Hypoxia stimulates the differentiation from monocytes into macrophages, increasing to phagocytosis activity

• Project/Area Number: 19790078
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Osaka City University (2008); Kyoto Pharmaceutical University (2007)
• Principal Investigator: OKA Mayuko Osaka City University, 大学院・医学研究科, 研究員 (40347498)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 低酸素 / マクロファージ / hypoxia-inducible factor-1α / 分化 / PPAR-γ / 動脈硬化 / hyoxia-inducible factor-1α / PPARγ

Research Abstract

単球からマクロファージへの分化は、macrophage colony-stimulating factorの分化因子により誘起されることが知られているが、分化因子をマクロファージ自身が産生するなど、その分化機構には不明な点が多い。そこで、今回、マクロファージの集積する部位が低酸素であることに着目し、低酸素状態でのhypoxia-inducible factor-1α (HIF-1α)の発現と単球の化学的性質の変化や単球からマクロファージへの分化の機構との関連について検討した。その結果、低酸素によりHIF-1α依存的な分化に関わる遺伝子の誘導が明らかになった。また、マクロファージだけでなく単球においても低酸素状態で食作用が促進された。これらの結果は、低酸素による単球からマクロファージへの分化の可能性を示唆する。

Research Products

• [Journal Article] Hypoxia stimulates the autocrine regulation of migration of vascular smooth muscle cells via HIF-1alpha-dependent expression of thrombospondin-1 (2008)
  • Author(s): Osada-Oka M, Ikeda T, Akiba S, Sato T.
  • Journal Title: J Cell Biochem 104 Pages: 1918-1926
• [Journal Article] Epoxyeicosatrienoic acids and/or their metabolites promote hypoxic response of cells (2008)
  • Author(s): Suzuki S, Ogura A, Osada-Oka M, Funae Y, Imaoka S
  • Journal Title: J Pharmacol Sci 108 Pages: 79-88
• [Journal Article] Group IVA phospholipase A2-associated production of MMP-9 in macrophages and formation of atherosclerotic lesions (2008)
  • Author(s): Ii H, Hontani N, Toshida I, Oka M, Sato T, Akiba S.
  • Journal Title: Biol. Pharm. Bull 31 Pages: 363-368
• [Journal Article] Inhibition of cytosolic phospholipase A2 suppresses production of cholesteryl ester through the reesterification of free cholesterol but not formation of foam cells in oxidized LDL-stimulated macrophages (2008)
  • Author(s): Ii H, Oka M, Yamashita A, Waku K, Uozumi N, Shimizu T, Sato T, Akiba S.
  • Journal Title: Biol. Pharm. Bull 31 Pages: 6-12
• [Journal Article] VEGF-enhanced proliferation under hypoxia by an autocrine mechanism in human vascular smooth muscle cells (2008)
  • Author(s): Osada-Oka M, Ikeda T, Imaoka S, Akiba S, Sato T
  • Journal Title: J Atheroscler Thromb 15 Pages: 26-33
• [Journal Article] Role of thrombospondin-1 in hypoxia-induced migration of humanvascular smooth muscle cells (2008)
  • Author(s): Takahashi M, Osada-Oka M, Ikeda T, Akiba S, Sato T.
  • Journal Title: Yakugaku Zasshi 128 Pages: 377-383
  • NAID: 110006646590
• [Journal Article] Hypoxia stimulates the autocrine regulation of migration of vascular smooth muscle cells via HIP-lalpha-dependent expression of thrombospondin-1 (2008)
  • Author(s): Osada-Oka M, Ikeda T, Akiba S, Sato T
  • Journal Title: J Cell Biochem 104 Pages: 1918-1926
  • Peer Reviewed
• [Journal Article] Group IVA phospholipase A2-associated production of MMP-9 in macrophages and formation of atherosclerotic lesions (2008)
  • Author(s): Ii H, Hontani N, Toshida I, Oka M, Sato T, Akiba S
  • Journal Title: Biol. Pharm. Bull 31 Pages: 363-368
  • Peer Reviewed
• [Journal Article] Inhibition of cytosolic phospholipase A_2 suppresses production of cholesteryl ester through the reesterification of free chole sterol but not formation of foam cells in oxidized LDL-stimu lated macrophages (2008)
  • Author(s): Ii H, Oka M, Yamashita A, Waku K, Uozumi N, Shimizu T, Sato T, Akiba S
  • Journal Title: Biol. Pharm. Bull 31 Pages: 6-12
  • Peer Reviewed
• [Journal Article] VEGF-enhanced proliferation under hypoxia by an autocrine mechanism in human vascular smooth muscle cells. (2008)
  • Author(s): M. Osada-Oka, et. al.
  • Journal Title: J. Atheroscler. Thromb. 15 Pages: 26-33
  • Peer Reviewed
• [Journal Article] The role of thrombospondin-1 in hypoxia-induced migration of human vascular smooth muscle cells. (2008)
  • Author(s): M. Osada-Oka, et. al.
  • Journal Title: Yakugaku Zasshi 128 Pages: 377-383
  • NAID: 110006646590
  • Peer Reviewed
• [Journal Article] Hypoxia stimulates the autocrine regulation of migration of vascular smooth muscle cells via HIF-1 alpha-dependent expression of thrombospondin-1 (2008)
  • Author(s): M. Osada-Oka, et. al.
  • Journal Title: J. Cell. Biochem. (In press)
  • Peer Reviewed
• [Journal Article] Effects of ligands for Ah receptor on hypoxic response of cells. (2007)
  • Author(s): Sawada T, Kubo T, Osada-Oka M, Imaoka S.
  • Journal Title: Organohalogen Compounds 69 Pages: 1916-1919
• [Journal Article] Suppression of oxidized LDL-induced PDGF receptor β activation byGinkgo Biloba extract reduces MMP-1 production in coronary smoothmuscle cells (2007)
  • Author(s): Akiba S, Yamaguchi H, Kumazawa S, Oka M, Sato T
  • Journal Title: J Atheroscler Thromb 14 Pages: 219-225
• [Journal Article] Suppression of oxidized LDL-induced PDGF receptor β activation by Ginkgo Biloba extract reduces MMP-1 production in coronary smooth muscle cells. (2007)
  • Author(s): S. Akiba, et. al.
  • Journal Title: J. Atheroscler. Thromb. 14 Pages: 219-225
  • Peer Reviewed
• [Journal Article] Effects of ligands for Ah receptor on hypoxic response of cells. (2007)
  • Author(s): T. Sawada, et. al.
  • Journal Title: Organohalogen Compounds 69 Pages: 1916-1919
  • Peer Reviewed
• [Presentation] 結核菌感染マクロファージにおけるhypoxia-inducible factor-1αの作用機構 (2009)
  • Author(s): 岡真優子,小林和夫,松本壮吉
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-03-13
• [Presentation] 抗酸菌の休眠誘導と遺伝子発現解析 (2009)
  • Author(s): 吉村満美子,仁木誠,岡真優子,尾関百合子,原田誠,田丸亜貴,立石善隆,西内由紀子,小林和夫,松本壮吉
  • Organizer: 第7回感染症沖縄フォーラム
  • Place of Presentation: 那覇
  • Year and Date: 2009-02-13
• [Presentation] Mycobacterial DNA-binding protein-1の新機能-鉄の酸化活性と貯蔵性- (2009)
  • Author(s): 岡真優子,高塚正樹,尾関百合子,吉村満美子,小林和夫,松本壮吉
  • Organizer: 第7回感染症沖縄フォーラム
  • Place of Presentation: 那覇
  • Year and Date: 2009-02-12
• [Presentation] 低酸素状態におけるマクロファージへの分化とhypoxia-inducible factor-1αの役割 (2008)
  • Author(s): 岡優子,寺坂美咲,夏目優太郎,松本壮吉,佐藤隆司
  • Organizer: 第6回がんとハイポキシア研究会
  • Place of Presentation: 広島
  • Year and Date: 2008-11-29
• [Presentation] Hypoxia stimulates the differentiation into macrophages, increasing to PPAR-γ expression and phagocytosis activity in THP-1 cells (2008)
  • Author(s): Mayuko Osada-Oka, Misaki Terasaka, Yutaro Natsume, Satoshi Akiba, Takashi Sato
  • Organizer: International Society on Oxygen Transport to Tissue 2008
  • Place of Presentation: Sapporo, Hokkaido
  • Year and Date: 2008-08-04
• [Presentation] Hypoxia stimulates the differentiation into macrophages, increasing to PPAR-γ expression and phagocytosis activity in THP-1 cells (2008)
  • Author(s): Osada-Oka M, Terasaka M, Natsume Y, Akiba S, Sato S
  • Organizer: International Society on Oxygen Transport to Tissue 2008
  • Place of Presentation: Sapporo
  • Year and Date: 2008-08-03
• [Presentation] 低酸素による転写因子hypoxia-inducible factor-1αの核移行を制御するホスホリパーゼA2分子種の同定 (2008)
  • Author(s): 岡真優子、高橋稔、秋葉聡
  • Organizer: 第55回日本生化学会近畿支部例会
  • Place of Presentation: 大阪
  • Year and Date: 2008-05-24
• [Presentation] 低酸素による転写因子hypoxia-inducible factor-1αの核移行を制御するホスホリパーゼA_2分子種の同定 (2008)
  • Author(s): 岡真優子, 高橋稔, 秋葉聡
  • Organizer: 第55回日本生化学会近畿支部例会
  • Place of Presentation: 大阪
  • Year and Date: 2008-05-24
• [Presentation] 低酸素状態での肝星細胞の活性化と肝線維化促進因子の誘導 (2008)
  • Author(s): 岡真優子、新田千徳、高台真太郎、南山幸子、竹村茂一、秋葉聡、佐藤隆司
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] 酸化LDLによるAT1受容体を介したEGF受容体のトランスアクチベーション作用 (2008)
  • Author(s): 八木聖子、岡真優子、喜多春菜、秋葉聡、佐藤隆司
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] 緑豆ペプチドによる血管平滑筋細胞遊走阻害効果に関する検討 (2008)
  • Author(s): 塩尻正俊,岡真優子,矢野桃子,橋本香織,佐藤健司,秋葉聡,佐藤隆司
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-26
• [Presentation] Role of iPLA2γ in the translocation of hypoxia-inducible factor-1α to the nucleus. Keystone symposia (2008)
  • Author(s): Osada-Oka M, Takahashi M, Akiba S, Sato T
  • Organizer: Molecular, cellular, physiological and pathogenic responses to hypoxia
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2008-01-18
• [Presentation] Role of iPLA_2γ in the translocation of hypoxia-inducible factor-1α to the nucleus. Keystone symposia: Molecular, cellular, physiological and pathogenic responses to hypoxia (2008)
  • Author(s): Mayuko Osada-Oka, Minoru Takahashi, Satoshi Akiba, Takashi Sato
  • Organizer: Keystone Symposia
  • Place of Presentation: Vancouver, Canada
• [Presentation] Role of iPLA2γ in the translocation of hypoxia-inducible factor-1α to the nucleus under normoxic and hypoxic conditions (2007)
  • Author(s): Osada-Oka M, Takahashi M, Akiba S, Sato T
  • Organizer: JST-ERATO Yamamoto Environmental Response Project International Symposium"The environmental response"
  • Place of Presentation: つくば
  • Year and Date: 2007-12-21
• [Presentation] 低酸素状態での星細胞の活性化とhypoxia-inducible factor-1αに依存した肝線維化促進因子の誘導 (2007)
  • Author(s): 新田千徳、岡真優子、秋葉聡、佐藤隆司
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] 低酸素により誘導されるマクロファージへの分化とhypoxia-inducible factor-1 alphaの役割 (2007)
  • Author(s): 岡真優子、秋葉聡、佐藤隆司
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-12
• [Presentation] 酸化LDLのAT1受容体を介したトランスアクチベーション作用によるマクロファージの泡沫化 (2007)
  • Author(s): 八木聖子、岡真優子、喜多春菜、秋葉聡、佐藤隆司
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] 低酸素によるNADPH-P450 reductase依存的なVEGFの発現と血管平滑筋細胞の増殖 (2007)
  • Author(s): 岡真優子、池田貴子、秋葉聡、佐藤隆司
  • Organizer: 第39回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-13
• [Presentation] 酸化LDLによるマクロファージの泡沫化におけるAT1受容体の役割 (2007)
  • Author(s): 岡真優子、喜多春菜、八木聖子、秋葉聡、佐藤隆司
  • Organizer: 第8回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 2007-06-07
• [Presentation] 低酸素が誘導する血管平滑筋細胞遊走因子としてのトロンボスポンジン-1の作用機構 (2007)
  • Author(s): 高橋 稔、岡 真優子、池田貴子、秋葉 聡、佐藤隆司
  • Organizer: 日本薬学会第127年会
  • Place of Presentation: 富山
• [Presentation] Hypoxia-inducible factor-1αの核への移行に働くCa^<2+>非依存性ホスホリパーゼA_2の機能 (2007)
  • Author(s): 岡 真優子、高橋 稔、秋葉 聡、佐藤隆司
  • Organizer: 日本薬学会第127年会
  • Place of Presentation: 富山
• [Presentation] 低酸素によるNADPH-P-450 reductase依存的なVEGFの発現と血管平滑筋細胞の増殖 (2007)
  • Author(s): 岡 真優子、池田貴子、秋葉 聡、佐藤隆司
  • Organizer: 第39回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 大阪
• [Presentation] 酸化LDLのAT1受容体を介したトランスアクチベーション作用によるマクロファージの泡沫化 (2007)
  • Author(s): 八木聖子、岡 真優子、喜多春菜、秋葉 聡、佐藤隆司
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会
  • Place of Presentation: 横浜
• [Presentation] 低酸素状態での星細胞の活性化とhypoxia-inducible factor-1αに依存した肝線維化促進因子の誘導 (2007)
  • Author(s): 新田千徳、岡 真優子、秋葉 聡、佐藤隆司
  • Organizer: 第39回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 大阪
• [Presentation] 低酸素により誘導されるマクロファージへの分化とhypoxia-inducible factor-1 alphaの役割 (2007)
  • Author(s): 岡 真優子、秋葉 聡、佐藤隆司
  • Organizer: 第39回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 大阪