Dataset Information

Corticosterone Preexposure Increases NF-?B Translocation and Sensitizes IL-1? Responses in BV2 Microglia-Like Cells.

ABSTRACT: Corticosterone (CORT), a critical mediator of the hypothalamus pituitary adrenal axis in rodents, is a stress hormone that is classically viewed as possessing immune-suppressive properties. CORT is now appreciated to also mediate the neuroimmune-priming effect of stress to innate-immune stimulation, and hence serves as a mechanistic link to the neuroimmune involvement in stress-related disorders. However, these dichotomous actions of CORT remain poorly defined. This study investigated the conditions and concentration dependency of CORT's actions required to prime the innate-immune system. Here, we measured the effect of CORT pretreatment on the downstream pro-inflammatory responses of BV2 mouse microglia-like cells stimulated by lipopolysaccharide (LPS). We quantified the concentration-dependent CORT-mediated attenuation and enhancement of LPS-stimulated inflammatory response. A high physiological concentration (500?nM) of CORT attenuated LPS-induced inflammatory IL-1? cytokine production in a glucocorticoid receptor-dependent manner. However, a low concentration (50?nM) of CORT increased expression and release of IL-1? in a mineralocorticoid receptor-dependent manner, with accompanied increases in NF-?B translocation and changes to related gene transcription. These results suggest that a mild elevation in CORT may cause selective adaptations in microglia-like cells to overrespond to a second immune challenge in a non-classical manner, thus partially explaining both pro- and anti-inflammatory effects of CORT reported in the literature.

SUBMITTER: Liu J

PROVIDER: S-EPMC5786551 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Corticosterone Preexposure Increases NF-κB Translocation and Sensitizes IL-1β Responses in BV2 Microglia-Like Cells.

Liu JiaJun J Mustafa Sanam S Barratt Daniel Thomas DT Hutchinson Mark Rowland MR

Frontiers in immunology 20180122

Corticosterone (CORT), a critical mediator of the hypothalamus pituitary adrenal axis in rodents, is a stress hormone that is classically viewed as possessing immune-suppressive properties. CORT is now appreciated to also mediate the neuroimmune-priming effect of stress to innate-immune stimulation, and hence serves as a mechanistic link to the neuroimmune involvement in stress-related disorders. However, these dichotomous actions of CORT remain poorly defined. This study investigated the condit ...[more]

PMID: 29403490

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Project description:Cleome rutidosperma DC. and Euphorbia thymifolia L. are herbal medicines used in traditional Indian and Chinese medicine to treat various illnesses. Reports document that they have antioxidant and anti-inflammatory activities; nonetheless, the molecular mechanisms involved in their anti-inflammatory actions have not yet been elucidated. The anti-neuroinflammatory activities and underlying mechanisms of ethanol extracts of Cleome rutidosperma (CR) and Euphorbia thymifolia (ET) were studied using lipopolysaccharide (LPS)-stimulated microglial cell line BV2. The morphology changes and production of pro-inflammatory mediators were assayed. Gene expression of inflammatory genes such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, and CC chemokine ligand (CCL)-2, as well as phase II enzymes such as heme oxygenase (HO)-1, the modifier subunit of glutamate cysteine ligase (GCLM) and NAD(P)H quinone dehydrogenase 1 (NQO1), were further investigated using reverse transcription quantitative-PCR (RT-Q-PCR) and Western blotting. The effects of CR and ET on mitogen activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling pathways were examined using Western blotting and specific inhibitors. CR and ET suppressed BV2 activation, down-regulated iNOS and COX-2 expression and inhibited nitric oxide (NO) overproduction without affecting cell viability. They reduced LPS-mediated tumor necrosis factor (TNF) and IL-6 production, attenuated IL-1β and CCL2 expression, but upregulated HO-1, GCLM and NQO1 expression. They also inhibited p65 NF-κB phosphorylation and modulated Jun-N terminal kinase (JNK) activation in BV2 cells. SP600125, the JNK inhibitor, significantly augmented the anti-IL-6 activity of ET. NF-κB inhibitor, Bay 11-7082, enhanced the anti-IL-6 effects of both CR and ET. Znpp, a competitive inhibitor of HO-1, attenuated the anti-NO effects of CR and ET. Our results show that CR and ET exhibit anti-neuroinflammatory activities by inhibiting pro-inflammatory mediator expression and production, upregulating HO-1, GCLM and NQO1, blocking NF-κB and modulating JNK signaling pathways. They may offer therapeutic potential for suppressing overactivated microglia and alleviating neurodegeneration.

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Dataset Information

Corticosterone Preexposure Increases NF-?B Translocation and Sensitizes IL-1? Responses in BV2 Microglia-Like Cells.

Publications

Corticosterone Preexposure Increases NF-κB Translocation and Sensitizes IL-1β Responses in BV2 Microglia-Like Cells.

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