Recognition of lipopolysaccharide by adiponectin

• Project/Area Number: 19790093
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: Saga University
• Principal Investigator: TSUKAMOTO Hiroki Saga University, 医学部, 助教 (70423605)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,630,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: 感染症 / 免疫学 / 薬学 / 生体分子 / 抗体

Research Abstract

病原体に共通の分子構造(pathogen-associated molecular patterns, PAMPs)は、Toll-like receptor(TLR)等のPAMPs受容体によって認識される。本研究では、脂肪細胞から特異的に分泌されるアディポネクチンが、PAMPsの一つ、グラム陰性細菌の細胞壁成分であるlipopolysaccharide(LPS)に結合することを、大腸菌リコンビナント蛋白質を作製し明らかにした。生化学的な解析により、その結合様式はこれまでに知られるTLR4を介したlipid A構造の認識ではなく、病原性に関わるO抗原糖鎖構造に依存することが示唆され、新しいPAMPsあるいは病原菌認識機構であることが示唆された。さらに、哺乳類細胞を用いてもリコンビナントアディポネクチンを作製し、LPSとの結合様式と翻訳後修飾との関連性及びその生物学的意義について検討を進めた。

Research Products

• [Journal Article] TEX101, a Germ Cell-Marker Glycoprotein, is Associated with Lymphocyte Antigen 6 Complex Locusk within the Mouse Testis Biochem (2008)
  • Author(s): Hiroshi Yoshitake, Hiroki Tsukamoto, Mayuko Maruyama-Fukushima, Kenji Takamori, Hideoki Ogawa, Yoshihiko Araki
  • Journal Title: Biophys. Res. Commun 372(2) Pages: 277-282
  • Peer Reviewed
• [Journal Article] TEX101, a Germ Cell- Marker Glycoprotein, is Associated with Lymphocyte Antigen 6 Complex Locus k within the Mouse Testis (2008)
  • Author(s): Yoshitake H
  • Journal Title: Biochem. Biophys. Res. Commun. 372(2) Pages: 277-282
  • Peer Reviewed
• [Journal Article] Preparation and Characterization of Agonistic Monoclonal Antibodies Against Toll-Like Receptor 4-MD-2 Complex (2007)
  • Author(s): Bahrun U, Kimoto M, Tsukamoto H, Tsuneyoshi N, Kohara J, Fukudome K
  • Journal Title: Hybridoma 26 Pages: 393-399
  • Peer Reviewed
• [Journal Article] Genomic organization and structure of the 5'-flanking region of the TEX101 gene : Alternative promoter usage and splicing generate transcript variants with distinct 5'-untranslated region (2007)
  • Author(s): Tsukamoto H, Takizawa T, Takamori K, Ogawa H, Araki Y
  • Journal Title: Mol Reprod Dev 74(2) Pages: 154-162
  • Peer Reviewed
• [Journal Article] Preparation of recombinant murine tumor necrosis factor-alpha in Escherichia coli : a rapid method to remove tags from fusion proteins by thrombin-cleavage and ion-exchange chromatography (2007)
  • Author(s): Tsukamoto H, Fukudome K, Kohara J, Nakatake H, Kimoto M
  • Journal Title: Protein Expr Purif 56(1) Pages: 138-44
  • Peer Reviewed
• [Journal Article] Penta-acylated lipopolisaccharide binds to murine MD-2 but 154-162 doesnot induce the oligomelization of TLR4 required for signal transduction. (2007)
  • Author(s): Tsuneyoshi N
  • Journal Title: Cellular Immunology 244(1) Pages: 57-64
  • Peer Reviewed
• [Journal Article] Genomic organization and structure of the 5'-flanking region of the TEX101 gene: Alternative promoter usage and splicinggenerate transcript variants with distinct 5'-untranslated region. (2007)
  • Author(s): Tsukamoto H
  • Journal Title: Mol Reprod Dev. 74(2) Pages: 154-162
  • Peer Reviewed
• [Journal Article] Preparation and Characterization of Agonistic Monoclonal Antibodies Against Toll-Like Receptor 4-MD-2 Complex. (2007)
  • Author(s): Bahrun U
  • Journal Title: Hybridoma 26(6) Pages: 393-399
  • Peer Reviewed
• [Presentation] 機能抑制型ヒトTLR4抗体Anti-human TLR4 monoclonal antibody which specifically prevents the LPS responses independently of Fc receptors (2008)
  • Author(s): Tsukamoto H, Kimoto M, Tsuneyoshi N, Fukudome K
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 日本免疫学会会誌38:169
  • Year and Date: 2008-12-02
• [Presentation] Anti- human TLR4 monoclonal antibody which specifically prevents the LPS responses independently of Fc receptors (2008)
  • Author(s): Tsukamoto H
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-12-02
• [Presentation] Adjuvant effects of agonistic anti-TLR4 monoclonal antibody in antibody induction (2007)
  • Author(s): Fukudome K, Kohara J, Tsukamoto H,Tsuneyoshi N, Kimoto M
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 日本免疫学会会誌37:227
  • Year and Date: 2007-11-22
• [Presentation] Adjuvant effects of agonistic anti-TLR4 monoclonal antibody in antibody induction. (2007)
  • Author(s): Fukudome K
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
• [Presentation] Oligomerization-independent TLR4-signaling in CD14-negative cells (2007)
  • Author(s): Tsukamoto H, Kohara J, Tsuneyoshi N, Kimoto M, Fukudome K
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 日本免疫学会会誌37:163
  • Year and Date: 2007-11-21
• [Presentation] Oligomerization-independent TLR4-signaling in CD14-negative cells. (2007)
  • Author(s): Tsukamoto H
  • Organizer: 第37回日本免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-21