently increased hippocampal NFκB activation detected by electrophoretic mobility shift assay at 6 h after surgery (P=.014; 2-factor ANOVA). Ischemia did not significantly affect NFκB activation nor was there interaction between diet and ischemia. Serum glucose and cortisol concentrations at 6 h postischemia were unaltered by diet or ischemia. A second experiment using gerbils of the same age and feeding paradigm demonstrated that PEM also increases hippocampal NFκB activation in the absence of surgery. These findings suggest that PEM, which exists in 16% of elderly patients at admission for stroke, may worsen outcome by increasing activation of NFκB. Since PEM increased NFκB activation independent of ischemia or surgery, the data also have implications for the inflammatory response of the many individuals affected globally by PEM.

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Glucocorticoids and Central Nervous System Inflammation

Cited by 31 publications

References 213 publications

Steroid hormone receptor expression and function in microglia

Steroid hormone receptor expression and function in microglia

Corticosterone suppresses cutaneous immune function in temperate but not tropical House Sparrows, Passer domesticus

Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

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