Xin-Hao Zhang

Overexpression of miR-125b, a Novel Regulator of Innate Immunity, in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

RATIONALE Eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) represents a hard-to-treat subtype of CRS. OBJECTIVES To determine the pattern of expression and biologic role of microRNAs (miRNAs) in CRS, particularly in eosinophilic CRSwNP. METHODS Global miRNA expression in sinonasal mucosa from controls, CRS without nasal polyps (CRSsNP), and patients with eosinophilic CRSwNP was compared using miRNA microarrays. MiR-125b expression was detected by means of quantitative reverse-transcriptase polymerase chain reaction. The cellular localization of miR-125b was determined by in situ hybridization. MiR-125b functional assays were performed on airway epithelial cells and mice. MiR-125b expression regulation was studied by tissue and cell culture. MEASUREMENTS AND MAIN RESULTS CRSsNP and eosinophilic CRSwNP exhibited distinct miRNA expression profiles. MiR-125b was specifically up-regulated in eosinophilic CRSwNP. MiR-125b was mainly expressed by sinonasal and bronchial epithelial cells. EIF4E-binding protein 1 (4E-BP1) was identified as a direct target of miR-125b. MiR-125b mimic or inhibitor enhanced or decreased IFN-α/β production elicited by dsRNA in vitro or in vivo, respectively. 4E-BP1 expression was decreased, whereas IFN regulatory factor-7 and IFN-β expression was increased, in eosinophilic CRSwNP. IFN-β mRNA levels positively correlated with IL-5 mRNA levels and eosinophil infiltration in sinonasal mucosa. IFN-β stimulated B cell-activating factor of the tumor necrosis factor family production in airway epithelial cells. miR-125b could be induced by lipopolysaccharide, dsRNA, and IL-10. CONCLUSIONS The up-regulated expression of miR-125b may enhance type I IFN expression through suppressing 4E-BP1 protein expression in airway epithelial cells, which potentially contributes to mucosal eosinophilia in eosinophilic CRSwNP.

Expression of osteopontin in chronic rhinosinusitis with and without nasal polyps

Background:  Osteopontin (OPN) is a multifunctional 34‐kDa extracellular matrix protein that can influence the inflammatory process. However, the presence of OPN in human sinonasal mucosa and its roles in the inflammatory process of chronic rhinosinusitis (CRS) are not clear. This study investigated the expression of OPN in human sinonasal mucosa, its cytokine‐driven expression regulation, and its effect on cytokine production in sinonasal mucosa.

Clara cell 10-kDa protein expression in chronic rhinosinusitis and its cytokine-driven regulation in sinonasal mucosa

Background:  Clara cell 10‐kDa protein (CC10) is a multifunction protein with anti‐inflammatory and immunomodulatory effects; hence we compared the CC10 expression between chronic rhinosinusitis (CRS) patients with and without nasal polyps (NPs), analyzed its association with disease severity and response to surgery, and explored its regulation via cytokines.

Chronic rhinosinusitis with and without nasal polyps is associated with decreased expression of glucocorticoid-induced leucine zipper

Background Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid‐induced leucine zipper (GILZ) is a recently described anti‐inflammatory mediator.

Histological and immunological observations of bacterial and allergic chronic rhinosinusitis in the mouse

Background The purpose of this study was to elucidate histological and immunologic features of mouse models of bacterial chronic rhinosinusitis (BCRS) and allergic chronic rhinosinusitis (ACRS). Methods A BCRS mouse model was established using Streptococcus pneumoniae inoculation plus Merocel (Medtronic, Jacksonville, FL) ostiomeatal obstruction for 12 weeks. An ACRS mouse model was developed by means of ovalbumin (OVA) i.p. injection and subsequent repeated OVA intranasal challenge for 12 weeks. Histological changes of sinonasal mucosa of both models were examined by means of hematoxylin and eosin staining for general morphology and inflammatory cell, periodic acid-Schiff staining for goblet cell, and Masson-trichrome staining for collagen. Enzyme-linked immunosorbent assay was used to detect the concentrations of various cytokines in nasal lavage fluid. Results Polymorphonuclear neutrophil infiltration in lamina propria was more obvious in the BCRS model, whereas eosinophil infiltration was more apparent in the ACRS model. Significant goblet cell and subepithelial gland hyperplasia, subepithelial fibrosis, epithelial thickening, and mononuclear cell infiltration were shown in both models with more severe extent found in the ACRS model. Interleukin (IL)-6 and tumor necrosis factor alpha levels in NLF from both models were increased and peaked at 1 week. Interferon gamma levels were also up-regulated in both models but reached maximum at 1 week in the BCRS model and 4 weeks in the ACRS model. IL-8 (CXCL8) levels were only increased in BCRS mice and peaked at 1 week, whereas IL-5, IL-13, and eotaxin (CCL11) levels were only enhanced in ACRS mice and peaked at 1 week. The Th1/Th2 ratio in BCRS mice was significantly higher than that in ACRS mice (6.68 ± 2.33 versus 1.37 ± 0.86; p < 0.01). Conclusion Histological and immunologic features of BCRS and ACRS mouse models were similar to those of human noneosinophilic and eosinophilic CRS, respectively. BCRS and ACRS mouse models have distinct immunologic characteristics and are applicable for CRS research.

CD8(+) T cells with distinct cytokine-producing features and low cytotoxic activity in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

CD8+ T cells are important effectors of cell‐mediated immunity; however, their contribution to the pathogenesis of CRS is unclear.

MicroRNA in Chronic Rhinosinusitis and Allergic Rhinitis

Inflammatory upper airway diseases, particularly chronic rhinosinusitis (CRS) and allergic rhinitis (AR), have a high worldwide prevalence. CRS and AR involve sustained and exaggerated inflammation that is associated with marked changes in gene and protein expression under tight regulation. A novel group of gene expression regulators is a class of short single-stranded RNA molecules termed microRNAs (miRNAs). miRNAs can cause gene silencing through degradation of target mRNAs or inhibition of translation. Dysregulated expression of miRNAs has been shown in various human diseases, such as cancer, inflammatory skin and bowel diseases, rheumatoid arthritis, and asthma. Although studies of miRNAs in inflammatory upper airway diseases are relatively new and few, emerging evidence implicates an involvement of miRNAs in shaping the inflammation pattern in upper airways. The purpose of this review is to provide an overview on our current understanding of miRNA expression and function in CRS and AR, and to underscore the potential for clinical usage of miRNAs in CRS and AR.

Expression of microRNA machinery proteins in different types of chronic rhinosinusitis.

Dysregulation of microRNAs (miRNAs) has recently been shown in chronic rhinosinusitis (CRS), the biogenesis and function of which are modulated by miRNA machinery proteins. The expression of these proteins in inflammatory airway diseases is unclear. The aim of this study was to investigate the expression of miRNA machinery components in CRS.

Distinct mucosal immunopathologic profiles in atopic and nonatopic chronic rhinosinusitis without nasal polyps in Central China

The role of atopy to aeroallergens in chronic rhinosinusitis without nasal polyps (CRSsNP) remains unclear. This study aimed to investigate the mucosal immunopathologic characteristics of CRSsNP with and without atopy to inhalant allergens.

Deficiency in interleukin-10 production by M2 macrophages in eosinophilic chronic rhinosinusitis with nasal polyps: IL-10+ M2 macrophages in CRSwNP

M2 macrophages are characterized by high interleukin‐10 (IL‐10) expression and are critical for resolving inflammation. Although increased accumulation of M2 macrophages has been demonstrated in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly the eosinophilic type, their functional relevance in CRSwNP remains poorly understood.