A novel therapy for sepsis by regulating soluble ULBP2

• Project/Area Number: 26462755
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Tottori University
• Principal Investigator: CHIKUMI HIROKI 鳥取大学, 医学部附属病院, 教授 (90283994)
• Co-Investigator(Kenkyū-buntansha): 清水 英治 鳥取大学, 医学部, 教授 (50187449) ; 高田 美也子 鳥取大学, 医学部, プロジェクト研究員 (50523643)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Kousuke 鳥取大学, 医学部附属病院, 助教 (60529402) ; MIYAKE Naomi 鳥取大学, 医学部, 特任教員 (90747205) ; KINOSHITA Naoki 鳥取大学, 医学部附属病院, 助教 (40750336)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 敗血症 / NK細胞 / ULBP2 / 可溶性ULBP2 / 免疫療法

Outline of Final Research Achievements

Sepsis is a leading cause of death in infectious disease patients in the world. One of the potential mechanism of sepsis is dysregulated host immune response to infectious agents. To date, the role of natural killer (NK) cells, an essential component of the innate immune system, in sepsis are scarcely studied. Therefore, we investigated the mechanism of functional dysregulation of NK cells in sepsis in connection with an inhibitory molecule of NK cells, soluble ULBP2 (sULBP2). We found that sULBP2 is elevated in a portion of septic patients. As a mechanism, we uncovered that cell surface ULBP2 is shed into serum as sULBP2 by ADAM17, but not by ADAM10 protease. Finally, we found that clarithromycin, a macrolide antibiotic, can reduce the amount of sULB2 by inhibiting the ADAM17 activities. These findings might be the cue to develop new agents for sepsis by modulating the NK cell function.

Research Products

• [Journal Article] γ-Tocotrienol Inhibits TGF-β1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells. (2018)
  • Author(s): Fukushima T, Yamasaki A, Harada T, Chikumi H, Watanabe M, Okazaki R, Takata M, Hasegawa Y, Kurai J, Yanai M, Yamamoto A, Sueda Y, Halayko AJ, Shimizu E.
  • Journal Title: Yonago Acta Med. Volume: 60 Pages: 16-23
  • NAID: 120005999117
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of antigen‐positive toxin‐negative enzyme immunoassay results for the diagnosis of toxigenic Clostridium difficile infection (2018)
  • Author(s): Akamatsu Y, Morishita S, Okamoto R, Okada K, Kitaura T, Miyake N, Yamaguchi K, Nakamoto M, Shimohiro H, Takata M, Yamasaki A, Burioka N, Shimizu E.
  • Journal Title: The Journal of Medical Investigation Volume: 65 Issue: 1.2 Pages: 131-135
  • DOI: 10.2152/jmi.65.131
  • NAID: 130006575562
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] γ-Tocotrienol Inhibits TGF-β1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells (2017)
  • Author(s): Fukushima T, Yamasaki A, Harada T, Chikumi H, Watanabe M, Okazaki R, Takata M, Hasegawa Y, Kurai J, Yanai M, Yamamoto A, Sueda Y, Halayko AJ, Shimizu E.
  • Journal Title: Yonago Acta Med Volume: 60 Pages: 16-23
  • NAID: 120005999117
  • Peer Reviewed / Open Access
• [Journal Article] Shewanella algae Bacteremia in an End-stage Renal Disease Patient: A Case Report and Review of the Literature (2017)
  • Author(s): Takata T, Chikumi H, Morishita S, Hamada S, Hoi S, Iyama T, Fukui T, Matono T, Fukuda S, Munemura C, Isomoto H.
  • Journal Title: Intern Med Volume: 56 Pages: 729-732
  • NAID: 130005450344
  • Peer Reviewed / Open Access
• [Journal Article] Properties of Achromobacter xylosoxidans highly resistant to aminoglycoside antibiotics. (2016)
  • Author(s): Nakamoto S, Goda N, Hayabuchi T, Tamaki H, Ishida A, Suzuki A, Nakano K, Yui S, Katsumata Y, Yamagami Y, Burioka N, Chikumi H, Shimizu E.
  • Journal Title: Jpn J Antibiot Volume: 69 Pages: 113-118
  • NAID: 40020827421
  • Peer Reviewed
• [Journal Article] 【Antimicrobial Stewardship Program(ASP)の理論と実際】 ASP推進における医師の役割 患者にとって有効で,かつ耐性菌を過剰に生じさせないためには (2016)
  • Author(s): 千酌浩樹
  • Journal Title: 化学療法の領域 Volume: 32 Pages: 1986-1993
• [Journal Article] Effect of Clarithromycin on the expression of UL16-binding protein 2 in human cells. (2015)
  • Author(s): Okada K, Chikumi H, et al.
  • Journal Title: Yonago Acta Medica Volume: 58 Pages: 31-38
  • NAID: 120005596728
  • Peer Reviewed / Open Access
• [Presentation] 薬剤耐性対策を考慮した感染症診療の実際 (2017)
  • Author(s): 千酌浩樹
  • Organizer: 平成29年度日本内科学会生涯教育講演会
  • Invited
• [Presentation] 血液培養検査を再考する (2017)
  • Author(s): 千酌浩樹
  • Organizer: 第32回日本環境感染学会総会・学術集会
  • Invited
• [Presentation] 高齢者感染症のpitfall (教育講演） (2016)
  • Author(s): 千酌浩樹
  • Organizer: 第64回日本学療法学会西日本支部総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-11-25
  • Invited
• [Presentation] 感染症と教育 卒前卒後にわたる感染症・感染制御教育への取り組み (2016)
  • Author(s): 千酌浩樹
  • Organizer: 第90回日本感染症学会総会・学術講演会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-04-15
• [Presentation] 肺癌細胞におけるEGFR阻害剤耐性獲得時の浸潤能とその機序の検討 (2014)
  • Author(s): 高田美也子、泉大樹、千酌浩樹、三宅直美、牧野晴彦、井岸正、清水英治
  • Organizer: 第23回日本がん転移学会総会
  • Place of Presentation: 金沢市文化ホール（金沢）
  • Year and Date: 2014-07-11