Aspirin-triggered lipoxin A4attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells

Background: microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (no) and several pro-inflammatory cytokines. lipoxins (lxs) and aspirin-triggered lxs (atls) are considered to act as 'braking signals' in inflammation. in the present study,we investigated the effect of aspirin-triggered lxa4(atl) on infiammatory responses induced by lipopolysaccharide (lps) in murine microglial bv-2 cells.methods: bv-2 cells were treated with atl prior to lps exposure,and the effects of such treatment production of nitric oxide (no),inducible nitric oxide synthase (inos),interleukin-1β (il-1β) and tumour necrosis factor-α (tnf-α) were analysed by griess reaction,elisa,western blotting and quantitative rt-pcr. moreover,we investigated the effects of atl on lps-induced nuclear factor-κb (nf-κb) activation,phosphorylation of mitogen-activated protein kinases (mapks) and activator protein-1 (ap-1) activation.results: atl inhibited lps-induced production of no,il-1β and tnf-α in a concentration-dependent manner. mrna expressions for inos,il-1β and tnf-α in response to lps were also decreased by atl. these effects were inhibited by boc-2 (a lxa4receptor antagonist). atl significantly reduced nuclear translocation of nf-κb p65,degradation of the inhibitor iκb-α,and phosphorylation of extracellular signal-regulated kinase (erk) and p38 mapk in bv-2 cells activated with lps. furthermore,the dna binding activity of nf-κb and ap-1 was blocked by atl.conclusions: this study indicates that atl inhibits no and pro-inflammatory cytokine production at least in part via nf-κb,erk,p38 mapk and ap-1 signaling pathways in lps-activated microglia. therefore,atl may have therapeutic potential for various neurodegenerative diseases. © 2011 wang et al; licensee biomed central ltd.