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Involvement of proinflammatory and anti-inflammatory mediators in the pathogenesis of sensorineural olfactory dysfunction

Research Project

Project/Area Number 17K11353
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionThe University of Tokyo

Principal Investigator

Kondo Kenji  東京大学, 医学部附属病院, 准教授 (40334370)

Co-Investigator(Kenkyū-buntansha) 菊田 周  東京大学, 医学部附属病院, 講師 (00555865)
有田 誠  国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (80292952)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords嗅覚障害 / 炎症性メディエーター / 抗炎症性メディエーター / 好酸球 / カロリー制限 / 鼻科学 / 嗅覚 / 炎症メディエーター
Outline of Final Research Achievements

(1)The infiltration of inflammatory cell types in mouse olfactory mucosa after injury was examined using cell-specific marker. Each inflammatory cell type infiltrated the mucosa with a specific spatiotemporal pattern, suggesting each of them plays a role in the induction/termination of inflammatory response. When eosinophils were experimentally depleted using anti-IL-5 antibody, the extent of neuroepithelial regeneration was not significantly different from that in control mice.
(2)Gene expression patterns and cell dynamics in the olfactory mucosa was compared between control and caloric restriction mice. Under caloric restriction , gene expression of several inflammatory cytokines, including IL-6, was elevated. Immunohistochemistry revealed that IL-6 receptors were actually distributed in the olfactory mucosa. At 1 week after the mucosal injury, the number of horizontal basal cells in the olfactory neuroepithelium was significantly decreased compared to the control group.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は直接的には難治性嗅覚障害の病態生理の理解、ひいては効果的な予防法の確立、治療法の開発の理論的基礎となり、感覚器医療の質的向上に寄与することによって患者に福音を与えることができる。また我々の研究結果は嗅神経組織の状態を食事によっても制御することが可能であることを示しており、本研究の成果として嗅覚の恒常性維持に寄与する栄養摂取のあり方を提言することが可能となり、将来の難治性嗅覚障害患者の発症を予防することで医療経済学的にも社会に貢献できる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (35 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (18 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 17 results,  Open Access: 9 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (3 results)

  • [Journal Article] Effects of Cigarette Smoke on the Nasal Respiratory and Olfactory Mucosa in Allergic Rhinitis Mice2020

    • Author(s)
      Ueha Rumi、Ueha Satoshi、Kondo Kenji、Nishijima Hironobu、Yamasoba Tatsuya
    • Journal Title

      Frontiers in Neuroscience

      Volume: 14 Pages: 126-126

    • DOI

      10.3389/fnins.2020.00126

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolism of odorant molecules in human nasal/oral cavity affects the odorant perception.2019

    • Author(s)
      Ijichi C, Wakabayashi H, Sugiyama S, Ihara Y, Nogi Y, Nagashima A, Ihara S, Niimura Y, Shimizu Y, Kondo K, Touhara K
    • Journal Title

      Chemical Senses

      Volume: 44 Issue: 7 Pages: 465-481

    • DOI

      10.1093/chemse/bjz041

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa2019

    • Author(s)
      Iwamura Hitoshi、Kondo Kenji、Kikuta Shu、Nishijima Hironobu、Kagoya Ryoji、Suzukawa Keigo、Ando Mizuo、Fujimoto Chisato、Toma-Hirano Makiko、Yamasoba Tatsuya
    • Journal Title

      Cell and Tissue Research

      Volume: 378 Issue: 2 Pages: 175-193

    • DOI

      10.1007/s00441-019-03047-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical practice guidelines for the management of olfactory dysfunction - Secondary publication.2019

    • Author(s)
      Miwa T, Ikeda K, Ishibashi T, Kobayashi M, Kondo K, Matsuwaki Y, Ogawa T, Shiga H, Suzuki M, Tsuzuki K, Furuta A, Motoo Y, Fujieda S, Kurono Y.
    • Journal Title

      Auris Nasus Larynx

      Volume: 46 Issue: 5 Pages: 653-662

    • DOI

      10.1016/j.anl.2019.04.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eosinophilic Upper Airway Inflammation in a Murine Model Using an Adoptive Transfer System Induces Hyposmia and Epithelial Layer Injury with Convex Lesions.2019

    • Author(s)
      Kanda A, Fujieda S, et al.
    • Journal Title

      Med Sci (Basel).

      Volume: 7(2) Issue: 2 Pages: 22-22

    • DOI

      10.3390/medsci7020022

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dose-Dependent Effects of Insulin-Like Growth Factor 1 in the Aged Olfactory Epithelium2018

    • Author(s)
      Ueha Rumi、Kondo Kenji、Ueha Satoshi、Yamasoba Tatsuya
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 10 Pages: 385-385

    • DOI

      10.3389/fnagi.2018.00385

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of the location of nasal polyps on olfactory airflow and olfaction2018

    • Author(s)
      Nishijima Hironobu、Kondo Kenji、Yamamoto Takahisa、Nomura Tsutomu、Kikuta Shu、Shimizu Yuya、Mizushima Yu、Yamasoba Tatsuya
    • Journal Title

      International Forum of Allergy & Rhinology

      Volume: 1 Issue: 6 Pages: 1-7

    • DOI

      10.1002/alr.22089

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cigarette Smoke-Induced Cell Death Causes Persistent Olfactory Dysfunction in Aged Mice2018

    • Author(s)
      Ueha Rumi、Ueha Satoshi、Kondo Kenji、Kikuta Shu、Yamasoba Tatsuya
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 10 Pages: 183-183

    • DOI

      10.3389/fnagi.2018.00183

    • NAID

      130007636263

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dorsal-zone-specific reduction of sensory neuron density in the olfactory epithelium following long-term exercise or caloric restriction2018

    • Author(s)
      Tuerdi Ayinuer、Kikuta Shu、Kinoshita Makoto、Kamogashira Teru、Kondo Kenji、Iwasaki Shinichi、Yamasoba Tatsuya
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 17300-17300

    • DOI

      10.1038/s41598-018-35607-w

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Environmental factors associated with allergic rhinitis symptoms in Japanese university students: A cross-sectional study2018

    • Author(s)
      Nishijima Hironobu、Suzuki Sayaka、Kondo Kenji、Yamasoba Tatsuya、Yanagimoto Shintaro
    • Journal Title

      Auris Nasus Larynx

      Volume: in press Issue: 5 Pages: 1006-1013

    • DOI

      10.1016/j.anl.2018.02.004

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reduction of Proliferating Olfactory Cells and Low Expression of Extracellular Matrix Genes Are Hallmarks of the Aged Olfactory Mucosa.2018

    • Author(s)
      Ueha R, Shichino S, Ueha S, Kondo K, Kikuta S, Nishijima H, Matsushima K, Yamasoba T.
    • Journal Title

      Front Aging Neurosci

      Volume: 10 Pages: 86-86

    • DOI

      10.3389/fnagi.2018.00086

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] InfraorbitalNerve Located Medially to Postoperative Maxillary Cysts: A Risk of EndonasalSurgery.2018

    • Author(s)
      Kondo K, Baba S, Suzuki S, Nishijima H, Kikuta S, Yamasoba T.
    • Journal Title

      ORL J Otorhinolaryngol Relat Spec

      Volume: 20 Issue: 1 Pages: 28-35

    • DOI

      10.1159/000486372

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low CT Attenuation Values of Sinonasal Benign Tumours Relative to the Brainstem Identify Schwannomas2018

    • Author(s)
      Nakada Tomoaki、Kikuta Shu、Mori Harushi、Shimizu Yuya、Nishijima Hironobu、Kondo Kenji、Yamasoba Tatsuya
    • Journal Title

      ORL

      Volume: 80 Issue: 1 Pages: 41-50

    • DOI

      10.1159/000487240

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of nasal septum perforation repair on nasal airflow: An analysis using computational fluid dynamics on preoperative and postoperative three-dimensional models2018

    • Author(s)
      Nomura Tsutomu、Ushio Munetaka、Kondo Kenji、Kikuchi Shigeru
    • Journal Title

      Auris Nasus Larynx

      Volume: 45 Issue: 5 Pages: 1020-1026

    • DOI

      10.1016/j.anl.2018.02.006

    • NAID

      130007742115

    • Related Report
      2018 Research-status Report
  • [Journal Article] Intravenous olfactory test latency correlates with improvement in post-infectious olfactory dysfunction2017

    • Author(s)
      Horikiri Kyohei、Kikuta Shu、Kanaya Kaori、Shimizu Yuya、Nishijima Hironobu、Yamasoba Tatsuya、Kondo Kenji
    • Journal Title

      Acta Oto-Laryngologica

      Volume: 137 Issue: 10 Pages: 1083-1089

    • DOI

      10.1080/00016489.2017.1325005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prolonged denervation induces remodeling of nasal mucosa in rat model of posterior nasal neurectomy2017

    • Author(s)
      Nishijima H, Kondo K, Toma-Hirano M, Kikuta S, Ando M, Ueha R, Yamasoba T.
    • Journal Title

      Int Forum Allergy Rhinol

      Volume: 7 Issue: 7 Pages: 670-678

    • DOI

      10.1002/alr.21952

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distribution, subtype population, and IgE positivity of mast cells in chronic rhinosinusitis with nasal polyps.2017

    • Author(s)
      Baba S, Kondo K, Suzukawa M, Ohta K, Yamasoba T.
    • Journal Title

      Ann Allergy Asthma Immunol

      Volume: 119 Issue: 2 Pages: 120-128

    • DOI

      10.1016/j.anai.2017.05.019

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laryngeal mucus hypersecretion is exacerbated after smoking cessation and ameliorated by glucocorticoid administration2016

    • Author(s)
      Ueha R, Ueha S, Kondo K, Nito T, Fujimaki Y, Nishijima H, Tsunoda K, Shand FH, Matsushima K, Yamasoba T.
    • Journal Title

      Toxicol Lett.

      Volume: 265 Pages: 140-146

    • DOI

      10.1016/j.toxlet.2016.11.023

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Caloric Restriction Reduces Basal Cell Proliferation and Results in the Deterioration of Neuroepithelial Regeneration following Olfactotoxic Mucosal Damage in Mouse Olfactory Mucosa2019

    • Author(s)
      Iwamura H, Kondo K, Kikuta S, Nishijima H, Suzukawa K, Ando M, Fujimoto C, Toma-Hirano M, Yamasoba T
    • Organizer
      Rhinoworld 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 嗅上皮再生を効果的に促進させるインスリンの点鼻投与時期について2019

    • Author(s)
      菊田 周、久保木章仁、岸本めぐみ、清水裕也、近藤健二、山岨達也
    • Organizer
      第58回日本鼻科学会総会・学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] タバコ煙と加齢による嗅覚障害の機序-嗅神経上皮障害を中心に-2019

    • Author(s)
      上羽瑠美、近藤健二、菊田周、山岨達也
    • Organizer
      第58回日本鼻科学会総会・学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Computational fluid dynamics of olfactory airflow2018

    • Author(s)
      Kondo K, Nishijima H, Yamasoba T
    • Organizer
      17th Korea-Japan Joint Meeting of ORL-HNS
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] アレルギー感作モデルマウスにおけるTRPV1及びTRPM8の発現の変化2018

    • Author(s)
      清水裕也、近藤健二、水嶋 優、井上雄太、西嶌大宣、菊田 周、山岨達也
    • Organizer
      第119回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cigarette smoke-induced cell death causes persistent olfactory dysfunction in aged mice2018

    • Author(s)
      Ueha R, Kondo K, Kikuta S, Yamasoba T
    • Organizer
      第57回日本鼻科学会総会・学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 嗅粘膜傷害・再生過程における炎症細胞浸潤の時間的空間的様式2018

    • Author(s)
      近藤健二, 菊田 周, 西嶌大宣, 上羽瑠美, 山岨達也
    • Organizer
      第57回日本鼻科学会総会・学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] インスリン点鼻投与による嗅上皮障害後の再生促進効果について2018

    • Author(s)
      菊田周、堀切教平、清水裕也、籠谷領二、上羽瑠美、近藤健二、山岨達也
    • Organizer
      第57回日本鼻科学会総会・学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 感冒後嗅覚障害の嗅覚予後と肥満との関連についての検討2018

    • Author(s)
      堀切教平、菊田 周、東 咲波、長野源太郎、清水裕也、籠谷領二、近藤健二、山岨達也
    • Organizer
      第57回日本鼻科学会総会・学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cigarette smoke-induced cell death causes persistent olfactory dysfunction in aged mice2018

    • Author(s)
      Ueha R, Kondo K, Kikuta S, Yamasoba T
    • Organizer
      64th American Rhinologic Society annual meeting
    • Related Report
      2018 Research-status Report
  • [Presentation] 嗅神経上皮傷害・再生過程における脂質メディエーターの関与2017

    • Author(s)
      近藤健二、菊田周、西嶌大宣、山岨達也、有田誠、磯部洋輔
    • Organizer
      第35回耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Effects of Caloric Restriction on the Olfactory Neuroepithelial Cell Dynamics2017

    • Author(s)
      Kenji Kondo
    • Organizer
      Rhinology World 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 嗅神経上皮傷害・再生過程における脂質メディエーターの関与2017

    • Author(s)
      近藤健二、菊田周、西嶌大宣、山岨達也、有田誠、磯部洋輔
    • Organizer
      第56回日本鼻科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Potential Roles of Lipid mediators in the Regeneration of Olfactory Neuroepithelium after injury2017

    • Author(s)
      Kenji Kondo, Shu Kikuta, Hironobu Nishijima, Tatsuya Yamasoba, Makoto Arita, Yosuke Isobe
    • Organizer
      The 3rd Rhinology Research Forum in Asia
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks]

    • URL

      http://utokyo-ent.org/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科 外科学専攻 感覚運動機能講座 耳鼻咽喉科・頭頸部外科学分野

    • Related Report
      2018 Research-status Report
  • [Remarks] 東京大学大学院医学系研究科 外科学専攻 感覚運動機能講座 耳鼻咽喉科・頭頸部外科学分野

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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