Regulatory mechanisms of cytokines in ECRS

• Project/Area Number: 18K16871
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Hokkaido University
• Principal Investigator: Suzuki Masanobu 北海道大学, 医学研究院, 助教 (70455658)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 好酸球性副鼻腔炎 / サイトカイン / 鼻ポリープ / TLR / SIRT1 / PolyIC / 鼻粘膜上皮細胞 / TLR3 / 自然免疫シグナル / 耳鼻咽喉科学 / アレルギー学 / 慢性副鼻腔炎 / リモデリング / MMP9 / エピジェネティック / HDAC

Outline of Final Research Achievements

In this study, we examined the regulatory mechanisms of cytokine expression and secretion in human primary nasal epithelial cells. Our focus has been put especially on TLR3 and NFkB signaling pathway. Multiplex assay and microfluidic qPCR assay were applied to reveal the time- and dose- dependency of the cytokine expression. We found most of cytokines are under control of TLR3 stimulation but other TLR stimulation rarely promoted the cytokines expression.

Academic Significance and Societal Importance of the Research Achievements

得られた結果からは鼻粘膜上皮細胞は自然免疫応答によってサイトカイン産生を制御していることが判明した。サイトカインは好酸球性副鼻腔炎などの副鼻腔炎症性疾患のに関与している。この制御はこれらの疾患の予防・治療などに応用できる可能性が示唆された。
特に、自然免疫受容体のTLR3はdsRNAを特異的に認識するレセプターであること、ウィルス増殖の際にはdsRNAが産生されること、また、急性鼻炎の多くはウィルス感染に起因することをあわせて考えると、この鼻粘膜上皮細胞における特異的な自然免疫応答は、生体において合目的的な機構と考えられた。一方で、疾患によってはこの応答が生体にとって不利に働くことも判明した。

Research Products

• [Int'l Joint Research] アデレード大学耳鼻咽喉科(オーストラリア)
• [Int'l Joint Research] アデレード大学耳鼻咽喉科頭頸部外科(オーストラリア)
• [Int'l Joint Research] アデレード大学耳鼻咽喉科頭頸部外科/The Betzel Hetzel Institute/The Queen Elizabeth Hospital(オーストラリア)
• [Journal Article] TRIM27 expression is associated with poor prognosis in sinonasal mucosal melanoma (2023)
  • Author(s): Kimura S、Suzuki M、Nakamaru Y、Kano S、Watanabe M、Honma A、Nakazono A、Tsushima N、Hatakeyama S、Homma A
  • Journal Title: Rhinology Journal Volume: - Issue: 0 Pages: 0-0
  • DOI: 10.4193/rhin22.405
  • Peer Reviewed / Open Access
• [Journal Article] Repetitive simulation training with novel 3D‐printed sinus models for functional endoscopic sinus surgeries (2022)
  • Author(s): Suzuki Masanobu、Miyaji Kou、Watanabe Ryosuke、Suzuki Takayoshi、Matoba Kotaro、Nakazono Akira、Nakamaru Yuji、Konno Atsushi、Psaltis Alkis James、Abe Takashige、Homma Akihiro、Wormald Peter‐John
  • Journal Title: Laryngoscope Investigative Otolaryngology Volume: 7 Issue: 4 Pages: 943-954
  • DOI: 10.1002/lio2.873
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical Characteristics of Patients and Factors Associated with Switching Biologics in Asthma (2022)
  • Author(s): Matsumoto-Sasaki Machiko、Simizu Kaoruko、Suzuki Masanobu、Suzuki Masaru、Kimura Hirokazu、Nakamaru Yuji、Ito Yoichi M、Homma Akihiro、Konno Satoshi
  • Journal Title: Journal of Asthma and Allergy Volume: Volume 15 Pages: 187-195
  • DOI: 10.2147/jaa.s348513
  • Peer Reviewed
• [Journal Article] The Quantification of Extracellular Trap Cell Death-Derived Products as Diagnostic Biomarkers for Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Eosinophilic Otitis Media (2021)
  • Author(s): Morita Shinya、Nakamaru Yuji、Fukuda Atsushi、Fujiwara Keishi、Suzuki Masanobu、Hoshino Kimiko、Honma Aya、Homma Akihiro
  • Journal Title: Otology & Neurotology Volume: 43 Issue: 3 Pages: e337-e343
  • DOI: 10.1097/mao.0000000000003431
  • Peer Reviewed
• [Journal Article] TLR Signals in Epithelial Cells in the Nasal Cavity and Paranasal Sinuses (2021)
  • Author(s): Suzuki Masanobu、Cooksley Clare、Suzuki Takayoshi、Ramezanpour Mahnaz、Nakazono Akira、Nakamaru Yuji、Homma Akihiro、Vreugde Sarah
  • Journal Title: Frontiers in Allergy Volume: 2 Pages: 1-11
  • DOI: 10.3389/falgy.2021.780425
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells (2021)
  • Author(s): Nakazono Akira、Nakamaru Yuji、Ramezanpour Mahnaz、Kondo Takeshi、Watanabe Masashi、Hatakeyama Shigetsugu、Kimura Shogo、Honma Aya、Wormald P. J.、Vreugde Sarah、Suzuki Masanobu、Homma Akihiro
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 11 Pages: 655666-655666
  • DOI: 10.3389/fcimb.2021.655666
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spontaneous regression of swollen submandibular glands in IgG4-related disease. (2019)
  • Author(s): Masanobu Suzuki, Yuji Nakamaru, Dai Takagi, Aya Honma, Takayoshi Suzuki, Emi Takakuwa, Shinya Morita, Sarah Vreugde, Akihiro Homma
  • Journal Title: Allergy and Rhinology Volume: 10
  • DOI: 10.1177/2152656718816738
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pseudomonas aeruginosa Exoprotein-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity. (2019)
  • Author(s): Li J, Ramezanpour M, Fong SA, Cooksley C, Murphy J, Suzuki M, Psaltis AJ, Wormald PJ, Vreugde S.
  • Journal Title: Front Cell Infect Microbiol. Volume: 9
  • DOI: 10.3389/fcimb.2019.00038
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sirtuin-1 Controls Poly (I:C)?Dependent Matrix Metalloproteinase 9 Activation in Primary Human Nasal Epithelial Cells (2018)
  • Author(s): Suzuki Masanobu、Ramezanpour Mahnaz、Cooksley Clare、Li Jian、Nakamaru Yuji、Homma Akihiro、Psaltis Alkis、Wormald Peter-John、Vreugde Sarah
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: 59 Issue: 4 Pages: 500-510
  • DOI: 10.1165/rcmb.2017-0415oc
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Mucosal zinc deficiency characterises nasal polyps and inhibits collagen production in nasal fibroblasts in vitro (2019)
  • Author(s): Masanobu Suzuki
  • Organizer: 5th Congress of European ORL-HNS
  • Int'l Joint Research
• [Presentation] MMP9 regulation by SIRT-1 in sinonasal epithelium. (2018)
  • Author(s): Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Jian Li, Yuji Nakamaru, Akihiro Homma, P.J. Wormald, and Sarah Vreugde
  • Organizer: 第119回日耳鼻総会
• [Presentation] MMP9 regulation in primary human nasal epithelial cells by activated innate immune system (2018)
  • Author(s): Masanobu Suzuki, Yuji Nakamaru, Dai Takagi, Aya Honma, Takayoshi Suzuki, Mahnaz Ramezanpour, Sarah Vreugde, and Akihiro Homma
  • Organizer: 第67回日本アレルギー学会
• [Presentation] SIRT-1 modifies MMP9 in primary nasal epithelial cells under inflammatory condition. (2018)
  • Author(s): Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Jian Li, Yuji Nakamaru, Akihiro Homma, P.J. Wormald, and Sarah Vreugde
  • Organizer: 37th Congress of the International Society of Inflammation and Allergy of the Nose
  • Int'l Joint Research
• [Book] Antibiofilm Strategies (2022)
  • Author(s): Katharina Richter, Kasper Norskov Kragh, Masanobu Suzuki et al.
  • Total Pages: 588
  • Publisher: Springer