Docosahexaenoic acid-containing choline phospholipid modulates LPS-induced neuroinflammation in vivo and in microglia in vitro

Background: neuroinflammatory processes are considered a double-edged sword,having both protective and detrimental effects in the brain. microglia,the brain's resident innate immune cells,are a key component of neuroinflammatory response. there is a growing interest in developing drugs to target microglia and control neuroinflammatory processes. in this regard,docosahexaenoic acid (dha),the brain's n-3 polyunsaturated fatty acid,is a promising molecule to regulate pro-inflammatory microglia and cytokine production. several works reported that the bioavailability of dha to the brain is higher when dha is acylated to phospholipid. in this work,we analyzed the anti-inflammatory activity of dha-phospholipid,either acetylated at the sn-1 position (acedopc,a stable form thought to have superior access to the brain) or acylated with palmitic acid at the sn-1 position (pc-dha) using a lipopolysaccharide (lps)-induced neuroinflammation model both in vitro and in vivo. methods: in vivo,adult c57bl6/j mice were injected intravenously (i.v.) with either acedopc or pc-dha 24h prior to lps (i.p.). for in vitro studies,immortalized murine microglia cells bv-2 were co-incubated with dha forms and lps. acedopc and pc-dha effect on brain or bv-2 pufa content was assessed by gas chromatography. lps-induced pro-inflammatory cytokines interleukin il-1β,il-6,and tumor necrosis factor (tnf) α production were measured by quantitative pcr (qpcr) or multiplex. il-6 receptors and associated signaling pathway stat3 were assessed by facs analysis and western-blot in vitro. results: in vivo,a single injection of acedopc or pc-dha decreased lps-induced il-6 production in the hippocampus of mice. this effect could be linked to their direct effect on microglia,as revealed in vitro. in addition,acedopc or pc-dha reduced il-6 receptor while only acedopc decreased il-6-induced stat3 phosphorylation. conclusions: these results highlight the potency of administered dha-acetylated to phospholipids-to rapidly regulate lps-induced neuroinflammatory processes through their effect on microglia. in particular,both il-6 production and signaling are targeted by acedopc in microglia. © 2017 the author(s).