Significance and expression of transforming growth factor beta in human nasal polyp tissue]

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of transforming growth factor beta (TGF-beta) in human inflammatory nasal polyps. METHODS: TGF-beta 1-3 in nasal polyp tissues and inferior turbinate mucosa of twenty-five polyposis patients were detected with immunohistochemistry alkaline phosphatase and anti-alkaline phosphatase (APAAP) method. The inferior turbinate mucosa of eight healthy volunteers were selected as control. Six polyp tissues were estimated with double immunolabeling and Western-blot analysis to compare the characterization of the TGF-beta isoforms expression and the proportion of macrophages and eosinophils in nasal polyp tissues. RESULTS: The expression of TGF-beta 1-3 in nasal polyps was significantly higher than that in nasal mucosa and indetecable in nasal mucosa from healthy volunteers; TGF-beta 1 was the main isoform detected in nasal polyps; TGF-beta positively was accompanied by numerous macrophage and eosinophil infiltration. CONCLUSIONS: TGF-beta mainly TGF-beta 1 is strongly expressed in nasal polyps and its mucosa, where it could be produced by macrophages and eosinophils. TGF-beta could induce modification of epithelium and connective tissue and therefore be involved in the pathogenesis of nasal polyposis.     

Expression of MCP-4 by TLR ligand-stimulated nasal polyp fibroblasts

CONCLUSION: These results indicate that nasal polyp fibroblasts contribute to innate immunity and eosinophilic inflammation such as nasal polyposis. OBJECTIVE: It is generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play an essential role in the pathogenesis of nasal polyposis. Nasal polyposis is characterized by chronic eosinophilic inflammation. The mechanisms that cause the predominance of eosinophilic infiltration in nasal polyposis have yet to be clarified. There is growing evidence that fibroblasts could be a major source of Th2 chemokines. Because the nasal and paranasal mucosae are the first respiratory tissues that environmental agents encounter, those tissues are exposed to injurious agents, including microorganisms and their breakdown products. We investigated whether nasal polyp fibroblasts produce a C-C chemokine, MCP-4, when stimulated with the breakdown products of microorganisms and a Th2 cytokine (interleukin (IL)-4). MATERIALS AND METHODS: Fibroblast lines were established from nasal polyp tissues. The expression of MCP-4 mRNA was evaluated by real-time RT-PCR. The amount of MCP-4 in the supernatants was measured by ELISA. RESULTS: TLR2, 3, 4 and 5 ligands, but not TLR7/8 or 9 ligands, induced small amounts of MCP-4. TLR2, 3, 4 and 5 ligands synergized with IL-4 to induce the production of MCP-4.     

Expression of MCP-4 by TLR ligand-stimulated nasal polyp fibroblasts

Conclusion. These results indicate that nasal polyp fibroblasts contribute to innate immunity and eosinophilic inflammation such as nasal polyposis. Objective. It is generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play an essential role in the pathogenesis of nasal polyposis. Nasal polyposis is characterized by chronic eosinophilic inflammation. The mechanisms that cause the predominance of eosinophilic infiltration in nasal polyposis have yet to be clarified. There is growing evidence that fibroblasts could be a major source of Th2 chemokines. Because the nasal and paranasal mucosae are the first respiratory tissues that environmental agents encounter, those tissues are exposed to injurious agents, including microorganisms and their breakdown products. We investigated whether nasal polyp fibroblasts produce a C-C chemokine, MCP-4, when stimulated with the breakdown products of microorganisms and a Th2 cytokine (interleukin (IL)-4). Materials and methods. Fibroblast lines were established from nasal polyp tissues. The expression of MCP-4 mRNA was evaluated by real-time RT-PCR. The amount of MCP-4 in the supernatants was measured by ELISA. Results. TLR2, 3, 4 and 5 ligands, but not TLR7/8 or 9 ligands, induced small amounts of MCP-4. TLR2, 3, 4 and 5 ligands synergized with IL-4 to induce the production of MCP-4.     

Possible involvement of nitric oxide and peroxynitrite in nasal polyposis

BACKGROUND: Nitric oxide (NO) is implicated in inflammation. Its role in the pathogenesis of nasal polyposis is not clear. METHODS: The expression of inducible NO synthase (iNOS), and the production of peroxynitrite represented by the formation of 3-nitrotyrosine (3-NT) were examined by immunohistochemistry in nasal polyps. The contents of superoxide dismutases (SODs) in nasal polyps and nasal mucosa were assessed by Western blot analyses. RESULTS: iNOS expression and 3-NT accumulation were noted in mucosal epithelium, vascular endothelium, and interstitial cells of nasal polyps. In comparison with our previous study on the nasal mucosa from patients with rhinitis, the stromal cells of the nasal polyp had higher labeling intensity for both iNOS and 3-NT. The polyp showed similar levels of CuZnSOD and MnSOD as those of nasal mucosa. CONCLUSIONS: The iNOS/NO system may be important in the pathophysiology of nasal polyposis. The increased peroxynitrite may result from increased iNOS expression but is not related to decreased SODs.     

白细胞介素-8和白细胞介素-3在人类鼻息肉和鼻息肉病中的表达

目的 :探讨白细胞介素 8(IL 8)和白细胞介素 3(IL 3)在人类鼻息肉及鼻息肉病中的表达情况。方法 :采用免疫组织化学方法检测 31例鼻息肉患者 (鼻息肉组 )、2 6例鼻息肉病患者 (鼻息肉病组 )的息肉组织及 14例正常中鼻甲黏膜 (对照组 )中IL 8和IL 3的表达。结果 :IL 8在对照组、鼻息肉组及鼻息肉病组 3组间呈递增性表达 ,且每两组间差异均有统计学意义 (均P <0 .0 1) ;IL 3在对照组、鼻息肉组及鼻息肉病组 3组间亦呈递增性表达 ,且每两组间差异均有统计学意义 (均P <0 .0 1〉。结论 :IL 8是鼻息肉诸多病因之一 ,对鼻息肉病的复发起重要作用 ;IL 8在鼻息肉及鼻息肉病之间的不同表达提示二者的发病机制有本质差异 ;IL 3对鼻息肉组织中嗜酸性粒细胞的大量浸润起重要作用 ,也是鼻息肉与鼻息肉病二者发病机制差异中的一个重要因素     

鼻息肉中活化糖皮质激素受体的定量分析

目的测量鼻息肉（nasal polyps,NP）组织细胞核中活化的糖皮质激素受体（glucocorticoid receptor,GR）蛋白水平。方法应用ELlSA方法定量测定NP组织细胞核内活化的GR的蛋白水平。NP组织从不并发支气管哮喘和并发支气管哮喘的（chronic rhinosinusitis,CRS）伴NP患者中取得。在后者,NP组织在（glucocorticoid,Glu）治疗前和治疗后分次取得。结果不并发支气管哮喘和并发支气管哮喘Glu治疗前的CRS伴NP患者中,活化GR蛋白水平没有显著性差异。Glu治疗后,GIu蛋白水平较治疗前显著增高。结论Glu上调NP组织细胞核内活化的GR蛋白水平,这对于发挥Glu的抗炎作用至关重要。     

Immunological features of patients with polypous ethmoiditis

34 patients with nasal polyps (NP) and 12 normal individuals were studied immunologically to investigate association of nasal polyp formation with disorders of general and local immunity. In NP patients there were decreased preoperative and early postoperative levels of peripheral blood T- and B-lymphocytes, functional activity of lymphocytes and neutrophils. In contrast to normal individuals, nasal secretion of NP patients contained degenerative epithelial cells and neutrophils, activated lymphocytes, monocytes and eosinophils. Nasal polyp tissues obtained after polypectomy contained more B-lymphocytes than T-lymphocytes. Lymphocytes and neutrophils in nasal polyps had elevated functional activity in tissue culture. We conclude that local hyperactivation of T- and B-lymphocytes as well as neutrophils contribute much to nasal polyp formation.     

Expression of mammaglobins A and B in nasal polyps is similar in patients with and without allergic rhinitis

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.     

Eotaxin和Eotaxin-2在鼻息肉病和鼻息肉组织中的表达及意义

目的：了解嗜酸粒细胞（EOs）趋化因子Eotaxin、Eotaxin-2在人鼻息肉病和鼻息肉组织中的表达情况,探讨鼻息肉与鼻息肉病发病机制上的异同。方法：采用免疫组织化学方法（SP法）检测15例鼻息肉病患者（鼻息肉病组）、13例鼻息肉患者（鼻息肉组）的息肉组织和8例行鼻中隔偏曲矫正术患者的中鼻甲组织（对照组）中Eotaxin和Eotaxin-2的表达。结果：Eotaxin-2在对照组、鼻息肉组和鼻息肉病组3组间呈递增表达,且每2组间比较均差异有统计学意义（均P〈0．05）;Eotaxin在鼻息肉病和鼻息肉组中的表达均显著高于对照组（均P〈0．05）,而在鼻息肉病组与鼻息肉组间表达差异无统计学意义。结论：Eotaxin和Eotaxin-2可能均参与了鼻息肉病与鼻息肉的炎症反应过程,Eotaxin-2在鼻息肉病和鼻息肉组织之间的不同表达提示它可能是鼻息肉病与鼻息肉发病机制不同的重要原因之一。     

鼻息肉组织和血清中MDA含量及ADA、SOD活性的测定及其意义

目的测定鼻息肉患者鼻息肉组织和血清中丙二醛(MDA)含量、腺苷脱氨酶(ADA)和超氧化物歧化酶(SOD)的活性,并探讨其意义及它们之间的相关关系。方法用比色法分别测定24例鼻息肉患者鼻息肉组织和血清中MDA含量、ADA和SOD的活性,另20例鼻中隔偏曲患者的下鼻甲黏膜和血清作为对照组。结果①实验组组织和血清中MDA含量、ADA活性显著高于对照组(P0.01);SOD活性显著低于对照组(P0.01);②实验组组织和血清中MDA与ADA呈正相关(r=0.66,P0.01),MDA和SOD呈负相关(-1r0)。结论鼻息肉患者清除自由基能力下降,脂质过氧化反应活跃,提示自由基代谢紊乱为鼻息肉的发病机制之一,为全身和局部有效治疗鼻息肉和预防鼻息肉复发提供理论依据。     

Expression of ecalectin, a novel eosinophil chemoattractant, in nasal polyps

CONCLUSION: Ecalectin, which is produced in the mucosa of nasal polyps, seems to play an important role in the accumulation and activation of eosinophils in nasal polyps, regardless of the presence or absence of atopic predisposition. OBJECTIVE: Ecalectin is a recently discovered eosinophil chemoattractant which elongs to the galectin family. We investigated the expression of ecalectin in nasal polyp tissues associated with various nasal and paranasal diseases in order to clarify the pathogenesis of eosinophilia in nasal polyposis. MATERIAL AND METHODS: Nasal polyps were taken from 56 patients diagnosed as having chronic sinusitis with nasal polyposis. The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin. RESULTS: The number of EG2- and ecalectin-positive cells was significantly higher in nasal polyps than control turbinates. Ecalectin-positive cells were observed in the subepithelial layer, where many EG2-positive cells were present. The number of ecalectin-positive cells correlated significantly with the number of EG2-positive cells in nasal polyps. Many ecalectin mRNA-positive cells were also observed in nasal polyps with an accumulation of EG2-positive cells.     

天然免疫蛋白PLUNC在鼻息肉中的表达及与鼻息肉临床特征的关联性

目的：探讨天然免疫蛋白腭、肺、鼻上皮克隆（PLUNC）在鼻息肉组织中的表达情况,分析PLUNC蛋白浓度与鼻息肉大小（鼻内镜记分）和手术后复发的关联性。方法：采用免疫组织化学和实时定量PCR检测鼻息肉组（28例鼻息肉患者,其中13例为术后复发患者）和对照组（16例钩突黏膜对照）PLUNC的组织染色定位和mRNA的表达情况,同时采用ELISA检测初发和复发鼻息肉组织中PLUNC的蛋白浓度差异,评估PLUNC蛋白浓度与息肉大小、鼻塞、流涕症状记分的相关性。结果：鼻息肉组织中PLUNC主要定位在黏膜上皮和腺体,染色强度记分显著低于对照的钩突组织（P〈0．01）;PLUNCmRNA表达水平也显著低于对照的钩突组织（P〈0．01）。初发和复发鼻息肉组织中PLUNC蛋白OD值分别为0．33±0．11和0．15±0．05,差异有统计学意义（P〈0．01）。小型和大型鼻息肉PLUNC蛋白OD值分别为0．32±0．14和0．19±0．07,差异有统计学意义（P〈0．05）。鼻息肉组织中PLUNC蛋白浓度与鼻塞和流涕记分存在显著负相关（r=-0．51和r=-0．57,P〈0．01）。结论：PLUNC的表达降低提示鼻息肉的发生可能与天然免疫反应的减弱有关,因此,上调天然免疫分子如PLUNC等的表达可作为干预鼻息肉发病的一个新策略。     

The effect of corticosteroid therapy on cyclooxygenase 2, vascular endothelial growth factor,and inducible nitric oxide synthase expression levels in nasal polyposis

Nasal and oral corticosteroid therapy is the ultimate treatment for sinonasal polyposis. Although there are numerous clinical studies regarding the factors associated with the formation of nasal polyposis, there is not enough literature on how these factors are influenced by steroid treatment. Twenty-one patients that had no prior medical therapy for nasal polyposis or had received medical therapy at least 6 months earlier were included in the study. Patients were treated with oral and nasal corticosteroid therapy. Nasal polyp biopsies were taken before and after medical treatment and immunohistochemical staining for cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were applied to the specimens. In this study, we tried to demonstrate the effects of corticosteroid therapy on nasal polyposis tissue immunohistochemically. There was no change at immunohistochemical expression level of COX-2; however, the decline of immunohistochemical expression levels of VEGF and iNOS was statistically significant. Short-term steroid therapy does not affect COX-2 level of the nasal polyposis tissue, but has an influence on iNOS and VEGF levels. Our findings were harmonious with those of the previous studies of the literature. Further studies are needed to demonstrate the long-term effects with a larger patient group.     

The effect of topical corticosteroid on basic fibroblast growth factor in nasal polyp tissue

BACKGROUND: The etiology of nasal polyposis and pathophysiological mechanisms of polyp formation is still poorly understood. Experimental models have suggested that nasal polyp growth requires extracellular matrix formation and is associated with fibroblast proliferation. Intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. Basic fibroblast growth factor (bFGF) is a potent angiogenesis factor and is mitogenic for a wide range of cell types. We investigated the alteration of bFGF levels in nasal polyp tissue after administration of topical corticosteroid. METHODS: Nasal polyp tissues were obtained from 36 patients with diffuse nasal polyposis before and after topical nasal steroid treatment. As a topical nasal steroid mometasone furoate was given for 4 weeks in a dosage of 200 microg/day. The bFGF levels were measured by competitive enzyme immunoassay method. RESULTS: The mean levels of tissue bFGF, before and after topical nasal steroid treatment, were 1485 +/- 826 ng/mg protein (range, 416-3434 ng/mg) and 1340 +/- 749 ng/mg protein (range, 330-3288 ng/mg), respectively. The levels of bFGF in nasal polyps were significantly lower than those before treatment after administration of topical nasal steroid (p = 0.011). CONCLUSION: Administration of topical nasal steroid decreases bFGF levels of nasal polyp. It may be suggested that one of the effects in diminishing the size of nasal polyps is by decreasing the bFGF.     

The role of allergy in the severity of nasal polyposis

BACKGROUND: Although patients with nasal polyposis frequently exhibit concomitant allergy, there is limited information about the impact of allergy on the severity of nasal polyposis. The goal of this study was to evaluate the role of allergy in the severity of nasal polyposis. METHODS: Polyp sizes, computed tomography (CT) scores, skin-prick test results, blood total eosinophil count, serum levels of total immunoglobulin E, symptom scores, and recurrences were analyzed in 83 patients with nasal polyposis. The results were compared between allergic and nonallergic patients with nasal polyposis. RESULTS: No association was found between the presence of allergy per skin-prick testing and polyp size, CT opacification, symptom scores, or recurrences (p > 0.05). In allergic patients, only the serum total eosinophil count correlated strongly with the results of CT (p = 0.005) but not with other parameters (p > 0.05). CONCLUSIONS: The results of this study show that, although patients with nasal polyposis frequently have allergies, the presence of allergy does not correlate with polyp size, symptom scores or rate of recurrence.     

Nods样模式识别受体在鼻息肉组织中的表达及意义

目的：探讨Nods（核苷酸结合寡聚化结构域,Nod Like receptors）样模式识别受体（PRR）在鼻息肉组织中的表达及作用。方法：分别采用实时定量RT—PCR、Western—Blot及免疫组织化学检测Nodl、Nod2、Nalp3mRNA及蛋白在鼻息肉组织中的表达（以正常下鼻甲黏膜作对照）。结果：实时定量RT—PCR显示,鼻息肉组织Nodl、Nod2、Nalp3mRNA表达与正常对照下鼻甲黏膜比较无显著差异。Western-Blot结果提示：鼻息肉组织Nodl表达高于对照组,两组Nod2、Nalp3无明显差异。免疫组织化学表明,三种模式受体在两组中均有表达,主要表达于上皮细胞、腺体上皮、炎性细胞（如嗜酸粒细胞）,但Nodl及Nalp3在鼻息肉中表达强于对照组（P〈0．05）,Nod2蛋白表达无显著差异。结论：在鼻息肉组织中,Nodl、Nod2及Nalp3均有表达,其中Nodl、Nalp3的表达高于对照组,说明Nodl、Nalp3有可能参与鼻息肉的发病。     

Nasal interleukin-5, immunoglobulin E, eosinophilic cationic protein, and soluble intercellular adhesion molecule-1 in chronic sinusitis, allergic rhinitis, and nasal polyposis

OBJECTIVE: To compare concentrations of interleukin-5 (IL-5), immunoglobulin E (IgE), eosinophilic cationic protein (ECP), and soluble intercellular adhesion molecule-1 (sICAM-1) in nasal secretion and serum of patients with chronic nonallergic sinusitis, allergic rhinitis, and nonallergic nasal polyposis to obtain information about the pathogenesis of these diseases. METHODS: Nasal secretion and serum were analyzed by routine enzyme-linked immunosorbent assay techniques. Nineteen patients with chronic nonallergic sinusitis, 24 patients with seasonal allergic rhinitis, and 18 patients with nonallergic nasal polyposis were included in the study. Eight healthy, nonallergic probands served as control subjects. RESULTS: Significantly elevated concentrations of IL-5 (5-fold, P < .05) and IgE (15-fold, P < .01) were detected in nasal secretion of patients with allergic rhinitis (IL-5, 51.8 +/- 13.2 pg/mL; IgE, 41.9 +/- 20.9 kU/L) or nonallergic nasal polyposis (IL-5, 57.9 +/- 36.9 pg(mL; IgE, 40.5 +/- 20.2 kU/L) compared with controls (IL-5, 10.6 +/- 7.8 pg/mL; IgE, 2.8 +/- 0.5 kU/L) or with patients with chronic nonallergic sinusitis (IL-5, 16.5 +/- 13.2 pg/mL; IgE, 5.4 +/- 3.1 kU/L). There were no significant differences between patients with allergic rhinitis and those with nonallergic nasal polyposis. Concentrations of ECP were significantly elevated (sixfold, P < .01) in patients with allergic rhinitis (297.8 ng/mL +/- 173.1) compared with controls (52.4 +/- 28.0 ng/mL) or patients with chronic nonallergic sinusitis (44.8 +/- 40.1 ng/mL), whereas twofold higher concentrations (not significant) of ECP were observed in patients with nonallergic nasal polyposis (107.1 +/- 26.6 ng/mL). Significantly elevated concentrations of sICAM-1 in nasal secretion (threefold, P < .05) were detected only in patients with chronic nonallergic sinusitis (79.4 +/- 45.6 ng/mL). The elevated sICAM-1 nasal secretion values in this group correlated significantly (P < .05) to the serum values. CONCLUSIONS: Equally elevated concentrations of IL-5 and IgE in patients with allergic rhinitis and nonallergic nasal polyposis implicated similar pathogenic processes in both diseases. Whereas the pathogenesis of allergic rhinitis is IgE-specific, the pathogenesis of nasal polyps is not as clear. IL-5 was suggested to play a pivotal role in tissue eosinophilia, which was confirmed by data in the present study. Elevated concentrations of ECP were suggested to result from tissue eosinophilia--a characteristic of both diseases. Elevated concentrations of sICAM-1 in patients with chronic nonallergic sinusitis pointed to its key role in the recruitment of neutrophils into the inflamed tissue, whereas an important role in eosinophil recruitment was ruled out.