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

Background: 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. methods. 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)- were evaluated. we also examined the spermidine's effect on the activity of nuclear factor-kappab (nf-b),and the phosphoinositide 3-kinase (pi3k)/akt and mitogen-activated protein kinases (mapks) pathways. results: pretreatment with spermidine prior to lps treatment significantly inhibited excessive production of no and pge 2in 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-,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-b p65 subunit into the nucleus,and the phosphorylation of akt and mapks. conclusions: the results indicate that spermidine appears to inhibit inflammation stimulated by lps by blocking the nf-b,pi3k/akt and mapks signaling pathways in microglia. © 2012 choi and park; licensee biomed central ltd.