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微生物成分が誘導するヒト樹状細胞遺伝子群の網羅的解析

Research Project

Project/Area Number 13206086
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (C)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionResearch Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses

Principal Investigator

瀬谷 司  大阪府立成人病センター, 研究所, 所長 (10301805)

Co-Investigator(Kenkyū-buntansha) 松本 美佐子  大阪府立成人病センター, 研究所・免疫学部門, 主任研究員 (30332456)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2001: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywords微生物成分 / 樹状細胞 / ジーンプロファイリング / Toll-like receptor / ウイルス感染 / dsRNA / 細菌感染 / peptidoglycan
Research Abstract

TLR3がウイルスのdsRNAをPAMPとして認識し、type 1 IFNを誘導することが判明した。一方、TLR2,TLR4は主にNK-kB/p38 MAPKを活性化する。両者の相違をDNA chip, cDNA subtractionなどの解析法で各種感染に応じた樹状細胞の応答の相違として網羅的にデータベース化することを企画している。以下の成果をえている
1.ヒトTLR1,TLR2,TLR3,TLR6,の抗体を作製した。TLR4の抗体は三宅博士(東大医科研)より入手した。各TLRの相互関係とリガンド応答性の機能解析中である。これらの抗体でヒト樹状細胞を検討した。樹状細胞にはTLR3を多く発現するpopulation, TLR2・4を多く発現するpopulationが存在し、subset-specificのTLR発現プロフィールが示唆された。この結果は樹状細胞が一様の細胞群ではなく、微生物認識において多様性をもつsubsetsの集合であること、RT-PCRなど従来の報告は蛋白発現と相違していることを示唆した。
2.HEK293 cellを用いたreporter gene assayでTLR2/4はNFkB,MAPKのpathwayを優位に活性化した。一方、TLR3はPKR pathwayを活性化した。PAMP/TLRの組み合わせで活性化経路が異なることが示された。
3.個体差についてgene chipで解析を開始した。まだcluster解析、profiling解析を開始した時点なので、個体差を議論できるまでに至っていない。疾患別の樹状細胞応答は次年度の目標とする予定である。

Report

(1 results)
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Inoue, N., A.Fukui, M.Nomura, M.Matsumoto, K.Toyoshima, T.Seya.: "A novel chicken membrane-associated complement-regulatory protein : Molecular cloning and functional characterization of a chicken membrane SCR protein"J.Immunol. 166. 424-431 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishiguchi, M., M.Matsumoto, T.Takao, M.Hoshino, Y.Shimonishi, S.Tsuji, N.A.Begum, O.Takeuchi, S.Akira, K.Toyoshima, T.Seya.: "Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by Toll-like receptor 2 : Role of N-terminal hydrophobic portion in its multiple functions"J.Immunol. 166. 2610-2616 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Seya T(out of 96 authors) et al.: "The RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium. Functional annotation meeting"Nature. 409. 685-690 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nomura, M., K.Matsumiya, M.Kitamura, A.Okuyama, M.Matsumoto, K.Toyoshima, T.Seya.: "Gnomic analysis of ideopathic infertile patients with sperm-specific depletion of CD46"Exp.Clin.Immunogen. 18. 42-50 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kikkawa, S., M.Matsumoto, K.Shida, Y.Fukumori, K.Toyoshima, T.Seya: "Human macrophages produce dimeric forms of IL-18 which can be detected with monoclonal antibodies specific for inactive IL-18"Biochem.Biophys.Res.Commun. 281. 461-467 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shida, K, M.Matsumoto, S.Kikkawa, H.Okamura, S.Tsuji, Y.Fukumori, K.Toyoshima, T.Seya.: "An alternative form of human IL-18 in human blood plasma : complex formation with IgM defined by monoclonal antibodies"J.Immunol. 166. 6671-6679 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Azuma, I., T.Seya.: "Cell wall skeleton of BCG : application to adjuvant immunotherapy for cancer(Review)"Int.Immunopharmacology. 1. 1249-1259 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsumoto, M., T.Seya, S.Kikkawa, S.Tsuji, K.Shida, M.Nomura, M.Kurita-Taniguchi, M.Higashiyama, H.Ohigashi, H.Yokouchi, H.Takami, A.Hayashi, I.Azuma, T.Masaoka, K.Kodama, K.Toyoshima: "Interferon gamma-producing ability in blood lymphocytes of patients with lung cancer through activation of the innate immune system by BCG-cell wall skeleton"Int.Immunopharmacology. 1. 1559-1569 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Moriwaki, Y., N.A.Begum, M..Kobayashi, M.Matsumoto, K.Toyoshima, T.Seya: "Mycobacterium bovis Bacillus Calmette-Guerin and its cell wall complex induce a novel lysosomal membrane protein, SIMPLE, that bridges the missing link between lipopolysaccharide and p53-inducible gene, LITAF(PIG7), and estrogen-inducible gene,EET-1"J.Biol.Chem. 276. 23065-23076 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsuji, S., J.Uehori, M.Matsumoto, Y.Suzuki, A.Matsuhisa, K.Toyoshima, T..Seya: "Human intelectin is a novel soluble lectin that recognizes galactofranose in carbohydrate chains of bacterial cell wall"J.Biol.Chem. 276. 23456-23463 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukui, A., N, Inoue, M.Matsumoto, M.Nomura, Y, Matsuda, K.Toyoshima, T.Seya.: "Molecular cloning and functional characterization of chicken Toll-like receptors : a single chicken Toll covers multiple molecular patterns"J.Biol.Chem.. 276. 47143-47149 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shiratori, I., S.Tsuji, M.Matsumoto, M.Nomura, K.Toyoshima, T.Seya.: "Molecular cloning and functional characterization of guinea pig IL-12"Int.Immunol. 13. 1129-1139 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Seya, T., M.Matsumoto, S.Tsuji, N.A.Begum, M.Nomura, I.Azuma, A.Hayashi, K.Toyoshima.: "Two receptor theory in innate immune activation : studies on the receptors for bacillus Culmet Guillen-cell wall skeleton (BCG-CWS)"Arch.Immunol.Ther.Exp.. 49 Suppl. 13-21 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shida K., H.Koizumi, M.Matsumoto, I.Shiratori, S.Kikkawa, S.Tsuji, N.A.Begum, K.Toyoshima, T.Seya: "High serum levels and additional species of IL-18 may participate in suppressing IgE levels in patients with atopic dermatitis"Immunol.Lett.. 79. 169-175 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Soldan S.S., A.Fogdell-Hahn, M.B.Brennan, B.B.Mittleman, L.Massacesi, T.Seya, S.Jacobson.: "Elevated serum and CSF levels of soluble HHV-6 cellular receptor, membrane cofactor protein(MCP ; CD46), in patients with multiple sclerosis"Ann.Neurol.. 50. 486-493 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Seya T., M.Matsumoto, I.Shiratori, Y.Fukumori, K.Toyoshima: "Protein polymorphism of human IL-18 identified by monoclonal antibodies"Int.J.Molec.Med. 8. 585-590 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koizumi, H., K.Sato-Matsumura, H.Nakamura, K.Shida, S.Kikkawa, M.Matsumoto, K.Toyoshima, T.Seya.: "Distribution of IL-18 and IL-18 receptor in human skin : various forms of IL-18 are produced in keratinocytes"Arch.Dermatol.Res.. 293. 325-333 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsujimura, A, K.Nunoue, N.Inoue, K.Shida, M.Kurita-Taniguchi, M.Matsumoto, M.Nomura, T.Takeya, T.Seya.: "Three soluble form messages of murine CD46 are produced by alternative mRNA splicing"J.Biochem. 130. 841-848 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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