Role of Staphylococcus aureus alpha-toxin and IL-22 in the pathogenesis of eosinophilic rhinosinusitis

• Project/Area Number: 25861562
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Okayama University
• Principal Investigator: Haruna Takenori 岡山大学, 大学病院, 医員 (70646182)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: IL-22 / 好酸球 / MUC１ / 副鼻腔炎 / 鼻茸 / アスピリ不耐 / 黄色ブドウ球菌 / 気道炎症 / MUC1 / アスピリン不耐 / マイクロアレイ / AHR / エンテロトキシン / αトキシン / サイトカイン / 溶血

Outline of Final Research Achievements

98.8% of Staphylococcus aureus detected in middle meatus of patients with chronic rhinosinusitis showed alpha-hemolysis, suggesting a high presence of alpha-toxin in the nose. Nasal polyp cells produced substantial amounts of IL-5, IL-13, IFN-gamma, IL-10 and IL-17A in response to alpha-toxin in ICAM-1 dependent manner. In addition, the polyp cells produced IL-22 in response to the toxin. Impairment of alpha-toxin-induced IL-10 production was associated with eosinophilic inflammation and lower airway obstruction. Furthermore, IL-22 induced MUC1 expression by nasal epithelial cells which was dependent on IL-22 receptor expression.

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] 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] 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] 慢性副鼻腔炎における黄色ブドウ球菌毒素の検出率の検討 (2015)
  • Author(s): 春名威範、岡野光博、檜垣貴哉、假谷伸、野山和廉、小山和久、金井健吾、藤原瑠美、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: 2015-02-28
• [Presentation] 慢性副鼻腔炎におけるIL-11の病態制御メカニズムの検討 (2014)
  • Author(s): 野山和廉、岡野光博、假谷伸、檜垣貴哉、春名威範、西﨑和則
  • Organizer: 第53回日本鼻科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-09-26
• [Presentation] 慢性副鼻腔炎における黄色ブドウ球菌毒素および鼻腔内細菌バイオフィルムについての検討 (2014)
  • Author(s): 春名威範、岡野光博、假谷伸、野山和廉、檜垣貴哉、金井健吾、小山貴久、西﨑和則
  • Organizer: 第32回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: ホテルクレメント徳島