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

dc.contributor.author Lei, Beilei
dc.contributor.author Mace, Brian
dc.contributor.author Dawson, Hana N
dc.contributor.author Warner, David S
dc.contributor.author Laskowitz, Daniel T
dc.contributor.author James, Michael L
dc.coverage.spatial United States
dc.date.accessioned 2017-05-01T17:22:04Z
dc.date.available 2017-05-01T17:22:04Z
dc.date.issued 2014
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/25080336
dc.identifier PONE-D-14-14610
dc.identifier.uri https://hdl.handle.net/10161/14241
dc.description.abstract 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.
dc.language eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0103969
dc.subject Animals
dc.subject Anti-Inflammatory Agents
dc.subject Cell Line
dc.subject Cyclooxygenase 2
dc.subject Drug Evaluation, Preclinical
dc.subject Extracellular Signal-Regulated MAP Kinases
dc.subject Female
dc.subject Lipopolysaccharides
dc.subject Mice
dc.subject Microglia
dc.subject NF-kappa B
dc.subject Nitric Oxide Synthase Type II
dc.subject Phosphorylation
dc.subject Progesterone
dc.subject Protein Processing, Post-Translational
dc.subject Protein Transport
dc.subject Receptors, Progesterone
dc.subject Tumor Necrosis Factor-alpha
dc.title Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia.
dc.type Journal article
duke.contributor.id Dawson, Hana N|0145799
duke.contributor.id Warner, David S|0116342
duke.contributor.id Laskowitz, Daniel T|0056656
duke.contributor.id James, Michael L|0225034
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/25080336
pubs.begin-page e103969
pubs.issue 7
pubs.organisational-group Anesthesiology
pubs.organisational-group Anesthesiology, Neuroanesthesia
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Neurobiology
pubs.organisational-group Neurology
pubs.organisational-group Neurology, Neurocritical Care
pubs.organisational-group Neurosurgery
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 9
dc.identifier.eissn 1932-6203
duke.contributor.orcid Laskowitz, Daniel T|0000-0003-3430-8815
duke.contributor.orcid James, Michael L|0000-0002-8715-5210


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