Xiao-Bo Long

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.

Comparison of efficacy of mometasone furoate versus clarithromycin in the treatment of chronic rhinosinusitis without nasal polyps in Chinese adults.

Background Although both nasal steroids and macrolide antibiotics have been recommended for the treatment of chronic rhinosinusitis without nasal polyps (CRSsNPs), whether there is any difference in their clinical efficacy remains unexplored. In addition, few studies have investigated their clinical efficacy in a Chinese population living in China, who present distinct inflammatory patterns compared with white patients in western countries. This study compares the efficacy of mometasone furoate and clarithromycin treatment in CRSsNP in Chinese adults in a preliminary prospective, open-label, randomized trial. Methods Forty-three CRSsNP patients were randomized to receive mometasone furoate nasal spray at 200 μg (n = 21) or clarithromycin tablet at 250 mg (n = 22) once daily for 12 weeks. Patients were assessed before the treatment and after 4, 8, and 12 weeks after treatment. Subjective symptoms were scored on a visual analog scale. Endoscopy physical findings were scored according to Lanza-Kennedy scoring system. Moreover, smoking and atopic status and coexistence of allergic rhinitis (AR) and asthma were recorded. Results Before the treatment, no significant difference in symptoms and nasal endoscopic physical findings were found between mometasone furoate and clarithromycin group. As early as 4 weeks after dosing, a significant reduction of total symptom scores, nasal obstruction, headache, rhinorrhea and overall burden scores, and mucosal swelling and nasal discharge scores were observed in both groups. No significant difference in symptom or endoscopic scores was observed between these two groups at any posttreatment observation time point. The coexistence of AR was correlated with lower scores of mucosal edema and nasal secretion in the mometasone furoate group after 12-week treatment. Conclusion Mometasone furoate and clarithromycin show a comparable clinical effect for CRSsNPs in Chinese adults. Mometasone furoate is more effective in improving edema and secretion for CRSsNP patients with concomitant AR.

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.

The cytokine-driven regulation of secretoglobins in normal human upper airway and their expression, particularly that of uteroglobin-related protein 1, in chronic rhinosinusitis

BackgroundThe involvement of secretoglobins (SCGBs) other than SCGB1A1 (Clara cell 10-kDa protein, CC10) in human airway diseases remains unexplored. Among those SCGBs, SCGB3A2 (uteroglobin-related protein 1, UGRP1) is particularly interesting, given its structure and function similarities with SCGB1A1 (CC10). The aim of this study was to investigate the expression regulation of SCGBs other than SCGB1A1 (CC10) in human upper airway, and their potential involvement, particularly that of SCGB3A2 (UGRP1), in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP).MethodsEight SCGB family members including SCGB3A2 (UGRP1), SCGB1C1 (ligand binding protein RYD5), SCGB1D1 (lipophilin A), SCGB1D2 (lipophilin B), SCGB1D4 (interferon-γ inducible SCGB), SCGB2A1 (mammaglobin 2), SCGB2A2 (mammaglobin 1), and SCGB3A1 (uteroglobin-related protein 2) were studied. The regulation of SCGBs mRNA expression in normal nasal mucosa by proinflammatory, Th1, and Th2 cytokines was studied through nasal explant culture. SCGBs mRNA expression levels in CRSsNP and CRSwNP patients and controls were compared. The mRNA levels were detected by means of quantitative reverse transcriptase-polymerase chain reaction. The protein expression of SCGB3A2 (UGRP1) was analyzed using immunohistochemistry.ResultsThe expression of SCGBs except SCGB1D2 (lipophilin B) could be found in upper airway and be differentially regulated by different cytokines. SCGB3A2 (UGRP1) mRNA expression was induced by Th1 cytokine, but suppressed by proinflammatory and Th2 cytokines. SCGBs mRNA expression was altered in CRS; particularly, SCGB3A2 (UGRP1) protein and mRNA expression was markedly decreased in both CRSsNP and CRSwNP and its protein levels inversely correlated with the number of total infiltrating cells, preoperative sinonasal CT scores, and postoperative endoscopy and symptom scores.ConclusionSCGBs except SCGB1D2 (lipophilin B) are expressed in human upper airway and their expression can be differentially regulated by inflammatory cytokines. SCGBs mRNA expression is altered in CRS. Reduced production of UGRP1, which is likely due, at least in part, to a local cytokine environment, may contribute to the hyper-inflammation in CRS and correlates with response to surgery.

Clara Cell 10-kDa Protein Gene Transfection Inhibits NF-κB Activity in Airway Epithelial Cells

Background Clara cell 10-kDa protein (CC10) is a multifunctional protein with anti-inflammatory and immunomodulatory effects. Induction of CC10 expression by gene transfection may possess potential therapeutic effect. Nuclear factor κB (NF-κB) plays a key role in the inflammatory processes of airway diseases. Method/Results To investigate potential therapeutic effect of CC10 gene transfection in controlling airway inflammation and the underlying intracellular mechanisms, in this study, we constructed CC10 plasmid and transfected it into bronchial epithelial cell line BEAS-2B cells and CC10 knockout mice. In BEAS-2B cells, CC10s effect on interleukin (IL)-1β induced IL-8 expression was explored by means of RT-PCR and ELISA and its effect on NF-κB classical signaling pathway was studied by luciferase reporter, western blot, and immunoprecipitation assay. The effect of endogenous CC10 on IL-1β evoked IL-8 expression was studied by means of nasal explant culture. In mice, CC10s effect on IL-1β induced IL-8 and nuclear p65 expression was examined by immunohistochemistry. First, we found that the CC10 gene transfer could inhibit IL-1β induced IL-8 expression in BEAS-2B cells. Furthermore, we found that CC10 repressed IL-1β induced NF-κB activation by inhibiting the phosphorylation of IκB-α but not IκB kinase-α/β in BEAS-2B cells. Nevertheless, we did not observe a direct interaction between CC10 and p65 subunit in BEAS-2B cells. In nasal explant culture, we found that IL-1β induced IL-8 expression was inversely correlated with CC10 levels in human sinonasal mucosa. In vivo study revealed that CC10 gene transfer could attenuate the increase of IL-8 and nuclear p65 staining in nasal epithelial cells in CC10 knockout mice evoked by IL-1β administration. Conclusion These results indicate that CC10 gene transfer may inhibit airway inflammation through suppressing the activation of NF-κB, which may provide us a new consideration in the therapy of airway inflammation.

Multidimensional endotypes of chronic rhinosinusitis and their association with treatment outcomes

The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.

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.