Role and mechanism of the expression of matrix metalloproteinase 9 and tumor necrosis factor α in upper and lower respiratory tract inflammation in rats

Objective To investigate the role and mechanism of matrix metalloproteinase 9(MMP-9) and tumor necrosis factor α (TNF-α) in the pathogenesis of allergic rhinitis (AR) and asthma (AS). Methods The rat models of AR and AS were made by injecting ovalbumin. The infiltration of eosinophils and mast cells were detected by hematoxylin-eosin (HE) staining and toluidine blue staining respectively, and the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue were examined by immunohistochemical staining ( SP method). The relationship of their expression with upper and lower respiratory tract inflammation was analyzed. SPSS 13.0 software was used to analyze the data. Results The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AR were ( 154.8±12.0)and (124. 0 ±8.2), (43. 2 ±7.6) and (34. 5 ±5.0) in the control groups, the difference was significant (t value were 24. 260, 29. 525 respectively, all P＜0.05). The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AS were (149.9±11.7)and(120.1±7.3), (48.6 ± 7. 6) and (39.1±5.2)in control groups, the difference was significant (t value were 22. 929 and 28. 530respectively, all P＜0.05).The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AR were (188.8±17.0), and (134.8±7.9), (57.6±23.3)and(40. 3 ± 8. 2 ) in control groups, the difference was significant (t value were 13. 836 and 26. 220, all P ＜0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AS were (179. 2 ± 15.4 ) and ( 153. 5 ± 10. 1 ), (70. 5 ±33. 1 ) and ( 33.8 ± 14. 0) in control groups, the difference was significant ( t value were 9. 412 and 21. 858, all P ＜0. 05). There was a correlation between the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue of AR ( r values were 0. 893 and 0. 700 respectively, P values were 0. 001 and 0. 024, respectively ) and AS ( r values were 0. 692 and 0. 644 respectively, P values were 0. 027and 0. 044 respectively) groups. Conclusions The inflammation is similar between AR and AS. The MMP9 and TNF-α may play an important role in the pathogenesis of upper and lower respiratory tract inflammation.     

基质金属蛋白酶9和肿瘤坏死因子α表达与大鼠上下呼吸道炎性反应一致性研究

目的 通过建立变应性鼻炎(allergic rhinitis,AR)和支气管哮喘(简称哮喘,asthma,AS)动物模型,探讨基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)和肿瘤坏死因子α(tumor necrosis factor,TNF-α)在上下呼吸道炎性反应一致性中的作用及机制.方法 以卵清蛋白辅以氢氧化铝致敏并激发制成AR和AS大鼠模型.HE染色和甲苯胺蓝染色分别检测AR和AS大鼠模型鼻黏膜及肺组织中嗜酸粒细胞、肥大细胞的表达,免疫组化SP法检测上述组织中MMP-9和TNF-α的表达,分析嗜酸粒细胞、肥大细胞、MMP-9和TNF-α表达与上下呼吸道炎性反应的关系.采用SPSS13.0软件对数据进行统计学分析.结果 MMP-9阳性细胞数在AR组鼻黏膜和肺组织中分别为 (154.8±12.0)、(124.0±8.2)个,在AR对照组分别为(43.2±7.6)、(34.5±5.0)个,差异有统计学意义(t值分别为24.260、29.525,P值均＜0.05);MMP-9阳性细胞数在AS组鼻黏膜和肺组织中分别为(149.9±11.7)、(120.1±7.3)个,在AS对照组分别为(48.6±7.6)、(39.1±5.2)个,差异有统计学意义(t值分别为22.929、28.530,P值均＜0.05).TNF-α阳性细胞数在AR组鼻黏膜和肺组织中分别为(188.8±17.0)、(134.8±7.9)个,在AR对照组分别为(57.6±23.3)、(40.3±8.2)个,差异有统计学意义(t值分别为13.836、26.220,P值均＜0.05);TNF-α阳性细胞数在AS组鼻黏膜和肺组织中分别为(179.2±15.4)、(153.5±10.1)个,在AS对照组分别为(70.5±33.1)、(33.8±14.0)个,差异有统计学意义(t值分别为9.412、21.858,P值均＜0.05).MMP-9与TNF-α在AR组鼻黏膜及肺组织中的表达分别呈正相关(r值分别为0.893和0.700,P值分别为0.001和0.024),二者在AS组鼻黏膜或肺组织中的表达分别呈正相关(r值分别为0.692和0.644,P值分别为0.027和0.044).结论 上下呼吸道炎性反应具有一致性,MMP-9和TNF-α可能在上下呼吸道炎性反应一致性中发挥重要作用.

Abstract：

Objective To investigate the role and mechanism of matrix metalloproteinase 9(MMP-9) and tumor necrosis factor α (TNF-α) in the pathogenesis of allergic rhinitis (AR) and asthma (AS). Methods The rat models of AR and AS were made by injecting ovalbumin. The infiltration of eosinophils and mast cells were detected by hematoxylin-eosin (HE) staining and toluidine blue staining respectively, and the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue were examined by immunohistochemical staining ( SP method). The relationship of their expression with upper and lower respiratory tract inflammation was analyzed. SPSS 13.0 software was used to analyze the data. Results The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AR were ( 154.8±12.0)and (124. 0 ±8.2), (43. 2 ±7.6) and (34. 5 ±5.0) in the control groups, the difference was significant (t value were 24. 260, 29. 525 respectively, all P＜0.05). The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AS were (149.9±11.7)and(120.1±7.3), (48.6 ± 7. 6) and (39.1±5.2)in control groups, the difference was significant (t value were 22. 929 and 28. 530respectively, all P＜0.05).The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AR were (188.8±17.0), and (134.8±7.9), (57.6±23.3)and(40. 3 ± 8. 2 ) in control groups, the difference was significant (t value were 13. 836 and 26. 220, all P ＜0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AS were (179. 2 ± 15.4 ) and ( 153. 5 ± 10. 1 ), (70. 5 ±33. 1 ) and ( 33.8 ± 14. 0) in control groups, the difference was significant ( t value were 9. 412 and 21. 858, all P ＜0. 05). There was a correlation between the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue of AR ( r values were 0. 893 and 0. 700 respectively, P values were 0. 001 and 0. 024, respectively ) and AS ( r values were 0. 692 and 0. 644 respectively, P values were 0. 027and 0. 044 respectively) groups. Conclusions The inflammation is similar between AR and AS. The MMP9 and TNF-α may play an important role in the pathogenesis of upper and lower respiratory tract inflammation.     

Expression of COX-2 and transcription factor CCAAT enhancer binding proteinβin refractory sinusitis with nasal polyps and its significance

Objective To study the expression and significance of COX-2 and C/EBP-βin refractory sinusitis with nasal polyps,and to explore the relationship between them and the recurrence of sinusitis with nasal polyps.Methods The protein expression of COX-2 and C/EBP-βin 20 cases of refractory sinusitis with nasal polyps,20 cases of sinusitis with nasal polyps and 20 cases of normal nasal mucosa were detected by western blot,and the relationship between the two was compared.Results The expression levels of COX-2 and C/EBP-βin refractory sinusitis with nasal polyps were significantly different from those in refractory sinusitis with nasal polyps(P<0.05);The expression levels of COX-2 and C/EBP-βin sinusitis tissues with nasal polyps were significantly different from those in normal nasal mucosa tissues(P<0.05);The expression levels of COX-2 and C/EBP-βin each group were significantly correlated(P<0.05).Conclusions The high expression of COX-2 and C/EBP-βmay be closely related to postoperative recurrence of sinusitis patients with nasal polyps.Both may be used as objective indicators to judge the postoperative follow-up and recurrence tendency of patients with sinusitis with nasal polyps..     

基质金属蛋白酶及组织金属蛋白酶抑制剂在鼻腔鳞状细胞癌中的表达及意义

目的 研究基质金属蛋白酶(matrix metalloproteinase,MMP)2、MMP-9及组织金属蛋白酶抑制剂(tissue inhibitor of metalloproteinase,TIMP)1、TIMP-2在鼻腔鳞状细胞癌中的表达及意义.方法 应用免疫组化S-P法检测50例鼻腔鳞状细胞癌和50例中鼻甲...     

突发性极重度聋与全聋的预后特点及差异

Objective To clarify the different prognostic characteristics between profound sudden sensorineural hearing loss (SSNHL) and total SSNHL. Methods The patients with SSNHL who visited Eye Ear Nose and Throat Hospital from June 2007 to September 2008 were reviewed retrospectively. All the 204 patients, with pure tone average (PTA) threshold more than 90 dB, were enrolled and divided into two groups, including total SSNHL and profound SSNHL groups. The relationship between recovery rate and prognostic factors including the age, complications, time period between onset and therapy was analyzed.Results There were 57 cases of total SSNHL and 147 cases of profound SSNHL in this series. Tinnitus was complained in more than 90% of the patients in both groups, which was higher than that of dizziness and ear fullness. Dizziness was present in 64. 9% (37/57) patient with total SSNHL group and 45.6% (67/147)patients with profound SSNHL, which had significant difference between the two groups (x2 = 5.72,P =0. 017). The PTA threshold improvement in total SSNHL group and profound SSNHL group was (36. 4 ±19.3) dB and (40. 2 ±21.3) dB respectively, which was no significant difference between the two groups (t = 1. 165 ,P =0. 245). The cured patients were all those received therapy within 1 week following the onset of SSNHL, which was of 2. 6% (1/38) patients in the total SSNHL group and 14. 3% (14/98) patients in the profound SSNHL group(P =0. 045). Furthermore, 3.5% (2/57) patients in total SSNHL group as well as 29. 9% (44/147) patients in profound SSNHL group obtained a good result with PTA threshold ≤50 dB after therapy(x2 = 15.92,P = 0. 001 ). In addition, the favorable prognosis was related with the onsettherapy time point( P = 0. 001 ), but not related to the patients' age. Conclusion Profound SSNHL and total SSNHL though both with PTA threshold > 90 dB had significant differences recovery rate and need to be studied separately.     

突发性极重度聋与全聋的预后特点及差异

Objective To clarify the different prognostic characteristics between profound sudden sensorineural hearing loss (SSNHL) and total SSNHL. Methods The patients with SSNHL who visited Eye Ear Nose and Throat Hospital from June 2007 to September 2008 were reviewed retrospectively. All the 204 patients, with pure tone average (PTA) threshold more than 90 dB, were enrolled and divided into two groups, including total SSNHL and profound SSNHL groups. The relationship between recovery rate and prognostic factors including the age, complications, time period between onset and therapy was analyzed.Results There were 57 cases of total SSNHL and 147 cases of profound SSNHL in this series. Tinnitus was complained in more than 90% of the patients in both groups, which was higher than that of dizziness and ear fullness. Dizziness was present in 64. 9% (37/57) patient with total SSNHL group and 45.6% (67/147)patients with profound SSNHL, which had significant difference between the two groups (x2 = 5.72,P =0. 017). The PTA threshold improvement in total SSNHL group and profound SSNHL group was (36. 4 ±19.3) dB and (40. 2 ±21.3) dB respectively, which was no significant difference between the two groups (t = 1. 165 ,P =0. 245). The cured patients were all those received therapy within 1 week following the onset of SSNHL, which was of 2. 6% (1/38) patients in the total SSNHL group and 14. 3% (14/98) patients in the profound SSNHL group(P =0. 045). Furthermore, 3.5% (2/57) patients in total SSNHL group as well as 29. 9% (44/147) patients in profound SSNHL group obtained a good result with PTA threshold ≤50 dB after therapy(x2 = 15.92,P = 0. 001 ). In addition, the favorable prognosis was related with the onsettherapy time point( P = 0. 001 ), but not related to the patients' age. Conclusion Profound SSNHL and total SSNHL though both with PTA threshold > 90 dB had significant differences recovery rate and need to be studied separately.     

Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

All-trans retinoic acid（ATRA） inhibits matrix metalloproteinase（MMP）-2 and MMP-9 in synovial fibroblasts, skin fibroblasts,bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells（HDPCs）. The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and-9 in HDPCs. The productions and messenger RNA（mRNA） expressions of MMP-2 and-9 were accessed by gelatin zymography and real-time polymerase chain reaction（PCR）, respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 mmol？L21ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs,which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.     

基质金属蛋白酶及其抑制剂在腮腺肿瘤中的表达

目的 :探讨基质金属蛋白酶 (MMP)及其组织抑制剂 (TIMP)与腮腺肿瘤的临床相关性。方法 :采用ABC法进行免疫组织化学染色 ,观察MMP 2、MMP 9及其TIMP 1,TIMP 2在 6 0例腮腺良性和恶性肿瘤中的表达 ,比较它们与临床特征的相关性及其各因子间的相关性。结果 :①腮腺恶性肿瘤有淋巴结转移和远处转移时TIMP 2的表达下调 (P <0 .0 1) ;②在腮腺良性肿瘤中 ,6 0岁以上患者MMP 2的表达明显增强 (P <0 .0 1) ;③MMP 2与MMP 9,MMP 9与TIMP 1,MMP 2与TIMP 2呈线性正相关性 (P <0 .0 5 )。结论 :在腮腺恶性肿瘤中 ,MMP 2与TIMP 2之间的平衡失调可能更为重要 ,TIMP 2表达的下调可作为肿瘤早期转移和浸润的标志之一。     

基质金属蛋白酶-2及其抑制剂和白细胞介素-6在中耳胆脂瘤的表达及意义

目的研究基质金属蛋白酶-2（matrix metalloproteinase-2,MMP-2）及其抑制剂（tissue inhibitor of metalloproteinase, TIMP-2）和白细胞介素-6（interleukin-6,IL-6）在中耳胆脂瘤中的表达,探讨其表达在胆脂瘤溶骨机制中的作用.方法应用免疫组化技术检测32例患者中耳胆脂瘤组织和10例正常人外耳道皮肤组织中MMP-2、 TIMP-2和IL-6的表达.结果 MMP-2在胆脂瘤上皮各层细胞中均有表达,基底层表达最强,棘层次之,颗粒层及角质层细胞表达较弱;TIMP-2在基底细胞层和棘细胞层有少量表达;IL-6的表达分布于胆脂瘤上皮全层,但在基底层细胞表达最弱,棘细胞层、颗粒层和角质层依次递增,染色最强的部位是颗粒层和角质层,而正常外耳道皮肤未见MMP-2、 TIMP-2、IL-6的表达.结论在胆脂瘤组织中存在MMP-2与TIMP-2的表达失衡,导致胆脂瘤的骨质破坏.同时胆脂瘤上皮高表达IL-6可能是MMPs过表达的原因.     

Prognostic value of matrix metalloproteinase 9 expression in patients with juvenile nasopharyngeal angiofibroma: Tissue microarray analysis

Objective

Although JNA is a benign neoplasm histopathologically, it has a propensity for locally destructive growth and remains a higher postoperative recurrence rate. The aim of this study was to analyze the expression and localization of MMP-9 in JNA using tissue microarray to elucidate its correlation with clinicopathological features and recurrence.

Materials and methods

The expression of MMP-9 was assessed by immunohistochemistry in a tissue microarray from 70 patients with JNA and 10 control subjects. Correlation between the levels of MMP-9 expression and clinicopathologic variables, as well as tumor recurrence, were analyzed.

Results

MMP-9 was detected in perivascular and extravascular less differentiated cells and stromal cells of patients with JNA but not in the matured vascular endothelial cells of these patients. The presence of MMP-9 expression in JNA was correlated with patient's age (p = 0.001). Spearman correlation analysis suggested that high expression of MMP-9 in JNA had negative correlation with patient's age (r = −0.412, p < 0.001). The recurrence rate in JNA patients with high MMP-9 expression was significantly higher than those with low MMP-9 expression (p = 0.002). In multivariate and ROC curve analysis, MMP-9 was a good prognostic factor for tumor recurrence of JNA.

Conclusion

Higher MMP-9 expression is a poor prognostic factor for patients with JNA who have been surgically treated.     

西安及深圳地区鼻咽癌组织中MMP-9和TIMP-1的表达及意义

目的:探讨鼻咽癌组织中基质金属蛋白酶9(MMP-9)和基质金属蛋白酶组织抑制剂-1(TIMP-1)的表达在陕西西安与深圳地区之间是否存在地域差别及其意义。方法:应用免疫组织化学方法分别检测西安地区21例、深圳地区22例鼻咽癌组织中MMP-9和TIMP-1表达的情况。结果:西安与深圳地区鼻咽癌组织中MMP-9阳性表达率分别为61.90%和68.18%;TIMP-1阳性表达率两地区分别为28.57%和31.82%。两地区鼻咽癌组织中MMP-9与TIMP-1表达均有显著负相关性。西安地区MMP-9表达与淋巴结转移有显著关系,TIMP-1则与淋巴结转移无相关性。两地区之间MMP-9、TIMP-1的表达差异无统计学意义(P>0.05)。结论:鼻咽癌组织中MMP-9、TIMP-1的表达在西安与深圳两地区之间无差别;MMP-9高表达在鼻咽癌浸润转移中有重要作用。     

细胞外基质金属蛋白酶诱导因子在喉鳞状细胞癌组织中的表达

目的：了解细胞外基质金属蛋白酶诱导因子(EMMPRIN)在喉鳞状细胞癌(LSCC)及喉癌前病变的表达情况,探讨其与LSCC浸润和转移的关系。方法：用免疫组织化学SP法对42例LSCC、28例喉癌前病变和20例正常喉组织中的EMMPRIN表达情况进行检测。结果：EMMPRIN在LSCC和喉癌前病变的阳性表达率分别为88．1％和57．1％,明显高于正常喉组织的5．0％,Ⅲ～Ⅳ期LSCC组织的强阳性表达率为76．0％,高于Ⅰ～Ⅱ期的强阳性表达率17．6％。伴有颈淋巴结转移的LSCC组织的EMMPRIN强阳性表达率高于无淋巴结转移组。结论：EMMPRIN在LSCC有较高的阳性表达。EMMPRIN的表达与LSCC的分期和是否存在淋巴结转移有关。LSCC组织EMMPRIN的表达影响LSCC的浸润和转移。     

Effects of cytokines on matrix metalloproteinase expression in oral squamous cell carcinoma in vitro

Conclusions. The intra-tumoral cytokines IL-6, hepatocyte growth factor (HGF) and tumour necrosis factor-α (TNF-α) stimulate oral cancer cells to enhanced secretion of matrix metalloproteinase (MMP)-1 and -9. These results contribute to an understanding of the extracellular events necessary for tumour progression.Objective. MMPs play an important role in enhanced intra-tumoral proteolytic activity, promoting angiogenesis and invasion by acting on extracellular matrix substances. Cytokines secreted by tumour-infiltrating immune cells, fibroblasts and tumour cells can modulate MMP expression and secretion by cancer cells. The objective of this study was to investigate the effects of IL-6, soluble IL-6 receptor (sIL-6R), HGF, TNF-α and IL-8 on MMP-1, -2 and -9 expression by two oral squamous cell carcinoma cell lines (UT-SCC-20A and -24A).Material and methods. ELISA was used to analyse secretion of total MMP protein and gelatin zymography was used for activity analysis.Results. IL-6 had a moderate stimulatory effect on MMP-1 secretion in both cell lines, whereas sIL-6R had no effect. When these cytokines were added together, a dose-dependent, synergistic stimulatory effect was observed. HGF also upregulated MMP-1 secretion, especially in one cell line (UT-SCC-24A), and a synergistic effect was observed when HGF was added to IL-6 in both cell lines. MMP-9 secretion by UT-SCC-24A was increased when stimulated with HGF and IL-6 combined with sIL-6R, whereas no effect was found in the other cell line. TNF-α stimulated MMP-9 secretion in both cell lines, but only stimulated MMP-1 secretion in one (UT-SCC-24A). The zymographic results were consistent with the ELISA results, indicating an upregulation of active enzyme when a stimulatory effect on protein expression was detected.     

基质金属蛋白酶-1及白细胞介素-1α mRNA在中耳胆脂瘤上皮中的表达

目的 探讨基质金属蛋白酶(matrix metalloproteinases, MMP1)及其组织抑制剂(tissue inhibitor of metalloproteinases, TIMP1)和白细胞介素-1α mRNA(interleukin-1-alpha messenger ribonucleic acid, IL-1α mRNA)在中耳继发性胆脂瘤上皮的表达,分析其表达在胆脂瘤上皮溶骨性破坏中的作用.方法分别应用免疫组化SP染色法和原位杂交技术检测MMP1、TIMP1和IL-1α在32例胆脂瘤和14例胆脂瘤患者外耳道皮肤中的表达情况.结果 MMP1在32例胆脂瘤上皮各层细胞均存在较强表达,定位在胞膜和胞浆,外耳道皮肤表达较弱;两种组织MMP1阳性表达的平均(±s,下同)吸光度(A值)分别为(2 018.26±174.89)和(1 428.35±123.39),差异有极显著性(t=10.69,P<0.01);TIMP1在两者中未见明显表达;外耳道皮肤仅基底层细胞可见散在IL-1α mRNA阳性表达细胞,平均吸光度(A值)为(566.27±148.94),胆脂瘤上皮除基底层细胞外,部分区域基底上层细胞也见阳性表达,平均吸光度(A值)为938.91±223.46,差异有极显著性(t=5.03,P<0.01).结论①MMP1在胆脂瘤上皮中高表达,并提示有MMP1和TIMP1表达失衡,与胆脂瘤骨吸收特性有关.②胆脂瘤上皮高表达的IL-1α可能是MMPs过表达的原因.