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Aberrant localization of FOXJ1 correlates with the disease severity and comorbidities in patients with nasal polyps.

ABSTRACT: Background:Upper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs). Methods:We elucidated localization patterns of FOXJ1 by performing immunofluorescence assays in nasal specimens and cytospin samples from controls and patients with NPs. We also assayed mRNA expression levels of FOXJ1 by using quantitative real-time polymerase chain reaction. Four localization patterns [normal (N), intermediate (I), mislocalization (M), and absence (A)] were defined. A semi-quantitative scoring system was applied for demonstrating FOXJ1 localization in five areas per paraffin section, with individual sections being scored between 0 and 2. Results:FOXJ1 localization score was significantly higher in samples from NPs than in controls (P?

SUBMITTER: Peng Y

PROVIDER: S-EPMC6234688 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Aberrant localization of FOXJ1 correlates with the disease severity and comorbidities in patients with nasal polyps.

Peng Yang Y Guan Wei-Jie WJ Tan Kai Sen KS Zhu Zhenchao Z Chen Zhuo Z Hong Haiyu H Wang Zhaoni Z Tian Tengfei T Zi Xiaoxue X Ong Yew Kwang YK Thong Mark M Shi Li L Yang Qintai Q Qiu Qianhui Q Wang De-Yun DY

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 20181114

<h4>Background</h4>Upper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs).<h4>Methods</h4>We elucidated localization patterns of FOXJ1 by performing immunofluorescence assays in nasal specimens and cytospi ...[more]

PMID: 30459817

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Project description:Background:Eosinophilic inflammation is a major phenotype associated with poorly controlled disease in nasal polyp patients. The difference between systemic and local eosinophilia in relation to disease control is poorly understood. Objective:To explore whether blood and polyp tissue eosinophil numbers are independent risk factors for poor disease control in patients with nasal polyp. Methods:By using the electronic medical records database and manual evaluation, 183 nasal polyp patients who had undergone endoscopic sinus surgery at least one year prior to the study with complete data of tissue specimens, baseline blood routine test, nasal endoscopy and sinus computed tomography, were identified and recruited to assess disease control based on the criteria of a European position paper on rhinosinusitis and nasal polyps 2012 (EPOS 2012). Multiple logistic regression model was used to determine the association between blood and tissue eosinophil numbers and risk of poor disease control by adjusting for demographics and comorbidities. Results:We broke down the cohort into 4 groups according to blood (0.3 ?× ?109/L) and tissue (10%) eosinophils. The patients without eosinophilic inflammation represented the largest group (41.5%). The group with concordant blood and tissue eosinophilia represented the second largest (31.2%), and the patients with isolated tissue (15.3%) or blood (12.0%) eosinophilia were relatively rare. Multiple logistic regression models found blood eosinophil count and tissue eosinophil percentage were independently associated with increased risk for poor disease control after adjustments for covariates related to poor treatment outcome. Furthermore, subjects with concordant blood and tissue eosinophilia had a higher risk for poor disease control than those with isolated blood or tissue eosinophilia. Conclusion:Concordant blood and tissue eosinophilia relates to a higher likelihood of poor disease control than isolated blood or tissue eosinophilia after adjustment of potential confounders in nasal polyp patients.

Project description:Background and objectivesInterleukin 10 (IL-10) is a potent anti-inflammatory cytokine. The dysregulation of IL-10 is associated with an enhanced immunopathologic response to infection, as well as with an increased risk for developing numerous autoimmune diseases. In this study, we investigated IL-10 expression in chronic rhinosinusitis with nasal polyps (CRSwNP) and assessed the possible role of IL-10 in the pathogenesis of CRSwNP.Materials and methodsThirty-five patients with CRSwNP, 12 patients with chronic rhinosinusitis without NP (CRSsNP) and 10 control subjects were enrolled in this study. NP tissues and uncinated tissues (UT) were collected for analysis. Dispersed NP cells (DNPCs) were cultured in the presence or absence of IL-25 and IL-10, and a flow cytometric assay was performed to identify the constitutive cell populations of the DNPCs. Murine NP (n = 18) models were used for the in vivo experiments. Real-time PCR, immunohistochemistry, western blotting analysis and ELISA were performed to measure the expression levels of the selected inflammatory cytokines and inflammation-associated molecules.ResultsThe mRNA expression levels of IL-10, IL-5, IL-17A, IL-25 and interferon gamma (IFN-γ) were significantly higher in the NP tissues than in the UT tissues. Strong positive correlations were observed between IL-10 and a variety of inflammatory cytokines (IL-5, IL-17A, IL-25, IFN-γ) and inflammation-associated molecules (B-cell activating factor; BAFF, CD19). Other than the IL-25 to IL-10 ratio, the expression ratios of the other measured inflammatory cytokines to IL-10 were significantly lower in the CRSwNP group than in the CRSsNP or control groups. Administrating IL-25 into the cultured DNPCs significantly increased the production of IL-10, but administrating IL-10 had no effect on the production of IL-25.ConclusionIncreased expression of IL-10, IL-10 related inflammatory cytokine, and IL-10 related B cell activation indicated that IL-10, a potent anti-inflammatory cytokine, has a pivotal role in the pathogenesis of CRSwNPs.

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Aberrant localization of FOXJ1 correlates with the disease severity and comorbidities in patients with nasal polyps.

Publications

Aberrant localization of FOXJ1 correlates with the disease severity and comorbidities in patients with nasal polyps.

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