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Analysis of apoptosis in alveolar macrophages induced by periodontopathic bacteria and development of a method of protection from pneumonia

Research Project

Project/Area Number 11557169
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Periodontal dentistry
Research InstitutionKyushu Dental College

Principal Investigator

NISHIHARA Tatsuji  Kyushu Dental College. Department of Oral Microbiology. Professor, 歯学部, 教授 (80192251)

Co-Investigator(Kenkyū-buntansha) KOSEKI Takeyoshi  National Infectious Diseases. Department of Oral Science, Senior Researcher, 口腔科学部, 主任研究官 (80291128)
KAKINOKI Yasuaki  National Minami-Fukuoka Hospital. Division of Dental Medicine. Director, 南福岡病院・歯科, 医長(研究職)
AKIFUSA Sumio  Kyushu Dental College. Department of Preventive Dentistry.Assistant, 歯学部, 助手 (40295861)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2000: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1999: ¥5,100,000 (Direct Cost: ¥5,100,000)
Keywordsalveolar macrophage / periodontitis / periodontopathic bacteria / bacterial infection / apoptosis / caspase / pneumonia / the aged / 要介護者 / 誤嚥性肺炎 / 細胞内感染 / カスパーゼ / 口腔ケア
Research Abstract

Infection of murine macrophages in vitro with periodontopathic bacterium Actinobacillus actinomycetemcomitans induces apoptotic cell death. In this study, we investigated the involvement of caspases in apoptotic cell death of A.actinomycetemcomitans-infected macrophages. Two peptide inhibitors of caspases, benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone(Z-VAD-FMK)and benzyloxycarbonyl-Asp-Glu-Val-Asp(OMe)-fluoromethyl katone(Z-DEVD-FMK), inhibited apoptotic cell death of mouse macrophage cell line J774.1 infected with A.actinomycetemcomitans. During the process of apoptosis, interleukin-1β(IL-1β) was detected in the culture supernatants of J774.1 cells. IL-1β secretion was blocked by the caspase-1 inhibitor, Z-VAD-FMK, indicating that caspase-1 is involved in not only the induction of apoptosis but also the IL-1β secretion from A.actinomycetemcomintas-infected J774.1 cells. Immunoblot analysis revealed that the infection of A.actinomycetemcomitans to J774.1 cells induced the cleavage of retinoblastoma protein(Rb), suggesting that caspase-3 was activated by A.actinomycetemcomitans-infection. The cytosol from A.actinomycetemcomitans-infected J774.1 cells induced Rb proteollysis in vitro, which was inhibited by the caspase-3 inhibitor, Z-DEVD-FMK.Furthermore, caspase-3-like activity was markedly increased in J774.1 cells infected with A.actinomycetemcomitans between 12h and 24 h, which was subsequently inhibited by the addition of caspase-3 inhibitor, Z-DEVD-FMK.These findings indings indicate that caspase-3 induces apoptosis in J774.1 cells infected with A.actinomycetemcomitans. Taken together, these results suggest that caspase-1 and caspase-3 are involved in the induction of apoptosis in A.actinomycetemcomitans-infected macrophages.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Nonaka, K,et al.: "Inuoluement of caspases in apoptotic cell death if macrophages infected with Actinobacillus actinomycetemcomitans"J.Periodont. Res.. 36. 40-47 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato, S.et al.: "Human epithelial celldeath caused by Actinobacillus actinomycetemcomitans infection"J.Med. Microbiol. 49. 739-745 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noguchi, K.et al.: "Cyclooxygenese-2-dependent prostaglandin production by perph eral blood monocytes stimulated with lipopolysacoharide isolated form periodon topathogenic bacteria"J.Periodontol. 71. 1575-1582 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishisaki, A.et al.: "caspase-3 activation during the process of apoptosis induced by a vacuolar type H^+-ATPases inhibitor"Biology of the Cell. 91. 507-514 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jimi, E.et al.: "Osteoclast differentiation factor acts a multifunctional regulator in murine osleoclast differentiation and function"J.Immunol. 163. 434-442 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Muro, M.et al.: "Inhibitory effect of lipoplysacharide on apoptotic cell death in macrophoges infected with Actinobacillus actinomycetemcomitans"FEMS Microbiol. Lett.. 175. 211-216 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Muto, A., M.Kizaki, H.Ueno, M.Kamata, Y.Kawai, K.Yamato, M.Ohguchi, T.Nishihara, H.P.Koeffler, and Y.Ikeda: "1, 25-Dihydroxyvitamin D3 induces differentiation of a retinoic acid-resistant APL cell line(UF-1)associated with expression of p21^<WAF1/CIP1> and p27^<KIP1>."Blood. 93. 2225-2233 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishisaki, A., K.Yamato, P.ten Dijke, S.Hashimoto, A.Nakao, K.Tamaki, K.Nonaka, H.Sugino, and T.Nishihara: "Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B cells."J.Biol.Chem.. 274. 13637-13642 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Muro, M., K.Nakashima, J.Tomioka, S.Kato, K.Nonaka, T.Yoshida, M.Inoue, T.Nishihara, and Y.Kowashi: "Inhibitory effect of lipopolysaccharide on apoptotic cell death in macrophages infected with Actinobacillus actinomycetemcomitans."FEMS Microbiol.Lett.. 175. 211-216 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koide, M., N.Okahashi, R.Tanaka, K.Kazuno, K.-I.Shibasaki, Y.Yamazaki, K.Kameko, N.Ueda, M.Ohguchi, Y.Ishihara, T.Noguchi, and T.Nishihara: "Inhibition of experimental bone resorption and osteoclast formation and survival by 2-aminoethanesulfonic acid."Arch.Oral Biol.. 44. 711-719 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Koide, M., Y.Murase, K.Yamato, T.Noguchi, N.Okahashi, and T.Nishihara: "Bone morphogenetic protein-2 enhances osteclast formation mediated by interleukin-1α through upregulation of osteoclast differentiation factor and cyclooxygenase-2."Biochem.Biophys.Res.Commun.. 259. 97-102 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Jimi, E., S.Akiyama, T.Tsurukai, N.Okahashi, K.Kobayashi, N.Udagawa, T.Nishihara, N.Takahashi, and T.Suda: "Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function."J.Immunol.. 163. 434-442 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ishisaki, A., S.Hashimoto, T.Amagasa, and T.Nishihara: "Caspase-3 activation during the process of apoptosis induced by a vacuolar type H^+-ATPases inhibitor."Biology of the Cell. 91. 507-514 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato, S., K.Nakashima, M.Inoue, J.Tomioka, K.Nonaka, T.Nishihara, and Y.Kowashi: "Human epithelial cell death caused by Actinobacillus actinomycetemcomitans infection."J.Med.Microbiol.. 49. 739-745 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noguchi, K., M.Yanai, M.Shitashige, T.Nishihara, and I.Ishikawa: "Cyclooxygenase-2-dependent prostaglandin production by peripheral blood monocytes stimulated with lipopolysaccharides isolated from periodontopathogenic bacteria."J.Periodontol.. 71. 1575-1582 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nonaka, K., A.Ishisaki, N.Okahashi, T.Koseki, S.Kato, M.Muro, K.Nakashima, T.Nishihara, and Y.Kowashi: "Involvement of caspases in apoptotic cell death of macrophaages infected with Actinobacillus actinomycetemcomitans."J.Periodont.Res.. 36. 40-47 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okahashi, N., Y.Murase, T.Koseki, T.Sato, K.Yamato, and T.Nishihara: "Involvement of cyclin-dependent kinase inhibitors p21^<WAF1/CIP1> and p27^<KIP1> in the differentiation of osteoclasts."J.Cell.Biochem.. 80. 339-345 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nonaka,K. et al.: "Involvement of caspases in apoptotic Cell death of macrophages infected with Actinobacillus actinomycetem-comitans"J.Periodont.Res.. 36. 40-47 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kato,S. et al.: "Human epithelial cell death caused by Actinobacillus actinomycetemcomitans infection"J.Med.Microbiol.. 49. 739-745 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Noguchi,K. et al.: "Cyclooxygenase-2-dependent prostaglandin production by peripheral blood monocytes stimulated with lipo-bolysaccharide isolated from periodontopathoge nic bacteria"J.Periodontol.. 71. 1575-1582 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 西原 達次: "口腔内環境と全身の関連 口腔内細菌と誤嚥性肺炎(1)"日本歯科評論. 687. 17-19 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishisaki,A.et al.: "Differential inhibition of Smad 6 and Smad 7 on bone morphogenetic protein-and activin-mediated growth arrest"J.Biol.Chem.. 274. 13637-13642 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Muro,M.et al.: "Inhibitory effect of lipopolysaccharide on apoptofic cell death in macrophages induced by Actinobacillus actinomycetemcomitans"FEMS Microbiol.Lett. 175. 211-216 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kobayashi,M.et al.: "Intracellular interleukin-1α production in human gingival fibroblasts is differentially regulated by various cytokines"J.Dent.Res.. 78. 840-849 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koide,M.et al.: "Bone morphogentic protein-2 enhances osteoclast formation mediated by interleukin-1α through upregulation of ODF"Biochem.Biophy.Res.Commun.. 259. 97-102 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jimi,E.et al.: "Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function"J.Immunol.. 163. 434-442 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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