title: Synergy between phenotypic modulation and ROS neutralization in reduction of inflammatory response of hypoxic microglia by using phosphatidylserine and antioxidant containing liposomes.
abstract: Neuroinflammation caused by microglial activation is a key contributing factor in neurological disorders such as those involving ischaemia. Excess production of reactive oxygen species (ROS) and nitric oxide (NO) stimulates the inflammatory response during ischaemia, significantly damaging cells. Inhibition of inflammatory activation of microglia is a promising potential treatment approach for neurological diseases. In this study, we introduce α-tocopherol and phosphatidylserine (PS) containing liposomes (PST-liposomes) to inhibit the microglial inflammatory response. PS is known to have anti-inflammatory effects on microglia by modulating the microglial phenotype, while α-tocopherol is an antioxidant, known to neutralize ROS. We found that both PS-containing liposomes (PS-liposomes) and PST-liposomes, as compared with phosphatidylcholine containing liposomes, significantly increased viability of hypoxia-treated microglia. The PST-liposomes functioned better than the PS-liposomes and we attribute this superior effect to a synergy between PS and α-tocopherol. This synergic action of PST-liposomes was illustrated in their ability, when incubated with microglia, to reduce NO and pro-inflammatory cytokine (TNF-α) production and increase anti-inflammatory cytokine (TGF-β1) production. Thus, the improved viability of hypoxia-treated microglia when treated with PST-liposomes involved anti-inflammatory effects, including ROS neutralization, as well as induction of a microglial phenotypic change. Our results suggest that PST-liposomes represent a potential therapeutic approach to reducing ischaemic injury in the brain.
authors.affiliation: a Graduate School of Systems Life Sciences , Kyushu University , Nishi-ku , Japan.
authors.forename: Md Zahangir
authors.initials: MZ
authors.lastname: Hosain
authors.affiliation: a Graduate School of Systems Life Sciences , Kyushu University , Nishi-ku , Japan.|b Faculty of Engineering, Department of Applied Chemistry , Kyushu University , Nishi-ku , Japan.|c Center for Future Chemistry, Kyushu University , Nishi-ku , Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.affiliation: a Graduate School of Systems Life Sciences , Kyushu University , Nishi-ku , Japan.|b Faculty of Engineering, Department of Applied Chemistry , Kyushu University , Nishi-ku , Japan.|c Center for Future Chemistry, Kyushu University , Nishi-ku , Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishimura
authors.affiliation: a Graduate School of Systems Life Sciences , Kyushu University , Nishi-ku , Japan.|b Faculty of Engineering, Department of Applied Chemistry , Kyushu University , Nishi-ku , Japan.|c Center for Future Chemistry, Kyushu University , Nishi-ku , Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D001921:Brain; D002417:Cattle; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D004527:Egg Proteins / Q000737:chemistry; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000633:toxicity; D008081:Liposomes; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism*; D010718:Phosphatidylserines / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004527:Egg Proteins; D008070:Lipopolysaccharides; D008081:Liposomes; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D024502:alpha-Tocopherol
keywords: inflammation; ischaemia; microglial alteration; phosphatidylserine; α-tocopherol