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2005 Fiscal Year Final Research Report Summary

Study on the mechanism of EBV reactivation and NK cell oncogenesis in hypersensitivity to mosquito bites

Research Project

Project/Area Number 16591113
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionNara Medical University

Principal Investigator

ASADA Hideo  Nara Medical University, Department of Dermatology, Associate Professor, 医学部, 助教授 (60252681)

Co-Investigator(Kenkyū-buntansha) NIIZEKI Hironori  Nara Medical University, Department of Dermatology, lecturer, 医学部, 講師 (10228124)
MIYAGAWA Sachiko  Nara Medical University, Department of Dermatology, Professor, 医学部, 教授 (30094626)
Project Period (FY) 2004 – 2005
Keywordshypersensitivity to mosquito bites / EB virus / reactivation / oncogene / NK cells / CD4^+T cells / cytokine
Research Abstract

Hypersensitivity to mosquito bites (HMB) is characterized by intense local skin symptoms, which consist of not only erythema or bulla but also ulceration or scarring, and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. Recent studies demonstrated the lymphoproliferation of EB virus (EBV) DNA-positive natural killer (NK) cells, including NK cell leukemia/lymphoma, in HMB patients. We previously demonstrated that CD4^+T cells of a patient with HMB proliferated well in response to mosquito salivary gland extracts (SGE) and played a key role in the reactivation of EBV from a latent state in NK cells. We also showed that mosquito bites can induce expression of the viral oncogene LMP1 in NK cells via mosquito antigen-specific CD4^+T cells, which is involved in the oncogenesis of NK cells in vivo. Here, we established long-term cultures of NK cells from the patients with HMB. When these cultured NK cells were cocultured with autologous CD4^+T cells stimulated by mosquito SGE, the expression of LMP1 and NK cell growth were enhanced. It was proved that mRNA and protein expressions of IL-4, IL-10, and TGF-β were upregulated in the CD4^+T cells by stimulation with the mosquito SGE. Adding a neutralizing antibody to IL-2 into the coculture of NK and mosquito SGE-stimulated CD4^+T inhibited the LMP1 mRNA expression, while adding a neutralizing antibody to TGF-β enhanced the LMP1 mRNA expression and suppressed the reactivation of EBV. On the other hand, neutralizing antibodies to IL-4 and IL-10 had no effects on LMP1 expression and NK cell growth. Furthermore, we investigated a patient with skin rash induced by ampicillin, and found that ampicillin might have played a key role in reactivation of EBV infection, implying that EBV reactivation contributed to the pathogenesis of skin rash in this patient. It suggests that the reactivation of EBV is related not only to HMB but also to other allergic diseases.

  • Research Products

    (18 results)

All 2005 2004

All Journal Article (15 results) Book (3 results)

  • [Journal Article] Mosquito salivary gland extracts induce EBV-infected NK cell oncogenesis via CD4+ T cells in patients with hypersensitivity to mosquito bites.2005

    • Author(s)
      Asada H, et al.
    • Journal Title

      J Invest Dermatol 125(5)

      Pages: 956-961

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ampicillin-induced cutaneous eruption associated with Epstein-Barr virus reactivation.2005

    • Author(s)
      Saito-Katsuragi M, Asada H, et al.
    • Journal Title

      J Am Acad Dermatol 52(5)

      Pages: S127-S128

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Enhanced T cell response to mosquito extracts by NK cells in hypersensitivity to mosquito bites associated with EB virus infection and NK cell lymphocytosis.2005

    • Author(s)
      Tokura Y, Matsuoka H, Koga C, Asada H, et al.
    • Journal Title

      Cancer Sci 96(8)

      Pages: 519-526

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 蚊アレルギー(蚊刺過敏症)2005

    • Author(s)
      浅田 秀夫
    • Journal Title

      Visual Dermatology 4(6)

      Pages: 610-616

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] EBウイルスに関連した特異な皮膚症状2005

    • Author(s)
      浅田 秀夫
    • Journal Title

      奈良県医師会医学会年報 18(1)

      Pages: 1-7

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ampicillin-induced cutaneous eruption associated with Epstein-Ban virus reactivation.2005

    • Author(s)
      Saito-Katsuragi M, et al.
    • Journal Title

      J Am Acad Dermatol 52(5)

      Pages: S127-S128

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Enhanced T cell response to mosquito extracts by NK cells in hypersensitivity to mosquito bites associated with EB virus infection and NK cell lymphocytosis.2005

    • Author(s)
      Tokura Y, et al.
    • Journal Title

      Cancer Sci 96(8)

      Pages: 519-526

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hypersensitivity to mosquito bites.2005

    • Author(s)
      Asada H
    • Journal Title

      Visual Dermatology 4(6)

      Pages: 610-616

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cutaneous manifestations associated with EB virus.2005

    • Author(s)
      Asada H
    • Journal Title

      The Annuals of the NARA Medical Association 18(1)

      Pages: 1-7

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 種痘様水疱症とEBウイルス感染2004

    • Author(s)
      浅田 秀夫
    • Journal Title

      アレルギー科 18(4)

      Pages: 299-305

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ウイルス感染と薬疹2004

    • Author(s)
      浅田 秀夫, 葛城麻実子
    • Journal Title

      アレルギーの臨床 24(14)

      Pages: 23-27

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] EBウイルス2004

    • Author(s)
      浅田 秀夫
    • Journal Title

      化学療法の領域 20(6)

      Pages: 19-24

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Hydroa vacciniforme and EB virus infection.2004

    • Author(s)
      Asada H
    • Journal Title

      Allergology 18(4)

      Pages: 299-305

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Viral infection and drug eruption.2004

    • Author(s)
      Asada H, et al.
    • Journal Title

      The allergy in practice 24(14)

      Pages: 23-27

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Epstein-Barr virus.2004

    • Author(s)
      Asada H
    • Journal Title

      Antibiotics & Chemotherapy 20(6)

      Pages: 19-24

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 今日の治療指針2005

    • Author(s)
      浅田 秀夫
    • Total Pages
      839
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 最新皮膚科学大系 特別巻12004

    • Author(s)
      浅田 秀夫
    • Total Pages
      151-7
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 皮膚疾患最新の治療2004

    • Author(s)
      浅田 秀夫
    • Total Pages
      113-4
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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