Role of disturbance of immune response in alcohol-related death

• Project/Area Number: 24390175
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Osaka University (2013-2014); Sapporo Medical University (2012)
• Principal Investigator: MATSUMOTO HIROSHI 大阪大学, 医学(系)研究科(研究院), 教授 (60263092)
• Co-Investigator(Kenkyū-buntansha): SUGIMOTO Kana 大阪大学, 大学院医学系研究科, 助教 (00581034)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: アルコール関連死 / 突然死 / 大腿骨頭壊死 / 自然免疫 / 免疫撹乱 / TLR4 / TLR7 / TLR９ / 臓器障害 / 骨頭壊死 / 熱中症 / 急性脳症 / アルコール / トール受容体 / TRIM21 / HSP

Outline of Final Research Achievements

We hypothesized that alcohol-related death can be caused by disturbance of immune system. We performed a variety of model rats such as a sudden death model, brain contusion model, ostemonecrosis of femoral head, hyperthermia and so on. In all the model rats, we confirmed the disturbance of immune system, especially innate immune system via TLR4, TLR7, or TLR9. In femoral head osteonecrosis model, we found TRIM21 can be strongly related to promote the pathogenesis.

Research Products

• [Journal Article] Experimental rat model for alcohol-induced osteonecrosis of the femoral head (2013)
  • Author(s): Okazaki S1, Nagoya S, Tateda K, Katada R, Mizuo K, Watanabe S, Yamashita T, Matsumoto H.
  • Journal Title: Int J Exp Pathol Volume: 94 Issue: 5 Pages: 312-319
  • DOI: 10.1111/iep.12035
  • Peer Reviewed
• [Journal Article] High risk of osteonecrosis of the femoral head in autoimmune disease patients showing no immediate increase in hepatic enzyme under steroid therapy (2013)
  • Author(s): S Okazaki, S Nagoya, M Yamamoto, K Tateda, H Takahashi, T Yamashita, H Matsumoto
  • Journal Title: Rheumatology International Volume: (in press) Issue: 1 Pages: 51-55
  • DOI: 10.1007/s00296-011-2295-y
  • Peer Reviewed
• [Journal Article] Weight bearing does not contribute to the development of osteonecosis of the femoral head. (2012)
  • Author(s): Okazaki S, Nagoya S, Tateda K, Katada R, Mizuo K, Watanabe S, Yamashita T, Matsumoto H
  • Journal Title: Int J Exp Pathol Volume: 93 Issue: 6 Pages: 458-462
  • DOI: 10.1111/j.1365-2613.2012.00836.x
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of MIR-124 under ethanol dependence and withdr awal (2012)
  • Author(s): Mizuo K, Katada R, Okazaki S, Tateda K, Watanabe S, Matsumoto H
  • Journal Title: Jpn J Alcohol Drug Depend Volume: 47 Pages: 155-163
  • Peer Reviewed
• [Journal Article] Ethanol-induced hyponatremia augments brain edema after traumatic brain injury. (2012)
  • Author(s): Katada R, Watanabe S, Ishizaka A, Mizuo K, Okazaki S, Matsumoto H.
  • Journal Title: Jpn J Alcohol Drug Depend Volume: 47 Pages: 68-74
  • NAID: 10030613687
  • Peer Reviewed
• [Journal Article] Expression of aquaporin-4 augments cytotoxic brain edema after traumatic brain injury during acute ethanol exposure (2012)
  • Author(s): Katada R, Nishitani Y, Honmou O, Mizuo K, Okazaki S, Tateda K, Watanabe S, Matsumoto H
  • Journal Title: Am J Pathol Volume: 180 Pages: 17-23
  • Peer Reviewed