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Chloroquine Treatment Suppresses Mucosal Inflammation in a Mouse Model of Eosinophilic Chronic Rhinosinusitis
- Source :
- Allergy, Asthma & Immunology Research
- Publication Year :
- 2020
- Publisher :
- The Korean Academy of Asthma, Allergy and Clinical Immunology and The Korean Academy of Pediatric Al, 2020.
-
Abstract
- Purpose The Toll-like receptor 9 (TLR9) signaling pathway is involved in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyposis. The aim of this study was to assess the therapeutic potential of the TLR9 pathway inhibitor chloroquine in CRS mice. Methods The expression of type I interferons (IFNs) in human CRS tissues was evaluated using quantitative polymerase chain reaction (qPCR), western blotting, and immunofluorescence. Mice were divided into 4 treatment groups: the control, nasal polyp (NP), chloroquine treatment (NP + Chlq), and dexamethasone treatment (NP + Dexa) groups. The effects of chloroquine on polyp formation and mucosal inflammation were examined by hematoxylin and eosin staining. The expression levels of type I IFN, B-cell activating factor (BAFF), TLR9, high mobility group box 1 (HMGB1), and proinflammatory cytokine expression levels were assessed using qPCR, western blot, or enzyme-linked immunosorbent assay. Results IFN-α and IFN-β mRNA levels were significantly higher in patients with eosinophilic NPs (EPs) than in healthy individuals or non-EP patients. The polyp score, epithelial thickness, mucosal thickness, and the number of eosinophils in nasal mucosa were significantly higher in the NP group compared with the control, NP + Chlq, and NP + Dexa groups. NP + Chlq or NP + Dexa significantly suppressed the induction of type I IFN and BAFF expression in the NP group; these treatments also significantly suppressed the induction of TLR9, HMGB1, interferon regulatory factors, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and Th cytokine expression in the NP group. The secreted levels of anti-dsDNA Immunoglobulin G (IgG) were significantly higher in the NP group than in the control, NP + Chlq, and NP + Dexa groups. There were significant positive correlations between BAFF and mRNA levels of IFN-α/β/the protein levels of anti-dsDNA IgG. Conclusions Chloroquine may be used for the treatment of patients with eosinophilic CRS.
- Subjects :
- Pulmonary and Respiratory Medicine
sinusitis
Immunology
models, animal
Mucous membrane of nose
Immunoglobulin G
Proinflammatory cytokine
03 medical and health sciences
rhinitis
0302 clinical medicine
therapeutics
medicine
Immunology and Allergy
030223 otorhinolaryngology
B-cell activating factor
Dexamethasone
nasal polyps
biology
business.industry
Interleukin
Chloroquine
Toll-like receptor 9
interferons
Real-time polymerase chain reaction
030228 respiratory system
biology.protein
Original Article
Tumor necrosis factor alpha
business
medicine.drug
Subjects
Details
- ISSN :
- 20927363 and 20927355
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Allergy, Asthma & Immunology Research
- Accession number :
- edsair.doi.dedup.....6aeb2929a7e25fbd79c56f073429f707