Anti-inflammatory effects of spermidine in lipopolysaccharide-stimulated BV2 microglial cells
Open Access
- 1 January 2012
- journal article
- Published by Springer Science and Business Media LLC in Journal of Biomedical Science
- Vol. 19 (1), 31
- https://doi.org/10.1186/1423-0127-19-31
Abstract
Spermidine, a naturally occurring polyamine, displays a wide variety of internal biological activities including cell growth and proliferation. However, the molecular mechanisms responsible for its anti-inflammatory activity have not yet been elucidated. The anti-inflammatory properties of spermidine were studied using lipopolysaccharide (LPS)-stimulated murine BV2 microglia model. As inflammatory parameters, the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were evaluated. We also examined the spermidine's effect on the activity of nuclear factor-kappaB (NF-κB), and the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) pathways. Pretreatment with spermidine prior to LPS treatment significantly inhibited excessive production of NO and PGE2 in a dose-dependent manner, and was associated with down-regulation of expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Spermidine treatment also attenuated the production of pro-inflammatory cytokines, including IL-6 and TNF-α, by suppressing their mRNA expressions. The mechanism underlying spermidine-mediated attenuation of inflammation in BV2 cells appeared to involve the suppression of translocation of NF-κB p65 subunit into the nucleus, and the phosphorylation of Akt and MAPKs. The results indicate that spermidine appears to inhibit inflammation stimulated by LPS by blocking the NF-κB, PI3K/Akt and MAPKs signaling pathways in microglia.Keywords
This publication has 41 references indexed in Scilit:
- NFκB: a promising target for natural products in cancer chemopreventionPhytotherapy Research, 2010
- Inflammation in neurodegenerative diseasesImmunology, 2010
- Synthetic polycation: Polynucleotide interactions determined using liquid chromatography with short monolithic columnsJournal of Separation Science, 2009
- NF-κB Signaling Pathway and Its Therapeutic Implications in Human DiseasesInternational Reviews of Immunology, 2008
- Effect of sildenafil citrate on interleukin-1β-induced nitric oxide synthesis and iNOS expression in SW982 cellsExperimental & Molecular Medicine, 2008
- Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar β amyloid peptide (1-42)-stimulated microgliaExperimental & Molecular Medicine, 2008
- Characterization of prostaglandin E2 generation through the cyclooxygenase (COX)-2 pathway in human neutrophilsBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007
- Oxidative stress and inflammation in the pathogenesis of activated polyamine catabolism-induced acute pancreatitisAmino Acids, 2007
- Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1β productionNeurobiology of Aging, 2004
- Inhibition by polyamines of lipid peroxide formation in rat liver microsomesBiochemical and Biophysical Research Communications, 1979