Studies on molecular basis of inhibitory effect of surfactant protein A against cytotoxicity of human b-defensin3.

• Project/Area Number: 24591173
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: ARIKI Shigeru 札幌医科大学, 医学部, 講師 (80464478)
• Co-Investigator(Renkei-kenkyūsha): KUROKI Yoshio 札幌医科大学, 医学部, 教授 (70161784)
• Research Collaborator: UEHARA Yasuaki
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 自然免疫 / 抗菌ペプチド / 肺コレクチン / サーファクタントタンパク質 / 感染症 / 肺サーファクタントタンパク質

Outline of Final Research Achievements

Antimicrobial peptides are host defense peptides with a broad spectrum of microbicidal activity. In this study, we suggested that combined use of hBD3 and SP-A-derived peptide (SAP01) is a candidate as a therapeutic reagent against infectious diseases. Binding of SAP01 to hBD3 attenuated cytotoxicity and excess inflammation induced by hBD3. Interestingly, SAP01 did not affect microbicidal activity at concentration sufficient for anti-cytotoxic activity. Because hBD3 also effectively kill drug-resistant microbes, there is appreciable interest in hBD3 for pharmaceutical applications.

Research Products

• [Journal Article] Distinct compartmentalization of SP-A and SP-D in the vasculature and lungs of patients with idiopathic pulmonary fibrosis. (2014)
  • Author(s): Nishikiori H, Chiba H, Ariki S, Kuronuma K, Otsuka M, Shiratori M, Ikeda K, Watanabe A, Kuroki Y, Takahashi H
  • Journal Title: BMC Pulm. Med. Volume: 14 Issue: 1 Pages: 196-196
  • DOI: 10.1186/1471-2466-14-196
  • Peer Reviewed / Open Access
• [Journal Article] The single N-glycan deletion mutant of soluble ErbB3 protein attenuates heregulinβ1-induced tumor progression by blocking of the HIF-1 and Nrf2 pathway. (2014)
  • Author(s): Takamiya R, Takahashi M, Uehara Y, Ariki S, Hashimoto J, Hasegawa Y, Kuroki Y
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 454 Issue: 3 Pages: 364-368
  • DOI: 10.1016/j.bbrc.2014.10.086
  • Peer Reviewed / Open Access
• [Journal Article] 肺サーファクタントの感染・炎症防御における役割 (2014)
  • Author(s): 高橋素子、有木茂、黒木由夫
  • Journal Title: 呼吸器内科 Volume: 26 Pages: 33-41
• [Journal Article] Surfactant protein D suppresses lung cancer progression by downregulation of epidermal growth factor signaling. (2014)
  • Author(s): Hasegawa Y. et al.
  • Journal Title: Oncogene Volume: in press
  • Peer Reviewed
• [Journal Article] Suppression of heregulin beta signaling by single N-glycan deletion mutant of soluble ErbB3 (2013)
  • Author(s): Takahashi M, Hasegawa Y, Ikeda Y, Wada Y, Tajiri M, Ariki S, Takamiya R, Nishitani C, Araki M, Yamaguchi Y, Taniguchi N, Kuroki Y.
  • Journal Title: J Biol Chem Volume: 288 Issue: 46 Pages: 32910-32921
  • DOI: 10.1074/jbc.m113.491902
  • Peer Reviewed
• [Journal Article] Surfactant Protein D Inhibits Adheren ce of Uropathogenic Escherichia coli to the Bladder Epithelial Cells and the Bacterium-induced Cytotoxicity (2012)
  • Author(s): Yuichiro Kurimura
  • Journal Title: The Journal of Biological Chemistry Volume: 287 Issue: 47 Pages: 39578-39588
  • DOI: 10.1074/jbc.m112.380287
  • Peer Reviewed
• [Journal Article] In vivo role of aldehyde reductase (2012)
  • Author(s): Motoko Takahashi
  • Journal Title: Bichim Biophys Acta Volume: 1820 Issue: 11 Pages: 1787-1796
  • DOI: 10.1016/j.bbagen.2012.07.003
  • Peer Reviewed
• [Journal Article] Implication of antigenic conversion of Helicobacter pylori lipopolysaccharides that involve interaction with surfactant protein D (2012)
  • Author(s): Yokota S, Amano K, Nishitani C, Ariki S, Kuroki Y, Fujii N.
  • Journal Title: Infection and Immunity Volume: 80 Issue: 8 Pages: 2956-2962
  • DOI: 10.1128/iai.00345-12
  • Peer Reviewed
• [Presentation] 肺サーファクタント蛋白質のEGFシグナル制御を介した抗腫瘍作用 (2014)
  • Author(s): 長谷川喜弘、高橋素子、有木茂、高宮里奈、上原康昭、橋本次朗、高橋弘毅、黒木由夫
  • Organizer: 第１３回肺サーファクタント分子病態研究会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-21
• [Presentation] Surfactant protein A-derived peptide decreases cytotoxicity of human b-defensin 3 without attenuating antimicrobial activity. (2014)
  • Author(s): Uehara Y, Ariki S, Takahashi M, Takamiya R, Hasegawa Y, Takahashi H, Kuroki Y
  • Organizer: American Thoracic Society International Conference 2014
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-05-20
• [Presentation] Surfactant proteins A and D suppress lung cancer progression by downregulation of EGF signaling. (2014)
  • Author(s): Hasegawa Y, Takahashi M, Ariki S, Takamiya R, Uehara Y, Hashimoto J, Takahashi H, Kuroki Y
  • Organizer: American Thoracic Society International Conference 2014
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-05-19
• [Presentation] Surfactant proteins A and D suppress epidermal growth factor signaling through interactions with N-glycans of receptor.
  • Author(s): Hasegawa Y. et al.
  • Organizer: 18th congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Yokohama, Japan
• [Presentation] Surfactant protein A-derived peptide protects lung epithelial cells from cytotoxic activity of human b-defensin 3.
  • Author(s): Uehara Y. et al.
  • Organizer: 18th congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Yokohama, Japan
• [Presentation] サーファクタント蛋白質AおよびDのEGFシグナル制御を介した抗腫瘍作用
  • Author(s): 長谷川喜弘 他
  • Organizer: 日本生化学会北海道支部例会
  • Place of Presentation: 札幌
• [Presentation] 肺サーファクタント蛋白質A由来ペプチドはヒトｂディフェンシン３の細胞傷害を抑制する
  • Author(s): 上原康昭 他
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜
• [Presentation] 可溶型EｒｂB３糖鎖欠損変異体とラパチニブのへレグリンシグナル抑制作用における相乗効果
  • Author(s): 高橋素子 他
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜
• [Presentation] 肺コレクチンによるEGFシグナルの制御機構
  • Author(s): 長谷川喜弘 他
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜