Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia.

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Lei, Beilei

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Mace, Brian

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Dawson, Hana N

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Warner, David S

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Laskowitz, Daniel T

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James, Michael L

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Peterson, Karin E

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United States

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2017-05-01T17:22:04Z

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2017-05-01T17:22:04Z

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2014

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Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO) and prostaglandin E2 (PGE2), mediated by inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone's effects on tumor necrosis factor alpha (TNF-α), iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways. LPS (30 ng/ml) upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury.

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https://www.ncbi.nlm.nih.gov/pubmed/25080336

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PONE-D-14-14610

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1932-6203

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https://hdl.handle.net/10161/14241

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eng

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Public Library of Science (PLoS)

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PLoS One

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10.1371/journal.pone.0103969

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Animals

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Anti-Inflammatory Agents

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Cell Line

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Cyclooxygenase 2

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Drug Evaluation, Preclinical

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Extracellular Signal-Regulated MAP Kinases

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Female

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Lipopolysaccharides

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Mice

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Microglia

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NF-kappa B

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Nitric Oxide Synthase Type II

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Phosphorylation

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Progesterone

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Protein Processing, Post-Translational

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Protein Transport

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Receptors, Progesterone

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Tumor Necrosis Factor-alpha

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Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia.

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Journal article

duke.contributor.orcid

Laskowitz, Daniel T|0000-0003-3430-8815

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James, Michael L|0000-0002-8715-5210

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/25080336

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e103969

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7

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Anesthesiology

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Anesthesiology, Neuroanesthesia

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Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Clinical Research Institute

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Duke Institute for Brain Sciences

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Institutes and Centers

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Institutes and Provost's Academic Units

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Neurobiology

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Neurology

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Neurology, Neurocritical Care

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Neurosurgery

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School of Medicine

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Surgery

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University Institutes and Centers

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Published online

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9

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