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Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells
- Source :
- PLoS ONE, Vol 7, Iss 2, p e32195 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Background Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. Although current studies indicate that resveratrol produces neuroprotection against neurological disorders, the precise mechanisms for its beneficial effects are still not fully understood. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells. Methodology/Principal Findings BV-2 cells were treated with resveratrol (25, 50, and 100 µM) and/or LPS (1 µg/ml). Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10), Akt, mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP-responsive element-binding protein (CREB) were measured by western blot. Resveratrol significantly attenuated the LPS-induced expression of NO, PGE2, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. Resveratrol increased PTEN, Akt and mTOR phosphorylation in a dose-dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR inhibitor, blocked the effects of resveratrol on LPS-induced microglial activation. In addition, mTOR inhibition partially abolished the inhibitory effect of resveratrol on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). Conclusion and Implications This study indicates that resveratrol inhibited LPS-induced proinflammatory enzymes and proinflammatory cytokines via down-regulation phosphorylation of NF-κB, CREB and MAPKs family in a mTOR-dependent manner. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of resveratrol.
- Subjects :
- Lipopolysaccharides
Phytochemistry
Interleukin-1beta
Nitric Oxide Synthase Type II
lcsh:Medicine
Resveratrol
chemistry.chemical_compound
Mice
NF-KappaB Inhibitor alpha
Molecular Cell Biology
Stilbenes
Phosphorylation
Cyclic AMP Response Element-Binding Protein
lcsh:Science
Cells, Cultured
Multidisciplinary
TOR Serine-Threonine Kinases
NF-kappa B
Cell biology
Chemistry
Neurology
Medicine
I-kappa B Proteins
Microglia
Research Article
Signal Transduction
Drugs and Devices
Cell Survival
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
Immunology
Biology
CREB
Nitric Oxide
Dinoprostone
Proinflammatory cytokine
Animals
RNA, Messenger
Protein kinase A
Protein kinase B
PI3K/AKT/mTOR pathway
Inflammation
Sirolimus
Tumor Necrosis Factor-alpha
lcsh:R
Immunity
Molecular biology
chemistry
Gene Expression Regulation
Cyclooxygenase 2
Cytoprotection
biology.protein
Clinical Immunology
lcsh:Q
Molecular Neuroscience
Proto-Oncogene Proteins c-akt
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....b29597170e4edcfef3260b382664afa9