Shixi Liu

Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma

BACKGROUND Nasal polyps often are associated with asthma. The phenotype of these patients is unknown. OBJECTIVE To identify the mucosal factors associated with asthma comorbidity, we analyzed the inflammatory patterns of nasal polyps. METHODS Nasal polyps from 70 Belgian patients, 34% with asthma, were analyzed for type of inflammation, T-cell cytokines, and IgE antibodies to Staphylococcus aureus enterotoxins. The same investigations were repeated in 93 Chinese patients with polyps, a group with a low asthma comorbidity rate (8%). RESULTS In Belgian patients with polyps, 54% of samples showed eosinophilic inflammation. A classification tree evaluation identified IL-5 as the main positive determinant. Enterotoxin IgE in tissue (37%) was associated with significantly increased total IgE and eosinophil cationic protein concentrations. Expression of enterotoxin IgE, total IgE at greater than 1,442 kU/L, and eosinophil cationic protein at greater than 17,109 μg/L in samples with a total IgE concentration of greater than 246 kU/L significantly predicted asthma (odds ratio, 5.8-13). Only 7.5% of the samples from Chinese patients with polyps showed eosinophilic inflammation. IL-5 was confirmed as a positive determinant of eosinophilic inflammation, and enterotoxin IgE in tissue (17% of patients) was associated with significantly increased total IgE and eosinophil cationic protein concentrations. The expression of IL-5 or total IgE at greater than 790 kU/L in samples with an IL-5 concentration of greater than 194 pg/mL significantly predicted comorbid asthma (odds ratio, 17.2-96). CONCLUSION Mucosal inflammation in nasal polyps orchestrated by T(H)2 cytokines and amplified by S aureus enterotoxins is characterized by an increased eosinophilic inflammation and formation of IgE antibodies. This phenotype is associated with comorbid asthma in white and Asian patients with nasal polyps.

Expression of TGF, matrix metalloproteinases, and tissue inhibitors in Chinese chronic rhinosinusitis

BACKGROUND To date there is no information on the expression of mediators associated with tissue remodeling in Asian patients with chronic rhinitis with (CRSwNP) or without (CRSsNP) nasal polyps. OBJECTIVES To study the expression of TGF-beta1, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), collagen, and regulatory T cells in Chinese patients with CRSwNP and CRSsNP. METHODS Thirty-six male and female subjects (12 patients with CRSwNP, 12 patients with CRSsNP, and 12 control subjects), age 17 to 60 years, were recruited into the study. Samples were collected from polyp and sinusoidal mucosal, ethmoidal mucosal, or inferior turbinate in the respective groups and assessed for TGF- beta1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 by immunoassay; collagen by histochemistry; and forkhead box P3 (FOXP3) mRNA by real-time PCR. RESULTS Patients with CRSwNP showed significantly lower concentrations of TGF-beta1, TIMP-1, TIMP-4, FOXP3, and collagen compared with patients with CRSsNP. Although there were no significant differences between the concentrations of MMP-7 and MMP-9 in patients with CRSwNP and CRSsNP, these were significantly increased compared with control patients. MMP-2 and TIMP-2 concentrations were not significantly different in any patient group, whereas TIMP-3 was not detectable. CONCLUSION Chronic rhinosinusitis with nasal polyps is characterized by a relative lack of TGF-ss expression versus CRSsNP. This finding may be causal for decreased collagen, TIMP-1/4, and FOXP3 expression in CRSwNP versus CRSsNP. TGF-ss serves as a main switch for different remodeling patterns in sinus disease.

The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps.

To To cite this article: Ba L, Zhang N, Meng J, Zhang J, Lin P, Zhou P, Liu S, Bachert C. The association between bacterial colonization and inflammatory pattern in Chinese chronic rhinosinusitis patients with nasal polyps. Allergy 2011; 66: 1296–1303.

The Development of Nasal Polyp Disease Involves Early Nasal Mucosal Inflammation and Remodelling

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by both a chronic inflammation and tissue remodelling; as indicated by extracellular matrix protein deposition, basement membrane thickening, goblet cell hyperplasia and subepithelial edema, with reduced vessels and glands. Although remodelling is generally considered to be consequence of persistent inflammation, the chronological order and relationship between inflammation and remodelling in polyp development is still not clear. The aim of our study was therefore to investigate the pathological features prevalent in the development of nasal polyps and to elucidate the chronological order and relationship between inflammation and remodelling, by comparing specific markers of inflammation and remodelling in early stage nasal polyps confined to the middle turbinate (refer to as middle turbinate CRSwNP) obtained from 5 CRSwNP patients with bilateral polyposis, mature ethmoidal polyps from 6 CRSwNP patients, and normal nasal mucosal tissue from 6 control subjects. Middle turbinate CRSwNP demonstrated significantly more severe epithelial loss compared to mature ethmoidal polyps and normal nasal mucosa. The epithelial cell junction molecules E-cadherin, ZO-1 and occludin were also expressed in significantly lower amounts in mature ethmoidal polyps compared to healthy mucosa. Middle turbinate CRSwNP were further characterized by significantly increased numbers of subepithelial eosinophils and M2 type macrophages, with a distinct lack of collagen and deposition of fibronectin in polyp part. In contrast, the turbinate area of the middle turbinate CRSwNP was characterized by an increase in TGF-β activated myofibroblasts expressing α-SMA and vimentin, an increase in the number of pSmad2 positive cells, as well as increased deposition of collagen. These findings suggest a complex network of processes in the formation of CRSwNP; including gross epithelial damage and repair reactions, eosinophil and macrophage cell infiltration, and tissue remodelling. Furthermore, remodelling appears to occur in parallel, rather than subsequent to inflammation.

Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis.

To cite this article: Liu F, Zhang J, Liu Y, Zhang N, Holtappels G, Lin P, Liu S, Bachert C. Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis. Allergy 2010; 65: 1149–1157.

Assessment of Sleep Impairment in Persistent Allergic Rhinitis Patients Using Polysomnography

Background: Although questionnaires have demonstrated an association between impairment of quality of sleep and symptoms in allergic rhinitis (AR) patients, to date there is no report of an objective assessment of sleep in patients with persistent allergic rhinitis (PER) as defined by ARIA guidelines. The aim of the present study was therefore to assess sleep disturbance in PER patients by polysomnography (PSG). Methods: Ninety-eight PER patients with moderate-to-severe nasal obstruction and 30 healthy volunteers were included in the study. All patients underwent PSG during nocturnal sleep to assess the presence and severity of sleep disorders. Peak nasal inspiratory flow (PNIF) was also measured to assess nasal resistance. Results: There were statistically significant, though clinically modest, differences between PER patients and healthy controls in most PSG parameters including sleep efficiency, arousal index, average SaO2, lowest SaO2, time spent with a saturation below 90%, and snoring time. Although the apnea-hypopnea index (AHI) was not significantly different between the 2 groups, 17 subjects (17.3%) in the PER group but none of the control subjects had an AHI >5. Patients with higher T5SS scores (12 ≤ T5SS ≤ 15) had a greater tendency to snore than did patients with lower scores (8 ≤ T5SS ≤ 11). Finally, PNIF in the PER group was significantly lower than in the control group. Weak correlations between the arousal index and PNIF, average SaO2, and PNIF were found. Conclusion: PSG showed modest changes in PER patients versus control subjects.

Effects of Bifidobacterium Breve Feeding Strategy and Delivery Modes on Experimental Allergic Rhinitis Mice

Background Different delivery modes may affect the susceptibility to allergic diseases. It is still unknown whether early intervention with probiotics would counteract this effect. Objectives The effect of different delivery modes on immune status and nasal symptoms was investigated on established allergic rhinitis (AR) mouse model. In addition, the immunoregulatory effects and mechanisms of different feeding manners with Bifidobacterium breve(B. breve) were examined. Methods Live lyophilized B. breve was orally administered to BALB/c mice born via vaginal delivery(VD) or cesarean delivery (CD) for 8 consecutive weeks, after which they were sensitized by ovalbumin(OVA) to establish experimental AR. Nasal symptoms, serum immunoglobulins, cytokines, splenic percentages of CD4+CD25+Foxp3+ regulatory T(Treg) cells and nasal eosinophil infiltration were evaluated. Results Compared with VD mice, mice delivered via CD demonstrated more serious nasal symptoms, higher concentrations of OVA-specific immunoglobulin (Ig) E, more nasal eosinophils and lower percentages of splenic CD4+CD25+Foxp3+Treg cells after establishing experimental AR. These parameters were reversed by administering B. breves hortly after birth. However, the effect of B. breve did not differ between different delivery modes. Conclusion CD aggravates the nasal symptoms of AR mice compared to VD. This is the first report that oral administration of B. breve shortly after birth can significantly alleviate the symptoms of AR mice born via both deliveries, probably via activation of the regulatory capacity of CD4+CD25+Foxp3+Treg cells.

Correlation between miR‐21 expression and laryngeal carcinoma risks: a meta‐analysis

To evaluate the expression and clinical significance of miR‐21 in the tissues of laryngeal carcinoma using meta‐analysis.

Correlation between mir-21 expression and laryngeal carcinoma risks.

To evaluate the expression and clinical significance of miR‐21 in the tissues of laryngeal carcinoma using meta‐analysis.

Vault RNAs partially induces drug resistance of human tumor cells MCF-7 by binding to the RNA/DNA-binding protein PSF and inducing oncogene GAGE6

Background Vault is the largest nonicosahedral cytosolic nucleoprotein particle, which is widely involved in induction of chemoresistance and lead to failure in long-term chemotherapy. Vault contains three different major vault proteins (MVPs) and four vault RNAs paralogues (vtRNAs, vtRNA1-1, vtRNA1-2, vtRNA1-3 and vtRNA2-1). Disruption of the MVPs do not induce hypersensitivity while expression of vtRNAs contributes to cells’ drug resistance, indicates that vtRNAs, but not MVPs play an important role in causing drug resistance. Polypyrimidine tract binding protein associated splicing factor (PSF) contributes to cell sensitivity to chemotherapy by its transcriptional activity, promotes us to figure out its potential association with vtRNAs. Methods We investigate the interaction between PSF and vtRNAs by electrophoretic mobility shift assays (EMSA) and RNA-immunoprecipitation (IP), and showed the binding between PSF and vtRNAs. Chromatin Immunoprecipitation (ChIP) was performed to detect the effects of vtRNAs on the interaction of PSF with GAGE6 promoter. The role of vtRNAs on chemoresistance in MCF-7 was detected by CCK-8 and EdU staining. The independent role of vtRNAs with MVP is detected by MVP or vtRNAs knockdown. Results The complex with vtRNA1-1 releases PSF, allowing transcription of GAGE6 to proceed. Then we showed that induction of GAGE6 caused drug resistance by promoting cell proliferation and colony formation in soft agar. Ectopic expression of shRNA targets to vtRNA1-1 further confirmed the role of vtRNA1-1 in regulating PSF transcriptional activity independent with the expression of MVP. By vtRNA1-1 or MVP knockdown, it is revealed that vtRNA1-1 caused chemoresistance independent of MVP. Furthermore, knockdown of GAGE6 does not cause drug resistance, indicates the GAGE6 is directly involved in cell proliferation, but not the drug resistance. Conclusion These results suggest that vtRNAs regulates cell proliferation, drug resistance, and possibly other physiological processes of humans, by complex formation with PSF.