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A murine model of eosinophilic chronic rhinosinusitis using the topical application of a vitamin D3 analog
- Source :
- Allergy. 76:1432-1442
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Background Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T-helper type 2 (Th2-type) response, and olfactory dysfunction. A master regulator of Th2-type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP-elicited basophils are a key factor in the pathogenesis of ECRS. Methods In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP-induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2-type inflammation was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). Results Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real-time PCR and ELISA revealed elevated expression of interleukin (IL)-4, IL-5, IL-13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice. Conclusions Our model of ECRS displayed Th2-type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS.
- Subjects :
- 0301 basic medicine
Thymic stromal lymphopoietin
Immunology
Mucous membrane of nose
Basophil
Mice
03 medical and health sciences
Nasal Polyps
0302 clinical medicine
Eosinophilia
Eosinophilic
Animals
Immunology and Allergy
Medicine
Sinusitis
CCL11
Cholecalciferol
Rhinitis
business.industry
respiratory system
Eosinophil
Eosinophils
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
030228 respiratory system
Chronic Disease
Cytokines
business
CCL24
Olfactory epithelium
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 13989995 and 01054538
- Volume :
- 76
- Database :
- OpenAIRE
- Journal :
- Allergy
- Accession number :
- edsair.doi.dedup.....e803153489b4cad3c4a660b4ca76add1