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Analysis of proteoglycan gene messages in human nasal mucosa and nasal polyp using dot blot hybridization.

It has been suggested that the formation and growth of nasal polyp require the remodeling of extracellular matrix. Proteoglycans (PGs) are major components of the extracellular matrix that maintain the integrity of structural tissue. The leucine-rich repeat PGs include lumican, decorin and biglycan and have many important biologic activities in various pathologic conditions, including the remodeling of the extracellular matrix. Therefore, these small-PG families may be involved in the formation and growth of nasal polyp. In the present study, surgical specimens of nasal polyps and nasal mucosa were assessed for expression of mRNA coding for lumican, decorin and biglycan using reverse transcriptase-polymerase chain reaction followed by dot blot hybridization. Lumican, decorin and biglycan mRNA were expressed in all tissue samples examined. Semiquantitative dot blot hybridization revealed that the levels of the lumican and biglycan messages are lower in nasal polyp tissues than in nasal mucosa. The decorin messages in nasal polyp were expressed at levels similar to those in nasal mucosa. These results suggest that lumican, decorin and biglycan may be important components of the extracellular matrix in nasal mucosa. Considering the function of these PGs, normal levels of decorin associated with low levels of biglycan and lumican may play a role in the pathogenesis of nasal polyposis.

Adult↗

[Expression and distribution of aquaporin-5 in human nasal polyps].

OBJECTIVE: To investigate the distribution and expression of aquaporin-5 (AQP-5) in nasal polyps and explore the role of AQP-5 in the formation of nasal polyps and the normal function of AQP-5 in the inferior turbinate. METHOD: AQP-5 were studied in 30 samples nasal polyps and 12 samples of inferior turbinates with immunochemistric staing. RESULT: The level of AQP-5 positive cells in the serous cells from nasal polyps were lesser than that from inferior turbinate, and the level of AQP-5 positive cells in the blood vessel endothelium from nasal polyps were more than that from inferior turbinate. CONCLUSION: AQP-5 may play the role in both the formation of nasal polyps and the function of normal nasal mucous membrane.

Adolescent↗

[Roles of CD43, CD20 and local IgE in the pathogenesis of nasal polyps].

OBJECTIVE: To estimate the roles of CD43, CD20 and total IgE in the pathogenesis of nasal polyps. METHOD: Twenty-six cases of nasal polyps and 20 cases of mucosa of middle turbinates were used in present study. RESULTS: The number of CD43+ cells, CD20+ cells and plasma cells in nasal polyps were significantly more than that in middle turbinates (P < 0.01). The positive rate of local IgE+ cells in nasal polyps was significantly higher than in middle turbinate (P < 0.01). CONCLUSION: There were active cellular immunity and humoral immunity in nasal polyps. Local allergy may play a role in the pathogenesis of nasal polyps.

Adolescent↗

Nasal polyps: a comparative study of morphologic and etiopathogenetic aspects.

16 nasal polyps belonging to 10 male subjects aged between 40 and 70, have been removed during the same number of ethmoidectomies; the polyps have been sectioned and specimens of mucosa corresponding to the pedicle and to the different parts of the body have been collected. During the operation parts of the mucosa of the inferior turbinates were removed. All the specimens have been prepared and observed at the scanning electron microscope. The epithelium of the inferior turbinates, of the small polyps and of the apical part of all polyps were almost normal. Marked alterations of the epithelial layer have been observed in bigger polyps. Surface characteristics of nasal polyps seem to be influenced by their relationship with neighbouring structures and by their position in the nasal cavity, but mostly by their size. On the basis of these findings the authors discuss the most recent etiopathogenetic theories of nasal polyps. They finally describe some peculiar findings concerning the mucosal layer of the polyps and of the inferior turbinates of three confirmed allergic subjects and discuss their possible clinical implications.

Adult↗

Determination of proliferative activity in nasal polyps.

AIMS: To determine the level of proliferative activity in 39 nasal polyps with clear cut distinct clinical behaviour patterns. METHODS: The 39 nasal polyps included 11 polyps labelled as "single" and taken from the lateral nasal wall and the middle turbinate; 12 polyps labelled as "massive" and relating to diffuse polyposis involving the entire nasal cavity; six polyps labelled as "ASA" and relating to nasal polyps from patients with acetylsalicylic acid intolerance and asthma; and 10 polyps from cystic fibrosis related polyposis. Cell proliferation was determined by two independent methods: first, the computer assisted microscope analysis of isolated Feulgen stained nuclei for the measurement of the percentage of cells in the S phase of the cell cycle; and second, the immunohistochemical evaluation of a proliferation associated protein by means of the MIB 1 monoclonal antibody. RESULTS: The cystic fibrosis related polyposis exhibited the highest proliferative activity of all the clinically identified nasal polyp groups. Acute inflammatory nasal polyps exhibited a higher cell proliferation than chronic ones. The results also show that while the immunohistochemical determination of cell proliferation by means of the MIB 1 monoclonal antibody is a valuable tool in determining cell proliferation in nasal polyps, the cytometrical image analysis of Feulgen stained nuclei is not useful for this purpose. CONCLUSION: Cell proliferation activity identifies cystic fibrosis as being distinct from the other nasal polyp groups.

Acute Disease↗

Expression of vasoactive intestinal peptide, substance P and bombesin-flanking peptide in nasal polyps.

The presence of neuropeptide-containing sensory, parasympathetic and sympathetic nerves in human nasal mucosa is well established. However, information regarding the neuropeptide distribution in nasal polyps is still lacking. The aim of this study was to compare immunohistologically the presence and distribution of substance P (SP), vasoactive intestinal peptide (VIP) and bombesin-flanking peptide (BFP) in normal nasal mucosa and nasal polyps. The expression was studied using Formalin-fixed and paraffin-embedded biopsy sections from 20 patients with nasal polyps and 10 controls with normal nasal mucosa from the anterior part of the inferior turbinate. Indirect immunohistochemistry (APAAP method) with mono- and polyclonal antibodies was used. None of the control group but 5 patients of the nasal polyp group had an atopic disease. Comparing localization and intensity of the immunohistological reaction in nasal mucosa and nasal polyp tissue, there was no difference in the expression of the three neuroendocrine substances. There was no difference of expression in the polyposis group itself concerning allergic and nonallergic subjects. The results indicate that VIP, SP and BFP have an equal distribution in nasal polyps and normal nasal mucosa.

Adult↗

[Relationship between allergic factors and chronic sinusitis with or without nasal polyps].

OBJECTIVE: To explore the effects of allergic factors in chronic sinusitis and nasal polyps. METHOD: Eosinophil in nasal secretions and allergen skin test of 1882 patients with chronic sinusitis and nasal polyps were examined before endoscopic sinus surgery. The occurrence ratios of allergic symptoms and syndromes were analyzed and compared with clinical stages of chronic sinusitis and nasal polyps. RESULTS: (1) Allergic symptoms (or syndromes) were presented in 60.4% (1137 cases) of patients in different degrees, 25.3% (477 cases) patients suffered from allergic rhinitis, 2.1% (39 cases) patients had asthma; (2) The morbidities of allergic rhinitis and asthma, the positive rates of eosinophil and allergen skin test, the occurrence rates of allergic symptoms were rising with the clinical stages in type I and type II, especially in type II stage 3; (3) There were 42.2% (795 cases) positive patients in allergen skin test, among them, 94% were sensitive to perennial allergens; (4) Allergic symptoms appeared in 26.3% (495 cases) patients, among them, 99.8% attacked perennially; (5) Of all patients, there were 38.9% (732 cases) had been operated cases before, among them 38.3% (280 cases) with allergy rhinitis. In chronic sinusitis with allergy rhinitis patients, 58.7% (477 cases) were suffered from operation. CONCLUSIONS: Allergic factors,especially perennial allergic rhinitis, are relative to clinical stages of chronic sinusitis and nasal polyps. Allergic rhinitis is an important factors in recurrence.

Adolescent↗

Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps.

BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.

Adult↗

[The effects of intranasal FP on the expression of aquaporin-2 in nasal polyps].

OBJECTIVE: To study the effects of intranasal FP on the expression of AQP-2 in nasal polyps. METHOD: Fourteen cases of type II phase 3 and 12 cases of type III nasal polyps were selected. FP were intranasally used in 7 cases of type II phase 3 and 6 cases of type III nasal polyps for 7 days before operation. The others, treated with nothing, were used as control. 26 nasal polyps were obtained and studied with immunohistochemical technique. RESULT: The volume of nasal polyps in FP-using group became smaller. Both the number of AQP-2 positive cells and the area density were significantly lower in the FP-using group than in the control group (P < 0.01). CONCLUSION: Under the action of intranasal FP the expression of AQP-2 reduced, so is the volume of nasal polyps. It indicated that AQP-2 contributed to edema of nasal polyps and FP may lesson edema through changing the expression of AQP-2.

Administration, Intranasal↗

Nasal allergy and nasal polyp with special reference to the mucosal IgE antibodies.

Immunologic conditions were studied in 8 patients with nasal allergies and nasal polyps and in 20 patients with nasal polyps. The present study showed the following: Nasal polyp mucosa contains a low level of mucosal IgE antibodies; nasal polyp mucosa is devoid of or deficient in the capacity of producing IgE antibodies; the presence of mucosal IgE antibodies in nasal polyp mucosa does not always imply the clinical manifestation of nasal allergies, and the antigen and antibody interaction does not always result in nasal symptoms.

Humans↗

Pattern of inflammation and impact of Staphylococcus aureus enterotoxins in nasal polyps from southern China.

BACKGROUND: This study analyzes the impact of Staphylococcus aureus enterotoxins (SAEs) and the inflammatory pattern in polyps from China. METHODS: Nasal tissue was obtained from 27 consecutive bilateral nasal polyps and 15 control patients and assayed for eotaxin, interleukin-5, soluble interleukin-2 receptor, transforming growth factor (TGF) beta, myeloperoxidase, eosinophil cationic protein, total IgE, and specific IgE to SAEs. Activated eosinophils were stained using EG2 antibodies in polyps from Chinese and comparative white patients. RESULTS: The number of EG2+ eosinophils was significantly lower in polyps from Chinese patients versus white patients. Chinese polyps showed significantly increased IgE and soluble interleukin-2 receptor versus control samples, whereas TGF-beta1 was significantly decreased. Ten of 27 samples in the polyp group versus 0 of 15 controls contained SAE-IgE (p < 0.01). TGF-beta1 was significantly down-regulated in SAE+ samples versus SAE- samples (p = 0.04). CONCLUSION: Nasal polyps from China are characterized by B- and T-cell activation, a minor eosinophilic inflammation compared with polyps from white subjects, and a decrease in TGF-beta1 in comparison with control inferior turbinate tissue. One-third of patients with polyps showed an IgE response to SAEs.

Adolescent↗

[Expression of tenascin and fibronectin in nasal polyps].

OBJECTIVE: To explore the role of tenascin (TN) and fibronectin (FN) in the pathophysiology of nasal polyp. METHODS: The expression of TN and FN in nasal polyps from 34 patients and in inferior turbinates from 20 patients with deviation of nasal septum was studied with immunohistochemical method. In patients with nasal polyps, the relations between expression and histopathologic characteristics, eosinophilias (EOS) infiltration, clinical staging and the size of nasal polyps were analyzed. RESULTS: (1) The gray score of TN and FN expression was 163.10 +/- 10.54 and 163.24 +/- 11.52 in nasal polyps respectively, whereas it was 175.49 +/- 9.29 and 173.93 +/- 7.92 in inferior turbinates respectively. The difference between two groups was significant(P < 0.01); (2) The expression of TN and FN in edematous type was significantly stronger than that in cystic fibrous and glandular type (P < 0.05); (3) The association between FN expression and EOS infiltration was significant(r = -0.60, P < 0.01); (4) The expression of TN and FN did not correlate with clinical staging and size(P > 0.05). CONCLUSION: Abnormal ECM may contribute to proliferation of epithelium, accumulation of EOS and edema formation, as a result, to enhance the development of nasal polyps.

Adolescent↗

[Effect of erythromycin on the expression of apoptotic gene on eosinophils in nasal polyps in vitro].

OBJECTIVE: To study the expression of apoptotic gene in nasal polyps and the possible effect of erythromycin on it. METHODS: Total 40 nasal polyps biopsies were detected the expression of Bcl-2, Bax, Bcl-xL as well as Fas protein on eosinophils by immunohistochemistry. The expression of Bax, Bcl-xL, Fas on eosinophils in 15 nasal polyps explants which cultured with or without erythromycin were detected also. RESULTS: In nasal polyps, the expression of Bcl-2, Bax, Bcl-xL and Fas protein on eosinophils are 5% (2/10), 65% (26/40), 40% (16/40) and 90% (36/40) respectively. As compared with inferior turbinate, there were significant difference in expression of Bax and Fas protein between two tissues (P < 0.05). After cultured with erythromycin, the expression of Bax protein increased (P < 0.05), but the expression of Bcl-xL and Fas protein had not changed. CONCLUSION: Bax may be the most significant gene which control the apoptosis of eosinophils in nasal polyps. And a possible mechaism which erythromycin promote the apoptosis of eosinophils is increase the expression of Bax.

Adolescent↗

Concentration, distribution and expression of interleukin-5 in human nasal polyp tissues.

OBJECTIVES: To study the concentration, distribution and expression of IL-5 in nasal polyp tissues and explore its significance in micro-environment differentiation of eosinophil accumulation. METHODS: The concentration and expression of IL-5 in nasal polyp tissues of 40 patients were determined by ELISA and immunohistochemistry and inferior turbinate mucosa from patients with nasal polyps and healthy volunteers were used as control. RESULTS: IL-5 concentration in polyp tissues was significantly higher than that in turbinate mucosa (P < 0.05). There was no significant difference in the turbinate mucosae between patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 concentrations in polyp tissues were markedly higher in patients with allergic rhinitis compared with those without (P < 0.05). IL-5 concentrations had no correlation with age and sex (P > 0.05). 80.1% of the eosinophils were positive for IL-5 and 90.9% of IL-5 positive cells were eosinophils. Only 3.7% of lymphocytes and neutrophils were positive for IL-5; IL-5 was not detectable in epithelial cells. IL-5 expression in eosinophils of polyp tissues was remarkably stronger than that of the turbinate mucosa (P < 0.05); there was no significant difference in the the turbinate mucosae between patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 expression of eosinophils in polyp tissue was significantly stronger in patients with allergic rhinitis compared with those without (P < 0.05). There was no significant difference in IL-5 expression in lymphocytes and neutrophils between polyp tissues and turbinate nasal mucosa (both P > 0.05). CONCLUSION: IL-5 is the key cytokine in eosinophilic pathologic mechanisms in nasal polyp tissues.

Adult↗

PCR analysis of nasal polyps, chronic sinusitis, and hypertrophied turbinates for DNA encoding bacterial 16S rRNA.

BACKGROUND: Nasal polyps are considered to result from chronic inflammation, but the initial or persisting stimulus for the inflammation is not known. A variety of bacteria and fungi have been cultured from nasal polyps, but approximately 35% have sterile cultures. Previously, Mycoplasma pneumoniae-specific DNA was detected in human nasal polyps using polymerase chain reaction (PCR) techniques, suggesting M. pneumoniae as a causative agent in the etiology of nasal polyps. METHODS: In this study, we tested for the presence of bacterial DNA in nasal polyps resected from 40 patients, in nasal mucosa membrane from 9 patients undergoing turbinectomy for hypertrophy, and in sinus mucosa membrane from 6 patients undergoing endoscopic surgery for chronic sinusitis. Tissue DNA was extracted and analyzed by PCR using M. pneumoniae specific primers for DNA that encode the 16S rRNA gene in 41 specimens (31 polyps, 6 turbinates, and 4 sinus), and by consensus sequence-based PCR using broad range primers for most eubacterial DNA encoding the 16S rRNA gene in 38 specimens (26 polyps, 7 turbinates, and 5 sinuses). RESULTS: Only two samples were positive for bacterial DNA encoding 16S rRNA: Streptococcus sp. DNA was isolatedfrom one polyp specimen and Pseudomonas aeruginosa DNA was isolated in one maxillary sinusitis specimen. No evidence of M. pneumoniae-specific DNA encoding 16S rRNA was found in any of the tissues. CONCLUSIONS: This study suggests that chronic bacterial infection is not a major component of nasal polyp etiology.

Base Sequence↗

Expression of RANTES by IL-1 beta and TNF-alpha stimulated nasal polyp fibroblasts.

OBJECTIVE: Accumulation of eosinophils (Eo) is one of the most characteristic feature of nasal polyps. However, the question remains why eosinophils accumulate into the nasal polyp tissue. RANTES (regulated upon activation, normal T cell expressed and presumably secreted) is a recently described chemokine that is said to play a role in the recruitment of eosinophils into inflammatory tissue sites. Fibroblasts are a rich source of cytokines and inflammatory mediators. The objective of this study was to demonstrated the expression of the chemokine RANTES in nasal polyp fibroblasts after stimulation with proinflammatory cytokines like TNF-alpha and IL-1 beta. METHODS: Fibroblast lines were established from human nasal polyp biopsy tissues taken from patients with chronic sinusitis who had no other associated diseases. Cultured nasal polyp fibroblasts were stimulated with TNF-alpha or IL-1 beta at various doses (0.1, 1.0, 1 ng/ml) or for various times (l, 6, 12, 24, 48, 72 h). To detect the RANTES gene expression, RT-PCR was performed. The resulting supernatants were assayed with ELISA for the level of RANTES. RESULTS: We demonstrated that TNF-alpha and IL-1 beta induced the gene expression and protein production of RANTES in nasal polyp fibroblasts. This responsiveness to TNF-alpha and IL-1 beta was time and dose-dependent. CONCLUSION: These findings suggest that nasal polypfibroblasts may also play an important role in the recruitment of Eo through the production of RANTES.

Cells, Cultured↗

Effect of prednisolone on cytokine synthesis in nasal polyps.

To investigate steroid effects on eosinophils and their associated cytokines in nasal polyps, we sampled nasal polyp tissue from 20 subjects during routine surgery. Freshley removed polyps were cut into small pieces and incubated in culture medium for 24 h in different concentrations of prednisolone (10(-2)-10(-6) mol/L). Cell viability was assessed by means of trypan dye exclusion of the supernatants. The number of eosinophils was quantified by means of cytocentrifuge smears stained by May-Giemsa-Grunwald stain. The cytokine protein content of interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by ELISA technique in supernatants and in homogenates of nasal polyp tissue. Our results revealed a significant reduction in the number of eosinophils and total number of vital cells at concentrations of 10(-3) and 10(-2) mol/L. GM-CSF and IL-5 protein levels were significantly reduced in supernatants and in homogenates after treatment with prednisolone, whereas IL-3 synthesis was not diminished. Corticosteroid effects known to inhibit synthesis of eosinophil-associated cytokines could be measured in terms of a significant decrease in IL-5 and GM-CSF protein level as well as in a decrease in the number of vital cells.

Cell Survival↗

[Effect of intranasal glucosteroid on the gene expression of interleukin-5 in nasal polyps].

OBJECTIVE: To investigate the effect of intranasal glucosteroid treatment on the expression of interleukin (IL)-5 gene in nasal polyps. METHODS: Nasal polyps from topical steroid treated patients (n = 20) and untreated patients (n = 20) were investigated with the technique of mRNA in situ hybridization. RESULTS: The majority of IL-5 mRNA positive cells in nasal polyps were lymphocytes or eosinophils. No statistical significance was found in the densities of IL-5 mRNA positive cells between allergic patients [(12.6 +/- 4.6)/0.25mm2] and nonallergic patients [(14.3 +/- 4.1)/0.25mm2] (t = -0.775, P > 0.05). Compared with the control group [(13.9 +/- 4.2)/0.25mm2], the density of IL-5 mRNA positive cells was decreased in the steroid-treated group [(10. 2 +/- 3.1)/0.25mm2], and the difference reached statistical significance (t = 3.114, P < 0.01). CONCLUSIONS: These findings indicate that topical steroid treatment may suppress the IL-5 gene expression, and steroids may inhibit eosinophil functions.

Administration, Intranasal↗