Tian Ying Li

Role of p63/p73 in epithelial remodeling and their response to steroid treatment in nasal polyposis

BACKGROUNDnNasal polyposis (NP) is recognized as aberrant epithelial remodeling, but the molecular mechanism underlying this process is poorly understood. Two important p53 homologues (p63 and p73) play a key role in orchestrating the epithelial development.nnnOBJECTIVEnWe intended to study whether p63 and p73 are involved in the epithelial remodeling seen in patients with NP and their response to oral glucocorticosteroid (GC) treatment.nnnMETHODSnNasal polyp tissues were obtained from 65 patients, and inferior turbinates were obtained from 19 control subjects without NP. Among patients with NP, 20 were treated with oral prednisone, so that 2 sets of polyp biopsy specimens were taken before (GC naive) and after (GC treated) treatment. Immunohistochemistry and quantitative PCR were performed to determine the expression levels of p63 and p73.nnnRESULTSnThe increase in p63-positive cell numbers was significant in GC-naive NP epithelium (46%) compared with that seen in control epithelium (5%), and it was positively related to the epithelial hyperplasia in patients with NP. The increase in N-terminal transactivation domain p73-positive cell numbers was found in 27% of GC-naive patients with NP and 16% of control subjects, with no statistical difference. The mRNA expression of both p63 and p73 was significantly upregulated in GC-naive patients with NP versus control subjects, and a positive correlation between the p63 and p73 mRNAs was found in all nasal tissues. Furthermore, the improvement of epithelial structure and reduction of p63 mRNA/protein levels were found in patients with NP after GC treatment.nnnCONCLUSIONSnOur results suggest that the ectopic expression of p63 in multiple cell layers is an important pathologic phenomenon in the epithelial remodeling seen in chronically inflamed airway epithelium (eg, in patients with NP), and its aberrant expression can be suppressed with GC treatment.

Oral steroids enhance epithelial repair in nasal polyposis via upregulation of the AP-1 gene network

Background: Chronic mucosal inflammation, epithelial damage and aberrant tissue remodelling are common features in nasal polyposis (NP). A study was undertaken to characterise the gene expression profile in NP tissues and to explore the molecular mechanisms underlying the ameliorative effects of glucocorticosteroids (GCs) in NP. Methods: Two sets of NP biopsies (before and after GC treatment) were taken from 10 patients with untreated (GC-naïve) bilateral NP. Biopsy specimens of inferior turbinate from 6 patients who underwent surgery for nasal septal deviation served as nasal mucosal controls. DNA microarrays containing 38u2009500 genes were used to characterise the global gene expression profile. Functional network analysis was applied to identify the key molecular pathways and genes in response to GC treatment (GC-treated). Selected genes were retested by quantitative RT-PCR and immunohistochemistry in the same polyps and control samples. Results: 64 genes were differentially expressed in GC-treated vs GC-naïve NP tissues. The highest scoring network was assembled around activation protein 1 (AP-1), a heterodimer of c-Fos and c-Jun oncoprotein, and five AP-1-related genes (COX-2, IL-6, AREG, HBEGF and EGR1) with tissue repair function. Quantitative PCR confirmed that AP-1 and its related genes were markedly repressed in GC-naïve polyps and were upregulated after GC treatment. Immunohistochemical staining indicated that epithelial restitution in GC-treated polyps was associated with increased expression of c-Jun protein. Conclusions: Oral steroids promote epithelial repair in NP via upregulation of the AP-1 (especially c-Jun) network and its related genes.

In vivo and in vitro studies of Th17 response to specific immunotherapy in house dust mite-induced allergic rhinitis patients.

T helper (Th)17 cells have been implicated in the development of allergic rhinitis (AR), but their response to specific immunotherapy (SIT) remains unclear. We investigated the impact of SIT on Th17 response and Th1/Th2 changes in AR patients. Blood samples from AR patients (nu200a=u200a20) who were monosensitized to house dust mite (HDM) were collected before the initiation of SIT (SIT-untreated) and after the end of 2-year SIT (SIT-treated) treatment. Twenty healthy volunteers were recruited as controls. In vitro HDM stimulation in peripheral blood mononuclear cells (PBMCs) was also performed. Expression levels of Th17 associated genes were determined in both PBMCs and plasma by PCR and ELISA, while Th17/Th1/Th2/IL10 producing cell proportions were evaluated in PBMCs by flow cytometry. The SIT effect was evaluated by assessing clinical symptoms. mRNA levels of Th17 specific genes (IL17 and RORC) were increased in SIT-untreated AR versus controls, and decreased following SIT treatment. SIT can change the production of Th17 associated genes (reduction of IL17, IL6, and IL23, but increase of IL27) in plasma from AR patients. Th2/Th1 ratio and proportions of Th17 cells were suppressed while IL10 producing CD4+ T cells were elevated after SIT. In vitro HDM challenge presents concordant patterns with in vivo findings: 1) increase of Th2 and Th17 response in AR patients; 2) suppression of IL10 producing CD4+ T cells in SIT-untreated AR but elevation in SIT-treated AR patients. Most importantly, a positive correlation between IL17 mRNA/protein levels and clinical symptom scores was observed. SIT significantly inhibits Th17 mediated inflammation in AR and IL17 may be a useful biomarker for both AR severity and SIT therapeutic effect. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000445774

Down-regulation of EMP1 is associated with epithelial hyperplasia and metaplasia in nasal polyps.

The aim of this study was to assess protein and mRNA expression of epithelial membrane protein 1 (EMP1) in the nasal mucosa of patients with nasal polyps (NP), and to determine what changes occur in response to glucocorticosteroid (GC) treatment.

Epidemiological characterization and risk factors of allergic rhinitis in the general population in Guangzhou City in china.

The prevalence of allergic rhinitis (AR) in China has increased with an apparent geographic variation. The current study aims to investigate the AR prevalence/classification, diagnosis/treatment conditions, trigger factors, and risk factors in the general population of Guangzhou, the third biggest city in China. A cross-sectional survey was performed in the citizens in Guangzhou from December 2009 to March 2010 by using a stratified multistage cluster sampling method. All subjects were asked to complete a comprehensive questionnaire via a face to face interview. A total of 9,899 questionnaires were valid. The prevalence rate of AR in the general population of Guangzhou was 6.24%, with a significant higher prevalence in urban area (8.32%) versus rural area (3.43%). Among the AR subjects, most (87%) were diagnosed with intermittent AR and 87% suffered from moderate-severe symptoms. High percentages of the AR patients did not have previously physician-based diagnosis (34%) or specific medical treatment (55%). Morning time, winter season, and cold air were the most common trigger factors of AR. Family history of AR, current living place, living place during babyhood, smoking, home renovation, and pet ownership were the significant risk factors associated with AR prevalence in the population. The study demonstrated comprehensive epidemiological and clinical information about the AR in Guangzhou population. Change of living environment and lifestyles had strong impacts on the prevalence of AR. Public health policies should help the patients benefit from a proper diagnosis/treatment and specifically target the local risk factors, in order to control the AR incidence.

Long-term Efficacy of Specific Immunotherapy on House Dust Mite–Induced Allergic Rhinitis in China

Objective Although the effect of specific immunotherapy (SIT) on allergic rhinitis (AR) has been well documented in developed countries, its long-term efficacy in patients in developing countries (such as China) is poorly understood. This study investigated the long-term therapeutic and preventive effects of SIT on house dust mite (HDM)–induced AR in patients from China. Design Historical cohort study. Setting University hospital. Subjects and Methods One hundred forty-six AR patients with/without asthma allergic to HDM were investigated for 5 years after initiation of a 3-year course of subcutaneous SIT (SIT group, n = 106) or no SIT (control group, n = 40). The clinical responses of all patients were evaluated at baseline, the stop point of SIT (third year), and 2 years after SIT termination (fifth year), by clinical index including symptom and rescue medication scores (SMS), visual analog scale (VAS), total immunoglobulin E (tIgE), and specific IgE (sIgE). Asthma was assessed by clinical evaluation. Results The decrease of SMS and VAS from baseline was significantly improved in the SIT group compared with controls at both the third and fifth year. For patients without asthma at baseline, the odds ratio for no asthma was 3.57 (95% confidence interval, 1.05-12.91; P < .05) in favor of SIT. The serum sIgE/tIgE ratio was significantly increased after SIT treatment in the SIT group, but it was not related to SIT efficacy. Conclusion SIT has a long-term effect of improving clinical symptoms and reducing the risk of development of asthma in Chinese AR patients.

Differential Expression Patterns of EGF, EGFR, and ERBB4 in Nasal Polyp Epithelium.

Epidermal growth factor receptors play an important role in airway epithelial cell growth and differentiation. The current study investigates the expression profiles of EGF, EGFR and ERBB4 in patients with nasal polyps (NP), and their response to glucocorticosteroid (GC) treatment. Fifty patients with NP (40 without GC treatment and 10 with oral GC) and 20 control subjects with septal deviation were recruited into the study. Protein levels of EGF, EGFR, and ERBB4 were evaluated by immune-staining. In healthy nasal epithelium, EGF and EGFR localized within p63+ basal cells, while ERBB4 localized within ciliated cells. GC-naïve NP epithelium showed weak expression of EGF in 90% of samples versus 5% of controls. EGFR was significantly increased in the epithelium with basal cell hyperplasia from GC-naïve NPs (78%, 31/40) compared to controls (23%, 4/17). EGFR was also found in some degranulating goblet cells. ERBB4 expression was significantly higher in hyperplastic epithelium from GC-naïve NPs (65%, 26/40) than in controls (6%, 1/17). GC treatment restored the EGF expression and normalized the EGFR and ERBB4 expression in NPs. Differential expression patterns of EGF, EGFR, and ERBB4 are essential in epithelial restitution and remodeling in nasal epithelium.

Histopathological features of sinonasal inverted papillomas in chinese patients

Nasal inverted papilloma (IP) is a benign tumor with high recurrence rates. Evidence of inflammation has been reported in IP in Caucasian studies. This study aimed to investigate the histopathological patterns and their associations with clinical characteristics in Chinese patients with IP.

Primary nasopharyngeal polyps: a case series on a rare clinical entity

Primary non-neoplastic polyps originating from the nasopharynx have not been reported in the English language literature. We present the clinical and histopathological features of three primary nasopharyngeal polyps. Clinical data of three patients with primary nasopharyngeal polyps treated at the Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University between 2005 and 2015 were analyzed and presented. Three male patients from 45 to 63xa0years presented with nasopharyngeal masses. CT or MRI examination showed nasopharyngeal space-occupying lesions. Two patients were initially diagnosed with nasopharyngeal angiofibroma and one patient with nasopharyngeal carcinoma. After surgical excision, based on the histological examination, the tissue masses were all diagnosed as inflammatory polyps. Histologically, the polyps demonstrated significant oedema, collagen deposition, leukocytic infiltration, and epithelial remodelling. Primary nasopharyngeal polyps represent a distinct clinical entity and should be considered in the differential diagnosis of nasopharyngeal masses.

Expression of Epithelial Cell Markers in Nasal Polyposis

OBJECTIVE: One major character of mucosal inflammation in nasal polyposis (NP) is abnormal epithelial remodeling. We sought to profile the NP epithelium by assessing the key markers of different epithelial cell types, including p63 (basal cells), p73 (ciliated cells), and MUC2 (goblet cells). METHOD: In this study, 69 NP and 19 controls of healthy inferior turbinate (IT) mucosa were obtained without steroid treatment. Epithelial structure and protein levels of p63, p73, and MUC2 were evaluated by histoand immunohistochemistry. Moreover, mRNA levels of p63 and p73 were determined by real-time RT PCR. RESULTS: NP exhibited significant epithelial hyperplasia (p 0.001) and increase of p63 protein expression (p 0.01) as compared to the control. The p63 protein level was also positively correlated with the hyperplastic status of NP and control epithelium (p 0.001). However, p73 and MUC2 protein levels were not significantly different between NP and control groups. In addition, the mRNA expression of p63 (p 0.001) and p73 (p 0.003) were up-regulated in NP versus controls; a positive correlation between the p63 and p73 mRNAs was also found in NP and control samples (p 0.001). CONCLUSION: These findings indicate that NP epithelial hyperplasia may be mainly attributed to the basal cell proliferation and elevated p63 level may be essential in NP epithelial remodeling.