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Development of a mouse model of eosinophilic chronic rhinosinusitis with nasal polyp by nasal instillation of an Aspergillus protease and ovalbumin

  • Rhinology
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Abstract

One subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by the development of a T-helper type 2 (Th2) response and eosinophilic infiltration. Here, we aimed to establish an eosinophilic CRSwNP murine model, which would be essential to understand the underlying pathogenesis and establish a treatment strategy. C57BL/6 mice were challenged intranasally with a mixture of an Aspergillus oryzae-derived protease (AP) and ovalbumin (OVA) for 6, 8, or 12 consecutive weeks (12 mice/group); control mice received the same volume of phosphate-buffered saline for 12 weeks (n = 12). Sinonasal samples were evaluated histologically, and interleukin (IL)-4, IL-5, IL-13, eotaxin, keratinocyte chemoattractant, and macrophage inflammatory protein-2 mRNA levels in sinonasal mucosa were measured by real-time PCR. Protein levels of Th2 cytokines, INF-γ, IL-17A, and chemokines in nasal lavage fluid, and total serum IgE were measured by ELISA. Greater eosinophil infiltration in the subepithelial layer was observed in the challenged groups, compared with the control group. Polypoid mucosal lesions were predominantly observed in the 12-week group, which also exhibited mucosal thickening on micro-CT scans. The IL-4, IL-5, and IL-13 mRNA and protein levels were elevated in the sinonasal mucosa and nasal lavage fluid. INF-γ and IL-17A were undetectable or not elevated relative to the control group levels. In contrast, eotaxin levels were particularly elevated in the sinonasal mucosa and nasal lavage fluid in the 12-week group. In conclusion, intranasal AP and OVA exposure successfully induced Th2-specific CRSwNP in a murine model.

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Eulji Medical Center, Eulji University School of Medicine, Seoul, Republic of Korea

    Ho Chan Kim

  2. Department of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea

    Ji Youn Lim, Seoyeon Kim, Ji Heui Kim & Yong Ju Jang

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  1. Ho Chan Kim
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  2. Ji Youn Lim
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  3. Seoyeon Kim
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  4. Ji Heui Kim
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Corresponding authors

Correspondence to Ji Heui Kim or Yong Ju Jang.

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Funding

This study was supported by Grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (2012R1A1A2020059) and the Ministry of Science, ICT, and Future Planning (2014R1A1A3050498).

Conflict of interest

The authors declare no potential conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study was approved by the Institutional Animal Care and Use Committee of the Asan Institute for Life Science (2015-12-012).

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Kim, H.C., Lim, J.Y., Kim, S. et al. Development of a mouse model of eosinophilic chronic rhinosinusitis with nasal polyp by nasal instillation of an Aspergillus protease and ovalbumin. Eur Arch Otorhinolaryngol 274, 3899–3906 (2017). https://doi.org/10.1007/s00405-017-4717-2

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  • DOI: https://doi.org/10.1007/s00405-017-4717-2

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