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Establishment of tretments for patients with atopic dermatitis based on the immunological background

Research Project

Project/Area Number 14570795
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionTohoku University

Principal Investigator

TERUI Tadashi  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (30172109)

Co-Investigator(Kenkyū-buntansha) OZAWA Maki  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (10333791)
OKUYAMA Ryuhei  Tohoku University, Hospital, Lecture, 医学部附属病院, 講師 (80292332)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsAtopic dermatitis / immuno-therapy / CpG oligodeoxynucleotide / eosinophilic inflammation / Th2 / interleukin 5
Research Abstract

The number of patients with severe atopic dermatitis (AD), who show an eosinophil-related late phase skin reaction and high levels of IgE, is increasing, although there is accumulating evidence revealing its pathomechanism. Ag-nonspecific immunosuppressants have been used for the treatment of AD. These therapeutic agents sometime cause the deterioration of the host immunologic defense. AD is associated with skewing of immune response towards Th2 phenotype. There is a real need for developing an antigen-specific treatment to selectively suppress Th2 cell-mediated responses. Oligodeoxynucleotides (ODN) containing CpG motifs have been highlighted as an immunomodulator that reduces Th2-mediated responses by biasing the T-cell response toward a Th1-dominant phenotype. To substantiate the effect of CpG ODN in the Th2-mediated skin inflammation, we introduced a unique cutaneous model of a protein-Ag-induced eosinophilic inflammation with increased levels of serum IgE in BALB/c by three-time i.p. priming with ovalbumin (OVA)/alum and following a week-OVA skin patching.. Intradermal administration of CpG ODN diminished the number of infiltrated eosinophils and IgE systemic response. Interestingly, intradermal CpG ODN at the site of OVA patching significantly augmented the inhibitory effects on both the eosinophil infiltration and IgE levels and more effective when administered with Ag. Our data suggest that a cutaneous administration of CpG ODN with Ag can work as a novel Ag-specific immunomodulator therapy to treat the cutaneous eosinophilic inflammation that can be found in patients with AD.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Nagisa Kunikata: "Peritumoral CpG oligodeoxynucleotide treatment inhibits tumor growth and metastasis of B16F10 melanoma cells"Journal of Investigative Dermatology. (印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kunikata N, et al.: "Peritumoral CpG oligodeoxynucleotide treatment inhibits tumor growth and metastasis of B16F10 melanoma cells"J Investigative Dermatology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada Mikiko: "Cutaneous late phase reaction in adult atopic dermatitis patients with high serum IgE antibody to Dermatophagoides farinae : Correlation with IL-5 production by allergen-stimulated peripheral blood mononuclear cells"Journal of Dermatological Science. 29巻・2号. 73-84 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shirota Hidekazu: "B cells capturing Ag conjugated with CpG oligodeoxynucleotides induce Th1 cells by elaborating IL-12"Journal of Immunology. 169巻・2号. 787-794 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtsu Hiroshi: "Plasma extravasation induced by dietary supplemented histamine in histamine-free mice"European Journal of Immunology. 32巻・6号. 1698-1708 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sano Kunio: "Oligodeoxynucleotides without CpG motifs work as adjuvant for the induction of Th2 differentiation in a sequence-independent manner"Journal of Immunology. 170巻・5号. 2367-2373 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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