Role of Macrophage Migration Inhibitory Factor in NLRP3 Inflammasome Expression in Otitis Media

• Kariya, Shin

• Okano, Mitsuhiro

• Zhao, Pengfei

• Maeda, Yukihide

• Kataoka, Yuko

• Higaki, Takaya

• Makihara, Seiichiro

• Nishihira, Jun

• Tachibana, Tomoyasu

• Nishizaki, Kazunori

抄録

Hypothesis: Macrophage migration inhibitory factor plays an important role in the expression of interleukin (IL)-1β and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in lipopolysaccharide-induced otitis media. Background: NLRP3 inflammasome and macrophage migration inhibitory factor are critical molecules mediating inflammation. However, the interaction between the NLRP3 inflammasome and macrophage migration inhibitory factor has not been fully examined. Methods: Wild-type mice and macrophage migration inhibitory factor gene-deficient (MIF−/−) mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline. The mice were sacrificed 24 hours after the injection. Concentrations of IL-1β, NLRP3, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain and a pyrin domain), and caspase-1 in the middle ear effusions were measured by enzyme-linked immunosorbent assay. Temporal bones were processed for histologic examination and immunohistochemistry. Results: In the immunohistochemical study using the wild-type mice, positive staining of macrophage migration inhibitory factor, NLRP3, ASC, and caspase-1 were observed in infiltrating inflammatory cells induced by lipopolysaccharide in the middle ear. The number of inflammatory cells caused by lipopolysaccharide administration decreased remarkably in the MIF−/− mice as compared with the wild-type mice. The concentrations of IL-1β, NLRP3, ASC, and caspase-1 increased in the lipopolysaccharide-treated wild-type mice. The MIF−/− mice with lipopolysaccharide had decreased levels of IL-1β, NLRP3, ASC, and caspase-1 as compared with the wild-type mice. Conclusion: Macrophage migration inhibitory factor has an important role in the production of IL-1β and the NLRP3 inflammasome. Controlling the inflammation by modulating macrophage migration inhibitory factor and the NLRP3 inflammasome may be a novel therapeutic strategy for otitis media.

収録刊行物

• Otology and Neurotology

  Otology and Neurotology 41 (3), 364-370, 2020-03

  Lippincott, Williams & Wilkins

キーワード

• Cytokine
• Infection
• Inflammation
• Interleukin
• NOD-like receptor
• Toll-like receptor

詳細情報

• CRID: 1050848650294881920
• NII論文ID: 120006886944
• NII書誌ID: AA1150514X
• ISSN: 15317129
• ISSN: 15374505
• DOI: 10.1097/mao.0000000000002537
• Web Site: https://ousar.lib.okayama-u.ac.jp/58553
• Web Site: https://journals.lww.com/10.1097/MAO.0000000000002537
• 本文言語コード: en
• 資料種別: journal article
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