Role of cytokines and chemokines in otitis media.

• Project/Area Number: 16K20249
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Okayama University
• Principal Investigator: Noda Yohei 岡山大学, 大学病院, 助教 (00587404)
• Research Collaborator: KARIYA Shin
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 中耳炎 / 炎症 / サイトカイン / ケモカイン / 細菌 / 好酸球 / 免疫 / シグナル伝達

Outline of Final Research Achievements

The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a critical molecule mediating interleukin-1 (IL-1) responses. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein. However, the role of the NLRP3 inflammasome and HMGB1 in otitis media has not been fully examined. We examined in this study the expression of NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), caspase-1, and HMGB1 in the middle ear in lipopolysaccharide-induced otitis media. NLRP3, ASC, caspase-1, and HMGB1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear cavity. Lipopolysaccharide induces NLRP3 inflammasome components and HMGB1 in the middle ear. The NLRP3 inflammasome and HMGB1 may play an important role in the pathogenesis of otitis media. Modulation of inflammasome-mediated inflammation may be a novel therapeutic strategy for otitis media.

Academic Significance and Societal Importance of the Research Achievements

慢性中耳炎や真珠腫性中耳炎の患者から病的な中耳組織を採取し、それらを用いて中耳炎の炎症を制御している因子の解析を行った。現時点では、慢性中耳炎や真珠腫性中耳炎を薬物療法で根治させることは困難で、手術が必要となる症例が多く認められるが、本研究を発展させることにより、手術を回避できる新規治療法を開発できる基本的なデータが得られた。手術受けるには入院が必要となるケースが多く、薬物による外来治療で根治できるようになれば、社会的・経済的な意義が大きい。