Yong-Hua Cui

Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese

BACKGROUND Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is reported to be different in inflammatory patterns of the sinonasal mucosa in white patients. Studies in nonwhite populations may further be helpful to understand the pathogenic mechanisms of CRS. OBJECTIVE To investigate the immunopathologic profiles of CRSwNP and CRSsNP in adult Chinese. METHODS Histologic characteristics of surgical samples were analyzed in 50 controls, 94 CRSsNP patients, and 151 CRSwNP patients. Tissue samples from 17 controls, 36 CRSsNP patients, and 45 CRSwNP patients were stained for CD3, CD4, CD8, CD20, CD68, myeloperoxidase, and dendritic cell lysosome-associated membrane protein. Expression profiles of transcription factors of T-cell subsets in relation to cytokines and a marker of natural killer T cell (Valpha24) were examined by means of quantitative RT-PCR. RESULTS Over half of CRSwNP patients presented noneosinophilic inflammation. CRSwNP had a higher number of eosinophils, plasma cells, and CD3(+), CD8(+), CD20(+), and CD68(+) cells and a lower myeloperoxidase expression rate than CRSsNP. Expression levels of transcription factors and cytokines of T(H)1/T(H)2/T(H)17 were increased, whereas the expression rate of Forkhead box p3 and TGF-beta1 was decreased in both CRSsNP and CRSwNP compared with controls. Comparing CRSsNP and CRSwNP, CRSsNP had higher levels of IFN-gamma expression, whereas only eosinophilic CRSwNP demonstrated an enhanced expression of GATA-3 and IL-5. Compared with noneosinophilic CRSwNP, an exaggerated T(H)2/T(H)17 reaction and Valpha24 expression were found in eosinophilic CRSwNP. CONCLUSION Both Chinese CRSsNP and CRSwNP patients demonstrate impaired regulatory T cell function and enhanced T(H)1/T(H)2/T(H)17 responses. CRSsNP is confirmed to be a predominant T(H)1 milieu, whereas T(H)2 skewed inflammation with predominant T(H)17 reactions, and infiltration of natural killer T cells can be demonstrated only in eosinophilic CRSwNP, but not in noneosinophilic CRSwNP.

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.

Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns

The remodeling patterns in different types of chronic rhinosinusitis (CRS) have rarely been compared, particularly the difference between eosinophilic and noneosinophilic CRS with nasal polyps (CRSwNP). Moreover, whether there is a link between remodeling and inflammation remains controversial.

Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults.

Over half of chronic rhinosinusitis with nasal polyps (CRSwNP) patients in China show noneosinophilic inflammation. The aim of this study was to compare the clinical characteristics of eosinophilic and noneosinophilic CRSwNP and to identify the predictors of 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.

Group II subfamily secretory phospholipase A2 enzymes : expression in chronic rhinosinusitis with and without nasal polyps

Background:  Group II subfamily secretory phospholipases A2 (sPLA2s) are the enzymes that can play a major role in inflammation. However, the presence of group II subfamily sPLA2s in human sinonasal mucosa and their roles in chronic rhinosinusitis (CRS) are not well known. The purpose of this study was to investigate the expression of group II subfamily sPLA2s in human sinonasal mucosa from controls and CRS patients with and without nasal polyps (NPs) and the regulation of expression by proinflammatory cytokines.

The expression of osteopontin and its association with Clara cell 10-kDa protein in allergic rhinitis

Background Osteopontin (OPN) is a multifunctional protein that has recently been linked to allergic diseases. Clara cell 10 kDa protein (CC10) is another protein linked to allergy, and has been suggested to have an inhibitory role in inflammatory airway diseases. At this time, it is not known whether OPN is involved in allergic rhinitis (AR) or if there is any association between CC10 and OPN in AR.