Exploration of new treatment for intractable upper airway inflammatory diseases using functional immune complexes

• Project/Area Number: 26670742
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Okayama University
• Principal Investigator: Okano Mitsuhiro 岡山大学, 医歯(薬)学総合研究科, 准教授 (60304359)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 黄色ブドウ球菌 / プロテインA / IgG / IFN-γ / IL-10 / IL-5 / 単球 / 免疫複合体

Outline of Final Research Achievements

Functional immune complexes consisting of Staphylococcal protein A (SpA) from S. aureus and immunoglobulins regulate type 2 inflammatory reaction including IL-5 and IL-13 production via several mechanisms such as IL-10 release. In addition, SpA-IgG immune complexes induced an expression of anti-inflammatory molecule X on monocytes. An antagonist for molecule X reversed the inhibitory effect of SpA-IgG immune complexes on staphylococcal enterotoxin B-induced cytokine production by nasal polyp cells. These results suggest that the induction of molecule X is one of the major mechanisms how this functional immune complexes show anti-inflammatory effect on upper airway inflammation.

Research Products

• [Journal Article] IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression. (2016)
  • Author(s): Noyama Y, Okano M, Fujiwara T, Kariya S, Higaki T, Haruna T, Makihara S, Kanai K, Koyama T, Taniguchi M, Ishitoya J, Kanda A, Kobayashi Y, Asako M, Tomoda K, Nishizaki K.
  • Journal Title: Allergology International Volume: 印刷中
  • NAID: 130005308495
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effect of prostaglandin D2 on VEGF release by nasal polyp fibroblasts. (2016)
  • Author(s): Kanai K, Okano M, Fujiwara T, Kariya S, Haruna T, Omichi R, Makihara S, Hirata Y, Nishizaki K.
  • Journal Title: Allergology International Volume: 印刷中 Issue: 4 Pages: 414-419
  • DOI: 10.1016/j.alit.2016.03.003
  • NAID: 130005431326
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulatory effect of TLR3 signaling on staphylococcal enterotoxin-induced IL-5, IL-13, IL-17A and IFN-γ production in chronic rhinosinusitis with nasal polyps (2016)
  • Author(s): Okano M, Fujiwara T, Kariya S, Higaki T, Makihara S, Haruna T, Noyama Y, Koyama T, Omichi R, Orita Y, Miki K, Kanai K, Nishizaki K.
  • Journal Title: Allergology International Volume: 65 Issue: 1 Pages: 96-102
  • DOI: 10.1016/j.alit.2015.08.005
  • NAID: 130005290330
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pulmonary function in never-smoker patients with chronic rhinosinusitis. (2015)
  • Author(s): Kariya S, Okano M, Higaki T, Noyama Y, Haruna T, Nishizaki K.
  • Journal Title: International Forum of Allergy and Rhinology Volume: 5 Issue: 11 Pages: 990-995
  • DOI: 10.1002/alr.21628
  • Peer Reviewed / Open Access
• [Journal Article] Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps. (2015)
  • Author(s): Okano M, Fujiwara T, Kariya S, Haruna T, Higaki T, Noyama Y, Makihara SI, Kanai K, Nishizaki K.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: ━ Issue: 2 Pages: 343-350
  • DOI: 10.1016/j.jaci.2014.10.058
  • Peer Reviewed / Open Access
• [Journal Article] Chronic rhinosinusitis patients have decreased lung function. (2014)
  • Author(s): Kariya S, Okano M, Higaki T, Noyama T, Haruna T, Ishihara T, MakinoT, Onoda T, Nishizaki K.
  • Journal Title: International Forum of Allergy and Rhinology Volume: 4 Issue: 10 Pages: 828-833
  • DOI: 10.1002/alr.21370
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cellular responses to Staphylococcus aureus alpha-toxin in chronic rhinosinusitis with nasal polyps. (2014)
  • Author(s): Okano M, Fujiwara T, Kariya S, Higaki T, Haruna T, Matsushita O, Noda Y, Makihara S, Kanai K, Noyama Y, Taniguchi M, Nishizaki K.
  • Journal Title: Allergology International Volume: 63 Pages: 563-573
  • NAID: 130004705227
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pulmonary function in patients with chronic rhinosinusitis and allergic rhinitis. (2014)
  • Author(s): Kariya S, Okano M, Oto T, Higaki T, Makihara S, Haruna T, Nishizaki K.
  • Journal Title: Journal of Laryngology and Otology Volume: 128 Issue: 3 Pages: 255-262
  • DOI: 10.1017/s0022215114000450
  • Peer Reviewed / Open Access
• [Journal Article] Local expression of IL-17A is correlated with nasal eosinophilia and clinical severity in allergic rhinitis. (2014)
  • Author(s): Makihara S, Okano M, Fujiwara T, Noda Y, Higaki T, Miyatake T, Kanai K, Haruna T, Kariya S, Nishizaki K.
  • Journal Title: Allergy and Rhinology Volume: 5 Issue: 1 Pages: 22-27
  • DOI: 10.2500/ar.2014.5.0078
  • Peer Reviewed / Open Access
• [Presentation] Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps (2015)
  • Author(s): Mitsuhiro Okano
  • Organizer: International Symposium on Recent Advances in Rhinosinusitis and Nasal Polyposis
  • Place of Presentation: パナマシティ(パナマ)
  • Year and Date: 2015-10-23
  • Int'l Joint Research
• [Presentation] Crosstalk of Staphylococcus aureus-derived components and COX metabolism in the pathogenesis of CRS (2015)
  • Author(s): Mitsuhiro Okano, Takenori Haruna and Kengo Kanai
  • Organizer: Rhinology Research Forum in Asia
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2015-10-17
  • Int'l Joint Research / Invited
• [Presentation] Chronic rhinosinusitis and lung function (2015)
  • Author(s): Mitsuhiro Okano
  • Organizer: World Congress of Rhinology
  • Place of Presentation: サンパウロ（ブラジル）
  • Year and Date: 2015-04-30
  • Int'l Joint Research / Invited
• [Presentation] Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps (2015)
  • Author(s): Mitsuhiro Okano
  • Organizer: Korean International Congress of Otorhinolaryngology Head and Neck Surgery
  • Place of Presentation: ソウル（韓国）
  • Year and Date: 2015-04-24
  • Int'l Joint Research / Invited
• [Presentation] Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps (2015)
  • Author(s): Mitsuhiro Okano
  • Organizer: Asian Research Symposium in Rhinology
  • Place of Presentation: 北京（中国）
  • Year and Date: 2015-04-10
  • Int'l Joint Research / Invited
• [Presentation] 黄色ブドウ球菌プロテインA-免疫複合体による免疫制御 (2015)
  • Author(s): 岡野光博、假谷伸、檜垣貴哉、春名威範、野山和廉、小山和久、金井健吾、牧原靖一郎、西﨑和則
  • Organizer: 第33回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-26 – 2015-02-28
• [Presentation] 黄色ブドウ球菌コンポーネントによる好酸球性副鼻腔炎の制御-“黄色ブドウ球菌理論（Staph. aureus theory）- (2014)
  • Author(s): 岡野光博
  • Organizer: 第33回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-09-25 – 2014-09-27
• [Book] 今日の治療指針 (2016)
  • Author(s): 岡野光博
  • Total Pages: 2096
  • Publisher: 中山書店
• [Book] EBM 耳鼻咽喉科・頭頸部外科の治療 2015-2016 (2015)
  • Author(s): 岡野光博、金井健吾
  • Total Pages: 687
  • Publisher: 中外医学社
• [Patent(Industrial Property Rights)] インターロイキン10産生促進剤 (2015)
  • Inventor(s): 岡野光博、西﨑和則、藤原田鶴子
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-03-19
  • Overseas