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

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Date
2014
Authors
Lei, Beilei
Mace, Brian
Dawson, Hana N
Warner, David S
Laskowitz, Daniel T
James, Michael L
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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.
Type
Journal article
Subject
Animals
Anti-Inflammatory Agents
Cell Line
Cyclooxygenase 2
Drug Evaluation, Preclinical
Extracellular Signal-Regulated MAP Kinases
Female
Lipopolysaccharides
Mice
Microglia
NF-kappa B
Nitric Oxide Synthase Type II
Phosphorylation
Progesterone
Protein Processing, Post-Translational
Protein Transport
Receptors, Progesterone
Tumor Necrosis Factor-alpha
Permalink
https://hdl.handle.net/10161/14241
Published Version (Please cite this version)
10.1371/journal.pone.0103969
Publication Info
Lei, Beilei; Mace, Brian; Dawson, Hana N; Warner, David S; Laskowitz, Daniel T; & James, Michael L (2014). Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia. PLoS One, 9(7). pp. e103969. 10.1371/journal.pone.0103969. Retrieved from https://hdl.handle.net/10161/14241.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Dawson

Hana Nenicka Dawson

Adjunct Assistant Professor in the Department of Neurology
Our laboratory studies the role of tau protein in neurodegeneration. Aggregated tau protein is a hallmark feature of a group of neurodegenerative dementias called tauopathies. This group of diseases accounts for a large majority of all dementias and includes Alzheimer's disease, Pick's disease and frontotemporal dementia to name a few. To model tauopathies, we overexpressed normal and mutated human tau protein or no tau protein in the central nervous system of transgenic mice. Several of t
James

Michael Lucas James

Professor of Anesthesiology
With a clinical background in neuroanesthesia and neurointensive care, I have a special interest in translational research in intracerebral hemorrhage and traumatic brain injury. I am fortunate to be part of a unique team of highly motivated and productive individuals who allow me to propel ideas from bench to bedside and the ability to reverse translate ideas from the bedside back to the bench.
Laskowitz

Daniel Todd Laskowitz

Professor of Neurology
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical settin
Warner

David Samuel Warner

Distinguished Distinguished Professor of Anesthesiology, in the School of Medicine
Humans may sustain a variety of forms of acute central nervous system injury including ischemia, trauma, vasospasm, and perinatal hypoxemia. The Multidisciplinary Neuroprotection Laboratories is dedicated to examining the pathophysiology of acute brain and spinal cord injury with particular reference to disease states managed in the perioperative or neurointensive care environments. Rodent recovery models of cerebral ischemia, traumatic brain injury, cardiopulmonary bypass, subarachnoid he
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Alphabetical list of authors with Scholars@Duke profiles.
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