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Elucidation of the pathophysiology of eosinophilic chronic rhinosinusitis focused on nasal NO and its application to new treatments

Research Project

Project/Area Number 19K18801
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionUniversity of Fukui

Principal Investigator

Yoshida Kanako  福井大学, 学術研究院医学系部門(附属病院部), 医員 (00773706)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords好酸球性副鼻腔炎 / 鼻腔一酸化窒素(NO) / 鼻茸 / LRP-1 / 内臓脂肪 / 鼻腔一酸化窒素(NO)
Outline of Research at the Start

好酸球性副鼻腔炎は難治再発性の鼻茸を特徴とし、喘息を高率に合併する慢性副鼻腔炎であり、指定難病に定められている。鼻茸形成と難治化の病態を解明し、術後再発の可能性が高い症例を早期に見出し、適切に介入することが今後の最大の課題と考えられる。我々はこれまでの研究により、鼻腔一酸化窒素(鼻腔NO)が好酸球性副鼻腔炎のバイオマーカーとなる可能性を見出した。
本研究では、鼻副鼻腔におけるNO産生メカニズムを解明し、好酸球性副鼻腔炎の病態形成への関与とバイオマーカーの確立、治療への応用を目的とする。

Outline of Final Research Achievements

To elucidate the mechanism of NO production in the sinonasal mucosa and the mechanism of nasal NO involved in the pathogenesis of eosinophilic chronic rhinosinusitis, this study focused on two NO production pathways. (1) In the LRP-1 (Low density lipoprotein receptor-related protein-1) cell membrane receptor-mediated pathway; we investigated the relationship between LRP-1 expression localization in the nasal mucosa and NO production. As a result, we found that low LRP-1 expression may be involved in the pathophysiology of eosinophilic chronic rhinosinusitis and low nasal NO production. (2) In the adipocytokine-mediated pathway produced by visceral adipose tissue;we found that the visceral fat area may be involved in the pathophysiology of eosinophilic chronic rhinosinusitis and NO production.

Academic Significance and Societal Importance of the Research Achievements

本研究により、鼻腔NOの低値が好酸球性副鼻腔炎の病態形成に関与することがわかった。そして、LRP-1発現が低値であること、内臓脂肪面積が高値であることが、鼻腔NO低値に関与し、鼻腔NO産生にはLRP-1の発現、内臓脂肪が関与する可能性が示唆された。
鼻・副鼻腔におけるNO産生メカニズムと好酸球性副鼻腔炎の病態形成への関与機序を解明できれば、鼻腔NOを好酸球性副鼻腔炎のバイオマーカーとして確立できると考える。また、鼻副鼻腔においてNOを誘導することが新規治療につながる可能性があると考える。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (5 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Baicalin suppresses type 2 immunity through breaking off the interplay between mast cell and airway epithelial cell2021

    • Author(s)
      Yoshida K, Takabayashi T, Kaneko A, Takiyama M, Sakashita M, Imoto Y, Kato Y, Narita N, Fujieda S.
    • Journal Title

      Journal of Ethnopharmacology

      Volume: 1;267 Pages: 113492-113492

    • DOI

      10.1016/j.jep.2020.113492

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of sensitization and prevalence of Japanese cedar pollen and mite-induced perennial allergic rhinitis between 2006 and 2016 in hospital workers in Japan2021

    • Author(s)
      Sakashita M, Tsutsumiuchi T, Kubo S, Tokunaga T, Takabayashi T, Imoto Y, Kato Y, Yoshida K, Kimura Y, Kato Y, Kanno M, Ogi K, Okamoto M, Narita N, Fujieda S.
    • Journal Title

      Allergology International

      Volume: 70 Issue: 1 Pages: 89-95

    • DOI

      10.1016/j.alit.2020.07.004

    • NAID

      130007966780

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis2020

    • Author(s)
      Imoto Y, Takabayashi T, Sakashita M, Kato Y, Yoshida K, Kidoguchi M, Koyama K, Adachi N, Kimura Y, Ogi K, Ito Y, Kanno M, Okamoto M, Narita N, Fujieda S.
    • Journal Title

      Biomolecules

      Volume: 18;10(11) Issue: 11 Pages: 1568-1568

    • DOI

      10.3390/biom10111568

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population.2020

    • Author(s)
      Kidoguchi M, Yoshida K, Noguchi E, Nakamura T, Morii W, Haruna T, Okano M, Yamashita Y, Haruna S, Hasegawa M, Yoshida N, Ninomiya T, Imoto Y, Sakashita M, Takabayashi T, Fujieda S.
    • Journal Title

      Allergology International

      Volume: 69(4) Issue: 4 Pages: 619-621

    • DOI

      10.1016/j.alit.2020.04.005

    • NAID

      130007926244

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced nasal nitric oxide levels in patients with eosinophilic chronic rhinosinusitis2019

    • Author(s)
      Yoshida K, Takabayashi T, Imoto Y, Sakashita M, Narita N, Fujieda S
    • Journal Title

      Allergology International

      Volume: 68 Issue: 2 Pages: 225-232

    • DOI

      10.1016/j.alit.2018.09.005

    • NAID

      130007633635

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eosinophilic chronic rhinosinusitis2019

    • Author(s)
      Fujieda S, Imoto Y, Kato Y, Ninomiya T, Tokunaga T, Tsutsumiuchi T, Yoshida K, Kidoguchi M, Takabayashi T
    • Journal Title

      Allergology International

      Volume: 68 Issue: 4 Pages: 403-412

    • DOI

      10.1016/j.alit.2019.07.002

    • NAID

      130007733129

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased expression of L‐plastin in nasal polyp of patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease2018

    • Author(s)
      Takabayashi Tetsuji、Tanaka Yukie、Susuki Dai、Yoshida Kanako、Tomita Kaori、Sakashita Masafumi、Imoto Yoshimasa、Kato Yukinori、Narita Norihiko、Nakayama Tsugihisa、Haruna Shinichi、Schleimer Robert P.、Fujieda Shigeharu
    • Journal Title

      Allergy

      Volume: 印刷中 Issue: 7 Pages: 1307-1316

    • DOI

      10.1111/all.13677

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 好酸球性副鼻腔炎の病態解明と新たな治療戦略2020

    • Author(s)
      藤枝重治、高林哲司、坂下雅文、意元義政、加藤幸宣、木戸口正典、吉田加奈子、小山佳祐、足立直人
    • Organizer
      第121回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Thrombin activatable fibrinolysis inhibitor(TAFI)がアレルギー炎症に与える影響の検討2020

    • Author(s)
      吉田加奈子、高林哲司、坂下雅文、意元義政、加藤幸宣、成田憲彦、藤枝重治
    • Organizer
      第38回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 好酸球性副鼻腔炎における鼻腔一酸化窒素濃度(NO)測定の可能性2019

    • Author(s)
      吉田加奈子、高林哲司、加藤幸宣、意元義政、坂下雅文、成田憲彦、藤枝重治
    • Organizer
      第120回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 黄ごん成分(Baicalin)が好酸球性副鼻腔炎の病態に与える影響の検討2019

    • Author(s)
      吉田加奈子、高林哲司、坂下雅文、意元義政、成田憲彦、藤枝重治
    • Organizer
      第68回日本アレルギー学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Baicalinが好酸球性副鼻腔炎の病態に与える影響の検討2019

    • Author(s)
      吉田加奈子、高林哲司、坂下雅文、意元義政、加藤幸宣、成田憲彦、藤枝重治
    • Organizer
      第58回日本鼻科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] 医薬組成物2020

    • Inventor(s)
      藤枝重治、高林哲司、吉田加奈子
    • Industrial Property Rights Holder
      藤枝重治、高林哲司、吉田加奈子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] アンジオテンシン変換酵素2の発現抑制剤、および、アンジオテンシン変換酵素2を受容体とするウイルスに対する抗ウイルス剤2020

    • Inventor(s)
      高林哲司、吉田加奈子、意元義政、藤枝重治
    • Industrial Property Rights Holder
      高林哲司、吉田加奈子、意元義政、藤枝重治
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-146169
    • Filing Date
      2020
    • Acquisition Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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