Essential role of HIF-1alpha in Mycobacterium tuberculosis-infected macrophage

• Project/Area Number: 21790130
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Environmental pharmacy
• Research Institution: Osaka City University
• Principal Investigator: OKA Mayuko Osaka City University, 大学院・医学研究科, 研究員 (40347498)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 低酸素 / 結核 / HIF-1alpha / マクロファージ / 肉芽腫 / HIF-lalpha

Research Abstract

Hypoxia-inducible factor-1α (HIF-1α) protein expressed in mouse pulmonary granulomas 6 weeks after infected with Mycobacterium tuberculosis, and the expression colocalized with that of M. tuberculosis antigen. Thus we focused to a role of HIF-1α into macrophages accumulated in granulomas. Our resulted investigated that the survival of M. tuberculosis in bone marrow derived macrophages (BMDM) from HIF-1α deficient mouse (HIF-1α^<-/->) is enhanced, compared with that in wild type BMDM (WT), which are post-stimulated with interferon-γ (IFN-γ) after infected with M. tuberculosis H37Rv. When infected with bacillus, the mRNA levels of 6 kinds of glycolytic enzymes were elevated in WT compared with HIF-1α^<-/->. In this study, we suggested that an increase of bacillus is controlled by HIF-1α.

Research Products

• [Journal Article] Currey research on Tuberculosis-Latent Mycobacterium tuberculosis infection (LTBI) and M.tuberculosis : Molecular mechanism of dormancy- (2011)
  • Author(s): Niki M, Niki M, Ozaki Y, Osada-Oka M, Matsumoto S.
  • Journal Title: 最新医学 Volume: 66 Pages: 149-155
  • Peer Reviewed
• [Journal Article] Glucose is necessary for stabilization of hypoxia-inducible factor-1α under hypoxia : Contribution of the pentose phosphate pathway to this stabilization. (2010)
  • Author(s): Osada-Oka M, Hashiba Y, Akiba S, Imaoka S, Sato T.
  • Journal Title: FEBS Lett. 584(14) Pages: 3073-3079
  • Peer Reviewed
• [Journal Article] Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice. (2010)
  • Author(s): Ozeki Y, Sugawara I, Udagawa T, Aoki T, Osada-Oka M, Tateishi Y, Hisaeda H, Nishiuchi Y, Harada N, Kobayashi K, Matsumoto S.
  • Journal Title: Int.Immunol. 22(3) Pages: 179-189
  • Peer Reviewed
• [Journal Article] Glucose is necessary for stabilization of hypoxia-inducible factor-1α under hypoxia : Contribution of the pentose phosphate pathway to this stabilization (2010)
  • Author(s): Osada-Oka M, Hashiba Y, Akiba S, Imaoka S, Sato T.
  • Journal Title: FEBS Lett. Volume: 584 Pages: 3073-3079
  • Peer Reviewed
• [Journal Article] Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice (2010)
  • Author(s): Ozeki Y, Sugawara I, Udagawa T, Aoki T, Osada-Oka M, Tateishi Y, Hisaeda H, Nishiuchi Y, Harada N, Kobayashi K, Matsumoto S.
  • Journal Title: Int.Immunol. Volume: 22 Pages: 179-189
  • Peer Reviewed
• [Journal Article] Transient role of CD4+CD25+ regulatory T cells in mycobacterial infection in mice. (2010)
  • Author(s): Ozeki, Y., Sugawara, I., Udagawa, T., Aoki, T., Osada-Oka M., Tateishi, Y., Hisaeda, H., Nishiuchi, Y., Harada, N., Kobayashi, K., Matsumoto, S.
  • Journal Title: Int Immunol 22 Pages: 179-189
  • Peer Reviewed
• [Journal Article] S-allylcystein is effective as a chemopreventive agent against porcine serum-induced hepatic fibrosis in rats. (2009)
  • Author(s): Shinkawa H, Takemura S, Minamiyama Y, Kodai S, Tsukioka T, Osada-Oka M, Kubo S, Okada S, Suehiro S.
  • Journal Title: Osaka City Med.J. 55(2) Pages: 61-69
  • Peer Reviewed
• [Journal Article] S-allylcysteine is effective as a chemopreventive agent against porcine serum-induced hepatic fibrosis in rats. (2009)
  • Author(s): Shinkawa, H., Takemura, S., Minamiyama, Y., Kodai, S., Tsukioka, T., Osada-Oka, M., Kubo, S., Okada, S., Suehiro, S.
  • Journal Title: Osaka City Med J 55 Pages: 61-69
  • Peer Reviewed
• [Presentation] 結核菌感染マクロファージのグルコース代謝調節を担うhypoxia-inducible factor-1αの役割 (2011)
  • Author(s): 岡真優子、合田亘人、小林和夫、松本壮吉
  • Organizer: 沖縄感染症フォーラム
  • Place of Presentation: 健康分化村 カルチャーリゾート フェストーネ、那覇市
  • Year and Date: 2011-02-11
• [Presentation] 結核菌感染マクロファージのグルコース代謝調節を担うhypoxia-inducible factor-1αの役割 (2011)
  • Author(s): 岡真優子
  • Organizer: 特定領域研究「感染現象のマトリックス」第9回感染症沖縄フォーラム
  • Place of Presentation: 沖縄
• [Presentation] Clinical practice for the diagnosis of latent mycobacterium tuberculosis infection (2010)
  • Author(s): Osada-Oka M, Hirayama Y, Kitada S, Tateishi Y, Maekura R, Sugimura H, Koide Y, Kobayashi K, Matsumoto S
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program : 14^<th> International Conference on Emerging Infectious Diseases in the Pacific Rim : Next Generation Diagnostics for Infectious Diseases
  • Place of Presentation: Penang, Malaysia
  • Year and Date: 2010-10-04
• [Presentation] A histon-like protein of mycobacteria possesses ferritin superfamily protein-like activities : ferric iron storage and ferrous iron oxidation (2010)
  • Author(s): Osada-Oka M, Takatsuka M, Kobayashi K, Matsumoto S
  • Organizer: The 10th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji Yumebutai International Conference Center, Awaji, Japan
  • Year and Date: 2010-09-09
• [Presentation] Transient role of CD4^+CD25^+ regulatory T cells in mycobacterial infection in mice (2010)
  • Author(s): Ozaki Y, Sugawara I, Udagawa T, Aoki T, Osada-Oka M, Tateishi Y, Hisaeda H, Nishiuchi Y, Harada N, Kobayashi K, Matsumoto S
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program : 45th Tuberculosis and Leprosy Research Conference
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-07-13
• [Presentation] Identification of a novel ferritin-like protein in Mycobacterium (2010)
  • Author(s): Osada-Oka M, Takatsuka M, Satoh EF, Ozeki Y, Yoshimura M, Inoue M, Kobayashi K, Matsumoto S
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program : 45th Tuberculosis and Leprosy Research Conference
  • Place of Presentation: Boston, USA
  • Year and Date: 2010-07-13
• [Presentation] Mycobacterial DNA-binding protein-1の新機能-鉄の酸化活性と貯蔵性- (2010)
  • Author(s): 岡真優子、高塚正樹、小林和夫、松本壮吉
  • Organizer: 第63回日本酸化ストレス学会学術集会
  • Place of Presentation: 神奈川県民ホール、横浜市
  • Year and Date: 2010-06-24
• [Presentation] 潜在性結核の診断法の確立に向けた臨床への橋渡し研究;第1報 (2010)
  • Author(s): 岡真優子、平山幸雄、立石善隆、小林和夫、松本壮吉
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2010-03-29
• [Presentation] 結核菌感染における制御性T細胞の関与 (2010)
  • Author(s): 尾関百合子、菅原勇、岡真優子、小林和夫、松本壮吉
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2010-03-29
• [Presentation] 潜在性結核菌に対する液性免疫応答の解析 (2010)
  • Author(s): 岡真優子、平山幸雄、立石善隆、小林和夫、松本壮吉
  • Organizer: 第8回感染症沖縄フォーラム
  • Place of Presentation: カルチャーリゾートフェストーネ(沖縄県)
  • Year and Date: 2010-02-12
• [Presentation] 感染マクロファージにおけるサイトカイン発現パターンの差異からみた肺MAC症の重症化機序の解明 (2010)
  • Author(s): 立石善隆、岡真優子、西内由紀子、小林和夫、前倉亮治、松本壮吉
  • Organizer: 第8回感染症沖縄フォーラム
  • Place of Presentation: カルチャーリゾートフェストーネ(沖縄県)
  • Year and Date: 2010-02-12
• [Presentation] Clinical practice for the diagnosis of latent mycobacterium tuberculosis infection. (2010)
  • Author(s): Mayuko Osada-Oka.
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program : 14^<th> International Conference on Emerging Infectious Diseases in the Pacific Rim : Next Generation Diagnostics for Infectious Diseases.
  • Place of Presentation: Penang, Malaysia
• [Presentation] A histon-like protein of mycobacteria possesses ferritin superfamily protein-like activities : ferric iron storage and ferrous iron oxidation. (2010)
  • Author(s): Mayuko Osada-Oka.
  • Organizer: The 10th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji, Japan
• [Presentation] Identification of a novel ferritin-like protein in Mycobacterium. (2010)
  • Author(s): Mayuko Osada-Oka.
  • Organizer: U.S.-Japan Cooperative Medical Sciences Program : 45th Tuberculosis and Leprosy Research Conference.
  • Place of Presentation: Boston, USA
• [Presentation] Mycobacterial DNA-binding protein-1の新機能-鉄の酸化活性と貯蔵性- (2010)
  • Author(s): 岡真優子
  • Organizer: 第63回日本酸化ストレス学会学術集会
  • Place of Presentation: 横浜
• [Presentation] 潜在性結核の診断法の確立に向けた臨床への橋渡し研究;第1報 (2010)
  • Author(s): 岡真優子
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: 横浜
• [Presentation] 潜在性結核に対する液性免疫応答の解析 (2010)
  • Author(s): 岡真優子
  • Organizer: 特定領域研究「感染現象のマトリックス」第8回感染症沖縄フォーラム
  • Place of Presentation: 沖縄
• [Presentation] 低酸素による肝星細胞の活性化とコラーゲンの産生における分子機構 (2009)
  • Author(s): 岡真優子、新川寛二、高台真太郎、南山幸子、竹村茂一
  • Organizer: 第23回肝類洞壁細胞研究会学術集会
  • Place of Presentation: ホテル京阪ユニバーサル・タワー(大阪府)
  • Year and Date: 2009-12-13
• [Presentation] 低酸素状態でのHIF-1α安定化におけるグルコースの作用機構 (2009)
  • Author(s): 岡真優子、今岡進、小林和夫、松本壮吉
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-12
• [Presentation] 結核菌感染にける制御性T細胞の役割検討 (2009)
  • Author(s): 尾関百合子、菅原勇、岡真優子、小林和夫、松本壮吉
  • Organizer: 第62回日本細菌学会関西支部会総会
  • Place of Presentation: 大阪府立大学(大阪府)
  • Year and Date: 2009-11-14
• [Presentation] A ferritin superfamily-like protein in mycobacteria (2009)
  • Author(s): Osada-Oka M., Takatsuka M., Sato F.E., Ozeki Y., Yoshimura M., Inoue M., Kobayashi K., Matsumoto S.
  • Organizer: The 9th Awaji International Forum on Infection and Lmmunity
  • Place of Presentation: Awaji Yumebutai(Hyogo)
  • Year and Date: 2009-09-09
• [Presentation] 低酸素状態でのHIF-1α安定化におけるグルコースの作用機構 (2009)
  • Author(s): 岡真優子
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Identification of a novel ferritin-like protein in Mycobacterium. (2009)
  • Author(s): Mayuko Osada-Oka.
  • Organizer: The 9th Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji, Japan
• [Book] からだと酸素の事典 (2009)
  • Author(s): 岡真優子, ら
  • Total Pages: 574
  • Publisher: 朝倉書店