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Changes in blood cytokine levels under stress conditions and their application to forensic diagnosis.

Research Project

Project/Area Number 19590684
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionKawasaki Medical School

Principal Investigator

TOMITA Masafumi  Kawasaki Medical School, 医学部, 准教授 (50113197)

Co-Investigator(Kenkyū-buntansha) KATSUYAMA Hironobu  川崎医科大学, 医学部, 教授 (00289175)
HIDAKA Kazuo  川崎医科大学, 医学部, 准教授 (00069064)
WATANABE Yoko  川崎医科大学, 医学部, 助教 (70135945)
Research Collaborator OKUYAMA Toshiko  川崎医科大学, 医学部, 研究補助員
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords中毒 / ストレス / サイトカイン / 覚せい剤 / パラコート / 遺伝子 / 水浸拘束ストレス / 覚醒剤 / グルココルチコイドレセプター / 多型 / toxicology / マウス / 胃粘膜障害 / IL-6 / 酸化ストレス / サイトカインレベル / グルココルチコイドレセプター多型
Research Abstract

The cytokines investigated were IFN-γ, IL-6, IL-10, IL-12p70, MCP-1 and TNF. First, we investigated the effect of paraquat (Pq) on cytokine levels using the model of Pq-poisoned mice. As the result, IL-6 and MCP-1 levels, both mRNA in tissues and protein levels in blood, significantly increased within 5 days after Pq exposure. The former may be an early marker and the latter be a late marker for lung acute damage. Now we examine the effect of anti IL-6 antibody to Pq-poisoned damage, which need further investigation. Next, we examined the effects of methamphetamine (MA) on cytokine levels using a water-immersion restraint stress (WRS) mouse model. The levels of the serum cytokines IL-6, IL-10 and TNF were increased by stress, and were markedly increased by MA under stress conditions ; in particular, the level of IL-6 was synergistically increased. On the other hand, MA resulted in significant suppression of the stress-induced gastric injury, although further studies are necessary to resolve the mechanism. We investigated the involvement of the GR polymorphism in stress response using ICR mice. Our results suggest that the GR gene polymorphism has a significant impact on the stress-induced output, including cytokines, corticosterone, Hsp70 levels in serum, and the gastric lesion index. These studies provide insights into the role of GR in individual responses to stress.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (29 results)

All 2010 2009 2008 2007 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (17 results) Book (1 results) Remarks (3 results)

  • [Journal Article] The effect of CAG repeat polymorphism in the glucocorticoid receptor on stress responses of mice exposed to waterimmersion restraint stress.2010

    • Author(s)
      Tomita M, Katsuyama H, Okuyama T, Watanabe Y, Hidaka K, Otsuki T, Nata M
    • Journal Title

      Int. J. Mol. Med. 25(3)

      Pages: 415-420

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] The effect of CAG repeat polymorphism in the glucocorticoid receptor on stress response of mice exposed to water-immersion restraint stress2010

    • Author(s)
      Masafumi Tomita
    • Journal Title

      International journal of molecular medicine 25

      Pages: 415-420

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methamphetamine protects against stress-induced gastric mucosal lesions in mice.2009

    • Author(s)
      Tomita M, Okuyama T, Katsuyama H, Watanabe Y, Hidaka K, et. al. (9人)
    • Journal Title

      Legal Med. (Tokyo) 11(s1)

    • NAID

      10027263439

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Methamphetamine protects against stress-induced gastric mucosal lesions in mice2009

    • Author(s)
      Masafumi Tomita
    • Journal Title

      Legal medicine(Tokyo) 11(sup.1)

    • NAID

      10027263439

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between serotonin transporter gene polymorphisms and depressed mood caused by job stress in Japanese workers.2008

    • Author(s)
      Katsuyama H, Tomita M, Hidaka K, Watanabe Y, et. al. (10人:2番目)
    • Journal Title

      Int. J. Mol. Med. 21(4)

      Pages: 499-505

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association between serotonin transporter gene polymorphisms and depressed mood caused by job stress in Japanese workers2008

    • Author(s)
      Katsuyama H, Tomita M, et. al.
    • Journal Title

      Int.J.Mol.Med. 21

      Pages: 499-505

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methamphetamine protects against stress-induced gastric mucosal lesions in mice.

    • Author(s)
      Masafumi Tomita
    • Journal Title

      Leg. Med. (Tokyo) (In press)

    • NAID

      10027263439

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 5HTT polymorphisms are associated with job stress in the Japanese workers.

    • Author(s)
      Hironobu Katsuyama
    • Journal Title

      Leg. Med. (Tokyo) (In press)

    • NAID

      10027263571

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] マウスでのストレス感受性とグルココルチコイドレセプター多型の関連2009

    • Author(s)
      富田正文, 他
    • Organizer
      日本DNA多型学会
    • Place of Presentation
      久留米
    • Year and Date
      2009-11-20
    • Related Report
      2009 Final Research Report
  • [Presentation] A polymorphism in the glucocorticoid receptor gene is associated with responses of mice exposed to stress2009

    • Author(s)
      富田正文
    • Organizer
      The 4th International Congress on Stress Responses in Biology and Medicine
    • Place of Presentation
      the Chateraise Gateaux Kingdom SAPPORO(札幌市)
    • Year and Date
      2009-10-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] グルココルチコイドレセプター(GR)遺伝子多型と入トレス感受性-マウスでの検討-2009

    • Author(s)
      富田正文
    • Organizer
      第36回日本トキシコロジー学会学術年会
    • Place of Presentation
      盛岡市民文化ホール(盛岡市)
    • Year and Date
      2009-07-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] グルココルチコイドレセプター(GR)遺伝子多型とストレス性胃内出血に関連性はあるのか?2009

    • Author(s)
      富田正文, 他
    • Organizer
      第93次日本法医学会学術全国集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-14
    • Related Report
      2009 Final Research Report
  • [Presentation] 覚醒剤及び身体拘束の心臓における遺伝子発現への影響2009

    • Author(s)
      篠根光太郎, 富田正文, 他
    • Organizer
      (第2報)第93次日本法医学会学術全国集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-14
    • Related Report
      2009 Final Research Report
  • [Presentation] グルココルチコイドレセプター(GR)遺伝子多型とストレス性胃内出血に関連性はあるのか?2009

    • Author(s)
      富田正文
    • Organizer
      第93次日本法医学会学術全国集会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪市)
    • Year and Date
      2009-05-14
    • Related Report
      2009 Annual Research Report
  • [Presentation] A polymorphism in the glucocorticoid receptor gene is associated with responses of mice exposed to stress2009

    • Author(s)
      Tomita Masafumi, et al.
    • Organizer
      The 4th International Congress on Stress Responses in Biology and Medicine.
    • Related Report
      2009 Final Research Report
  • [Presentation] Glucocorticoid receptor polymorphism is a determinative factor in stress induced gastric injury.2008

    • Author(s)
      Masafumi Tomita, et al.
    • Organizer
      The 7^<th> ISALM
    • Place of Presentation
      大阪
    • Year and Date
      2008-09-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] メタンフェタミンによる血中サイトカインレベルの変化-ストレスによる影響について-2008

    • Author(s)
      富田正文, 他
    • Organizer
      第35回日本トキシコロジー学会学術年会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-27
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] 水浸拘束stressにおける血中サイトカインレベルに及ぼすメタンフェタミンの影響2008

    • Author(s)
      富田正文, 他
    • Organizer
      第92次日本法医学会学術全国集会
    • Place of Presentation
      長崎
    • Year and Date
      2008-04-24
    • Related Report
      2009 Final Research Report
  • [Presentation] 水浸拘束stressにおける血中サイトカインレベルに及ぼすメタンフェタミンの影響2008

    • Author(s)
      富田正文, ら
    • Organizer
      第92次日本法医学会総会
    • Place of Presentation
      長崎
    • Year and Date
      2008-04-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] 水浸拘束ストレスと血中サイトカインレベル-予備的検討2007

    • Author(s)
      富田 正文, ら
    • Organizer
      第24回日本法医学会中四国地方会
    • Place of Presentation
      松山(愛媛)
    • Year and Date
      2007-11-10
    • Related Report
      2007 Annual Research Report
  • [Presentation] マウスパラコート肺モデル早期での遺伝子発現とサイトカインレベルの変化2007

    • Author(s)
      富田正文, 他
    • Organizer
      第34回日本トキシコロジー学会学術年会
    • Place of Presentation
      東京
    • Year and Date
      2007-06-27
    • Related Report
      2009 Final Research Report
  • [Presentation] マウスパラコート肺モデル早期での遺伝子発現変化とサイトカイン2007

    • Author(s)
      富田 正文, ら
    • Organizer
      第34回日本トキシコロジー学会学術年会
    • Place of Presentation
      タワーホール船堀(東京)
    • Year and Date
      2007-06-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] マウスパラコート肺モデルでの肺障害初期に関与する遺伝子の検討2007

    • Author(s)
      富田 正文, ら
    • Organizer
      第29回日本フリーラジカル学会/日本過酸化脂質・フリーラジカル学会第31回大会(合同学会)
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2007-06-09
    • Related Report
      2007 Annual Research Report
  • [Presentation] パラコートによる肺destructive phaseでの遺伝子発現変化2007

    • Author(s)
      富田 正文, ら
    • Organizer
      第91次日本法医学会総会
    • Place of Presentation
      秋田ビューホテル(秋田)
    • Year and Date
      2007-05-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] パラコートによる肺destructive phaseでの遺伝子発現変化2007

    • Author(s)
      富田正文、石川隆紀
    • Organizer
      第91次日本法医学会学術全国集会
    • Place of Presentation
      秋田
    • Year and Date
      2007-05-16
    • Related Report
      2009 Final Research Report
  • [Book] DNA多型2009

    • Author(s)
      勝山博信, 伏見滋子, 富田正文, 奥山敏子, 日高和夫, 渡辺洋子, 為近美栄
    • Publisher
      東洋書店
    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://www.kawasaki-m.ac.jp/med/study/info.php?id=302

    • Related Report
      2009 Final Research Report
  • [Remarks]

    • URL

      http://www.kawasaki-m.ac.jp/med/study/info.php?id=302

    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.kawasaki-m.ac.jp/med/study/info.php?id=302

    • Related Report
      2008 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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