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Background: Genetic studies on chronic inflammatory diseases have resulted in an emphasis on the epithelial interface with the environment and the genes that influence this interaction. This study examines the expression of key epithelial genes implicated in the pathogenesis of other inflammatory disorders for their role in chronic rhinosinusitis (CRS)., Methods: Epithelial cells were collected from the inferior turbinate, middle turbinate, and/or uncinate from 62 subjects undergoing sinonasal surgery. Patient groups included 21 CRS patients with nasal polyposis, 23 CRS patients without nasal polyposis, and 18 controls. Samples were analyzed for S100A7, S100A8, S100A9, SLC9A3R1, G-protein-coupled receptor for asthma, and serine protease inhibitor kazal type 5 (SPINK5) by quantitative real-time polymerase chain reaction. Immunohistochemistry (IHC) was performed to analyze expression of SPINK5 lympho epithelial kazal-type inhibitor (LEKTI) in sinonasal samples., Results: Expression of S100A7 and S100A8 was significantly decreased in CRS with and without nasal polyps when compared with controls. S100A9 expression was significantly decreased in CRS without nasal polyps, and SPINK5 expression was significantly decreased in CRS with nasal polyps. SPINK5 (LEKTI) protein was detected in sinonasal tissue and was significantly decreased in polyp samples using IHC., Conclusion: This study shows marked reductions in the level of expression of several genes involved in epithelial barrier maintenance and repair in the inflammatory state of CRS.

Background: The pathogenesis of nasal polyps still is not clear. This disease is believed to be inflammation related. Previous research has indicated that apoptosis in inflammatory cells is an important factor in the resolution of inflammation. Survivin is regarded as a novel member of the group of inhibitors of apoptosis proteins. It is overexpressed in a number of tumor types. The objective of this study was to investigate the expression of the survivin gene in human nasal polyps., Methods: We investigated the expression of survivin in nasal polyps of adult patients with chronic rhinosinusitis. Specimens of nasal polyps were harvested during endonasal sinus surgery (n=22), and the normal mucosa surrounding the nasal polyp tissues or inferior turbinate tissues served as control (n=7). Immunohistochemical staining, reverse transcription polymerase chain reaction (RT-PCR), and Western blotting were performed for detecting the expression of survivin in the nasal polyps., Results: This study has clearly shown that immunoreactivity of survivin significantly increased in the nasal polyp compared with nasal mucosa specimens surrounding nasal polyps (p<0.001). The higher expression of survivin Western blotting and RT-PCR also was observed in the nasal polyp but not in normal nasal mucosa., Conclusion: With a markedly increased expression of survivin in nasal polyps at both the mRNA and the protein levels, we believe the elevated expression of survivin might play an important role of development in nasal polyps.

Background: The causes of nasal polyposis remain unclear. Mammaglobins have been implicated in its pathogenesis. However, their association with the occurrence of nasal polyps in the presence of allergic rhinitis (AR) has not been explored. The aim of this study was to compare the expression levels of mammaglobins A and B with the nasal polyps of patients with and without AR., Methods: Thirty-one patients with bilateral nasal polyposis underwent skin-prick tests to specific aeroallergens. Nasal polyp tissues were obtained from all patients and divided into two groups as nasal polyps with and without AR depending on clinical history and the skin-prick test results. All polyp tissues were analyzed for the levels of mammaglobin A and mammaglobin B by using real-time quantitative polymerase chain reaction technique., Results: Of the 16 samples from patients having nasal polyps with AR, only 1 sample expressed a detectable level of mammaglobin A (1/16). There was no detectable expression of mammaglobin A in tissues from the group of nasal polyps without AR (0/15). Expression of mammaglobin B was detected in all nasal polyp tissues from both groups. The expression of mammaglobin B was not significantly different between nasal polyps with AR (median, 25th-75th percentiles; 0.023, 0.013-0.046) and nasal polyps without AR (0.032, 0.007-0.16)., Conclusion: Expression levels of mammaglobins A and B in nasal polyps are not different between patients with and without AR. Our findings suggest that mammaglobins' implication in the pathogenesis of nasal polyps is independent of an underlying AR.

Background: Nasal polyposis is probably a multifactorial disease, but so far, no genetic susceptibility factor has been identified. The observed associations between the ADRB2 argl6gly polymorphism and asthma-related phenotypes as well as those between nasal polyposis and asthma have prompted us to evaluate the potential involvement of this polymorphism in sinonasal polyposis., Methods: We enrolled in our study, 56 patients and 47 sex- and age-matched controls. Genomic DNA from cases and controls was extracted and genotype was assessed by a polymerase chain reaction amplification/Nco I digestion assay. Statistical analysis was performed using JMP software (version 5.1)., Results: The "number of arg alleles" is significantly higher in cases than in controls (p = 0.0386 at t-test; substantially confirmed by nonparametric tests, p = 0.0396 by Wilcoxon/Kruskal-Wallis tests)., Conclusion: Although results of this study are preliminary because of the small size of the sample, the arg16 allele seems to be associated with an increased risk of sinonasal polyposis suggesting ADRB2 as a susceptibility gene. This finding, if confirmed, would have a clinical value in helping to assess the genetic risk for sinonasal polyposis thus opening new perspectives for the study of molecular factors underlying the development of nasal polyps.

Background: The aim of this study was to investigate the expression of MUC5AC and MUC5B messenger RNAs (mRNAs) and localization of these proteins in human sinus mucosa of chronic rhinosinusitis (CRS) and CRS with nasal polyposis (CRS/NP)., Methods: Maxillary sinus ostia mucosa was harvested from patients undergoing endoscopic sinus surgery for CRS, CRS/NP, and non-CRS pathologies (control). Then, sinus mucosa was analyzed using reverse-transcription polymerase chain reaction to detect mRNA of MUC5AC and MUC5B. Hematoxylin and eosin staining and immunofluorescent staining were used to localize MUC5AC and MUC5B proteins in the sinus mucosa., Results: mRNAs of MUC5AC and MUC5B in the sinus mucosa of CRS and CRS/NP were significantly increased compared with that in normal sinus mucosa (p < 0.01), and no significant difference was found between the mucosa of CRS and that of CRS/NP (p > 0.05). MUC5AC protein was expressed mainly in the goblet cells, and MUC5B expression was located in the submucosal glands cells and the epithelia of sinus mucosa. ARPC in staining of MUC5AC and MUC5B were found no different between the CRS group and the CRS/NP group (p > 0.05), whereas they were significantly lower in the normal group compared with the other two groups, respectively (p < 0.05)., Conclusion: This study showed that MUC5AC and MUC5B mucin genes were up-regulated in sinus mucosa of CRS and CRS/NP. MUC5AC and MUC5B may play an important role in the pathogenesis of CRS and NP.

Background: The objective of this study was to investigate the spectrum of inflammatory gene expression in patients with nasal polyposis., Methods: The cDNA microarray technique was used to identify gene expression in tissue samples from nasal polyps and adjacent inflammatory nasal mucosa of 21 patients with nonallergic nasal polyposis. To validate the microarray analysis, we compared the expression of five genes by reverse transcription-polymerase chain reaction (RT-PCR): tumor necrosis factor, IL-5, IL-9, fibroblast growth factor, and transforming growth factor (TGF)-beta1., Results: We tested 96 different inflammatory genes in our samples. Thirty-six genes exhibited differences in expression between the two tissue types. In all 36 genes the level of expression was greater in the inflammatory mucosa than the polyps. The RT-PCR confirmed the cDNA results., Conclusion: We believe that the high expression of TGF-beta1 in inflammatory mucosa compared with the low expression in polyps may reflect an important role in the inhibitory mechanisms of nasal polyposis.

Background: Recruitment of macrophages is crucial to the pathogenesis of the nasal polyp (NP) because this disease is believed to be inflammation related. Information regarding the expression of C-C chemokine ligand 2 (CCL2), an essential modulator of monocyte chemotaxis in nasal polyp fibroblasts (NPFs), remains unavailable. In this study, the effects of tumor necrosis factor (TNF)-a on CCL2 expression in NPFs and the signaling pathway involved were investigated., Methods: Primary cultures of NPFs were established from NPs. The expressions of CCL2, c-Fos, and c-Jun mRNAs in NPF after TNF-a stimulation were detected by Northern blot. Western blot was used to examine the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Activator protein (AP) 1/DNA interactions were evaluated by electrophoretic mobility shift assay (EMSA)., Results: Northern blot showed that TNF-alpha stimulated CCL2 gene expression in NPFs. Significant increase of B-Raf, phosphorated MAPK including mitogen-activated ERK-activate kinase (MEK)1/2, extracellular signal-related kinase 1/2, and p38 were detected by Western blot. c-Fos and c-Jun mRNAs were induced by TNF-alpha, and PD98059 (MEK inhibitor) and SB203580 (p38 inhibitor) abolished the up-regulation of c-Fos. EMSA revealed that TNF-a increased AP-1/DNA binding, and PD98059 and SB203580 attenuated this reaction, possibly via reducing c-Fos synthesis. PD98059 and curcunmin (AP-1 inhibitor) markedly suppressed the TNF-alpha-induced CCL2 expression, whereas the effect of SB203580 was less noted., Conclusion: TNF-alpha induces CCL2 transcription in NPFs. B-Raf/MEK/ERK signaling cascade and to a less extent the p38 pathway are responsible for c-Fos activation and the subsequent AP-1/DNA interaction leading to CCL2 expression.

Background: Tissue remodeling is an important characteristic of nasal polyps (NPs). However, the mechanisms underlying the remodeling processes are poorly defined. This study investigated the role of transforming growth factor (TGF) beta1 and eosinophils in the expression of tenascin C (Tn-C), an extracellular matrix glycoprotein, in NPs., Methods: The protein expression of Tn-C and TGF-beta1 was examined by means of immunohistochemistry in NPs and normal control inferior turbinate tissues. Furthermore, cell culture, quantitative RT-PCR, and in situ immunocytofluorescence techniques were used to investigate the direct effect of TGF-beta1 and eosinophils on Tn-C production in primary nasal epithelial cells., Results: Tn-C protein expression was significantly up-regulated in NP tissues and correlated with TGF-beta1+ eosinophils. TGF-beta1 and eosinophils dramatically induced Tn-C mRNA and protein expression in nasal epithelial cells. The effect of eosinophils could be inhibited partly by a neutralizing antibody to TGF-beta1., Conclusion: Eosinophil-derived TGF-beta1 may contribute, at least in part, to the tissue remodeling in NPs.

Background: The aim of this study was to determine the expression of cell cycle regulation genes in patients with inverted papilloma (IP) and compare this with expression in patients with nasal polyps (NPs)., Methods: Tissue from 18 patients with IP and 5 patients with NPs were stained by immunohistochemistry techniques for p53 and p27. Measurement of the gene expression was performed by three assessors, who we blinded with respect to the specimens., Results: The mean score for p53 expression (3.33) was significantly higher in the IP group than the NP group (1.46). The mean difference between IP and NPs was 1.80 (CI, 1.15-2.46; p = 0.003). Additionally, we showed in a number of individuals variation in the p53 expression within the same specimen. There was no difference in the mean scores for p27, with the mean difference 0.79 (CI, 0.30-1.89; p = 0.147)., Conclusion: Our study established a significantly increased expression of p53 in IP when compared with NPs. Additionally, there appear to be two different cell populations identified within the same specimens, which exhibited variation in their p53 expression.

Background: Although many studies have implicated interleukin (IL)-4 promoter polymorphisms as potential determinants of disease susceptibility, there are no reports on the association between IL-4 promoter polymorphisms and nasal polyps. The aim of this study was to investigate the relationship between an IL-4 promoter polymorphism and nasal polyps., Methods: The C-590T promoter polymorphism of the IL-4 gene was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 106 Korean chronic rhinosinusitis patients with or without nasal polyps and 70 healthy Korean subjects., Results: The frequency of the T allele at position -590 of the IL-4 gene in a Korean population was 0.85, which was significantly higher than those of other ethnic groups, and the T/T allele at position -590 of IL-4 was associated with protection against nasal polyps if compared with the C/C allele (relative risk, 0.529; 95% confidence interval, 0.307-0.912; p = 0.028)., Conclusion: T-590, which is dominant at position -590 of the IL-4 promoter, appears to be associated with a protective mechanism against nasal polyps in Korean populations.

Although several investigations have revealed the influence of cytokines, allergy, and environmental factors in polyp development, the etiology of nasal polyps is still unknown. To estimate the biology of this common disease the operative specimens of 50 patients who underwent surgery for polyps of the nasal cavity and the paranasal sinuses were examined; of these, 10 patients had recurrent disease and 23 patients had an allergy. The investigations included routine histology and quantitative DNA measurements, along with immunohistochemical identification of proliferation markers (i.e., MIB-1; proliferating cell nuclear antigen, PCNA). Histologically, most polyps revealed an infiltration with lymphocytes, eosinophilic granulocytes, and plasma cells. Twenty-five percent had a squamous metaplasia of the respiratory epithelium. Quantitative DNA analysis demonstrated diploid stemlines and lack of aneuploid cells with a DNA content exceeding 5c in most cases. Immunohistochemical detection of proliferation markers showed low proliferation rates in all cases. In 27 polyps no MIB-1 expression was detected, and in 7 polyps no PCNA expression was detected. The polyps of the 23 patients with proven allergic diathesis did not reveal higher scores for the parameters of DNA analysis (i.e., ploidy status and percentage of aneuploid cells) and proliferation scores. Nasal polyps of 10 patients with recurrent disease displayed higher scores for proliferation markers, and in five cases aneuploid cells with 5c exceeding rate (5cER) of 1.5-11.7% were detected. According to these results, polyps of the nasal cavity and paranasal sinuses showed low proliferation scores and were diploid. The data demonstrated that there was no increase of proliferation activity or ploidy shift toward aneuploidy in patients with allergy. Nevertheless, in recurrent disease some increase in proliferation activity and some changes in the parameters of the DNA analysis occurred, indicating more aggressive behavior of recurrent polyps in single cases.

Nasal polyps are the most common mass lesions found in the nose and their etiology is unknown. Nasal polyps from cystic fibrosis (CF) patients are histologically distinct from nasal polyps from patients without CF. It has been suggested that a mutation (G551D) of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may play a role in nasal polyp formation in patients without CF. To investigate the possibility that this or other CFTR gene exon mutations are required for nasal polyp formation, the CFTR gene exons were sequenced from peripheral blood DNA derived from an adult patient with edematous eosinophilic nasal polyps and no personal or family history of CF. No mutations or deletions were identified in any of the CFTR exons. A single polymorphism (A or G) was found in exon 10, base pair 1540, amino acid 470. This polymorphism was detected in 11 of 16 subjects (69%) with edematous eosinophilic nasal polyps and 10 of 21 normal subjects (48%) without nasal polyps and was not statistically significant (p = 0.316). These results demonstrate that mutations of the CFTR coding region are not a prerequisite for the formation of edematous eosinophilic nasal polyps.

Nasal polyps are found in 36% of patients with aspirin intolerance, 7% of those with asthma, 0.1% in children, and about 20% in those with cystic fibrosis. Other conditions associated with nasal polyps are Churg-Strauss Syndrome, allergic fungal sinusitis, and cilia dyskinetic syndrome, (Kartagener's) and Young Syndrome. Nasal polyps are statistically more common in nonallergic asthma versus allergic asthma (13% vs 5%, P < 0.01). About 40% of patients with surgical polypectomies have recurrences. There appears to be a hereditary factor for developing nasal polyps. A classification system for staging nasal polyps is proposed in order to standardize treatment, consider differential diagnosis, and harvest meaningful comparative research information.

The purpose of this study is to determine whether a hereditary factor exists for nasal polyps. Fifty patients (27 male, 23 female; age range 14-86 years) had a personal history of nasal polyps. These were confirmed by physician reports, polypectomy pathology reports, or direct visualization. These 50 patients were questioned concerning the existence of a familial history (parents, siblings, or children) of nasal polyps. A control group of 30 patients without nasal polyps was obtained by matching sex, age, personal history of atopy, and allergy skin test results to patients with a personal history of nasal polyps. Familial history of nasal polyps was obtained from the control group by direct interview. Seven of 50 (14%) of the group with nasal polyps had a familial history of nasal polyps. Of those seven, three patients had more than one immediate family member with a positive family history (two patients with two family members (sister, mother; 2 sisters) and one patient with three family members (3 brothers)). Among the control group, 0 of 30 (0%) had a familial history of nasal polyps. This difference is statistically significant (P value is 0.0414). This study suggests that there exists a hereditary factor for development of nasal polyps.