Anti-inflammatory effects of spermidine in lipopolysaccharide-stimulated BV2 microglial cells

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.Microglia are glial cells that function as the prime effector cells in the immune defense and inflammatory responses in the central nervous system (CNS) [1-3]. These cells are activated in response to environmental stress and produce various bioactive molecules, including nitric oxide (NO), prostaglandin E2 (PGE2), reactive oxygen species, and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which function to restore CNS homeostasis by clearing damaged cells and debris [4,5]. However, prolonged microglial activation can cause chronic neuroinflammation and promote neuronal injury due to increased production of neurotoxic pro-inflammatory mediators, and can eventually le