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Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a serious inflammatory condition. Nasal fluids (NFs) present a noninvasive alternative to nasal biopsy for studying CRSwNP pathogenesis. We aimed to compare the protein and mRNA inflammation signature between nasal polyps (NPs) and NFs. Method: The performance of polyvinyl alcohol (PVA) sponges and NFs absorbable device (NFAD) for collecting NFs from 20 patients with CRSwNP was compared using the Luminex assay. The other group consisted of four healthy controls and an additional 21 CRSwNP patients (including eosinophilic CRSwNP [ECRSwNP] and non-eosinophilic CRSwNP [NECRSwNP]) for protein quantification by Olink platform and gene expression evaluation by RNA-sequencing. Spearman's analysis was performed to detect correlations between protein expression levels in NFs and clinical assessment variables. Results: NFAD-collected NFs contained at least a 2-fold higher concentration of cytokines than that obtained using PVA sponge, and these cytokines levels are significantly associated with NPs (ρ > 0.45, p < 0.05). Differentially expressed proteins between NFs and NPs were significantly correlated in the ECRSwNP subgroup compared with controls (ρ = 0.41, p < 0.01). Levels of Th2/IL-13, MCP4, and CCL4, characteristic of eosinophilic infiltration, were increased in ECRSwNP patients. A significant correlation between gene and protein expression was observed (ρ = 0.34, p < 0.01). PDL2 levels in NFs were positively correlated with ECRSwNP postoperative recurrence, the nasal VAS, and SNOT-22 scores (ρ > 0.68, p < 0.05 for all). Conclusion: Our study revealed similarities and discrepancies in inflammatory signatures between NPs and NFs in the same CRSwNP patient. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy (AIT) is the only etiological and potentially curative therapy for allergic rhinitis (AR). Objectives: We sought to investigate the role of epigenetic regulator enhancer of zeste homolog 2 (EZH2) in the activation of dendritic cells (DCs) in AIT. Method: In this study, EZH2 expression in circulating myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were evaluated using flow cytometry. Clinical information from 56 AR patients receiving AIT was collected, including 30 subjects with subcutaneous immunotherapy (SCIT) and 26 subjects with sublingual immunotherapy (SLIT). In vitro, the effect of EZH2 inhibitor, 3 Deazaneplanocin A (DZNep), on the phenotypic and functional activation of monocyte-derived DCs (moDCs) was evaluated. Results: EZH2 expression in circulating mDCs and pDCs were both negatively correlated to treatment time of AIT (r = –0.39, p = 0.003 and r = –0.47, p = 0.0002, respectively). Furthermore, there was a higher correlation between EZH2 expression and AIT treatment time in the SCIT group compared to that of the SLIT group in mDCs (r = –0.42, p = 0.02 vs. r = –0.23, p = 0.26)and pDCs (r = –0.52, p = 0.003 vs. r = –0.33, p = 0.10). In vitro, the co-stimulatory molecules on moDCs, such as CD80, CD86, and CD83, were significantly inhibited by DZNep in a dose-dependent manner. The -DC-driven T-cell proliferation was suppressed by DZNep (MD = 22.88, 95% CI 7.809–37.96, p < 0.05). Conclusions: Our study shows that EZH2, which is required in the activation of DCs, mediates the epigenetic modification in AIT and stresses the importance of patient adherence during AIT. [ABSTRACT FROM AUTHOR]

The T helper 2 (Th2)-type response was considered the hypostasis of allergic airway diseases, including asthma and allergic rhinitis (AR). However, more recent studies have suggested that allergic airway inflammation also depends on innate immunity and is closely related to group 2 innate lymphoid cells (ILC2s). This study evaluated the ILC2 levels of asthma subjects, patients with asthma and AR, and healthy individuals, regarding how to investigate the relationship between clinical data and ILC2 levels. It was found that asthma patients and asthma with AR patients had higher ILC2 levels compared to healthy subjects. ILC2s were positively correlated with the percentage of eosinophils in patients with asthma and AR, but not with pulmonary function. ILC2 levels were higher in mild asthma subjects than in patients with severe asthma. This study provides a new interpretation of the pathogenesis of allergic airway inflammation and may provide a new direction for the diagnosis and assessment of allergic airway diseases. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the possible mechanism of osteopontin (OPN) in the tumor progression of nasopharyngeal carcinoma (NPC). Methods: Twenty NPC specimens and 10 normal biopsy specimens were analyzed, and the expression of OPN and enhancer of zeste homolog 2 (EZH2) was examined by immunohistochemical staining. Moreover, the expression of EZH2 in NPC cell lines was examined using quantitative reverse transcription polymerase chain reaction and Western blot analysis in the presence of recombinant human (rh) OPN and specific inhibitors. NPC cell migration and invasion were evaluated using a transwell chamber in the presence of rhOPN and/or EZH2 siRNA. Results: The immunoreactivity of OPN and EZH2 was significantly enhanced in NPC specimens compared with the normal controls (p < 0.05). EZH2 expression in NPC specimens was significantly associated with OPN expression and tumor stage (p < 0.05). Moreover, rhOPN significantly stimulated EZH2 expression in the NPC cell line through a MAPK-mediated pathway and significantly stimulated migration and invasion of the NPC cell line (p < 0.05), which was notably inhibited by EZH2 siRNA transfection (p < 0.05). Conclusion: Our findings suggest that OPN may promote tumor progression of NPC through an EZH2-dependent pathway. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To evaluate the possible mechanism of osteopontin (OPN) in the tumor progression of nasopharyngeal carcinoma (NPC). Methods: Twenty NPC specimens and 10 normal biopsy specimens were analyzed, and the expression of OPN and enhancer of zeste homolog 2 (EZH2) was examined by immunohistochemical staining. Moreover, the expression of EZH2 in NPC cell lines was examined using quantitative reverse transcription polymerase chain reaction and Western blot analysis in the presence of recombinant human (rh) OPN and specific inhibitors. NPC cell migration and invasion were evaluated using a transwell chamber in the presence of rhOPN and/or EZH2 siRNA. Results: The immunoreactivity of OPN and EZH2 was significantly enhanced in NPC specimens compared with the normal controls (p < 0.05). EZH2 expression in NPC specimens was significantly associated with OPN expression and tumor stage (p < 0.05). Moreover, rhOPN significantly stimulated EZH2 expression in the NPC cell line through a MAPK-mediated pathway and significantly stimulated migration and invasion of the NPC cell line (p < 0.05), which was notably inhibited by EZH2 siRNA transfection (p < 0.05). Conclusion: Our findings suggest that OPN may promote tumor progression of NPC through an EZH2-dependent pathway. [ABSTRACT FROM AUTHOR]