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Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model.

ABSTRACT: Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-?, and tumor necrosis factor (TNF)-? levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.

SUBMITTER: Shin SH

PROVIDER: S-EPMC7297365 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model.

Shin Seung-Heon SH Ye Mi-Kyung MK Lee Dong-Won DW Chae Mi-Hyun MH Choi Sung-Yong SY

PloS one 20200616 6

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 o ...[more]

PMID: 32544181

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Project description:PurposeThe 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.MethodsThe 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.ResultsIFN-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.ConclusionsChloroquine may be used for the treatment of patients with eosinophilic CRS.

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Dataset Information

Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model.

Publications

Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model.

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