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The role of DAMPs on induction and termination of inflammatory responses induced by necrotic cells.

Research Project

Project/Area Number 21590078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionToho University

Principal Investigator

NAGATA Kisaburo  東邦大学, 理学部, 准教授 (10291155)

Co-Investigator(Kenkyū-buntansha) KOBAYASHU Yoshiro  東邦大学, 理学部, 教授 (10134610)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords免疫学 / necrosis / neutrophil / inflammation / chemokine / DAMPs
Research Abstract

In order to examine the mechanism, we used an inflammation model induced by injection of several types of necrotic cells into the peritoneal cavity in this study. The injection of necrotic P388 cells(leukemia cells) and necrotic peritoneal neutrophils(necrotic activated neutrophils), which were obtained from the peritoneal cavity upon injection of thioglycollate broth, induced the infiltration of neutrophils and subsequently that of monocytes/macrophages, whereas the injection of necrotic thymocytes and necrotic bone marrow neutrophils(necrotic resting neutrophils) did not. These results suggested that the induction of inflammatory response induced by necrotic cells depend on the cell type undergoing necrosis. In agreement with induction of cell infiltration, the injection also induced the production of KC and MIP-2, and subsequently that of MCP-1 only when necrotic P388 cells or necrotic activated neutrophils were injected. Although the level of KC was higher than that of MIP-2, both anti-KC Ab and anti-MIP-2 Ab significantly inhibited the infiltration of neutrophils. These results indicate that KC and MIP-2 play important roles in the infiltration of neutrophils into the site of injection of necrotic cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (37 results)

All 2012 2011 2010 2009 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (24 results) Remarks (1 results)

  • [Journal Article] Suppression of MIP-2 production by annexin A1 and A4 during coculturing of macrophages with late apoptotic human peripheral blood neutrophils2012

    • Author(s)
      Iwasa, T., Takahashi, R., Nagata, K., and Kobayashi, Y.
    • Journal Title

      Biochemica et Biophysica Acta

      Volume: 1822 Pages: 204-211

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-9 Receptor Gene is Transcriptionally Regulated by Nucleolin in T-Cell Lymphoma Cells2011

    • Author(s)
      Yi, S., Kakinuma, S., Nishimura, M., Kobayashi, Y., Nagata, K., and Shimada, Y
    • Journal Title

      Molecular Carcinogenesis

      Volume: (現在Web公開のみ) Issue: 8 Pages: 619-627

    • DOI

      10.1002/mc.20834

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the estrous cycle by neutrophils via opioid peptides2011

    • Author(s)
      Sasaki, S., Tamaki, Y., Nagata, K., and Kobayashi, Y.
    • Journal Title

      J. Immunol

      Volume: 187 Pages: 774-780

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The importance of infiltrating neutrophils in SDF-1 production leading to regeneration of the thymus after whole-body X-irradiation2011

    • Author(s)
      Nakayama, E., Shiratsuchi, Y., Kobayashi, Y., and Nagata, K.
    • Journal Title

      Cellular Immunol

      Volume: 268 Pages: 24-28

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Apoptotic neutrophils and nitric oxide regulate cytokine production by IFN-g-stimulated macrophages2011

    • Author(s)
      Shibata, T., Nagata, K., and Kobayashi, Y.
    • Journal Title

      Cytokine

      Volume: 53 Pages: 191-195

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the estrous cycle by neutrophils via opioid peptides2011

    • Author(s)
      Sasaki, S., Tamaki, Y., Nagata, K., Kobayashi, Y.
    • Journal Title

      J.Immunol.

      Volume: 187 Pages: 74-780

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The importance of infiltrating neutrophils in SDF-1 production leading to regeneration of the thymus after whole-body X-irradiation2011

    • Author(s)
      Nakayama, E., Shiratsuchi, Y., Kobayashi, Y, Nagata, K.
    • Journal Title

      Cellular Immunol.

      Volume: 268 Pages: 24-28

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apoptotic neutrophils and nitric oxide regulate cytokine production by IFN-γ-stimulated macrophages.2011

    • Author(s)
      Shibata, T., Nagata, K., Kobayashi, Y.
    • Journal Title

      Cytokine

      Volume: 53 Pages: 191-195

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The mechanism underlying the appearance of late apoptotic neutrophils and subsequent TNF-α production at a late stage during Staphylococcus aureus bioparticle-induced peritoneal inflammation in inducible NO synthase-deficient mice2010

    • Author(s)
      Shibata, T., Nagata, K., and Kobayashi, Y.
    • Journal Title

      Biochemica et Biophysica Acta

      Volume: 1802 Pages: 1105-1111

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The mechanism underlying the appearance of late apoptotic neutrophils and subsequent TNF-α production at a late stage during Staphylococcus aureus bioparticle-induced peritoneal inflammation in inducible NO synthase-deficient mice.2010

    • Author(s)
      Shibata, T., Nagata, K., Kobayashi, Y.
    • Journal Title

      Biochemica et Biophysica Acta.

      Volume: 1802 Pages: 35-40

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the estrous cycle by neutrophil infiltration into the vagina2009

    • Author(s)
      Sasaki, S., Nagata, K., and Kobayashi, Y.
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 382 Pages: 35-40

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the estrous cycle by neutrophil infiltration into the vagina2009

    • Author(s)
      Sasaki, S., Nagata, K., Kobayashi, Y.
    • Journal Title

      Biochem.Biophys.Res.Commun. 382

      Pages: 35-40

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Effect of aging on inflammatory responses to apoptotic cells2011

    • Author(s)
      高橋澪、小林芳郎、永田喜三郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification of S100A9 protein producing cell in inflammatory responses induced by necrotic neutrophils2011

    • Author(s)
      玉置豊、小林芳郎、永田喜三郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of aging on inflammatory responses to necrotic cells2011

    • Author(s)
      山口正昭、小林芳郎、永田喜三郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Presentation] Regulation of phagocytic responses of macrophages by soluble and particulate β-glucan2011

    • Author(s)
      富沢由、永田喜三郎、小林芳郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Presentation] 老化促進モデルマウス(SMP30/GNL-/-)におけるアポトーシス細胞の貪食除去応答2011

    • Author(s)
      高橋澪、石神昭人、小林芳郎、永田喜三郎
    • Organizer
      第12回Pharmaco-Hematology Symposium
    • Place of Presentation
      富山
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of aging on inflammatory responses to apoptotic cells2011

    • Author(s)
      高橋澪、小林芳郎、永田喜三郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification of S100A9 protein producing cell in inflammatory responses induced by necrotic neutrophils2011

    • Author(s)
      玉置豊、小林芳郎、永田喜三郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effect of aging on inflammatory responses to necrotic cells2011

    • Author(s)
      山口正昭、小林芳郎、永田喜三郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulation of phagocytic responses of macrophages by soluble and particulate β-glucan2011

    • Author(s)
      富沢由、永田喜三郎、小林芳郎
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 老化促進モデルマウス(SMP30/GNL-/-)におけるアポトーシス細胞の貪食除去応答2011

    • Author(s)
      高橋澪、石神昭人、小林芳郎、永田喜三郎
    • Organizer
      第12回Pharmaco-Hematology Symposium
    • Place of Presentation
      富山大学(富山県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effect of aging on inflammatory responses to dead cells2010

    • Author(s)
      Nagata, K., Takahashi, R., Yamaguchi, M., Totsuka S., Ishigami, A., and Kobayashi Y.
    • Organizer
      14^<th> International Congress of immunology
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] The role of Annexins I and IV in macrophage response to apoptotic cells2010

    • Author(s)
      Iwasa, T., Nagata, K., and Kobayashi Y.
    • Organizer
      14^<th> International Congress of immunology
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of aging on inflammatory responses to dead cells. 14^<th> International Congress of immunology.2010

    • Author(s)
      Nagata, K., Takahashi, R., Yamaguchi, M., Totsuka S., Ishigami, A., Kobayashi Y.
    • Organizer
      14^<th> International Congress of immunology.
    • Place of Presentation
      神戸ポートピアホテル(兵庫県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] The role of Annexins I and IV in macrophage response to apoptotic cells.2010

    • Author(s)
      Iwasa, T., Nagata, K., Kobayashi Y.
    • Organizer
      14^<th> International Congress of immunology.
    • Place of Presentation
      神戸国際展示場(兵庫県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 炎症の終息における一酸化窒素の役割2009

    • Author(s)
      柴田岳彦、永田喜三郎、小林芳郎
    • Organizer
      第39回日本免疫学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] 接触過敏症における好中球浸潤に対するIL-10の役割2009

    • Author(s)
      山田真里亜、永田喜三郎、小林芳郎
    • Organizer
      第39回日本免疫学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] アポトーシス細胞の貪食におけるAnnexin I, IVの役割2009

    • Author(s)
      岩佐卓哉、永田喜三郎、小林芳郎
    • Organizer
      第39回日本免疫学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report
  • [Presentation] Necrotic cell type-dependent induction of inflammatory response2009

    • Author(s)
      Nagata, K., Miho, N., and Kobayashi Y.
    • Organizer
      The 6^<th> Joint Seminar on Biomedical Sciences
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] A critical role of nitric oxide in the resolution of inflammation. Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology2009

    • Author(s)
      Kobayashi Y., Shibata T., and Nagata, K.
    • Organizer
      International Cytokine Society, & International Society for Interferon and Cytokine Research
    • Place of Presentation
      Lisbon, Portugal
    • Related Report
      2011 Final Research Report
  • [Presentation] Regulation of the estrous cycle by opioid peptides from neutrophils infiltrated into female genital organ2009

    • Author(s)
      Sohichiro S., Nagata, K., and Kobayashi Y.
    • Organizer
      The 9^<th> world congress on inflammation
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Regulation of the estrous cycle by opioid peptides from neut rophils infiltrated into female genital organ2009

    • Author(s)
      Sohichiro S., Nagata, K., Kobayashi Y.
    • Organizer
      The 9^<th> world congress on inflammation
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] Necrotic cell type-dependent induction of inflammatory response2009

    • Author(s)
      Nagata, K., Miho, N., Kobayashi Y.
    • Organizer
      The 6^<th> Joint Seminar on Biomedical Sciences
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] A critical role of nitric oxide in the resolution of inflammation2009

    • Author(s)
      Kobayashi Y., Shibata T., Nagata, K.
    • Organizer
      Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society, & International Society for Interferon and Cytokine Research
    • Place of Presentation
      Lisbon, Portugal
    • Related Report
      2009 Annual Research Report
  • [Presentation] アポトーシス細胞の食食における Annexin I,IVの役割2009

    • Author(s)
      岩佐卓哉, 永田喜三郎, 小林芳郎
    • Organizer
      第39回日本免疫学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.biomol.sci.toho-u.ac.jp/lab/nagata_lab/index.html

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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