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The development of a new therapeutic moleculefor Japanese cedar pollinosis by proteomics analysis in the serum of patients treated with sublingual immunotherapy

Research Project

Project/Area Number 20390441
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionUniversity of Fukui

Principal Investigator

FUJIEDA Shigeharu  University of Fukui, 医学部, 教授 (30238539)

Co-Investigator(Kenkyū-buntansha) NOGUCHI Emiko  筑波大学, 人間総合科学研究科, 准教授 (40344882)
YAMADA Takechiyo  福井大学, 医学部附属病院, 講師 (70283182)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2010: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2009: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2008: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Keywords鼻科学 / アレルギー学 / スギ花粉症 / 舌下免疫療法 / 網羅的蛋白解析 / アポ蛋白A-4 / DAF / Filaggrin / ORMDL3 / Intelectin-1 / スフィンゴシン1リン酸 / 遺伝子多型 / IL-17 / アポ蛋白A-IV / IL-33 / CpG-DNA / 乳酸菌 / PD-L1 / C4A / トランスサイレチン / Hepatocyte nuclear factor 4α
Research Abstract

Seasonal allergic rhinitis caused by Japanese cedar (SAR-JC) is the most common allergic disease in Japan. The results of our recent study showed that about 30% of Japanese individuals develop allergic symptoms during JC pollination season. Allergen-specific immunotherapy (SIT) is the only available treatment that can provide long-term remission after discontinuation of treatment. Sublingual immunotherapy (SLIT), oral administration of the allergen, was introduced as a safety method. We found that apolipoprotein A-IV (apoA-IV) were significantly increased in SLIT-treated patients. The serum levels of apoA-IV correlated with the clinical effect. The amount of histamine released from the basophils in vitro was greatly reduced after the addition of recombinant apoA-IV in the medium. Our genetic studies found the association of polymorphisms of IL-33, DAF and Filaggrin with SAR-JC. They are possible therapeutic targets for SAR-JC.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (39 results)

All 2011 2010 2009 2008 Other

All Journal Article (31 results) (of which Peer Reviewed: 31 results) Presentation (7 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Interleukin-19 Downregulates Interleukin-4- Induced Eotaxin Production in Human Nasal Fibroblasts.2011

    • Author(s)
      Higashino M, Fujieda S
    • Journal Title

      Allergol Int. in press

    • NAID

      130004477105

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Platelet derived endothelial cell growth factor/Thymidine phosphorylase enhanced human IgE production.2011

    • Author(s)
      Yamamoto H, Fujieda S
    • Journal Title

      Allergol Int. 60(1)

      Pages: 79-85

    • NAID

      10031143302

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of IL17RB during natural allergen exposure in patients with seasonal allergic rhinitis.2011

    • Author(s)
      Matsumoto Y, Fujieda S
    • Journal Title

      Allergol Int. 60(1)

      Pages: 87-92

    • NAID

      10031143303

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cough reflex induced by capsaicin inhalation in patients with dysphagia.2011

    • Author(s)
      Imoto Y, Fujieda S
    • Journal Title

      Acta Otolaryngol. 131(1)

      Pages: 96-100

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A randomized, double-blind, placebocontrolled study of Ten-Cha (Rubus suavissimus) on house dust mite allergic rhinitis.2011

    • Author(s)
      Yonekura S, Fujieda S
    • Journal Title

      Auris Nasus Larynx. 38(5)

      Pages: 600-607

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of oral olopatadine hydrochloride for the treatment of seasonal allergic rhinitis: A randomized, double-blind, placebo-controlled study.2010

    • Author(s)
      amamoto H, Fujieda S
    • Journal Title

      Allergy Asthma Proc. 31(4)

      Pages: 296-303

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Apolipoprotein A-IV is a candidate target molecule for the treatment of seasonal allergic rhinitis.2010

    • Author(s)
      Makino Y, Fujieda S
    • Journal Title

      Allergy Clin Immunol. 126(6)

      Pages: 1163-1169

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] LL5{beta} directs the translocation of Filamin A and SHIP2 to sites of PtdIns(3,4,5) P3 accumulation and PtdIns(3,4,5)P3 localization is mutually modified by co-recruited SHIP2.2010

    • Author(s)
      Takabayashi T, Fujieda S
    • Journal Title

      JBiol Chem. 285(21)

      Pages: 16155-16165

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] S2554X mutation in the filaggrin gene is associated with allergen sensitization in the Japanese population.2010

    • Author(s)
      Imoto Y, Fujieda S
    • Journal Title

      JAllergy Clin Immunol. 125(2)

      Pages: 498-500

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Poly(I : C) induces BLyS-expression of airway fibroblasts through phosphatidylinositol 3-kinase.2010

    • Author(s)
      Yamada T, Fujieda S
    • Journal Title

      Cytokine. 50(2)

      Pages: 163-169

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of allergic rhinitis and sensitization to common aeroallergens in a Japanese population.2010

    • Author(s)
      Sakashita M, Fujieda S
    • Journal Title

      Int Arch Allergy Immunol. 151(3)

      Pages: 255-261

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bax-gene transfer enhances apoptosis by steroid treatment in human nasal fibroblasts.2010

    • Author(s)
      Kimura Y, Fujieda S
    • Journal Title

      Eur Arch Otorhinolaryngol. 267(1)

      Pages: 61-66

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Apolipoprotein A-IV is a candidate target molecule for the treatment of sea sonal allergic rhinitis.2010

    • Author(s)
      Makino Y, Noguchi E, et al.
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 126 Pages: 1163-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Poly (I : C) induces BLyS-expression of airway fibroblasts through phosphatid ylinositol 3-kinase.2010

    • Author(s)
      Yamada T, Lizhong S, et al.
    • Journal Title

      Cytokine.

      Volume: 50 Pages: 163-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] S2554X mutation in the filaggrin gene is associated with allergen sensitizat ion in the Japanese population.2010

    • Author(s)
      lmoto Y, Enomoto H, et al.
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 125 Pages: 498-500

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of allergic rhinitis sensitization to common aeroallergens in a Japanese population.2010

    • Author(s)
      Sakashita M.Hirota T, et al.
    • Journal Title

      Int Arch Allergy Immunol.

      Volume: 151 Pages: 255-61

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of oral olopatadine hydrochloride for the treatment of seasonal alle rgic rhinitis: A randomized, double-blind, placebo-controlled study.2010

    • Author(s)
      Yamamoto H, Yamada T, et al.
    • Journal Title

      Allergy Asthma Proc

      Volume: 31 Pages: 296-303

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LL5beta directs the translocation of filamin A and SHIP2 to sites of phosp hatidylinositol 3, 4, 5-triphosphate (Ptdlns (3, 4, 5) P3) accumulation, and Ptdlns (3, 4, 5) P3 localization is mutually modified by co-recruited SHIP2.2010

    • Author(s)
      Takabayashi T, Xie MJ, et al.
    • Journal Title

      J Biol Chem.

      Volume: 285 Pages: 16155-65

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bax-gene transfer enhances apoptosis by steroid treatment in human nasal fibroblasts.2010

    • Author(s)
      Kimura Y, Sugimoto C, et al.
    • Journal Title

      Eur Arch Otorhinolaryngol.

      Volume: 267 Pages: 61-6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Associations between decay-accelerating factor polymorphisms and allergic respiratory diseases.2009

    • Author(s)
      Kawai T, Fujieda S
    • Journal Title

      Clin Exp Allergy. 39(10)

      Pages: 1508-1514

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharides increase the amount of CXCR4, and modulate the morphology and invasive activity of oral cancer cells in a CXCL12-dependent manner.2009

    • Author(s)
      Takabayashi T, Fujieda S
    • Journal Title

      Oral Oncol. 45(11)

      Pages: 968-973

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of Allergic Rhinitis and Sensitization to Common Aeroallergens in a Japanese Population2009

    • Author(s)
      Sakashita M, Hirota T, et al
    • Journal Title

      Int Arch Allergy Immunol 151

      Pages: 255-261

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Associations between decay-accelerating factor polymorphisms and allergic respiratory diseases2009

    • Author(s)
      Kawai T, Takeshita S, et al.
    • Journal Title

      Clin Exp Allergy 39

      Pages: 1508-1514

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipopolysaccharides increase the amount of CXCR4, and modulate the morphology and invasive activity of oral cancer cells in a CXCL12-dependent manner2009

    • Author(s)
      Takabayashi T, et al.
    • Journal Title

      Oral Oncol. 45

      Pages: 968-973

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A randomized double-blind comparative study of sublingual immunotherapy for cedar pollinosis.2008

    • Author(s)
      Okubo K, Fujieda S
    • Journal Title

      Allergol Int. 57

      Pages: 265-275

    • NAID

      10024419926

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population : a family and case-control study.2008

    • Author(s)
      Enomoto H, Fujieda S
    • Journal Title

      J Hum Genet. 53

      Pages: 615-621

    • NAID

      10021249695

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of serum interleukin-33 level and the interleukin-33 genetic variant with Japanese cedar pollinosis.2008

    • Author(s)
      Sakashita M, Fujieda S
    • Journal Title

      Clin Exp Allergy 38

      Pages: 1875-1881

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A randomized double-blind comparative study of sublingual immunotherapy for cedar pollinosis.2008

    • Author(s)
      Okubo K, Gotoh M, et al.
    • Journal Title

      Allergol Int. 57

      Pages: 265-275

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population : a family and case-control study.2008

    • Author(s)
      Enomoto H, Hirata K, et al.
    • Journal Title

      J Hum Genet. 53

      Pages: 615-621

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of serum interleukin-33 level and the interleukin-33 genetic variant with Japanese cedar pollinosis.2008

    • Author(s)
      Sakashita M, Yoshimoto T, et al.
    • Journal Title

      Clin Exp Allergy 38

      Pages: 1875-1881

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of IL17RB during Natural Allergen Exposure in Patients with Seasonal Allergic Rhinitis.

    • Author(s)
      Matsumoto Y, Noguchi E, et al.
    • Journal Title

      Allegol Int.

      Volume: (In press)

    • NAID

      10031143303

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] アレルギー疾患のプロオテオミクス2010

    • Author(s)
      野口恵美子、藤枝重治
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Year and Date
      2010-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 網羅的遺伝子解析によるスギ花粉症に関する遺伝子の同定2010

    • Author(s)
      意元義政、野口恵美子、有波忠雄、藤枝重治
    • Organizer
      第60回日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京
    • Year and Date
      2010-11-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] アレルギー増悪因子としてのウイスル感染2010

    • Author(s)
      坂下雅文、藤枝重治
    • Organizer
      第49回日本鼻科学会基礎問題研究会
    • Place of Presentation
      札幌
    • Year and Date
      2010-08-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] スギ花粉症患者における鼻上皮細胞の網羅的遺伝子解析2010

    • Author(s)
      意元義政、野口恵美子、有波忠雄、藤枝重治
    • Organizer
      第49回日本鼻科学会基礎問題研究会
    • Place of Presentation
      札幌
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Association of serum interleukin-33 level and the interleukin-33 genetic variant with seasonal allergic rhinitis of Japanese cedar2009

    • Author(s)
      Fujieda S, Sakashita M.
    • Organizer
      XIX ENT World congress IFOS 2009
    • Place of Presentation
      Sao Paulo
    • Year and Date
      2009-06-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] アレルギー性鼻炎を考える:遺伝子・蛋白解析から治療まで2008

    • Author(s)
      藤枝重治
    • Organizer
      第58回日本アレルギー秋季学術大会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] スギ花粉症における網羅的遺伝子・蛋白解析2008

    • Author(s)
      藤枝重治
    • Organizer
      第20回日本アレルギー学会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-13
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Patent(Industrial Property Rights)] アレルギー疾患の治療薬且つ治療効果マーカー2008

    • Inventor(s)
      藤枝重治、高橋昇、大澤陽子、窪誠太、有波忠雄、野口恵美子、牧野友香、内田和彦、大久保公裕
    • Industrial Property Rights Holder
      藤枝重治、野口恵美子
    • Filing Date
      2008-03-04
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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