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Sample records for il-6 il-8 mmp-9

  1. Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

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    Reis Sabrina

    2012-06-01

    Full Text Available Abstract Background Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC. Methods MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003. Invasive tumors (pT1-pT2 had higher expression levels of MMP-9 than superficial tumors (pTa (p = 0.026. The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048. Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003 and IL-8 (p = 0.005. Conclusion We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.

  2. Relationship of MMP-2 and MMP-9 expression of SGC7901 with IL-8 in vitro%IL-8与胃癌细胞SGC7901MMP-2和MMP-9表达的关系

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    林晓; 王娅兰

    2005-01-01

    目的探讨趋化因子白介素-8(IL-8)与胃癌细胞SGC7901细胞胶原酶MMP-2和MMP-9表达的关系.方法体外细胞培养,MTT法及免疫组化方法检测细胞增殖率及MMP-2,MMP-9蛋白表达.结果 IL-8处理组SGC7901细胞MMP-2表达较对照组(无IL-8)比较,具有显著增强(P<0.05),而MMP-9无明显差异.结论 IL-8能促进细胞SGC7901 MMP-2表达,而对MMP-9无明显影响.

  3. Porphyromonas gingivalis decreases osteoblast proliferation through IL-6-RANKL/OPG and MMP-9/TIMPs pathways

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    Le Xuan

    2009-01-01

    Full Text Available Background: Porphyromonas gingivalis, an important periodontal pathogen, is closely associated with inflammatory alveolar bone resorption. This bacterium exerts its pathogenic effect indirectly through multiple virulence factors, such as lipopolysaccharides, fimbriae, and proteases. Another possible pathogenic path may be through a direct interaction with the host′s soft and hard tissues (e.g., alveolar bone, which could lead to periodontitis. Aims and Objectives: The aim of the present study was to investigate the direct effect of live and heat-inactivated P gingivalis on bone resorption, using an in vitro osteoblast culture model. Results: Optical microscopy and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide MTT assay revealed that live P gingivalis induced osteoblast detachment and reduced their proliferation. This effect was specific to live bacteria and was dependent on their concentration. Live P gingivalis increased IL-6 mRNA expression and protein production and downregulated RANKL and OPG mRNA expression. The effect of live P gingivalis on bone resorption was strengthened by an increase in MMP-9 expression and its activity. This increase was accompanied by an increase in TIMP-1 and TIMP-2 mRNA expression and protein production by osteoblasts infected with live P gingivalis. Conclusion: Overall, the results suggest that direct contact of P gingivalis with osteoblasts induces bone resorption through an inflammatory pathway that involves IL-6, RANKL/OPG, and MMP-9/TIMPs.

  4. [Value of IL-6 and IL-8 in the diagnosis of neonatal sepsis].

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    Zhao, Feng-Xia; Liu, Guang-Hui; Zhang, Jian

    2015-12-01

    To explore the significance of interleukin-6 (IL-6) and IL-8 in the diagnosis of neonatal sepsis. This was a prospective study conducted between August 2014 and February 2015. A total of 140 neonates who were suspected infectious were enrolled and classified into a sepsis group (n=49) and a local infection group (n=91). Sixty-one neonates who were non-infectious served as the control group. Serum levels of IL-6 and IL-8 were measured before treatment and 3 days after treatment. The value of serum IL-6 and IL-8 for the diagnosis of neonatal sepsis was assessed by receiver operating characteristic (ROC) curve analysis. Before treatment, serum levels of IL-6 and IL-8 in the sepsis group were higher than those in the local infection and control groups (Psepsis group remained higher than that in the local infection and control groups (Pneonatal sepsis were 87.8%, 79.6% and 81.6% respectively; when the cut-off value of serum IL-8 was 54 pg/mL, the sensitivity, specificity and accuracy of serum IL-6 for the diagnosis of neonatal sepsis were 77.6%, 63.8% and 67.2% respectively. With the combination of serum IL-6 and IL-8 levels, the sensitivity, specificity and accuracy for the diagnosis of neonatal sepsis were 71.4%, 86.2% and 82.6% respectively. IL-6 and IL-8 participate in the inflammatory response and the serum levels of both vary with the severity of infection. The diagnostic value of IL-6 for neonatal sepsis is higher than IL-8. The combined detection of serum levels IL-6 and IL-8 may increase the accuracy of diagnosis of neonatal sepsis.

  5. DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

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    Fan Wanhu; Chen Ruilin; Yue Jinsheng; Liu Zhengwen; Zhang Shulin

    2006-01-01

    Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

  6. Diagnostic significance of IL-6 and IL-8 in tubal ectopic pregnancy.

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    Rajendiran, Soundravally; Senthil Kumar, G P; Nimesh, Archana; Dhiman, Pooja; Shivaraman, K; Soundararaghavan, S

    2016-10-01

    As there are no specific non-invasive markers for the diagnosis of tubal ectopic pregnancy, our objective in the present study was to explore the role of inflammatory cytokines IL-6 and IL-8 in the diagnosis of ruptured tubal ectopic pregnancy. Twenty-eight women with tubal ectopic pregnancy, 31 patients with intrauterine abortion and 29 gestational age matched women having normal intrauterine pregnancy were included in the study. Five millilitre of blood was collected at the time of admission, serum was separated and stored at -70 °C for subsequent analysis of β hCG, IL-6 and IL-8 levels. The level of IL-6 was a significant increase in the women with tubal ectopic pregnancy compared to intrauterine abortion and normal pregnancy. IL-8 levels decrease significantly in the tubal ectopic pregnancy and in intrauterine abortion patients when compared with the normal pregnancy group. At the cutoff of 26.48 pg/ml IL-6 level predicted the tubal ectopic pregnancy with moderate accuracy. Therefore, it can be concluded that measurement of IL-6 may have relevance in the diagnosis of ectopic pregnancy as a novel inflammatory serum biomarkers.

  7. Serum Levels of Il-8, Tnf-α And Il-6 in Children with Atopic Dermatitis

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    Perihan Öztürk

    2012-08-01

    Full Text Available In­tro­duc­ti­on: Atopic dermatitis (AD is associated with an imbalance between T helper 1 (Th1 and T helper 2 (Th2 cells. It is chronic relapsing inflammatory skin disease affecting especially the children. Recently, it has been intensively studied and new aspects regarding the immunopathogenesis are suggested. Studies about the role of cytokines on formation of atopic diseases are rather new and most of them are based on in vitro observations. It is not completely clear yet how cytokines regulate diseases in vivo and studies about this subject are rather limited. In this study; the serum levels of IL-8, TNF-α, IL-6 and the relationship between these parameters and the disease severity in a group of children with AD were investigated.Materials and Methods: The severity of AD was assessed by the same dermatologist using the Scoring Atopic Dermatitis (SCORAD index system. IL-8, TNF-α, and IL-6 levels were measured by ELISA method.Results: Serum levels of IL-8, TNF-α and IL-6 were determined and were found statistically significantly higher in patients than controls. A statistically significant correlation between serum levels of IL-8, TNF-α, and IL-6 and SCORADs in children with AD was determined.Conclusion: These results show that serum levels of IL-8, TNF-α, and IL-6 may be used as important markers in the assessment of disease severity and follow-up of child patients with AD. As a result, the role of cytokines and the relationship between cytokines in the immunopathogenesis of AD are rather complex and still not clearly clarified, further investigations are required to understand this complex process. (Jo­ur­nal of Cur­rent Pe­di­at­rics 2012; 10: 50-4

  8. Serum Levels of IL-1β, IL-6, TGF-β, and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting

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    Rongrong Zhang

    2015-01-01

    Full Text Available Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS. Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1β, IL-6, TGF-β, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1β, IL-6, TGF-β, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

  9. IL-1b, IL-6 and IL-8 Levels in Gyneco-Obstetric Infections

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    Beatriz Basso

    2005-01-01

    Full Text Available Objective. During pregnancy cytokines and inflammatory mediators stimulate the expression of prostaglandin, the levels of which determine the onset of labor. The aim of this work was to study interleukin IL-1β, IL-6 and IL-8 levels in the vaginal discharge, serum and urine of pregnant women with genitourinary infection before and after specific treatment. One hundred and fifty-one patients were studied during the second or third trimester of their pregnancy.

  10. Expression ofVEGF,IL-6,IL-8 in serum and peritoneal fluid of patients with endometriosis

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    Yu-Xiang Fan

    2015-01-01

    Objective:To explore the expression of VEGF, IL-6, and IL-8 in serum and peritoneal fluid of patients with endometriosis (EMT) and their clinical significances.Methods:EMT patients who were pathologically diagnosed after laparoscopy from February, 2014 to February, 2015 were included in the study and served as the observation group. Moreover, patients with benign ovarian tumor and healthy women who came for physical examination at the same period were selected and served as the disease control group and normal control group, respectively for correlation analysis. The levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid of subjects in the three groups were compared.Results:The levels of serum VEGF, IL-6, and IL-8 in the observation group were significantly higher than those in the disease control group and the normal control group (P0.05). The levels of VEGF, IL-6, and IL-8 in peritoneal fluid in the observation group were significantly higher than those in the disease control group (P<0.05). With the increasing of EMT staging, the levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid were correspondingly elevated. The levels of VEGF, IL-6, and IL-8 in serum and peritoneal fluid at stageⅢ-Ⅳ were significantly higher than those at stageⅠ-Ⅱ(P<0.05).Conclusions:VEGF, IL-6 and IL-8 are highly expressed in serum and peritoneal fluid of patients with EMT. With the progression of the disease, the expression of VEGF, IL-6 and IL-8 shows an increasing trend. Clinical detection of the changes of VEGF, IL-6, and IL-8 levels in serum and peritoneal fluid can monitor the progression of EMT condition.

  11. Comparison of IL-6, IL-8 Concentrations in H. pylori- and non-H. pylori-associated Gastritis

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    Gontar Alamsyah Siregar

    2014-12-01

    Full Text Available BACKGROUND: Helicobacter pylori is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. The gastric mucosal levels of the proinflammatory cytokines Interleukin 6 (IL-6 and IL-8 have been reported to be increased in H. pylori infection, but the serum levels in H. pylori infection is still controversial. The purpose of this study was to investigate the serum levels of IL-6 and IL-8 in H. pylori infection. METHODS: A cross sectional study was done on eighty consecutive gastritis patients admitted to endoscopy units at Adam Malik General Hospital and Permata Bunda Hospital, Medan, Indonesia from May-October 2014. Histopathology was performed for the diagnosis of gastritis. Rapid urease test for diagnosis of H. pylori infection. Serum samples were obtained to determine circulating IL-6 and IL-8. Univariate and bivariate analysis (independent t test were done. RESULTS: There were 41.25% patients infected with H. pylori. Circulatory IL-6 levels were significantly higher in H. pylori-infected patients compared to H. pylori negative, but there were no differences between serum levels of IL-8 in H. pylori positive and negative patients. CONCLUSIONS: The immune response to H. pylori promotes systemic inflammation, which was reflected in an increased level of serum IL-6. Serum levels of IL-8 were not significantly different between H. pylori positive and negative. KEYWORDS: Helicobacter pylori, gastritis, IL-6, IL-8, cytokine.

  12. Regulatory Effect of E2, IL-6 and IL-8 on the Growth of Epithelial Ovarian Cancer Cells

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    Yue Wang; Jie Yang; Yan Gao; Yongrui Du; Leyuan Bao; Wenyan Niu; Zhi Yao

    2005-01-01

    To determine the regulatory effects of estrogen and cytokine IL-6 and IL-8 on the growth of epithelial ovarian cancer (OVCA), we first examined the status of estrogen receptors (ERα and ERβ), IL-6 receptor (IL-6Rα and gp130), and IL-8 receptor (IL-8RA and IL-8RB) on five epithelial OVCA cell lines by semiquantitative RT-PCR and Western blot analysis. Results showed that the expressions of these receptors were variable on the five cells.Those OVCA cells expressing the receptors were selected to study related molecular mechanism. MTT assay was performed to observe the effects of 17β-estradiol (E2), IL-6 and IL-8 on cell proliferation. We discovered that E2 markedly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner.Tamoxifen (Txf), an ER inhibitor, completely blocked the proliferation of the E2-induced cells, and IL-6- or/and IL-8-neutralizing antibody only showed partially blocking activity. IL-6 and IL-8 were able to significantly stimulate CAOV-3 and OVCAR-3 cell proliferation in a time- and dose-dependent manner, which had a potential synergistic effect on CAOV-3 cells but not on OVCAR-3 cells. The cell proliferation induced by these two cytokines was abolished completely by their specific neutralizing antibodies, partially by Txf, but not by unrelated goat IgG.Taken together, our results suggested that estrogen, IL-6 and IL-8 could modulate OVCA growth by forming a reciprocal cascade with amplifying effect. Cellular & Molecular Immunology.

  13. Clinical Significance of Determination of Serum IL-6, IL-8 and TNF Contents in Patients with Lung Cancer%肺癌患者血清IL-6,IL-8和TNF活性测定的临床意义

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    吴家明

    2004-01-01

    目的:探讨了肺癌患者血清中IL-6IL-8和TNF含量的变化.方法:应用酶联免疫吸附法和放免法测定了40例肺癌患者血清中IL-6IL-8和TNF含量,且与35名正常健康人作比较.结果:肺癌患者血清中IL-6IL-8和TNF水平均非常显著地高于正常人(P<0.01),术后IL-6IL-8和TNF水平下降.结论:测定肺癌患者血清中IL-6IL-8和TNF含量对判断患者的免疫状态有一定的临床价值.

  14. Effect of orthodontic force on inflammatory periodontal tissue remodeling and expression of IL-6 and IL-8 in rats

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    Jian-Hao Yang; Zheng-Chen Li; Wei-Dong Kong; Wu Zhang; Ying-Ping Jia; Yue-Lan Zhang; Lin-Bo Liu; Xue-Ping Han

    2013-01-01

    ABSTRACT Objective:To investigate effect of orthodontic force on inflammatory periodontal tissue remodeling and expression ofIL-6 andIL-8 in rats.Methods:EightySD rats were randomly divided into4 groups, blank control group(groupA) with5 rats, treatment normal group(group B) with25 rats, inflammation control group(group(groupC) with25 rats, inflammation treatment group(groupD) with25 rats.Immunohistochemistry and histomorphometric analysis was performed to measure the expression ofIL-6,IL-8 and the first molar to the recent movement in the distance.Results:The expression ofIL-8 reached a maximum on day5 and declined thereafter in groupB; the expression ofIL-6 reached a maximum on day5 in groupB.The expression ofIL-6 andIL-8 was gradually weakened with time in groupC.The expression of IL-6 andIL-8 were high, and reached a maximum on day5 and declined thereafter in groupD. AD of positive cells in groupD were higher than groupB at each time point(P<0.05).The time which0.49N orthodontic force was loaded was longer, orthodontic tooth movement distance was greater.Movement distance in groupD were longer than groupB(P<0.05).Conclusions:Orthodontic force as well as inflammatory stimulus can evoke the expression ofIL-6 andIL-8. Under the combined effects of inflammation and orthodontic force, the expression ofIL-6,IL-8 will increase.

  15. Protein kinase A enhances lipopolysaccharide-induced IL-6, IL-8, and PGE2 production by human gingival fibroblasts

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    Ara Toshiaki

    2012-03-01

    Full Text Available Abstract Objective Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. Interleukin (IL-6, IL-8, and the chemical mediator prostaglandin E2 (PGE2 are known to play important roles in inflammatory responses and tissue degradation. Recently, we reported that the protein kinase A (PKA inhibitor H-89 suppresses lipopolysaccharide (LPS-induced IL-8 production by human gingival fibroblasts (HGFs. In the present study, the relevance of the PKA activity and two PKA-activating drugs, aminophylline and adrenaline, to LPS-induced inflammatory cytokines (IL-6 and IL-8 and PGE2 by HGFs were examined. Methods HGFs were treated with LPS from Porphyromonas gingivalis and H-89, the cAMP analog dibutyryl cyclic AMP (dbcAMP, aminophylline, or adrenaline. After 24 h, IL-6, IL-8, and PGE2 levels were evaluated by ELISA. Results H-89 did not affect LPS-induced IL-6 production, but suppressed IL-8 and PGE2 production. In contrast, dbcAMP significantly increased LPS-induced IL-6, IL-8, and PGE2 production. Up to 10 μg/ml of aminophylline did not affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantly increased at 100 μg/ml. Similarly, 0.01 μg/ml of adrenaline did not affect LPS-induced IL-6, IL-8, or PGE2 production, but they were significantly increased at concentrations of 0.1 and 1 μg/ml. In the absence of LPS, H-89, dbcAMP, aminophylline, and adrenaline had no relevance to IL-6, IL-8, or PGE2 production. Conclusion These results suggest that the PKA pathway, and also PKA-activating drugs, enhance LPS-induced IL-6, IL-8, and PGE2 production by HGFs. However, aminophylline may not have an effect on the production of these molecules at concentrations used in clinical settings (8 to 20 μg/ml in serum. These results suggest that aminophylline does not affect inflammatory responses in periodontal disease.

  16. Clinical significance of detection of serum interleukin(IL-6),tumr necrosis factor and urine IL-6 and IL-8 levels in patients with hepatocirrhosis%肝硬化患者血清IL-6、TNF和尿液IL-6IL-8检测的临床意义

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    周彦

    2001-01-01

    目的探讨细胞因子在肝硬化发病中的作用.方法采用双抗体夹心Elisa法对54例肝硬化患者和35例正常人血清白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)和尿液IL-6IL-8进行检测.结果肝硬化患者血清中IL-6、TNF和尿液IL-6IL-8含量较对照组明显升高(P<0.01),血IL-6、TNF含量GN与尿液量白蛋白呈高度正相关:尿液IL-6IL-8呈显著正相关(r=0.5728,P<0.05).结论肝硬化患者病程中TNF、IL-6IL-8均处于高活性状态,IL-6与体液免疫反应亢进所致的免疫病理损伤有关,IL-6IL-8、TNF参与肾脏的免疫损伤、可作为判定患者预后和转归指标.

  17. Enhanced chemosensitization in multidrug-resistant human breast cancer cells by inhibition of IL-6 and IL-8 production.

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    Shi, Zhi; Yang, Wei-Min; Chen, Li-Pai; Yang, Dong-Hua; Zhou, Qi; Zhu, Jin; Chen, Jun-Jiang; Huang, Ruo-Chun; Chen, Zhe-Sheng; Huang, Ruo-Pan

    2012-10-01

    Drug resistance remains a major hurdle to successful cancer treatment. Many mechanisms such as overexpression of multidrug-resistance related proteins, increased drug metabolism, decreased apoptosis, and impairment of signal transduction pathway can contribute multidrug resistance (MDR). Recent studies strongly suggest a close link between cytokines and drug resistance. To identify new targets involved in drug resistance, we established a multidrug-resistant human breast cancer cell line MCF-7/R and examined the cytokine profile using cytokine antibody array technology. Among 120 cytokines/chemokines screened, IL-6, IL-8, and 13 other proteins were found to be markedly increased in drug-resistant MCF-7/R cell line as compared to sensitive MCF-7/S cell line, while 7 proteins were specifically reduced in drug-resistant MCF-7/R cells. Neutralizing antibodies against IL-6 and IL-8 partially reversed the drug resistance of MCF-7/R to paclitaxel and doxorubicin, while a neutralizing antibody against MCP-1 had no significant effect. Inhibition of endogenous IL-6 or IL-8 by siRNA technology significantly enhanced drug sensitivity of MCF-7/R cells. Furthermore, overexpression of IL-6 or IL-8 expression by transfection increased the ADM resistance in MCF-7/S cells. Our data suggest that increased expression levels of IL-6 and IL-8 may contribute to MDR in human breast cancer cells.

  18. 前列腺液IL-6IL-8在诊断BPH合并CP的临床意义%The clinical significance of IL-6 and IL-8 in EPS in diagnosis of BPH with chronic prostatitis

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    李兴斌; 王海峰; 常丛旺; 杨宇; 郭鹏飞; 赖建平

    2012-01-01

    Objective To investigate the significance that the concentration levels change of IL-6 and IL-8 in EPS were used to distinguish simple BPH and BPH with chronic prostatitis. Methods Patients with BPH who needed prostate surgery could through prostatic massage to get EPS before surgery, then the Concentration of IL-6 and IL-8 were measured. The prostate tissue specimens were Collected in surgery, according to the pathological prostatitis diagnosis standard to confirm research object of patients who had simple BPH and BPH with chronic prostatitis. Results The IL-6 and IL-8 in EPS which BPH with chronic prostatitis expressed was higher than simple BPH. Conclusion The Concentration levels of IL-6 and IL-8 in EPS which were close to patients whether BPH with chronic prostatitis were more effective to distinguish simple BPH and BPH with chronic prostatitis.%目的 探讨前列腺液(EPS)内IL-6(白细胞介素6)、IL-8浓度水平对区分单纯良性前列腺增生(BPH)和BPH合并慢性前列腺炎(CP)的意义.方法 100例前列腺手术的BPH病人,在术前行前列腺液IL-6IL-8浓度检测.术中取前列腺组织标本,根据病理前列腺炎诊断标准确定单纯BPH患者与BPH合并CP患者.结果 BPH合并CP病人EPS中IL-6、L-8浓度较单纯BPH病人明显升高(P<0.01或P<0.05).结论 EPS中IL-6IL-8浓度水平与BPH患者是否伴发CP的关系密切,二者在区别单纯BPH与BPH合并CP时具有较高价值.

  19. Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in Weil's syndrome.

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    Kyriakidis, Ioannis; Samara, Pinelopi; Papa, Anna

    2011-05-01

    Studies on cytokine levels in Weil's syndrome are lacking. In this study, TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels were measured in 44 serum samples of patients diagnosed with Leptospira interrogans serovar icterohaemorrhagiae infection. TNF-α levels linked with pulmonary hemorrhagic implications, while elevated sTNFR1 and IL-10 levels linked with fatal cases. IL-6 and IL-8 did not seem to affect the outcome of the disease. Immune response pattern in Weil's syndrome bears resemblance to other patterns described for hemorrhagic fevers. IL-10/TNF-α ratio is proposed as a marker for prognosis.

  20. The Expression of IL-6,IL-8 and TNF-αin Plasma of Breast Cancer Patients%乳腺癌患者血浆中IL-6IL-8及TNF-α的表达

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    刘杨; 陈利琴; 王文斌; 缪文青; 黄明; 陈大平

    2016-01-01

    目的:探讨血浆中白细胞介素( IL)-6、IL-8及肿瘤坏死因子-α( TNF- a)与乳腺癌发生发展、临床分期及骨转移的关系。方法:111例乳腺肿瘤患者根据病理结果分为乳腺良性肿瘤组( n=50)、乳腺癌组( n=61),50例健康妇女作为正常对照组,采用酶联免疫吸附( ELISA)法分别检测3组患者血浆中IL-6IL-8及TNF-α的水平,分析3项指标与乳腺癌临床分析、肿瘤转移以及年龄(≥50岁和<50岁)的关系。结果:乳腺癌组血浆IL-6IL-8及TNF-α水平明显高于良性肿瘤组和正常对照组( P<0.05);随着乳腺癌临床分期的提高,IL-6IL-8及TNF-α水平逐渐升高( P<0.05);乳腺癌骨转移患者血浆IL-6IL-8及TNF-α水平明显高于乳腺癌无转移及乳腺癌其他脏器转移患者( P <0.05);年龄对乳腺癌患者血清 IL-6IL-8及 TNF-α水平影响不大( P >0.05)。结论:血清IL-6IL-8及TNF-α水平与乳腺癌的发生发展有关。%Objective:To discussthe relatiohship betweeh plasma ihterleukih(IL)-6,IL-8 ahd tumor hecrosis factor-α( TNF-α)ahd the developmeht,clihical stage ahd bohe metastasis of breast cahcer. Methods:Accordihg to the pathological results,111 cases of breast cahcer patiehtswere divided ihto behigh breast tumor group( n =50 ),breast cahcer group( n =61 ),50 healthy womeh as cohtrol group. Plasma IL-6,IL-8 ahd TNF-α levels of hormal cohtrol group,breast behigh tumor group ahd breast cahcer of 3 groups were measured by ehzyme-lihked immuhosorbeht( ELISA). Theh their cor-relatioh with clihical biological characteristics of breast cahcer was ahalyzed. Results:Plasma IL-6, IL-8 ahd TNF-α levels ih breast cahcer group were sighificahtly higher thah those ih behigh tumor group( P0 . 05 ). Conclusion:Plasma IL-6 ,IL-8 ahd TNF-αlevels may be associated with the developmeht of breast cahcer.

  1. Effects of ulinastatin and docataxel on breast tumor growth and expression of IL-6, IL-8, and TNF-α

    Directory of Open Access Journals (Sweden)

    Luo Jie

    2011-02-01

    Full Text Available Abstract Objective This study investigated the effects of Ulinastatin (UTI and docataxel (Taxotere, TAX on tumor growth and expression of interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α in breast cancer. Methods MDA-MB-231 human breast carcinoma cells were cultured in vitro and injected into nude mice to establish breast tumor xenografts in vivo. Cultured cells and mice with tumors were randomly divided into four groups for treatment with TAX, UTI, and TAX+UTI. The effects of these drug treatments on cell proliferation and apoptosis was measured using the MTT assay and the Annexin V/propidium iodide (PI double-staining method, respectively. IL-6, IL-8, and TNF-α expression levels were determined by measuring mRNA transcripts in cultured cells by RT-PCR and cytokine proteins in solid tumors using immunohistochemistry. Results UTI, TAX, and UTI+TAX inhibited the growth of MDA-MB-231 cells in vitro and tumors in vivo. These two drugs, particularly when used in combination, promote tumor cell apoptosis and down-regulate the expression IL-6, IL-8, and TNF-α cytokines. Conclusion Both UTI and TAX inhibited the growth of MDA-MB-231 breast carcinoma cells. UTI enhanced the inhibitory effect of TAX by a mechanism consistent with the down-regulated expression of IL-6, IL-8, and TNF-α.

  2. Glycine tomentella Hayata inhibits IL-1β and IL-6 production, inhibits MMP-9 activity, and enhances RAW264.7 macrophage clearance of apoptotic cells

    Directory of Open Access Journals (Sweden)

    Sun Yu-Shu

    2010-11-01

    Full Text Available Abstract Background To assess the effects of Glycine tomentella Hayata (GTH, a traditional herbal medicine for treatment of rheumatic diseases on the expression of the proinflammatory cytokines and on the clearance of apoptotic cells by macrophages. Methods RAW264.7 cells were cultured with lipopolysaccharide (LPS in the presence or absence of ethanol extract of GTH. The expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α, and inducible nitric oxide synthase (iNOS and transglutaminase 2 (TG2 were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA. Matrix metalloproteinase (MMP-2 and MMP-9 were assayed by gelatin zymography. For detecting uptake of apoptotic cells, RAW264.7 cells were cultured with carboxyfluorescein diacetate (CFDA-stained apoptotic cells and assayed by flow cytometry. Results The major components of GTH analyzed by high-performance liquid chromatography (HPLC chromatogram were daidzein (42.5%, epicatechin (28.8%, and naringin (9.4%. GTH treatment inhibited the expression of proinflammatory cytokines IL-1β, IL-6 and MMP-9 but did not affect the expression of TNF-α and iNOS. GTH significantly enhanced the expression of TG2 and the clearance of apoptotic cells by RAW264.7 macrophages. Conclusions GTH inhibits proinflammatory cytokine secretion and MMP-9 activity, enhances apoptotic cell uptake and up-regulates TG2 expression. Our data show that GTH might have beneficial effects on rheumatic diseases.

  3. IL-6IL-8在三氯乙烯致敏豚鼠血清中的变化%Variation of IL-6 and IL-8 levels in serum of guinea pigs sensitized by trichloroethylene

    Institute of Scientific and Technical Information of China (English)

    汪亮; 汪立杰; 戴丹; 沈彤; 朱启星

    2010-01-01

    目的 通过豚鼠致敏最大值试验(guinea pig maximization teat,GPMT)方法建立豚鼠致敏模型,检测并比较TCE致敏豚鼠与未致敏豚鼠血清中IL-6IL-8的水平,探讨IL-6IL-8在三氯乙烯(TCE)过敏性皮炎中的作用.方法 将豚鼠随机分为空白对照组,溶剂(橄榄油)对照组,DNCB阳性对照组和TCE处理组.采用GPMT法建立豚鼠致敏模型.根据致敏结果及末次激发后采血的不同时点将TCE处理组分为TCE未致敏24 h组,TCE致敏24 h组.TCE未致敏72 h组,TCE致敏72 h组.用ELISA试剂盒测定血清中IL-6IL-8的含量.结果 DNCB组致敏率为100%,TCE组致敏率为62.1%.溶剂对照组与空白对照组差异均无统计学意义.与溶剂对照组相比,TCE未致敏24 h组IL-6水平降低,差异有统计学意义(P<0.05),TCE未致敏72 h组与TCE未致敏24 h组相比,IL-6水平明显升高,差异有统计学意义(P<0.05).与溶剂对照组相比,TCE未致敏72组IL-8水平明显降低,差异有统计学意义(P<0.05).结论 血清中细胞因子IL-6IL-8水平在TCE诱导的致敏组和未致敏组豚鼠间,仅个别时间段的差异有统计学意义,提示两者可能仅在一定时间段中发挥作用.

  4. Increase in IL-6, TNF-a, and MMP-9, but not sICAM-1, concentrations depends on exercise duration

    DEFF Research Database (Denmark)

    Reihmane, Dace; Jurka, Antra; Tretjakovs, Peteris

    2013-01-01

    It has been suggested that exercise intensity is of importance in the regulation of increase in pro-inflammatory molecules, but there is still a debate about the effect of duration on these molecules. Therefore, the effect of exercise duration on the serum concentrations of interleukin-6 (IL-6......), tumour necrosis factor-α (TNF-α), soluble form of intercellular adhesion molecule-1 (sICAM-1), and matrix metalloproteinase-9 (MMP-9) was studied in 22 half-marathon (HM) and 18 marathon (M) male amateur runners who completed their exercise task in 1.8 ± 0.2 (mean ± standard deviation) and 3.6 ± 0.4 h......, respectively (thus, average speed was 11.7 ± 1.5 and 11.9 ± 1.8 km h−1, respectively). Blood was sampled 2 days before, 15 min after, and 28 h after the race. IL-6, TNF-α, and MMP-9 always increased immediately after exercise, but the increase was larger (P

  5. 新生儿败血症血清IL-6IL-8、PCT检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    胡新民; 徐美玉; 蒋晓天

    2002-01-01

    目的:探讨新生儿败血症时血清IL-6IL-8、PCT的变化.方法:IL-6IL-8用ELISA双夹心法,PCT用放射免疫法.结果:新生儿败血症血清IL-6IL-8、PCT明显升高.结论:IL~6、IL-8、PCT可作为新生儿败血症的早期诊断指标.

  6. Clinical Value of IL-6 and IL-8 in Serum of Cases with Breast Cancer%乳腺癌患者血清中IL-6IL-8测定的临床价值

    Institute of Scientific and Technical Information of China (English)

    李明; 张金业; 林兰; 刘继斌

    2011-01-01

    Objective To investigate a new attempt on serological diagnosis of breast cancer. Methods The serum IL-6 and IL-8 in 60 cases with breast cancer,30 cases of benign disease,and 40 healthy controls were tested by using ELISA method. Results There were significantly different among control group,benign breast and breast cancer group. There were a certain relationship between serum IL-6 and IL-8 and staging and prognosis in breast cancer. Conclusion IL-6 and IL-8 may be involved in breast cancer occurrence and development of the whole process. It could reflect changes in the biological behavior and prognosis of breast cancer,their monitoring has important clinical significance.%目的 为乳腺癌诊断提供血清学新尝试.方法 60例乳腺癌患者均来自于2009年3月~2010年3月南通市肿瘤医院病例,均为女性,年龄27~78岁,平均年龄57岁.所有患者均经手术病理证实且术前未经过化疗、放疗、内分泌及生物治疗.乳腺良性患者女性30例,年龄21~63岁,平均年龄36岁.对照组:健康体检者女性40例,年龄19~47岁,平均年龄33岁.所有研究对象近半年内未服用过免疫调节剂和激素类药物.采用酶联免疫吸附(ELISA)方法检测乳腺癌患者血清中IL-6IL-8.结果 对照组、乳腺良性患者组以及乳腺癌组三者之间差异有统计学显著性意义(P<0.05);乳腺癌血清IL-6IL-8水平与分期以及预后有一定的关系(P<0.05).结论 IL-6IL-8可能参与了乳腺癌发生、发展的全过程,它的变化可间接反映乳腺癌的生物学行为和预后,对其监测具有重要的临床意义.

  7. Bacterial endotoxin activates retinal pigment epithelial cells and induces their degeneration through IL-6 and IL-8 autocrine signaling.

    Science.gov (United States)

    Leung, Kar Wah; Barnstable, Colin J; Tombran-Tink, Joyce

    2009-04-01

    Inflammation is a major contributing factor to many blinding disorders including uveitis, diabetic retinopathy, and age-related macular degeneration. Here we examined the response of the retinal pigment epithelium (RPE) to physiological levels of lipopolysaccharide (LPS) to understand the role of this epithelium in inflammatory retinal conditions. Expression of a group of inflammatory mediators was identified by gene array analysis and confirmed by PCR and immunocytochemistry in primary human RPE cultures and ARPE19. The effects of LPS on the expression of these cytokines and RPE survival were examined by PCR, Luminex bead, and MTT assays. RPE cells express many cytokine receptors including IL-1R, -4R, -6R, -8RA, IFNAR1, IFNGR1/2 and secrete a range of pro- and anti-inflammatory cytokines including IL-4, -6, -8, -10, -17, IFN-gamma, MCP-1, and VEGF. LPS increases IL-13RA1 and IFNAR1, and decreases IL-7R receptor expression. It also increases RPE secretion of IL-4, -6, -8, -10, IFN-gamma and MCP-1, and is toxic to RPE cells at LC(50)=17.7 microg/ml. LPS toxicity is mediated by IL-6 and IL-8 through an autocrine feedback loop. Silencing IL-6R and IL-8RA gene expression by siRNA blocks death by their respective ligands or LPS. These findings imply that RPE cells are acutely sensitive to inflammatory stress and that over secretion of IL-6 and IL-8 by this epithelium during inflammatory stimulus may be an underlying factor in the progression of some retinal pathologies.

  8. Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.

    Science.gov (United States)

    Hartman, Zachary C; Poage, Graham M; den Hollander, Petra; Tsimelzon, Anna; Hill, Jamal; Panupinthu, Nattapon; Zhang, Yun; Mazumdar, Abhijit; Hilsenbeck, Susan G; Mills, Gordon B; Brown, Powel H

    2013-06-01

    Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.

  9. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

    National Research Council Canada - National Science Library

    Jonge, de, E; Friederich, P.W; Vlasuk, G.P; Rote, W; Vroom, M.B; Levi, M.M; Poll, van der, T

    2003-01-01

    .... Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma...

  10. Mast cell-derived TNF-α and histamine modify IL-6 and IL-8 expression and release from cutaneous tumor cells

    DEFF Research Database (Denmark)

    Artuc, Metin; Guhl, Sven; Babina, Magda

    2011-01-01

    The coincidence of skin tumors and elevated mast cell (MC) numbers has been known for many years. However, it has remained controversial whether, in this context, MCs promote or inhibit tumor growth. Addressing this problem, different melanoma and squamous cell carcinoma cell lines were co-cultivated...... with primary, dermal MC for 24 h and gene or protein expression of cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) estimated. Co-culture with MCs led to an increase in IL-8 gene expression and IL-8 protein release from melanoma cells and IL-6 and IL-8 gene expression...... and protein release from squamous cell carcinoma cells, respectively. Moreover induction of IL-6 and IL-8 was primarily regulated by MC-derived TNF-α. Our data suggest an interplay between MCs and tumor cells, which results in altered cytokine release and may, thus, have an impact on tumor growth, invasion...

  11. Luteolin 8-C-β-fucopyranoside inhibits invasion and suppresses TPA-induced MMP-9 and IL-8 via ERK/AP-1 and ERK/NF-κB signaling in MCF-7 breast cancer cells.

    Science.gov (United States)

    Park, Su-Ho; Kim, Jung-Hee; Lee, Dong-Hun; Kang, Jeong-Woo; Song, Hyuk-Hwan; Oh, Sei-Ryang; Yoon, Do-Young

    2013-11-01

    Matrix metalloproteinase 9 (MMP-9) and interleukin-8 (IL-8) play major roles in tumor progression and invasion of breast cancer cells. The present study was undertaken to investigate the inhibitory mechanism of cell invasion by luteolin 8-C-β-fucopyranoside (named as LU8C-FP), a C-glycosylflavone, in human breast cancer cells. We investigated whether LU8C-FP would inhibit MMP-9 activation and IL-8 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 breast cancer cells. LU8C-FP suppressed TPA-induced MMP-9 and IL-8 secretion and mRNA expression via inhibition of the MAPK signaling pathway and down-regulation of nuclear AP-1 and NF-κB. TPA-induced phosphorylation of ERK 1/2 was suppressed by LU8C-FP, whereas JNK and p38 MAPK phosphorylation were unaffected. In addition, LU8C-FP blocked the ERK 1/2 pathways following expression of MMP-9 and IL-8. These results suggest LU8C-FP may function to suppress invasion of breast cancer cells through the ERK/AP-1 and ERK/NF-κB signaling cascades.

  12. 溃疡性结肠炎患者血清IL-6IL-8、TNF-α水平变化及意义

    Institute of Scientific and Technical Information of China (English)

    任保从

    2010-01-01

    目的 观察溃疡性结肠炎(UC)患者血清IL-6IL-8、TNF-α水平变化,并探讨其意义.方法 UC患者60例(UC组),对照组30例.采用ELISA法检测两组血清IL-6IL-8、TNF-α.结果 UC组血清IL-6IL-8、TNF-α水平明显高于对照组(P均<0.05);重度UC患者血清IL-6IL-8、TNF-α水平高于轻中度、中度高于轻度 (P均<0.05).结论 UC患者血清IL-6IL-8、TNF-α水平升高,检测血清IL-6IL-8、TNF-α有助于UC病情的判断.

  13. 口腔鳞状细胞癌患者唾液中CEA、IL-6IL-8含量的检测

    Institute of Scientific and Technical Information of China (English)

    杜娟; 颜雨春

    2010-01-01

    目的 通过对口腔鳞状细胞癌(OSCC)患者唾液中癌胚抗原(CEA)、白细胞介素6(IL-6)和白细胞介素8(IL-8)含量的测定和分析,探讨唾液中CEA、IL-6IL-8含量在口腔鳞状细胞癌诊断中的意义.方法 选取35例OSCCT1或T2期患者为病例组,35例身体健康的正常人为对照组.采用ELISA法测定所有样本唾液中的CEA、IL-6IL-8含量.结果 OSCC患者唾液中的CEA、IL-6IL-8浓度均显著高于正常人,差异具有统计学意义(P<0.01).结论 唾液中CEA、IL-6IL-8的含量对诊断OSCC具有一定的临床意义,唾液中肿瘤标记物的检测可作为诊断OSCC的一种辅助手段.

  14. IL-6 and IL-8 in cerebrospinal fluid from patients with aseptic meningitis and bacterial meningitis: their potential role as a marker for differential diagnosis

    Directory of Open Access Journals (Sweden)

    Vitor Laerte Laerte Pinto Junior

    Full Text Available Cytokines are molecules that act as mediators of immune response; cerebral spinal fluid (CSF IL-6 is found in all meningeal inflammatory diseases, but IL-8 is associated with acute bacterial meningitis (ABM. A case control study was done to ascertain the discriminatory power of these cytokines in differentiating ABM from aseptic meningitis (AM; IL-6 and IL-8 CSF concentrations were tested through ELISA in samples collected from patients who underwent investigation for meningitis. Sixty patients, 18 with AM, nine with bacteriologic confirmed ABM and 33 controls, assisted in 2005 (MA and controls and 2007 (ABM were included. Differently from controls, IL-6 concentrations were increased both in MA and ABM patients (p < 0.05. CSF IL-8 levels were higher in ABM than in AM and controls (p < 0.05. Discriminatory power in ABM as assessed by the area under receiver operator (ROC curve was 0.951 for IL-8, using a cut-off of 1.685 ng/dL (100% of sensitivity and 94% of specificity. The CSF concentration of both IL-6 and IL-8 are increased in the presence of meningeal inflammation, IL-8 could be an important tool to differentiate ABM from AM.

  15. Polarized secretion of interleukin (IL-6 and IL-8 by human airway epithelia 16HBE14o- cells in response to cationic polypeptide challenge.

    Directory of Open Access Journals (Sweden)

    Alison Wai-ming Chow

    Full Text Available BACKGROUND: The airway epithelium participates in asthmatic inflammation in many ways. Target cells of the epithelium can respond to a variety of inflammatory mediators and cytokines. Damage to the surface epithelium occurs following the secretion of eosinophil-derived, highly toxic cationic proteins. Moreover, the surface epithelium itself is responsible for the synthesis and release of cytokines that cause the selective recruitment, retention, and accumulation of various inflammatory cells. To mimic the damage seen during asthmatic inflammation, the bronchial epithelium can be challenged with highly charged cationic polypeptides such as poly-L-arginine. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human bronchial epithelial cells, 16HBE14o- cells, were "chemically injured" by exposing them to poly-l-arginine as a surrogate of the eosinophil cationic protein. Cytokine antibody array data showed that seven inflammatory mediators were elevated out of the 40 tested, including marked elevation in interleukin (IL-6 and IL-8 secretion. IL-6 and IL-8 mRNA expression levels were elevated as measured with real-time PCR. Cell culture supernatants from apical and basolateral compartments were collected, and the IL-6 and IL-8 production was quantified with ELISA. IL-6 and IL-8 secretion by 16HBE14o- epithelia into the apical compartment was significantly higher than that from the basolateral compartment. Using specific inhibitors, the production of IL-6 and IL-8 was found to be dependent on p38 MAPK, ERK1/2 MAPK, and NF-kappaB pathways. CONCLUSIONS/SIGNIFICANCE: The results clearly demonstrate that damage to the bronchial epithelia by poly-L-arginine stimulates polarized IL-6 and IL-8 secretion. This apically directed secretion of cytokines may play an important role in orchestrating epithelial cell responses to inflammation.

  16. RETRACTED: Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies.

    Science.gov (United States)

    Sisto, Margherita; Lisi, Sabrina; Lofrumento, Dario Domenico; Cucci, Liana; Mitolo, Vincenzo; D'Amore, Massimo

    2010-09-20

    The aim of this study was to analyze the Furin-TNF-α-converting enzyme (TACE)-amphiregulin (AREG)-IL-6/IL-8 secretion pathway in non-neoplastic human salivary gland epithelial cells (SGECs) stimulated with anti-Ro/SSA autoantibodies (Abs). We examined whether anti-Ro/SSA Abs-mediated TACE activation is responsible for AREG activation. As recent studies have demonstrated that AREG could induce proinflammatory cytokines secretion in epithelial cells, we discuss how TACE-mediated AREG shedding, caused by anti-Ro/SSA Abs treatment, could have a critical role in TNF-α-induced IL-6 and IL-8 secretion by SGEC. Furthermore, the effects of TNF-α blockade on AREG expression and TNF-α-AREG-mediated IL-6 and IL-8 secretion were evaluated. We have discovered that the upregulation of AREG occurs through TNF-α produced after anti-Ro/SSA Abs uptake via Fcγ receptors. Biological drug adalimumab and the gene silencing technique were used to study the AREG-IL-6/IL-8 secretion pathway, demonstrating that (i) adalimumab-mediated TNF-α blocking and TNF-α gene silencing provoke a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated SGEC; (ii) AREG gene silencing has a potent inhibitory effect on TNF-α-induced IL-6 and IL-8 secretion in SGEC treated with anti-Ro/SSA Abs; (iii) an inspection of the kinetics of cytokine production after exogeni TNF-α and AREG addition, and the use of cycloheximide in the presence of exogenous TNF-α as stimulant, clarified that TNF-α induces IL-6 and IL-8 secretion through AREG.Laboratory Investigation advance online publication, 20 September 2010; doi:10.1038/labinvest.2010.168.

  17. Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors.

    Science.gov (United States)

    Kushlinskii, N E; Timofeev, Yu S; Solov'ev, Yu N; Gerstein, E S; Lyubimova, N V; Bulycheva, I V

    2014-08-01

    Serum levels of sRANKL, RANK, OPG, IL-8, IL-6, IL-16, MMP-2, and calcitonin were measured by ELISA in patients with malignant, borderline, and benign bone tumors and in healthy individuals (control). Serum levels of RANK, OPG, IL-8, IL-6, and the OPG/sRANKL ratio were significantly higher, while the level of MMP-2 was significantly lower in patients with bone tumors than in controls. Serum concentration of IL-16 in osteosarcoma patients was significantly lower than in chondrosarcoma patients. No significant differences between bone sarcomas of different differentiation were detected for any of the studied markers. Calcitonin level depended on the tumor location and type.

  18. Muscle glycogen depletion following 75-km of cycling is not linked to increased muscle IL-6, IL-8, and MCP-1 mRNA expression and protein content

    Directory of Open Access Journals (Sweden)

    David Christopher Nieman

    2016-09-01

    Full Text Available The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N=20 participated in a 75-km cycling time trial (168±26.0 min, with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2±17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5±2.8-, 45.3±7.8-, and 8.25±1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5±14.1%, 347±68.1%, and 148±21.3%, respectively (all, P<0.001. Serum myoglobin and cortisol increased 32.1±3.3 to 242±48.3 mg/mL, and 295±27.6 to 784±63.5 nmol/L, respectively (both P<0.001. Plasma IL-6, IL-8, and MCP-1 increased 0.42±0.07 to 18.5±3.8, 4.07±0.37 to 17.0±1.8, and 96.5±3.7 to 240±21.6 pg/mL, respectively (all P<0.001. Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r=0.462, P=0.040, with change in myoglobin related to plasma IL-8 (r=0.582, P=0.007 and plasma MCP-1 (r=0.457, P=0.043, and muscle MCP-1 protein (r=0.588, P=0.017; cortisol was related to plasma IL-8 (r=0.613, P=0.004, muscle IL-8 protein (r=0.681, P=0.004, and plasma MCP-1 (r=0.442, P=0.050. In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1.

  19. 支气管肺炎患儿治疗前后血清IGF-Ⅱ、IL-6IL-8和TNF-α检测的临床意义%Clinical Significance of Determination of Changes of Serum IGF-Ⅱ,IL-6,IL-8,TNF-α Levels After Treatment in Children with Bronchopneamonia

    Institute of Scientific and Technical Information of China (English)

    冯越

    2011-01-01

    Objective To explore the clinical significance of changes of serum IGF-Ⅱ; IL-6; IL-8 and TNF-α levels after treatment in children with bronchopneamonia. Methods Serum IGF- Ⅱ; IL-6; IL-8 and TNF-a levels with RIA were detected both before and after treatment in 33 patients with children bronchopneumonia as well as in 35 controls. Results Before treatment; serum IGF-Ⅱ; IL-6; IL-8 and TNF-a levels were significantly higher in the patients than those in the controls ( P 0. 05 ) . Conclusions Seram IGF- Ⅱ; IL-6; IL-8 and TNF-a could take part in the pathogenesis of children bronchopneumonia in various ways and determination of these levels was clinically important.%目的:探讨支气管肺炎患儿治疗前后血清IGF-Ⅱ、IL-6IL-8和TNF-α的变化及其临床意义.方法:应用放射免疫分析对33例支气管肺炎患儿进行了治疗前后血清IGF-Ⅱ、IL-6IL-8和TNF-α检测,并与35名正常健康儿作比较.结果:支气管肺炎患儿在治疗前血清IGF-Ⅱ、IL-6IL-8和TNF-α水平显著地高于正常儿组(P<0.01).结论:IGF-Ⅱ、IL-6IL-8和TNF-α以不同的方式参与了患儿的发病,其水平的检测对了解病情、指导治疗具有重要的临床价值.

  20. Effect of remifentanil on serum IL-6, IL-8, and IL-10 in patients undergoing laparoscope cholecystectomy%雷米芬太尼对腹腔镜胆囊切除术患者IL-6IL-8和IL-10的影响

    Institute of Scientific and Technical Information of China (English)

    尹罗庚; 袁玉萍; 周红云; 庄建伟; 吴文玉; 丁德威

    2006-01-01

    目的 观察全麻下雷米芬太尼与芬太尼对腹腔镜胆囊切除术(LC)患者白细胞介素(IL)-6IL-8和IL-10的影响.方法 20例LC患者,随机分为两组,每组10例.雷米芬太尼组(Ⅰ组)和芬太尼组(Ⅱ组),分别测定麻醉诱导前、气腹手术前、气腹手术后0.5 h、术毕0.5 h、术后24 h的血清IL-6IL-8和IL-10的水平.结果 IL-6IL-8和IL-10在创伤后1~1.5 h开始升高,IL-6的变化最早,IL-8、IL-10在手术结束时逐渐升高,IL-6IL-8在术后24 h仍在继续上升(P<0.05),而IL-10则有不升或缓升趋势.IL-10对IL-6IL-8的升高有一定的平衡作用.组间比较,术后24 hⅠ组IL-6IL-8较Ⅱ组都有明显升高(P<0.01).结论 与芬太尼相比,雷米芬太尼可更为有效地减轻创伤刺激后IL-6IL-8和IL-10的释放.

  1. Serum IL-1β, IL-6, IL-8, and TNF-α Levels in Early Diagnosis and Management of Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    A. Nese Citak Kurt

    2007-01-01

    Full Text Available Aim. To determine serum IL-1β, IL-6, IL-8, and TNF-α levels in neonatal sepsis at the time of diagnosis and after therapy, and to show the meaningful on the follow up. Methods. This prospective study was performed on newborns who were hospitalized for neonatal sepsis and who were classified as culture-proven sepsis (n=12, as culture-negative sepsis (n=21, and as healthy newborns (n=17. Results. At the time of diagnosis, serum IL-1β, IL-6, IL-8, and TNF-α levels of culture-proven sepsis were significantly higher than those of the control groups (P<.05. At the time of diagnosis, IL-1β, IL-6, IL-8, and TNF-α levels of culture-proven sepsis and culture-negative sepsis were significantly higher than levels at the seventh day after antibiotic treatment. Conclusion. Serum IL-1β, IL-6, IL-8, and TNF-α are mediators of inflammation and can be used at the diagnosis and at the evaluation of the therapeutic efficiency in neonatal sepsis.

  2. Expression of IL-8, IL-6 and IL-1β in tears as a main characteristic of the immune response in human microbial keratitis.

    Science.gov (United States)

    Santacruz, Concepcion; Linares, Marisela; Garfias, Yonathan; Loustaunau, Luisa M; Pavon, Lenin; Perez-Tapia, Sonia Mayra; Jimenez-Martinez, Maria C

    2015-03-03

    Corneal infections are frequent and potentially vision-threatening diseases, and despite the significance of the immunological response in animal models of microbial keratitis (MK), it remains unclear in humans. The aim of this study was to describe the cytokine profile of tears in patients with MK. Characteristics of ocular lesions such as size of the epithelial defect, stromal infiltration, and hypopyon were analyzed. Immunological evaluation included determination of interleukine (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α in tear samples obtained from infected eyes of 28 patients with MK and compared with their contralateral non-infected eyes. Additionally, frequency of CD4+, CD8+, CD19+ and CD3-CD56+ cells was also determined in peripheral blood mononuclear cells in patients with MK, and compared with 48 healthy controls. Non-significant differences were observed in the size of the epithelial defect, stromal infiltration, and hypopyon. Nevertheless, we found an immunological profile apparently related to MK etiology. IL-8 > IL-6 in patients with bacterial keratitis; IL-8 > IL-6 > IL-1β and increased frequency of circulating CD3-CD56+ NK cells in patients with gram-negative keratitis; and IL-8 = IL-6 > IL-1β in patients with fungal keratitis. Characterization of tear cytokines from patients with MK could aid our understanding of the immune pathophysiological mechanisms underlying corneal damage in humans.

  3. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takao [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kibe, Toshiro [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Nishizawa, Yoshiaki [Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Hijioka, Hiroshi; Fujii, Tomomi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ueda, Masahiro [Natural Science Centre for Research and Education, Kagoshima University, 1-21-24 Koorimoto, Kagoshima 890-8580 (Japan); Nakamura, Norifumi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kiyono, Tohru [Department of Virology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuouku, Tokyo 104-0045 (Japan); Kishida, Michiko, E-mail: kmichiko@m2.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2014-09-05

    Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

  4. 消化性溃疡病患者治疗前后血清GM-CSF、IL-8IL-6水平检测的临床意义%Clinical significnce of measurement of changes of sercan GM-CSF、IL-8IL-6 levels after-crentment in patients with peptic alcer

    Institute of Scientific and Technical Information of China (English)

    漆以芹

    2009-01-01

    Objective To explore the changes of serclm GM-CSF、IL-8 and IL-6 levels both before and after treatment in paticents with peptic ulcer.Metheds Serccm GM-CSF IL-8 and IL-6 levels were measured with RIA in 36 patients with peptic celcer both Before and after treatment as well as in 35 controls.Results Before freatment,the serclun GM-CSF IL-8 and IC-6 levels were significantly higher in the patients than those in the contrels(P0.05).Conclusions Abnormal higher sercun GM-CSF.IL-8 and IL-6 levels played inuportant role in the pathogenesis of peptic ulcer.%目的 探讨了消化性溃疡病患者治疗前后血清GM-CSF、IL-8IL-6水平的变化及意义.方法 应用放射免疫法对36例消化性溃疡患者进行了血清GM-CSF、IL-8IL-6水平测定,并与35名正常健康人作比较.结果 消化性溃疡患者在治疗前血清GM-CSF、IC-8和IL-6水平非常显著地高于正常人组(P<0.01),经中西医结合治疗3个月后则与正常人比较无显著性差异(P<0.01),结论 血清GM-CSF、IL-8IL-6水平异常升高是消化性溃疡病发病的病理因素之一,有重要的临床价值.

  5. Clinical significance of detecting serum levels of TNF-α, IL-10, IL-8 and IL-6 in patients with Breast cancer%乳腺癌患者血清IL-6IL-8、IL-10和TNF-α的水平变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    王治伟; 迟琼; 万利

    2012-01-01

    目的 探讨乳腺癌患者血清中IL--6IL-8、IL-10和TNF-α水平与乳腺癌发病的关系.方法 应用放射免疫分析方法检测50例乳腺癌患者不同时期血清IL-6IL-8、IL-10和TNF-α水平,并与30例正常者对照比较.结果 乳腺癌患者活动期血清中IL-6IL-8和TNF-α的含量显著高于缓解期和对照组,IL-10含量显著低于缓解期和对照组.缓解期IL-6IL-8、IL-10和TNF-α含量与对照组比较差异无统计学意义(P>0.05).活动期IL-6IL-8表达水平与TNF-α呈正相关,与IL-10呈负相关.结论 乳腺癌患者活动期IL-10表达水平降低,IL-6IL-8和TNF-α 表达水平升高,使体内免疫调节失衡,从而成为乳腺癌患者病因之一.乳腺癌患者血清中IL-6IL-8、IL-10和TNF-α水平与疾病严重程度显著相关.

  6. COPD患者血清IL-6IL-8、hs-CRP和IL-18检测的临床意义%Clinical Relevance of Determination the Changes on Serum IL-6, IL-8,hs-CRP and IL-18 Levels in Patients with Chronic Obstructive Pulmonary Diseases(COPD)

    Institute of Scientific and Technical Information of China (English)

    赵庆琪; 姚加平

    2012-01-01

    目的:观察慢性阻塞性肺疾病(COPD)患者治疗前后血清IL-6IL-8、hs-CRP和IL-18水平的变化及临床意义.方法:应用放射免疫分析和免疫比浊法对32例COPD患者进行了治疗前后血清IL-6IL-8、hs-CRP和IL-8检测,并与35名正常健康人作比较.结果:COPD患者在治疗前血清IL-6IL-8、hs-CRP和IL-18水平均非常显著地高于正常人组(P<0.01),经中西医结合治疗1个月后与正常人组比较仍有差异(P<0.05).结论:IL-6IL-8、hs-CRP和IL-18的测定,可适用为一种筛选方法,其变化可能以不同的方式参与了COPD的发病,此外,该些项目的检测对了解病情、指导治疗具有重要的临床价值.%Objective To observe the clinical significance of changes on serum IL-6, IL-8, hs-CRP and BL-18 levels after treatment in patients with COPD. Methods Serum 11-6, IL-8 (with RIA) , serum hs-CRP(with immunotubidimetry) levels were measured both before and after treatment in 32 patients with COPD as well as in 35 normal controls. Results Before treatment, the serum IL-6, IL-8, hs-CRP, IL-18 levels were significantly higher than those in controls (P < 0.01). After 1 month of treatment the serum IL-6, IL-8, hs-CRP and IL-18 dropped markedly but remained higher difference than those in controls ( P < 0.05 ). Conclusion Measurement of serum IL-6,IL-8,hs-CRP and IL-18 were suitable to be used as a screening method. Besides, it could take part in pathogenesis of COPD in various ways and the changes of these items levels is of important values to realize pathosis and therapeutic effect.

  7. Expressions of IL-6 and IL-8 in normal gastric tissue, gastric ulcer and gastric cancer%IL-6IL-8在正常胃组织、胃溃疡及胃癌组织中的表达

    Institute of Scientific and Technical Information of China (English)

    赵志威; 朴大勋; 姜涛; 张哲男; 王剑冰; 荆琼优

    2014-01-01

    目的 探讨白细胞介素(IL)-6IL-8在正常胃组织、胃溃疡及胃癌组织中的表达情况.方法 采用酶联免疫吸附法(ELISA)测定正常对照组(33例)、胃溃疡患者(30例)和准备手术的胃癌患者(52例)血浆中IL-6IL-8的表达水平,并随访胃癌患者术后1周的IL-6IL-8表达水平;免疫组织化学法检测胃癌周围正常组织(45例)、胃溃疡组织(35例)和胃癌组织(45例)标本中IL-6IL-8的表达.结果 胃癌患者(术前和术后)血浆中IL-6IL-8的表达明显高于胃溃疡和正常对照组(均P<0.0l),胃癌患者术后IL-6IL-8水平较术前明显降低(P<0.01).癌周正常组织、胃溃疡和胃癌组织中IL-6IL-8蛋白阳性表达率依次上升,且差异有统计学意义(x2=38.87,P<0.01;x2=42.23,P<0.01).结论 IL-6IL-8在胃癌患者血浆和胃癌组织中均表达上调,检测患者血浆和病理组织中的IL-6IL-8水平有助于判断病情和评估预后.

  8. The study of the relationship between Helicobacter pylori CagA and VacA genotype and IL-6, IL-8%幽门螺杆菌CagA和VacA基因型与IL-6IL-8的关系研究

    Institute of Scientific and Technical Information of China (English)

    郭皓; 戚艳丽; 张世同; 李慧; 金建军

    2016-01-01

    目的 观察幽门螺杆菌(Helicobacter pylori,H.pylori)的不同基因型与IL-6IL-8之间的关系,了解H.pylori的致病机制.方法 采集91例经14C尿素呼气试验检测为H.pylori(+)患者血清,采用酶联免疫吸附试验(ELISA)对CagA、VacA进行定性分析,对IL-6IL-8进行定量分析.结果 CagA(+)与CagA(-)中所含IL-6IL-8含量差异有统计学意义(=6.55、t=7.348,P<0.001);VacA(+)与VacA(-)中所含IL-6IL-8含量差异有统计学意义(t=6.418、t=6.977,P<0.001);CagA、VacA均阳性中所含IL-6IL-8的含量较CagA、VacA均阴性差异有统计学意义(=6.438、t=7.231,P<0.001);CagA阳性患者血清中IL-6IL-8含量呈正相关(r=0.672,P<0.01),VacA阳性患者血清中IL-6IL-8含量呈正相关(r=0.664,P<0.01).结论 CagA、VacA基因型与IL-6IL-8之间有密切关系,IL-6IL-8在H.pylori的致病机制中起重要作用,细胞因子在H.pylori感染诱导的炎症反应涉及多种细胞及多种细胞因子的相互作用.

  9. Messenger RNA expression of IL-6 and IL-8 in allergen-induced late-phase cutaneous reactions (LPR) in Schneiderian membrane subjects%白细胞介素6(IL-6)和IL-8mRNA在变应原诱导的鼻粘膜晚期反应标本的表达

    Institute of Scientific and Technical Information of China (English)

    吕俊华; 宇丽; 孙英

    2001-01-01

    目的:测定IL-6IL-8变应原诱导的鼻粘膜晚期反应标本中mRNA的表达。方法:采用原位杂交技术,测定变应原诱导的10例变态反应性鼻炎病人的鼻粘膜标本表达IL-6IL-8mRNA阳性细胞数。结果:在10例标本中,2种细胞因子的阳性表达率分别为9/10和10/10。与对照相比,变应原诱导的鼻粘膜标本表达IL-6IL-8mRNA阳性细胞数明显增加(P<0.05和P<0.01)。结论:IL-6IL-8mRNA表达增加可作为变态反应性鼻炎晚期的标志。%Objective:To detect mRNA expression of IL-6 and IL-8 in allergen-induced late-phase cutaneous reactions in schneiderian membrane subjects. Methods:Cryostat sections from rhinitis biopsies from 24 h allergen-induced late-phase cutaneous reactions (LPR) in 10human atopic subjects were hybridization with 35S-labeled RNA probes for IL-6 and IL-8.Results:mRNA was detected for IL-6 (9/10) and IL8 (10/10).Compared with the control, there were significant increases in the numbers of ce11 expreasing mRNA expression for IL-6 and IL-8(P<0.05, P<0.01). Conclusion: The augmentation of mRNA expression of IL-6 and IL-8 maybe regarded as the mark of rhinits in IL PR.

  10. Clinical Significance of Determination of Changes of Serum TNF-α, IL-6 and IL-8 Levels After Treatment in Patients with Chronic Prostatitis%慢性前列腺炎患者治疗前后血清TNF-α、IL-6IL-8检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    孟晓波

    2008-01-01

    目的:探讨了慢性前列腺炎患者治疗前后血清TNF-α、IL-6IL-8水平的变化及意义.方法:应用放射免疫分析对42例慢性前列腺炎患者进行了血清TNF-α、IL-6IL-8检测,并与35名正常健康人作比较.结果:慢性前列腺炎患者在治疗前血清TNF-α、IL-6IL-8水平均非常显著地高于正常人组(P<0.01),经综合治疗后2周,除TNF-α水平与正常人比较无差异外,血清IL-6IL-8水平与正常人比较仍有显著性差异(P<0.05).结论:血清TNF-α、IL-6IL-8可能以不同的方式参与了慢性前列腺炎的发病,其检测对了解病情、指导治疗具有重要的临床价值.

  11. COPD患者治疗前后血清hs-CRP、TNF-α、IL-6IL-8检测的临床意义%Clinical Significance of Determination of Serum hs-CRP, TNF-α, IL-6 and IL-8 Levels After Treatment in Patients with Chronic Obstructive Pulmonary Disease

    Institute of Scientific and Technical Information of China (English)

    胡蓉

    2007-01-01

    目的:探讨慢性阻塞性肺疾病(COPD)患者治疗前后血清hs-CRP、TNF-α、IL-6IL-8水平的变化及意义.方法:应用放免法和免疫比浊法对46例COPD患者进行治疗前后血清hs-CRP、TNF-α、IL-6IL-8检测,并与35名正常健康人作比较.结果:COPD患者在治疗前血清hs-CRP、TNF-α、IL-6IL-8水平均非常显著地高于正常人组(P<0.01),综合治疗后2周,除hs-CRP水平与正常人比较无差异外,TNF-α、IL-6IL-8水平与正常人组比较仍有显著性差异(P<0.05).结论:hs-CRP、TNF-α、IL-6IL-8可能以不同的方式参与了COPD的发病,其水平的检测对于了解病情、指导治疗具有重要的临床价值.

  12. DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Recent studies have shown that i mmunomodu-lation abnor mities have a significant role in hemor-rhagic fever withrenal syndrome(HFRS).The hy-perfunction of humoral i mmune response will causeexcessive generation of antigen-antibody complexes,leading to secondary i mmune reaction.It will alsocause hypofunction of sti muli,increase in CD8T+cells and cellular i mmunomodulation dysfunc-tion[1-3].Using ELISA,we detected the dynamicchange of the concentrations of seruminterleukin-6(IL-6),urine tumor necrosis fact...

  13. Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in hemorrhagic fever with renal syndrome.

    Science.gov (United States)

    Kyriakidis, Ioannis; Papa, Anna

    2013-07-01

    It is generally accepted that the pathogenesis of hantavirus infections is the result of virus-mediated host immune response. Hantaviruses, and mainly Dobrava-Belgrade virus, are present in Greece, and cause to humans hemorrhagic fever with renal syndrome (HFRS). Serum IL-6, IL-8, IL-10, TNF-α and sTNFR1 levels were measured in 29 HFRS Greek patients. Significant higher sTNFR1, IL-6, IL-8 and IL-10 levels were observed in severe than in mild/moderate cases, while TNF-α did not seem to be associated with disease severity. Correlations between cytokine levels and their fluctuation over time after onset of the illness, along with comparisons from previously published data on the field, led in building an immune response pattern for HFRS.

  14. 热化疗治疗非小细胞肺癌对IL-2、IL-6IL-8、IL-10及TNF的影响%Effect of thermochemotherapy on levels of IL-2 ,IL-6 ,IL-8 ,IL-10 and TNF in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李新民; 尉继伟; 刘治邦; 刘建国

    2014-01-01

    目的 探讨热化疗治疗非小细胞肺癌(NSCLC)对白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、白细胞介素-10(IL-10)及肿瘤坏死因子(TNF)的影响.方法 回顾性分析大同大学附属医院2004年10月至2013年1月收治的134例NSCLC患者,进行热疗联合NP方案化疗(NVB+ DDP),并分别在治疗前、治疗3个周期后、治疗6个周期后、治疗结束后3个月对患者血清中IL-2、IL-6IL-8、IL-10及TNF的变化进行监测.结果 热化疗3个周期后,IL-2、TNF水平逐渐增高,明显高于治疗前;IL-6IL-8和IL-10水平明显低于化疗前.热化疗6个周期后,血IL-6IL-8、IL-10、IL-2和TNF都有所下降,其中IL-2、TNF浓度显著低于化疗3个周期后的水平.热化疗结束后3个月,血IL-6IL-8、IL-10水平继续下降;而IL-2、TNF浓度逐渐增高,低于化疗3个周期后的水平,但高于治疗前水平.结论 热化疗治疗NSCLC对IL-2、TNF水平有明显的增高作用,而对IL-6IL-8、IL-10有降低作用.%Objective To investigate the effect of hot therapy on interleukin-2 (IL-2),interleukin-6 (IL-6),interlerukin-8 (IL-8),interleukin-10 (IL-10) and tumor necrosis factor (TNF) in nonsmall cell lung cancer(NSCLC).Methods One hundred and thirty-four patients with NSCLC,admitted to our hospital from October 2004 to January 2013,received hot therapy and vinorelbine plus cisplatin (NP) chemotherapy.The IL-6,IL-8,IL-10 and TNF level before therapy,after 3 cycles,after 6 cycles and 3 months after chemotherapy were observed.Results IL-2 and TNF levels increased gradually after 3 cycles of hot therapy,and were significant higher than those before therapy.Compared to before therapy,IL-6,IL-8 and IL-10 levels significantly decreased.IL-6,IL-8,IL-10,IL-2 and TNF levels all decreased at 6 months after hot therapy.IL-2 and TNF levels were significant lowered than those of 3 cycles after chemotherapy.IL-6,IL-8 and IL-10 continued to decrease 3 months after the end of

  15. The expression of lysophosphatidic acid, its receptors, and IL-6 and IL-8 in breast cancer%溶血磷脂酸及其受体和IL-6 IL-8在乳腺癌进展中的表达变化与意义

    Institute of Scientific and Technical Information of China (English)

    涂福平; 黄莉; 王祥财; 许明君; 王钇力; 衷敬华

    2013-01-01

    Objective:This work aimed to investigate the expression level of lysophosphatidic acid (LPA) and its receptors. The paper also discussed the interrelationship among the LPA, the receptors, and IL-6 and IL-8 in breast cancer tissues. Methods:The ex-pressions of the 3 hypo-types of LPA receptor in the breast cancer and paraneoplastic tissues were detected using semi-quantitative re-verse transcription polymerase chain reaction. The plasma levels of LPA, IL-6 and IL-8 were respectively detected in healthy subjects and in patients with benign breast tumor using the LPA biochemistry and enzyme linked immunosorbent assay kits. Results:The plas-ma LPA level was significantly higher in patients with breast cancer metastasis than in those with local breast cancer (P<0.01), benign breast tumor (P<0.01), and healthy volunteers (P<0.01). In addition, the IL-6 and IL-8 plasma levels were higher in the group with me-tastasis compared with the other three groups, too (P<0.01). LPA1 expression level was higher in breast cancer tissue than in benign breast tumor (P<0.05) and in normal breast tissue (P<0.05). There was a significantly positive correlation between the plasma LPA and the plasma IL-6 in patients with breast cancer (P<0.01), and between the plasma LPA and IL-8 (P<0.01). Conclusion:LPA expressions on the endogenous IL-6 and IL-8 in patients with breast cancer may have an up-regulation. Moreover, the detection of the LPA, IL-6, and IL-8 expression levels may have some predictable effects on metastatic breast cancer, especially bone metastases.%  目的:探讨溶血磷脂酸(lysophosphatidic acid,LPA)及其受体和IL-6IL-8在乳腺癌进展中的表达及临床意义。方法:采用半定量RT-PCR方法检测乳腺肿瘤组织和瘤旁组织中LPA受体的表达水平。采用LPA生化测定法和酶联免疫吸附(ELISA)法分别检测乳腺肿瘤患者和健康妇女的血浆LPA、IL-6IL-8水平。结果:术后复发转移乳腺癌患者血浆LPA、IL

  16. The effect of phytic acid on the expression of NF-kappaB, IL-6 and IL-8 in IL-1beta-stimulated human colonic epithelial cells.

    Science.gov (United States)

    Wawszczyk, Joanna; Kapral, Małgorzata; Hollek, Andrzej; Weglarz, Ludmiła

    2012-01-01

    Intestinal epithelial cells play an important role in the mucosal immune and inflammatory reactions via the expression and secretion of proinflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8). The expression of both interleukins is regulated by nuclear factor KB (NF-kappaB). Phytic acid (IP6) is an essential component of high fiber diet. It is physiologically present in the human large gut at concentrations reaching 4 mM. It exhibits pleiotropic health beneficial effects including anti-oxidant and anti-tumor activities. Recent studies showed that IP6 can modulate immune functions of intestinal epithelium through regulation of proinflammatory cytokines secretion. The aim of this study was to analyze the effect of IP6 on the expression of IL-6 and IL-8 as well as p50 and p65 subunits of NF-kappaB and its inhibitor IkappaBalpha in Caco-2 cells stimulated with IL-1beta. A kinetic study of mRNAs expression in cells was performed after their treatment with 1 and 2.5 mM IP6 for 3, 6 and 12 h. Quantification of the genes expression was carried out using real time QRT-PCR technique. IP6 at all used concentrations had no influence on transcription of p65 gene and modulated expression of p50 and IkappaBalpha genes in Caco-2 cells. Treatment of cells with IP6 resulted in a marked decrease in both IL-6 (at 3 and 6 h) and IL-8 expression (3 h). The results of these studies suggest that IP6 may exert immunoregulatory effects on intestinal epithelium by influencing transcriptional activity of genes encoding p50 subunit of NF-kappaB, its inhibitor IkappaBalpha and proinflammatory cytokines IL-6 and IL-8.

  17. Baicalin downregulates Porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling.

    Directory of Open Access Journals (Sweden)

    Wei Luo

    Full Text Available Periodontal (gum disease is one of the main global oral health burdens and severe periodontal disease (periodontitis is a leading cause of tooth loss in adults globally. It also increases the risk of cardiovascular disease and diabetes mellitus. Porphyromonas gingivalis lipopolysaccharide (LPS is a key virulent attribute that significantly contributes to periodontal pathogenesis. Baicalin is a flavonoid from Scutellaria radix, an herb commonly used in traditional Chinese medicine for treating inflammatory diseases. The present study examined the modulatory effect of baicalin on P. gingivalis LPS-induced expression of IL-6 and IL-8 in human oral keratinocytes (HOKs. Cells were pre-treated with baicalin (0-80 µM for 24 h, and subsequently treated with P. gingivalis LPS at 10 µg/ml with or without baicalin for 3 h. IL-6 and IL-8 transcripts and proteins were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of nuclear factor-κB (NF-κB, p38 mitogen-activated protein kinase (MAPK and c-Jun N-terminal kinase (JNK proteins was analyzed by western blot. A panel of genes related to toll-like receptor (TLR signaling was examined by PCR array. We found that baicalin significantly downregulated P. gingivalis LPS-stimulated expression of IL-6 and IL-8, and inhibited P. gingivalis LPS-activated NF-κB, p38 MAPK and JNK. Furthermore, baicalin markedly downregulated P. gingivalis LPS-induced expression of genes associated with TLR signaling. In conclusion, the present study shows that baicalin may significantly downregulate P. gingivalis LPS-upregulated expression of IL-6 and IL-8 in HOKs via negative regulation of TLR signaling.

  18. 乳腺癌患者手术前后血清IL-6IL-8和VEGF-A水平变化及临床意义%Clinical significance of level changes of serum IL-6, IL-8 and VEGF-A in patients with breast cancer before and after operations

    Institute of Scientific and Technical Information of China (English)

    陈坤; 王晓刚; 李狄航; 孔勇

    2014-01-01

    目的 探讨乳腺癌患者手术前后血清白细胞介素-6(IL-6)、IL-8和血管内皮生长因子-A (VEGF-A)水平变化及其临床意义.方法 42例乳腺癌患者根据不同临床分期采取改良根治术或保乳术治疗,分别检测健康体检者和乳腺癌患者手术前3d、术后7d血清IL-6IL-8和VEGF-A水平.结果 乳腺癌患者术前血清IL-6IL-8和VEGF-A水平均高于对照组(P<0.01),术后各期乳腺患者血清IL-6IL-8和VEGF-A水平均显著下降(P< 0.05或P<0.01).不同分期乳腺癌患者组间比较,血清IL-6IL-8和vEGF-A水平差异均具有统计学意义(P<0.05).结论 乳腺癌患者体内IL-6IL-8和VEGF-A水平存在高表达,且在一定程度上影响疾病发展,及时检测并诊断该类因子水平有助于了解乳腺癌患者疾病发展和预后.

  19. Application value of serum TNF-α, IL-6, IL-8, IL-10 in children mycoplasma pneumoniae pneumonia%血清TNF-α、IL-6IL-8、IL-10在儿童肺炎支原体肺炎中的应用价值

    Institute of Scientific and Technical Information of China (English)

    李锦; 郭瑞雪; 王金虎

    2015-01-01

    目的:对血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和白细胞介素-10(IL-10)浓度在儿童肺炎支原体肺炎(MPP)中的应用价值进行探讨。方法90例肺炎支原体肺炎患儿作为肺炎组,其中轻症组50例,重症组40例;100例健康体检儿童作为对照组,对比肺炎组与对照组血清TNF-α、IL-6IL-8和IL-10指标及轻症组与重症组血清中的各因子浓度。结果对照组与肺炎组治疗前血清中TNF-α、IL-6IL-8和IL-10浓度差异具有统计学意义(P0.05), TNF-α、IL-6IL-8浓度均显著低于重症组,差异具有统计学意义(P0.05). They had much lower TNF-α, IL-6, IL-8 than the severe group, and their differences had statistical significance (P<0.05).Conclusion Serum TNF-α, IL-6, IL-8, IL-10 have certain correlation with mycoplasma pneumoniae pneumonia, and they are closely correlated with MPP degree. They can be used as evaluation indexes for clinical diagnosis, treatment and prognosis.

  20. The Effect of Montelukast on the Levels of IL-6,IL-8 and IL-10 in Patients with Bronchial Asthma%孟鲁司特对支气管哮喘患者血清IL-6IL-8和IL-10水平的影响

    Institute of Scientific and Technical Information of China (English)

    许成

    2012-01-01

    Objective To explore the effect of Montelukaat on serum IL-6,IL-8 and IL-10 levels in patients with bronchial asthma. Methods Serum TL-6,TLS (with RIA) ,IL-10 (with ELISA) levels were measured in 31 patients after Montelukast treatment with bronchial asthma as well as in 35 normal healthy controls. Result Before treatment serum IL-6, IL-8 levels in the asthma group were significantly higher than those in controls (P<0.01). While the IL-10 level was undoubtedly lower than that in the controls (P <0.01). After treatment, the serum IL-6, IL-8 and IL-10 levels were still significantly (P<0.05). Conclusion Montelukast treatment could bring about some regulatory effect on serum IL-6, IL-8 and IL-10 levels in patients with asthma and furthermore reducing the severity of inflammation and enhancing remission.%目的 探讨孟鲁司特在支气管哮喘患者体内IL-6IL-8和IL-10水平的影响.方法 应用放射免疫分析和酶联法对31例支气管哮喘患者应用孟鲁司特治疗前后血清IL-6IL-8和IL-10水平的变化,并与35名正常健康人作比较.结果 支气管哮喘患者在治疗前血清IL-6IL-8水平非常显著地高于正常人组(P<0.01),而IL-10水平显著地低于正常人组(P<0.01),经治疗2周后与正常人组比较仍有显著性差异(P<0.05).结论 孟鲁司特对支气管哮喘患者血清IL-6IL-8和IL-10有一定程度的调节作用,从而降低患者体内的炎症水平,促进病情缓解和好转.

  1. 急性颅脑损伤后血清IL-6IL-8IL-10含量变化及意义%The content change and significance of serum IL-6, IL-8 and IL-10 in patients with acute brain trauma

    Institute of Scientific and Technical Information of China (English)

    梁敏; 汤树洪; 甘渭河

    2013-01-01

    目的 探讨急性颅脑损伤后免疫功能紊乱的相关炎性介质与时间动态变化的关系,即血清中促炎细胞因子IL-6IL-8和抗炎细胞因子IL-10 的含量变化及临床意义.方法 采用放射免疫分析法检测急性颅脑损伤患者150 例,分为轻、中、重型3组血清IL-6IL-8、IL-10含量的变化,分析血清中IL-6IL-8、IL-10含量之间的动态关系与急性颅脑损伤分级以及变化趋势.结果 重型组1 d、2 d、3 d、7 d、14 d5个时间点的IL-6IL-8、IL-10水平较轻、中型明显升高;IL-6 水平于第2天达到最高峰,IL-8水平于第3天达到最高峰,IL-10水平于第7天达到最高峰;IL-6IL-8、IL-10达到最高峰后均出现迅速下降趋势.结论 血清中IL-6IL-8、IL-10 水平的变化与急性脑损伤程度呈正相关,即脑损伤程度越重,IL-6IL-8、IL-10的水平越高.

  2. Dynamic changes of IL-2, sIL-2R, IL-6 and IL-8 in children with mycoplasma pneumonia and their clinical significance%肺炎支原体肺炎IL-2、sIL-2R、IL-6IL-8检测

    Institute of Scientific and Technical Information of China (English)

    刘文彬; 赵文利; 汤雪琴; 袁丽

    2012-01-01

    目的 探讨肺炎支原体肺炎(MPP)急性期和恢复期免疫功能动态变化及临床意义.方法 检测IL-2、sIL-2R、IL-6IL-8均采用ELISA双抗体夹心法.结果 与对照组比较,MPP患儿急性期sIL-2R、IL-6,IL-8值均明显升高(P<0.01),IL-2值均明显下降(P<0.01),与急性期比较,MPP患儿恢复期IL-2值均明显升高(P<0.01),而sIL-2R、IL-6IL-8值均明显下降(P<0.01);与对照组比较,MPP患儿恢复期IL-2、sIL-2R、IL-6IL-8均无明显改变(P>0.05).结论 MPP患儿存在细胞免疫功能低下及紊乱,IL-2、sIL-2R、IL-6IL-8值恢复较快,检测MPP患儿免疫功能,特别是IL-2、sIL-2R、IL-6IL-8水平对疗效及预后的判定有重要价值.%Objective To observe the dynamic changes of IL-2, sIL-2R, IL-6 and IL-8 in children with mycoplasma pneumonia( MPP) and to study their clinical significance. Methods The serum levels of IL-2, sIL-2R, IL-6 and IL-8 in 40 children with MPP during the acute stage and convalescent stage were examined with double-antibody sandwich enzyme-linked immu-nosobent assay, and the results were compared with those in 30 normal children. Results The levels of slL-2R, IL-6 and IL-8 were higher and IL-2 was lower during acute stage than those in the normal subjects (P <0. 01). Compared those during the convalescent stage, the level of IL-2 was higher and sIL-2R, IL-6 and IL-8 were lower (P <0. 01) during the acute stage. There were not any significant differences of the levels of these four substances between the normal children and MPP children during the convalescent stage. Conclusion The cellular immune function of children with MPP is impaired and the changes of IL-2, sIL-2R, IL-6 and IL-8 can be used to evaluate the curative effects and prognosis of MPP in children.

  3. CA153、IL-6IL-8与乳腺癌骨转移相关性探讨%Study on the correlation between CA153, IL-6, IL-8 levels and bone metastasis in patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    杨士军; 谭维琴; 鲍艳梅

    2011-01-01

    目的 探讨糖类抗原153(CA153)及细胞因子[白细胞介素6(IL-6)、白细胞介素8(IL-8)]与乳腺癌骨转移的关系.方法 对103例乳腺癌根治手术后患者行单光子发射型(SPECT)骨显像,采用放射免疫法检测血清CA153,放射免疫分析法检测IL-6IL-8水平,与健康对照组(36例)进行对比分析.结果 骨转移组患者血清CA153、IL-6IL-8水平明显升高,与无骨转移组及健康对照组比较差异均有统计学意义(P0.05).结论 CA153对于预测乳腺癌骨转移、筛选行全身骨显像患者具有重要意义;IL-6IL-8参与乳腺癌骨转移的发生和发展过程,检测IL-6IL-8对于乳腺癌骨转移的病理研究和预防、治疗可能具有重要价值.%Objective To investigate the corelation of CA153,IL-6,IL-8 and breast cancer bone metastasis. Methods 103 breast cancer patients after radical surgery were scanned by single photon emission computer tomography(SPECT). Immunoradiometric assay(IRMA) method was used to assay the serum.level of CA153,and radioimmunoassay(RIA) method was used to assay serum level of IL-6,IL-8;At the same time,the result was analyzed against the control group of 36 normal people. Results In breast cancer patients group with bone metastasis, the serum level of CA153, IL-6, IL-8 were significantly higher than normal people(P<0.05) ,while the serum level of CA153,IL-6 and IL-8 in cancer patients group without bone metastasis and in control group were not statistically significant different(P>0.05). Conclusion CA153 has great significance in predicting breast cancer bone metastasis and screening whole body bone imaging;IL-6, IL-8 is engaging in the occurrence and development of bone metastasis, assaying the serum levels of IL-6,IL-8 are of great value to pathology research,prevention and treatment of breast cancer bone metastasis.

  4. 脑胶质瘤患者血清IL-6IL-8、IL-10和TNF-α的表达及临床意义%The Expression of IL-6, IL-8, IL-10 and TNF-α in Serum of Glioma and Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    李春生; 张朋军

    2013-01-01

    [Purpose] To explore the diagnostic value of serum interleukin-6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF-α) for glioma. [Materials and methods] The content of IL-6, IL-8, IL-10 and TNF-α in the healthy control group, the low-grade gliomas group and the high-grade gliomas group were detected by Luminex 200. [Results] Compared to the healthy control group, IL-6, IL-8, and TNF-α in the low-grade gliomas group showed significantly different, IL-6, IL-8, IL-10 and TNF-α in the high-level group of glioma showed significantly different. Compared to the low-grade gliomas Group, IL-6, IL-10 and TNF-α in the high-grade gliomas showed significantly different. When we discriminated the low-grade gliomas and high-grade gliomas, the best indicators was IL-10, and the diagnostic sensitivity and specificity were 74.90% and 65.80%, respectively. When the IL-6, IL-10 and TNF-α were combined, the sensitivity and specificity were 92.30% and 93.10%, respectively. [Conclusion] IL-6, IL-10 and TNF-α joint diagnostic value showed significant improvedment when compared to the individual indicators. It may provide a auxiliary method for brain the clinical diagnosis of glioma.%  [目的]探讨血清中白介素6(IL-6)、IL-8、IL-10和肿瘤坏死因子(TNF-α)对于脑胶质瘤的诊断价值。[材料与方法]分别检测健康对照组、低级别脑胶质瘤组和高级别脑胶质瘤组中IL-6IL-8、IL-10和TNF-α的含量。[结果]与健康对照组比较,低级别脑胶质瘤组的IL-6IL-8和TNF-α有统计学差异,高级别脑胶质瘤组的IL-6IL-8、IL-10和TNF-α均具有统计学差异。与低级别脑胶质瘤组相比较,高级别脑胶质瘤组的IL-6、IL-10和TNF-α有统计学差异。其中区分低级别脑胶质瘤和高级别脑胶质瘤的诊断价值最好的指标为IL-10,其诊断灵敏性和特异性分别为74.90%和65.80%。IL-6、IL-10和TNF-α联合检测时其灵敏性和特异性分别为92.30%和93.10%。[结论]证实IL

  5. Clinical Significance of Determination of Changes of Serum of TNF-α, IL-6, IL-8,IL-10 Levels After Treatment in Patients with Condyloma Acuminatum%尖锐湿疣患者治疗前后血清TNF-α、IL-6IL-8、IL-10检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王亚平

    2007-01-01

    目的:探讨了尖锐湿疣患者治疗前后血清TNF-α、IL-6IL-8、IL-10水平变化及意义.方法:应用RIA和ELISA对40例尖锐湿疣患者进行了血清TNF-α、IL-6IL-8、IL-10水平检测并与35名正常健康人作比较.结果:在治疗前尖锐湿疣患者血清IL-6IL-8低于正常对照组.TNF-α、IL-10水平均非常显著地高于正常对照组(P<0.01),经治疗3个月后与正常对照组比较仍有显著性差异(P<0.05).结论:检测尖锐湿疣患者血清TNF-α、IL-6IL-8、IL-10水平的变化对疾病的治疗、预后观察有重要的临床价值.

  6. Clinical Significance of Measurement of Changes of Serum TNF-α, IL-6 and IL-8 Centent After Treatment in Patients with Pregnancy Induced Hypertension (PIH)%妊高征患者治疗前后血清TNF-α、IL-6IL-8检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王桂英

    2008-01-01

    目的:探讨了妊高征患者治疗前后血清TNF-α、IL-6IL-8水平的变化及意义.方法:采用放射免疫分析对36例妊高征患者进行了血清TNF-α、IL-6IL-8水平检测并与35名正常孕妇作比较.结果:在治疗前血清TNF-α、IL-6IL-8水平非常显著地高于正常孕妇组(P0.05).结论:炎性细胞因子TNF-α、IL-6IL-8在妊高征的发病机理中具有重要的作用,有一定的临床价值.

  7. Clinical significance on the changes of serum IL-6,IL-8 and IL-10 levels in children with H.pylori infection%幽门螺杆菌感染患儿血清 IL-6IL-8、IL-10水平变化

    Institute of Scientific and Technical Information of China (English)

    陈一; 阎晓莉; 李华; 拜康利

    2003-01-01

    为探讨各种细胞因子在幽门螺杆菌相关性胃肠粘膜病中的作用机理及意义,采用 ELISA法,检测 35例幽门螺杆菌阳性患儿血清 IL-6IL-8、 IL-10水平,并与幽门螺杆菌阴性组 31例作对照.结果显示两组间 IL-6IL-8分布水平差异有极显著性( P<0.001);两组间 IL-10分布水平差异有显著性( P<0.05).幽门螺杆菌阳性组与阴性组 IL-6平均秩和之差为 16.38,均数分别为 108.46pg/ml及 51.32pg/ml; IL-8平均秩和之差为 34,均数分别为 163.09pg/ml及 92.36pg/ml; IL-10平均秩和之差为- 3.32,均数分别为 12.56pg/ml及 15.88pg/ml.幽门螺杆菌阳性组血清 IL-6IL-8间呈正相关( r=0.349, P<0.001); IL-10与 IL-6IL-8间无明显相关性.提示细胞因子 IL-6IL-8、 IL-10均参与了幽门螺杆菌感染后的致病过程;幽门螺杆菌感染胃肠粘膜产生的炎症反应损伤与 IL-6IL-8的过量产生有关,血清 IL-10对炎症有抑制作用,从而为临床诊治幽门螺杆菌相关性疾病提供理论依据.

  8. Changes and significance of IL-6, IL-8 and TNF-α in serum of breast cancer patients before and after chemotherapy%化疗前后乳腺癌患者血清中IL-6IL-8及TNF-α的变化及意义

    Institute of Scientific and Technical Information of China (English)

    杨明德; 李冬梅; 于慧玲

    2015-01-01

    目的:探讨化疗前后乳腺癌患者血清中IL-6IL-8及TNF-α的变化及意义.方法:选择住院手术乳腺癌术后1个月、化疗1个疗程(21天)患者50例,化疗前、后均静脉采血,同期选取体检健康女性30例作为对照组亦静脉采血,均留取血清待测.采用ELISA酶联免疫法检测IL-6IL-8及TNF-α的蛋白水平,采用流式细胞免疫学法检测IL-6IL-8及TNF-α的细胞阳性百分率.结果:与对照组比较,化疗前乳腺癌组患者血清中IL-6IL-8、TNF-α的蛋白水平及细胞阳性百分率均升高,差异有统计学意义(P<0.01);化疗后患者血清中IL-6IL-8、TNF-α的蛋白水平及细胞阳性百分率均略升高,差异无统计学意义(P>0.05);化疗前乳腺癌组患者血清中IL-6IL-8、TNF-α的蛋白水平及细胞阳性百分率明显高于化疗后患者,差异有统计学意义(P<0.01).结论:化疗能够通过降低乳腺癌患者血清中IL-6IL-8、TNF-α的水平抑制肿瘤的浸润和转移,这为乳腺癌的临床治疗提供新的靶点.

  9. Clinical Significance of Determination of Changes of Serum CA153, IL-6, IL-8 and TNF-α Levels in Patients with Breast Cancer%乳腺癌患者手术治疗前后血清CA153、IL-6IL-8和TNF-α测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    王昭昕

    2006-01-01

    目的:探讨了乳腺癌患者手术治疗前后血清CA153、IL-6IL-8和TNF-α含量的变化.方法:分别应用放射免疫分析和酶联免疫分析对38例乳腺癌患者进行了手术治疗前后血清CA153、IL-6IL-8和TNF-α含量检测,并与30名正常健康人作比较.结果:乳腺癌患者手术前血清CA153、IL-6IL-8和TNF-α水平非常显著地高于正常人组(P<0.01),3个月后已降至正常人组水平(P>0.05).手术切除1年后复发者血清IL-6IL-8和TNF-α水平持续异常,未复发者基本接近正常.结论:检测血清CA153、IL-8IL-6和TNF-α的水平与乳腺癌患者的病情和预后密切相关,具有一定的临床实用价值.

  10. Study on the Changes of Serum IL-6 ,IL-8 and IL-10 Levels in Patients with Chronic Hepatitis and its Clinical Significance%慢性肝炎患者血清IL-6IL-8、IL-10的变化及其临床意义

    Institute of Scientific and Technical Information of China (English)

    刁慕言

    2006-01-01

    目的探讨慢性肝炎患者血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和白细胞介素-10(IL-10)在慢性肝炎发展过程中的含量变化及其临床意义.方法用放射免疫分析法检测80例慢性肝炎患者和40例正常对照组血清IL-6IL-8和IL-10的水平.结果各组慢性肝炎患者血清IL-6IL-8含量高于正常对照组,差异有统计学意义(P<0.05);IL-10低于正常对照组,差异有统计学意义(P<0.01).IL-6IL-8和IL-10水平的变化与慢性肝炎病变程度密切相关.结论细胞因子IL-6IL-8和IL-10在慢性肝炎发展过程中相互作用,联合检测其水平的变化对探讨慢性肝炎的诊断和预后具有重要意义.

  11. Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma.

    Science.gov (United States)

    Fuchigami, Takao; Kibe, Toshiro; Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio; Nishizawa, Yoshiaki; Hijioka, Hiroshi; Fujii, Tomomi; Ueda, Masahiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Michiko

    2014-09-05

    Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. ICH 患者血清和血肿液中 IL-4、IL-6IL-8、IL-10的变化研究%Hematoma fluid and serum of patients with acute cerebral hemorrhage about IL-4, IL-6, IL-8, and IL-10 Changes

    Institute of Scientific and Technical Information of China (English)

    赵金安; 白西民

    2016-01-01

    目的:观察急性脑出血(ICH)患者血清和血肿液中 IL-4、IL-6IL-8、IL-10的变化。方法:选取80例在我院治疗的基底节区脑出血患者,按照发病时间将患者分为5组(发病时间≤6h、6h <发病时间≤12h、12h <发病时间≤24h、24h <发病时间≤72h、3d <发病时间≤7d),检测各组血清和血肿液中 IL-4、IL-6IL-8、IL-10的含量以及出血量和水肿量;另选取21例健康体检者,检测其血清 IL-4、IL-6IL-8、IL-10的含量作对照。结果:IL-4、IL-6IL-8、IL-10在患者静脉血、血肿液中的浓度均显著高于正常对照组,而患者静脉血与血肿液中 IL-4、IL-6IL-8、IL-10浓度比较,差异无统计学意义。基底节区脑出血患者发病时间≤6h 与正常对照组比较,除 IL-10浓度升高不明显外,IL-4、IL-6IL-8浓度均明显升高;24h <发病时间≤72h 时,IL-4、IL-6IL-8浓度与其他各时段比较,以及3d <发病时间≤7d时,IL-10浓度与其他各时段比较,差异均具有统计学意义。各时段出血量和水肿量比较,差异均无统计学意义,出血量和水肿量均在发病时间≤6h至12h <发病时间≤24h 逐渐增大,12h <发病时间≤24h 达到峰值。结论:ICH 患者静脉血、血肿液中 IL-4、IL-6IL-8浓度可以作为早期检测(≤6h)ICH 的指标,并可通过不同炎症因子的含量变化判断 ICH 患者发病时间,且患者发病一周内周围脑组织出血量和水肿量变化不大。%Objective To observe the changes of IL-4, IL-6, IL-8, IL-10 in serum and hematoma of ICH. Methods 80 cases ICH patients were divided into five groups(<6h, 6-12h, 12-24h, 24-72h, 3-7d). The control group were 21 healthy persons serum. The content of IL-4, IL-6, IL-8, IL-10 in different time were compared and the amount of bleeding and edema. Results IL-4, IL-6, IL-8, IL-10 in patients with venous hematoma fluid concentrations were

  13. Synergistic cooperation between methamphetamine and HIV-1 gsp120 through the P13K/Akt pathway induces IL-6 but not IL-8 expression in astrocytes.

    Directory of Open Access Journals (Sweden)

    Ankit Shah

    Full Text Available HIV-1 envelope protein gp120 has been extensively studied for neurotoxic effects that have been attributed to the increased expression of various proinflammatory cytokines in the CNS. Recently we have shown that methamphetamine (MA also increases expression of proinflammatory cytokines in astrocytes. However, combined effect of gp120 and MA is not known. The present study was undertaken to determine cumulative effect and the mechanism(s/pathways involved in the functional interaction between gp120 and MA in SVGA astrocytes. Our results clearly suggest that gp120 and MA affect IL-6 but not IL-8 in a synergistic manner and this synergy was mediated by PI3K/Akt and NF-κB pathways. Inhibition of either of these pathways could abrogate the increased expression of IL-6 due to MA or gp120 alone, as well as the increased expression of IL-6 when the astrocytes were treated with both gp120 and MA. These results were confirmed by both, using chemical inhibitors/siRNA as well as western blotting. This study therefore provides novel information regarding the interaction between MA and gp120 in terms of the expression of IL-6 and the mechanisms underlying potential synergy between MA and gp120 in astrocytes.

  14. Effect of psychological nursing on expression levels of serum TNF-α, IL-6 and IL-8 in patients after breast cancer operation%心理护理对乳腺癌术后患者血清中TNF-α、IL-6IL-8蛋白表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    程光文

    2014-01-01

    目的:观察心理护理对乳腺癌术后患者血清中TNF-α、IL-6IL-8蛋白表达水平的影响.方法:将70例乳腺癌患者随机分为常规护理组和心理护理组各35例,两组乳腺癌患者均于术后第1天采血及术后第7天采血;选择同期体检健康妇女20例作为正常对照组.采用ELISA方法检测血清中TNF-α、IL-6IL-8的蛋白含量,采用实时荧光定量法检测TNF-α、IL-6IL-8 mRNA的表达水平.结果:与术后第1天相比较,术后第7天常规护理组TNF-α、IL-6IL-8的蛋白含量及mRNA的表达水平均降低,差异有统计学意义(P<0.05),术后第7天心理护理组TNF-α、IL-6IL-8的蛋白含量及mRNA的表达水平均明显降低,差异有统计学意义(P<0.01);术后第7天常规护理组TNF-α、IL-6IL-8的蛋白含量及mRNA的表达水平仍高于心理护理组,差异有统计学意义(P<0.05).结论:心理护理能进一步降低乳腺癌患者血清中炎性因子的表达水平,从而增强患者免疫力及提高术后生活质量.

  15. The Study of BALF TNF-α,IL-6,IL-8,IL-10 Concentration in Critically Ill Pneumonia Mycoplasma Pneumonia Patients%重症肺炎支原体肺炎肺泡灌洗液中TNF-α、IL-6IL-8、IL-10水平观察

    Institute of Scientific and Technical Information of China (English)

    叶新明; 钱克俭

    2010-01-01

    目的 检测重症肺炎支原体肺炎患者支气管肺泡灌洗液(bronchial tube pulmonary alveolus syringe fluid,BALF)中肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(Interleukin-8,IL-8)白细胞介素-10(Interleukin-10,IL-10)浓度,探讨其临床意义.方法 收住ICU的重症肺炎支原体肺炎患者36例,其CPIS评分>6分为CPIS高分组共15例,CPIS评分<6分为CPIS低分组共21例;正常对照组24例.取支气管肺泡灌洗液检测TNF-α、IL-6IL-8、IL-10水平.结果 重症肺炎支原体肺炎无论CPIS高分组和CPIS低分组支气管肺泡灌洗液中TNF-α、IL-6IL-8、IL-10水平明显高于对照组,差异有统计学意义(P0.05).2组治疗后恢复期TNF-α、IL-6IL-8、IL-10水平均明显下降(P<0.01).结论 TNF-α、IL-6IL-8、IL-10在重症肺炎的发生发展中起重要作用,是重症肺炎支原体肺炎诊断的重要因素之一.利用支气管肺泡灌洗液检测TNF-α、IL-6IL-8、IL-10水平变化对临床诊断治疗及预后有一定的临床价值.

  16. Sterile trauma to normal human dermis invariably induces IL1beta, IL6 and IL8 in an innate response to "danger".

    Science.gov (United States)

    Sjögren, Florence; Anderson, Chris

    2009-01-01

    Microdialysis allows the study of the local production and temporal resolution of cytokines in living skin. Samples were taken from the normal skin of 10 healthy subjects for 24-28 h after insertion of a concentric microdialysis catheter, and analysed with a Luminex bead-based assay. Interleukin-1 beta (IL1b), IL6 and IL8 were seen in all subjects at all time-points after the first hour. Levels peaked at 5-8 h, equilibrating to lower levels at 24 h. Immunohistological double staining for human leukocyte antigen (HLA)-DR and intracellular cytokines on biopsies taken after catheter removal showed many stained cells in the dermis, in contrast to the few cells stained in the epidermis. This study demonstrates the reactive capability of the dermis when provoked separately from the epidermis. The production of IL1b, IL6 and IL8 occurs invariably in what can be termed an innate, dermal response to "danger"; in this case in the form of sterile needle trauma.

  17. Blood Serum Levels of IL-2, IL-6, IL-8, TNF-α and IL-1β in Patients on Maintenance Hemodialysis

    Institute of Scientific and Technical Information of China (English)

    Jacek Rysz; Maciej Banach; Aleksandra Cialkowska-Rysz; Robert Stolarek; Marcin Barylski; Jaroslaw Drozdz; Piotr Okonski

    2006-01-01

    Cytokines are essential mediators of immune response and inflammatory reactions. Patients with chronic renal failure (CRF) commonly present with abnormalities of immune function related with impaired kidney function and the accumulation of uremic toxins in addition to bioincompatibility of dialyzer membranes. During a hemodialysis (HD) session, cytokines are released mainly by monocytes activated by endotoxin-type compounds in dialyzer fluid,complement factors and direct contact with dialyzer membrane. The study included 15 CRF patients, aged 36.4 ± 2.9 years, on regular HD maintenance therapy for mean 68 ± 10 months and 15 healthy controls. It was designed to assess serum levels of a panel of inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8 and TNF-α in CRF patients on regular maintenance HD before, 20, 60 and 240 minutes of a single HD session in parallel with C-reactive protein (CRP) as an additional parameter. CRP concentration was increased in HD patients when compared with healthy controls. The concentrations of IL-1, IL-6, IL-8 and TNF-α were increased, whereas the serum level of IL-2 was not altered during a single HD session.

  18. 雌激素与IL-6IL-8在卵巢癌细胞中的调节作用%Regulation of estrogen, interleukin-6 and interleukin-8 in ovarian cancer cells

    Institute of Scientific and Technical Information of China (English)

    王越; 杨洁; 高燕; 东莉洁; 姚智

    2008-01-01

    Objective To discover the reciprocal regulation and its molecular mechanism of estro-gen, IL-6 and IL-8 in ovarian cancer cells. Methods Based on our previous studies, the effect of 17β-estradiol (E2) on the expression levels of IL-6, IL-8 and their respective receptors was investigated. Mean-while, the effect of IL-6/IL-8 on estrogen receptor (ER) expression and estrogen-dependent transcriptional activation was analyzed. Gene expression profile analysis revealed that CAOV-3 and OVCAR-3 cells, which express ER, IL-6 and IL-8 receptors, were suitable models for this study. Results We found that E2 not only enhanced IL-6/IL-8 secretion via NF-κB signaling pathway, but also modulated IL-6 and IL-8 receptors expression. Tamoxifen (Txf), an ER antagonist, completely abolished E2-stimulated IL-6/IL-8 expression. On the other hand, in the absence of estrogen, both cytokines increased ERα expression, decreased ERβ ex-pression, and activated estrogen-dependent transcriptional activation, which was completely blocked by Txf. Pretreatment of OVCAR-3 with p38 MAPK, MEK1/2 or ErbB2 MAPK inhihitors, respectively, IL-6-media-ted ER activation was blocked, while IL-8-indueed ER activation was blocked by Src inhibitor. Conclusion These data suggest that estrogen, IL-6 and IL-8 may form a mutual amplifying signaling which contributes to the growth and development of ovarian carcinoma.%目的 探讨雌激素与IL-6IL-8在卵巢癌细胞中的交互调节作用及作用机制.方法 选择兼有雌激素受体(estrogen receptor,ER)及IL-6IL-8受体表达的卵巢癌细胞系CAOV-3和OVCAR-3作为研究模型,分别探讨17B-雌二醇(estradiol,E2)对IL-6IL-8及其受体表达的作用以及IL-6IL-8对EB表达及ER转录活性的作用.结果 一方面E2不仅可经NF-κB途径促进卵巢癌细胞IL-6IL-8分泌,而且还对二者受体的表达具有一定的调节作用.E2诱导的促IL-6IL-8分泌作用可被其受体阻断剂他莫昔芬(tamoxifen,Txf)完

  19. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia.

    Science.gov (United States)

    Sun, Jia; Su, Junwei; Xie, Yirui; Yin, Michael T; Huang, Ying; Xu, Lijun; Zhou, Qihui; Zhu, Biao

    2016-01-01

    Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP) at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P = 0.008, R (2) = 0.258), HBDH (P = 0.001, R (2) = 0.335), and Ferritin (P = 0.005, R (2) = 0.237). Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P < 0.001; 1.11 ± 0.72, P = 0.043), larger AUC (95% CI 0.781-1.000, P < 0.001; 95% CI 0.592-0.917, P = 0.043), and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

  20. Plasma IL-6/IL-10 Ratio and IL-8, LDH, and HBDH Level Predict the Severity and the Risk of Death in AIDS Patients with Pneumocystis Pneumonia

    Directory of Open Access Journals (Sweden)

    Jia Sun

    2016-01-01

    Full Text Available Objective. To identify blood biomarkers to predict severity and mortality in AIDS PCP patients. Methods. Biomarkers including clinical parameters and plasma inflammatory cytokines were assessed in 32 HIV-infected patients with Pneumocystis pneumonia (PCP at time of admission. Predictive value of the biomarkers for clinical severity and in-hospital mortality was evaluated by corresponding ROC curve. Results. Levels of CRP, WBC, LDH, HBDH, and Ferritin were significantly higher in the severe and nonsurvivor AIDS PCP patients. These important biochemical indicators have inverse correlation with oxygenation index, especially levels of LDH (P=0.008, R2=0.258, HBDH (P=0.001, R2=0.335, and Ferritin (P=0.005, R2=0.237. Plasma IL-8 and IL-6 levels were significantly higher in patients with PaO2/FiO2 ≤ 200 mmHg and nonsurvivors than in those with PaO2/FiO2 > 200 mmHg and survivors. Severe and nonsurvival groups showed higher ratio of mean IL-6/IL-10 level (1.78 ± 1.56, P<0.001; 1.11 ± 0.72, P=0.043, larger AUC (95% CI 0.781–1.000, P<0.001; 95% CI 0.592–0.917, P=0.043, and more significantly inverse correlation with the oxygenation index. Conclusion. Plasma IL-8, LDH, and HBDH levels and IL-6/IL-10 ratio could be helpful for early evaluation of the severity and predicting fatal outcomes in AIDS PCP patients.

  1. 分娩镇痛后产妇血清IL-6IL-8、IL-10的变化%Effect of analgesia with continued epidural block on the serum IL-6, IL-8 and IL-10 in parturients

    Institute of Scientific and Technical Information of China (English)

    修玉芳; 黄东林; 王颖; 肖龙

    2013-01-01

    目的:观察罗哌卡因连续硬膜外阻滞进行分娩镇痛对产妇血清中IL-6IL-8、IL-10的影响.方法:将200例产妇随机分为观察组和对照组各100例.观察组在宫口开至2 ~3 cm时,开始采用连续硬膜外阻滞进行分娩镇痛;对照组按产科常规处理.观察两组产妇分娩镇痛前30 min、分娩镇痛后2h、分娩后24 h、48 h和72 h等5个时点的IL-6IL-8、IL-10水平的变化.结果:两组产妇分娩镇痛后血清IL-6IL-8、IL-10水平与分娩镇痛前比较均有升高(P<0.01),且多在分娩后24 h达峰值,对照组较观察组升高更为明显(P<0.05).结论:罗哌卡因连续硬膜外阻滞进行分娩镇痛可有效降低产妇分娩后炎性应激反应.%Objective:To observe the effect of labor analgesia with continued epidural block on the serum IL-6,IL-8 and IL-10 in parturients.Methods:Two hundreds of labor women were divided into two groups with 100 cases each group.One hundred parturients were selected as labor analgesia group (group I) and the others were as nature delivery group without analgesia (group II).Analgesia was used when utero-cervical was opened to 2 ~ 3 cm.The levels of serum IL-6,IL-8 and IL-10 were observed at five time points:before labor analgesia,at 2 h after the labor analgesia,at 24,48,72 h after delivery.Results:The levels of serum IL-6,IL-8 and IL-10 were increased significantly after labor analgesia,reached at peak values at 24 h (P < 0.05),and then gradually declined but still higher than the baseline values.The serum IL-6,IL-8 and IL-10 were significantly higher at 2 and 24 h in group Ⅱ than those in group I (P < 0.05).Conclusion:Labor analgesia with continued epidural block is safe and effective.Epidural analgesia can reduce the level of serum IL-6,IL-8 and IL-10 and inflammatory response during delivery.

  2. 过敏性哮喘患者外周血IL-2、IL-4、IL-6IL-8水平的变化%Change of the Level of IL-2, IL-4, IL-6 and IL-8 of Irritability Asthma Patients

    Institute of Scientific and Technical Information of China (English)

    王爱华; 李全新

    2000-01-01

    为了观察白细胞介素在哮喘发病中的作用,该文分别对哮喘发作期20例 ,缓解期12例患者及正常对照组10例进行了血清IL-2、IL-4、IL-6IL-8的测定,结果发现 ,发作期患者血清IL-2水平下降,而IL-4、IL-6IL-8水平均增高,缓解期均恢复至正常水平.提示这些细胞因子在哮喘发病过程中起着重要作用.

  3. 参麦注射液对急性肺挫伤患者TNF-α、IL-6IL-8的影响%Effects of Shenmai injection on TNF-α、 IL-6 and IL-8 in patients with acute pulmonary contusion

    Institute of Scientific and Technical Information of China (English)

    杨剑虹; 陈晓娟; 唐忠志

    2011-01-01

    目的 观察参麦注射液对急性肺挫伤患者炎性细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)的影响.方法 选择70例急性肺挫伤患者,随机分为对照组和治疗组,各35例.两组均给予常规西医治疗,治疗组在此基础上加用参麦注射液治疗,两组疗程均为7 d.观察急性肺挫伤患者平均住院时间、肺部感染率、急性呼吸窘迫综合征(ARDS)发生率,比较两组患者血清TNF-α、IL-6IL-8变化情况.结果 治疗组患者平均住院时间、肺部感染率、ARDS发生率均较对照组明显降低(P均<0.05=;治疗7 d 后,治疗组患者血清TNF-α、IL-6IL-8水平较对照组有明显降低(P<0.05或P<0.01=.结论 参麦注射液能显著减少急性肺挫伤患者炎性细胞因子TNF-α、IL-6IL-8的产生,抑制炎症反应.%Objective To observe the effects of shenmai injection on tumor necrosis factor-a(TNF-α) 、Interleukin-6( IL-6 ) and Interleukin-8 (IL-8) levels in patients with acute pulmonary contusion. Methods 70 patients with acute pulmonary contusion were randomly divided into routine treatment group ( n = 35) and shenmai injection treatment group ( n = 35 ). Both groups were given routine treatment, while the patients of shenmai injection treatment group were given shenmai injection in addition, for 7 day. Average stay, incidence of pulmonary infection and respiratory distress syndrome (ARDS) in patients with acute pulmonary contusion were observed. The changes of serum TNF-α, IL-6 and IL-8 levels were compared in both groups. Results The average stay, incidence of pulmonary infection and ARDS ( P < 0.05 ) in shenmai injection treatment group were significantly decreased, the serum TNF-α、 IL-6 and IL-8 levels in shenmai injection treatment group were lower than those in routine treatment group (P < 0.01 or P < 0.05 ) after 7 day. Conclusion shenmai injection can significantly reduce the production of

  4. Change of IL-1β, IL-6, IL-8 ,TNF-α, IL-10 in cerebrospinal fluid after brain injury and its clinical significance%脑外伤患者脑脊液IL-1β、IL-6IL-8、TNF-α、IL-10水平变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    吕丽霞; 张玲; 韩媛; 张国栋; 李巍; 杨萍; 张飚

    2013-01-01

    目的 探讨脑外伤时不同时期脑脊液IL-1β、IL-6IL-8、TNF-α、IL-10的水平变化及临床意义.方法 选择48例脑外伤患者,其中重型26例、轻型22例;高颅内压25例、低颅内压23例.分别留取伤后12、24、36、72 h的脑脊液标本,采用酶联免疫吸附法检测伤后各时间点脑脊液IL-1β、IL-6IL-8、TNF-α、IL-10水平.另取查体健康者28例为对照组.结果 与对照组相比,脑外伤患者脑脊液中IL-6、IL-1β、TNF-α、IL-8和IL-10水平均显著增高(P均<0.01).脑外伤重型组脑脊液IL-6、IL-1β、TNF-α和IL-8峰值水平高于与轻型组(P均<0.01);高颅内压组脑脊液中IL-1β峰值水平高于低颅内压组(P<0.01).结论 脑外伤后脑脊液炎性细胞因子水平升高,可作为预测脑损伤严重程度的指标.%Objective To investigate the concentration change of the inflammatory cytokines (IL-1 β,IL-6,IL-8,TNF-α,IL-10) in cerebrospinal fluid at different periods of time after traumatic brain injury.Methodds In this study,48 patients with traumatic brain injury were enrolled,the cerebrospinal fluid samples were collected in 12 h,24 h,36 h and 72 h after traumatic brain injury,the concentration of the inflammatory cytokines were detected with enzyme-linked immunosorbent assay.Results Compared with that in control group,there were significantly increased concentrations of IL-1 β,IL-6,IL-8,TNF-α,IL-10 in patients with traumatic brain injury(all P < 0.01).Peak concentrations of IL-6,IL-1 β,TNF-α and IL-8 of cerebrospinal fluid in patients with severe brain injury were significantly higher than those in patients with mild brain injury(all P < 0.01).Peak concentration of IL-1 β in patients with high intracranial pressure was higher than that in patients with low intracranial pressure(P <0.01).Conclusion The levels of IL-1 β,IL-6,IL-8,TNF-α and IL-10 increase after the traumatic brain injury,which may be one of the probable biomarkers for the severity

  5. In-vitro suppression of IL-6 and IL-8 release from human pulmonary epithelial cells by non-anticoagulant fraction of enoxaparin.

    Directory of Open Access Journals (Sweden)

    Madhur D Shastri

    Full Text Available Enoxaparin, a mixture of anticoagulant and non-anticoagulant fractions, is widely used as an anticoagulant agent. However, it is also reported to possess anti-inflammatory properties. Our study indicated that enoxaparin inhibits the release of IL-6 and IL-8 from A549 pulmonary epithelial cells. Their release causes extensive lung tissue damage. The use of enoxaparin as an anti-inflammatory agent is hampered due to the risk of bleeding associated with its anticoagulant fractions. Therefore, we aimed to identify the fraction responsible for the observed anti-inflammatory effect of enoxaparin and to determine the relationship between its structure and biological activities.A549 pulmonary epithelial cells were pre-treated in the presence of enoxaparin and its fractions. The levels of IL-6 and IL-8 released from the trypsin-stimulated cells were measured by ELISA. The anticoagulant activity of the fraction responsible for the effect of enoxaparin was determined using an anti-factor-Xa assay. The fraction was structurally characterised using nuclear magnetic resonance. The fraction was 2-O, 6-O or N-desulfated to determine the position of sulfate groups required for the inhibition of interleukins. High-performance size-exclusion chromatography was performed to rule out that the observed effect was due to the interaction between the fraction and trypsin or interleukins.Enoxaparin (60 μg/mL inhibited the release of IL-6 and IL-8 by >30%. The fraction responsible for this effect of enoxaparin was found to be a disaccharide composed of α-L-iduronic-acid and α-D-glucosamine-6-sulfate. It (15 μg/mL inhibited the release of interleukins by >70%. The 6-O sulphate groups were responsible for its anti-inflammatory effect. The fraction did not bind to trypsin or interleukins, suggesting the effect was not due to an artefact of the experimental model.The identified disaccharide has no anticoagulant activity and therefore eliminates the risk of bleeding

  6. 性病患者58例血清IL-2、IL-6IL-8水平的检测及其临床意义

    Institute of Scientific and Technical Information of China (English)

    高英举

    2002-01-01

    目的探讨血清白细胞介素-2(IL-2)、白细胞介素-6(IL-6),白细胞介素-8(IL-8)在性病患者血清中水平及临床意义.方法应用双抗体夹心EliSA法检测了58例性病患者血清中IL-2、IL-6IL-8水平.结果 58例性病患者血清中,IL-2、IL-6IL-8水平分别为(6.4±3.2) ng/ml、(0.15±0.06) ng/ml、(0.34±0.13) ng/ml、而IL-8则显著高于正常人组(P<0.01),其中IL-2、IL-6则明显低于正常人组(P<0.01).结论性病患者的发生与发展与IL-2、IL-6降低和IL-8升高密切相关,检测IL-2、IL-6IL-8血清水平有助于性病的判断和治疗的选择.

  7. Ketamine suppresses the substance P-induced production of IL-6 and IL-8 by human U373MG glioblastoma/astrocytoma cells.

    Science.gov (United States)

    Yamaguchi, Keisuke; Kumakura, Seiichiro; Murakami, Taisuke; Someya, Akimasa; Inada, Eiichi; Nagaoka, Isao

    2017-03-01

    The neuropeptide substance P (SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous systems. SP has been shown to induce the expression of pro-inflammatory cytokines implicated in the pathogenesis of several disorders of the human brain via the neurokinin-1 receptor (NK-1R). Ketamine, an intravenous anesthetic agent, functions as a competitive antagonist of the excitatory neurotransmission N-methyl-D‑aspartate (NMDA) receptor, and also antagonizes the NK-1R by interfering with the binding of SP. In the present study, we investigated the anti-inflammatory effects of ketamine on the SP-induced activation of a human astrocytoma cell line, U373MG, which expresses high levels of NK-1R. The results from our experiments indicated that ketamine suppressed the production of interleukin (IL)-6 and IL-8 by the U373MG cells. Furthermore, ketamine inhibited the SP-induced activation of extracellular signal‑regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). Taken together, these observations suggest that ketamine may suppress the SP-induced activation (IL-6 and IL-8 production) of U373MG cells by inhibiting the phosphorylation of signaling molecules (namely ERK1/2, p38 MAPK and NF-κB), thereby exerting anti‑inflammatory effects. Thus, ketamine may modulate SP-induced inflammatory responses by NK-1R‑expressing cells through the suppression of signaling molecules (such as ERK1/2, p38 MAPK and NF-κB).

  8. IL-17、IL-6IL-8在子痫前期孕妇血清及胎盘组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    吴海英

    2013-01-01

    目的:研究子痫前期孕妇血清及胎盘组织中IL-17、IL-6IL-8表达方式和意义。方法将本院2012-2013年子痫前期孕妇30例设为观察组,另选同期正常孕妇30例设为对照组。酶联免疫吸附法(ELISA)检测两组孕妇血清中IL-17、IL-6IL-8,免疫组化法检测胎盘中IL-17、IL-6IL-8的表达水平。结果观察组血清IL-17、IL-6IL-8高于对照组、组织胎盘IL-6指数低于对照组(P0.05)。结论炎性细胞因子IL-17、IL-6IL-8和子痫前期之间存在明显联系,是临床诊断子痫前期孕妇的重要指数,值得重视。

  9. 社区获得性肺炎患者血清及支气管肺泡灌洗液中IL-6IL-8和IL-10水平变化及其临床意义%The levels of IL-6,IL-8 and IL-10 in serum and bronchoalveolar lavage fluid in patients with community-acquired pneumonia and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    丁静; 魏希强; 孙伟

    2015-01-01

    目的::探讨社区获得性肺炎( CAP)患者血清和支气管肺泡灌洗液( BALF)中炎症因子白细胞介素( IL)-6IL-8和IL-10水平的变化及其临床意义。方法:选取CAP患者50例( CAP组),入院第1天进行临床肺部感染评分,0.05);而CAP组血清中IL-8水平在入院第30天仍保持较高水平,显著高于对照组(P0. 05). The level of IL-8 in serum of CAP patients remained at a high level on day 30 of admission,which was significantly higher than that in control group(P <0. 01). Conclusions:The IL-6,IL-8 and IL-10 were involved in the pathogenesis of community-acquired pneumonia. The levels of IL-6 and IL-10 in serum and levels of IL-6,IL-8 and IL-10 in BALF can reflect the severity of pulmonary infection. The detection of IL-6,IL-8 and IL-10 in serum has certain clinical value in the early diagnosis of CAP.

  10. Influence of IL-6, IL-8, and TGF-β1 gene polymorphisms on the risk of human papillomavirus-infection in women from Pernambuco, Brazil

    Science.gov (United States)

    de Lima, Sérgio Ferreira; Tavares, Mayara Mansur Fernandes; de Macedo, Jamilly Lopes; de Oliveira, Renata Santos; Heráclio, Sandra de Andrade; Maia, Maria de Mascena Diniz; de Souza, Paulo Roberto Eleutério; Moura, Ronald; Crovella, Sergio

    2016-01-01

    Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil. We analysed 108 healthy uninfected women (HC) and 108 HPV-positive women with cervical lesions. Genetic polymorphisms were assessed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. Comparison of the distribution of the genotypic and allelic frequencies of the IL-18 +396 T>G polymorphism between HPV infected woman an uninfected controls showed that the GG genotype and G allele were both more frequent in the HC group, and were associated with protection from HPV infection (p = 0.0015; OR = 0.29 CI95% = 0.13-0.61; p = 0.0005; OR = 0.45 CI95% 0.29-0.7, respectively). Individuals from the control group could have previously had HPV infection that was spontaneously eliminated; however, it was undetectable at the time of sample collection. Based on our findings, we hypothesize that the IL-8 +396 G>T polymorphism could interfere with susceptibility to HPV infection, by modulating the ability of immune system to fight the virus. PMID:27783717

  11. Overexpression of S100A7 protects LPS-induced mitochondrial dysfunction and stimulates IL-6 and IL-8 in HaCaT cells.

    Directory of Open Access Journals (Sweden)

    Wenyan Sun

    Full Text Available S100A7 (or psoriasin is distributed in the cytoplasm of keratinocytes of normal human epidermis, and it is overexpressed in many epidermal inflammatory diseases. Lipopolysaccharide (LPS induces mitochondrial function changes, which play important roles in multiple cellular mechanisms including inflammation. Although S100A7 expression is regulated by various factors in the human epidermis during inflammation, whether S100A7 interacts with mitochondria in keratinocytes is not clear.Our study was designed to investigate whether S100A7 could prohibit mitochondrial dysfunction and stimulate cytokines in cultured normal HaCaT cells treated with LPS.We generated HaCaT cells that constitutively express enhanced green fluorescence protein (EGFP-S100A7 (S100A7-EGFP or EGFP alone, as a control. Here, we show that S100A7-EGFP HaCaT cells exhibit an increase in mitochondrial DNA (mtDNA copy number and mitochondrial membrane potential (MMP. qRT-PCR revealed that expression of three main mitochondrial biogenesis-associated genes was significantly increased: PPAR-coactivator-1alpha (PGC-1α, the mitochondrial transcription factor A (Tfam and nuclear respiratory factor-1 (NRF1. S100A7 overexpression increased mtDNA content and effectively increased intracellular adenosine 5'-triphosphate (ATP production, while decreasing reactive oxygen species (ROS generation. S100A7 overexpression also significantly decreased the expression of Mfn2 and increased DRP1 expression compared with control EGFP cells. S100A7 down-regulated the expression of the autophagy-related proteins Beclin-1 and LC3B. S100A7 also increased expression of IL-6 and IL-8 cytokines. Knockdown of S100A7 decreased MMP and disrupted mitochondrial homeostasis.These findings demonstrate that S100A7 stimulates mitochondrial biogenesis and increases mitochondrial function in HaCaT cells treated with LPS; and S100A7 also promotes secretion of IL-6 and IL-8.

  12. Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes.

    Science.gov (United States)

    Luo, Millore X M; Wong, Sunny H; Chan, Matthew T V; Yu, Le; Yu, Sidney S B; Wu, Feng; Xiao, Zhangang; Wang, Xiaojuan; Zhang, Lin; Cheng, Alfred S L; Ng, Simon S M; Chan, Francis K L; Cho, Chi H; Yu, Jun; Sung, Joseph J Y; Wu, William K K

    2015-10-01

    Hepatitis B virus (HBV) and one of its encoded proteins, HBV X protein (HBx), have been shown to induce autophagy in hepatoma cells. Substantial evidence indicates that autophagy is a potent suppressor of inflammation. However, sporadic reports suggest that autophagy could promote pro-inflammatory cytokine expression and inflammation in some biological contexts. Here, we show that overexpression of HBx induces LC3B-positive autophagosome formation, increases autophagic flux and enhances the expression of ATG5, ATG7, and LC3B-II in normal hepatocytes. Abrogation of autophagy by small interfering RNA against ATG5 and ATG7 prevents HBx-induced formation of autophagosomes. Autophagy inhibition also abrogates HBx-induced activation of nuclear factor-κB (NF-κB) and production of interleukin-6 (IL-6), IL-8, and CXCL2. These findings suggest that autophagy is required for HBx-induced NF-κB activation and pro-inflammatory cytokine production and could shed new light on the complex role of autophagy in the modulation of inflammation.

  13. APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients%APE1/Ref-1 siRNA抑制多发性骨髓瘤骨髓基质细胞IL-6IL-8分泌的体外研究

    Institute of Scientific and Technical Information of China (English)

    谢家印; 王阁; 王东; 李梦侠; 向德兵; 杨镇洲; 杨宇馨; 李增鹏; 曾林立; 仲召阳

    2009-01-01

    目的 体外通过APE1/Ref-1 siRNA敲低多发性骨髓瘤骨髓基质细胞(bone marrow stromal cells,BMSCs)APE1/Ref-1的表达,观察BMSCs的增殖及分泌细胞因子IL-6IL-8的变化,初步探讨BMSCs APE1/Ref-1表达的功能特点.方法 通过免疫细胞化学染色法定量榆测35例初治、11例复发/难治多发性骨髓瘤患者及10例正常人BMSCsAPE1/Ref-1的表达特点及其差异,经Adv5-APE1/Ref-1 siRNA感染BMSCs后,流式细胞仪检测BMSCs细胞周期的变化;ELISA法检测BMSCs分泌IL-6IL-8的水平变化情况.结果 多发性骨髓瘤BMSCs的APE1/Ref-1蛋白阳性表达率显著高于正常BMSCs APE1/Ref-1蛋白阳性表达率(P<0.05),且多发性骨髓瘤BMSCs的APE1/Ref-1呈细胞核及核浆共间表达方式.Adv5-APE1/Ref-1 siRNA感染敲低多发性骨髓瘤及正常BMSCs APE1/Ref-1的表达量呈进行性减少(P<0.01),同时发现APE1/Ref-1 siRNA对多发性骨髓瘤BMSCs抑制作用更明显.Adv5-APE1/Ref-1 siRNA感染BMSCs后对正常人及骨髓瘤患者BMSCs分泌细胞因子IL-6IL-8的量有显著的抑制作用,特别是感染72 h后,骨髓瘤患者及正常人的BMSCs分泌IL-6[初治患者(246.29±46.51)pg/ml,复发/难治患者(365.09±75.25)pg/ml]、IL-8[初治患者(118.77±18.08)pg/ml,复发/难治患者(188.71±33.76)pg/ml]的量最低,与其他时段比较差异有统计学意义(P<0.01).结论 多发性骨髓瘤BMscs APE1/Ref-1的表达特点不同于正常BMSCs,可能导致其功能差异;APE1/Ref-1 siRNA敲低了MM BMSCsAPE1/Ref-1的表达,同时明显抑制了其IL-6IL-8的分泌,减少了对骨髓瘤细胞的促增殖和凋亡作用.

  14. 慢性乙型肝炎和肝功能衰竭患者血清IL-32、IL-6IL-8检测的意义

    Institute of Scientific and Technical Information of China (English)

    陈海芬

    2015-01-01

    目的 探讨血清白细胞介素(IL)-32、IL-6IL-8检测在慢性乙型肝炎和肝功能衰竭中的意义.方法 分别选取慢性乙型肝炎患者(130例)、肝功能衰竭患者(40例)和健康对照者(60例),比较3组间和不同病情严重程度的乙型肝炎患者间的IL-32、IL-6IL-8水平.结果 肝炎组和肝衰竭组的IL-32、IL-8IL-6均高于对照组(均P< 0.05),肝衰竭组的IL-32、IL-8IL-6均高于肝炎组(均P<0.05);且病情越严重,IL-32、IL-8IL-6值越高(均P< 0.05).结论 IL-32、IL-8IL-6细胞因子的水平会随着病情严重程度的增加而增加,可以用于判断病情的严重程度,对病情加以评估,有重要的临床意义.

  15. 宫颈癌患者外周血中IL-6IL-8和IL-17的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    姜波

    2015-01-01

    目的:探讨宫颈癌患者外周血中IL-6IL-8和IL-17的表达及临床意义.方法:选择2011年1月至2012年12月期间50例宫颈癌患者为研究对象,按照临床分期分为Ⅰ期(16例)、Ⅱ期(24例)和Ⅲ期(10例).另选择CIN患者50例作为CIN组,选择健康女性50例为对照组.统计受试者血清IL-6IL-8和IL-17水平,并对血清IL-6IL-8和IL-17表达与年龄、宫颈癌病程、临床分期、高危型人乳头瘤病毒(HR-HPV)感染、BMI进行相关性分析.结果:宫颈癌组血清IL-6IL-8和IL-17水平高于CIN组和对照组,差异有统计学意义(P<0.01),CIN组血清IL-6IL-8和IL-17水平高于对照组,差异有统计学意义(P<0.01);随着宫颈癌临床分期的增加,IL-6IL-8和IL-17的表达呈增强趋势,且3组间两两比较差异均有统计学意义(P<0.01);HR-HPV阳性组血清IL-6IL-8和IL-17水平高于HR-HPV阴性组,差异有统计学意义(P<0.01);血清IL-6IL-8和1L-17表达与宫颈癌临床分期、HR-HPV感染均呈正相关(P<0.05),血清IL-6IL-8和IL-17表达之间均呈正相关(P<0.05).结论:宫颈癌患者血清中IL-6IL-8和IL-17呈高表达,宫颈癌中IL-6IL-8和IL-17的表达与宫颈癌的发生、进展及HR-HPV感染密切相关.

  16. IL-8MMP-9、 INF-γ的检测对结核性脑膜炎及病毒性脑膜炎发病的意义%Detection of interleukin-8, matrix metalloproteinase-9 and interferon gamma levels in the cerebrospinal fluid of patients with tuberculous meningitis and viral meningitis

    Institute of Scientific and Technical Information of China (English)

    朱飞; 张家堂; 邢小微; 贺路星; 赵威; 郎森阳; 于生元

    2012-01-01

    目的 探讨脑脊液中白细胞介素-8(IL-8)、基质金属蛋白酶-9(MMP-9)、干扰素-γ(INF-γ)含量的检测对结核性脑膜炎及病毒性脑膜炎的临床诊断价值. 方法 选取解放军总医院、解放军第三0九医院自2010年8月至2011年11月住院的患者,其中结核性脑膜炎组20例,病毒性脑膜炎组15例,非感染性神经系统疾病组20例.用ELISA法检测3组患者脑脊液IL-8MMP-9、INF-γ含量,并进行比较分析. 结果 结核性脑膜炎组患者脑脊液中IL-8MMP-9、INF-γ的含量高于病毒性脑膜炎组和非感染性神经系统疾病组差异有统计学意义(P<0.05).病毒性脑膜炎组患者脑脊液中IL-8MMP-9含量高于非感染性神经系统组(P<0.05).病毒性脑膜炎组患者脑脊液中INF-γ含量与非感染性神经系统疾病组比较差异无统计学意义(P>0.05). 结论 脑脊液中IL-8MMP-9、INF-γ含量的检测对结核性脑膜炎具有一定的辅助诊断意义.IL-8MMP-9在病毒性脑膜炎的发病和进展中亦起到一定作用.临床上若在患者脑脊液中检测到高水平的INF-γ,较之IL-8、MMP-9对于结核性脑膜炎更具诊断价值.%Objective To investigate the diagnostic values of interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9) and interferon gamma (INF-γ) levels in patients with tuberculous meningitis and viral meningitis by detecting the contents of these biomarkers in the cerebrospinal fluid (CSF). Methods Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-8,MMP-9 and INF-γ in the CSF of patients with tuberculous meningitis (n=20),viral meningitis (n=15) and noninfectious neurologic diseases (n=20) who admitted to our hospital from August 2010 to November 2011. Results The IL-8,MMP-9 and INF-γlevels in the samples from the tuberculous meningitis patients were significantly higher than those from either viral meningitis or noninfectious neurologic diseases (P<0.05).The contents of IL-8

  17. Efects of Trimetazidine On-pump Coronary Artery Bypass Grarting in Patients with IL-6, IL-8%曲美他嗪对非体外循环冠脉搭桥术患者IL-6IL-8的影响

    Institute of Scientific and Technical Information of China (English)

    宋书田; 张彬; 张楠; 杨明; 白传明; 周继梧

    2011-01-01

    目的:观察曲美他嗪对非体外循环冠状动脉(冠脉)旁路移植术(of-pump coronary artery bypass,OPCAB)患者白介素6(interleukin-6,IL-6)和白介素8(interleukin-8,IL-8)浓度的影响.方法:将103例于我院择期行OPCAB的冠心病患者随机分为曲美他嗪组(52例)和对照组(51例).分别于术前、吻合旁路血管开放后6h、12h、24h、48h抽取静脉血,采用放免法检测血清IL-6IL-8浓度.结果:2组患者临床特征及手术桥血管情况无统计学意义.曲美他嗪组IL-6浓度在术后6h[(225±16)、(515±81)ng/L]和术后12h[(172±5)、(285±11)ng/L]明显低于对照组(P<0.05).曲美他嗪组的IL-8浓度在术后12h[(638±30)、(893±59)ng/L]和24h[(497±16)、(589±26)ng/L]显著低于对照组(P<0.01).结论:曲美他嗪可降低OPCAB患者IL-6IL-8的释放.%Objective:To observe the effects of trimetazidine on serum of the patients ,interleukin-6 and interleukin-8 underwent offpump coronary artery bypass.Methods:One hundred and three patients who underwent off-pump coronary artery bypass randomly divided into trimetazidine group(52 cases) and control group(51 cases).To draw vein blood preoperative,postoperative six hours,postoperative twelve hours,postoperative twenty-four hours and postoperative forty-eight hours for analyze interleukin-6 and interleukin-8.Results:There was no significant difference between two groups of clinical characterizes and grafts.The serum interleukin-6 of trimetazidine group was lower than control group after surgery six hours and twelve hours, respectively(P<0.05).The serum interleukin-8 of trimetazidine group was lower than control group after surgery twelve hours and twenty-four hours, respectively(P<0.01).Conclusion:Trimetazidine may reduce the release of the serum level of interleukin-6 and interleukin-8 the patients underwent off-pump coronary artery bypass.

  18. Genome-wide association study of genetic variants in LPS-stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine response in a Danish Cohort

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Albrechtsen, Anders; Thørner, Lise Wegner

    2013-01-01

    Cytokine response plays a vital role in various human lipopolysaccharide (LPS) infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL)-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF)-α cytokine production....

  19. Effects of Traditional Chinese Medicine Qingre Lishi Yin on Expressions of IL-6mRNA and IL-8mRNA and IL-10mRNA and Secretion of IL-8 and IL-10 in HaCaT Cells%中药清热利湿饮对HaCaT细胞表达IL-6mRNA、IL-8mRNA、IL-10mRNA及分泌IL-8、IL-10的影响

    Institute of Scientific and Technical Information of China (English)

    范玉; 杜锡贤; 张春红

    2014-01-01

    目的:揭示中药清热利湿饮对人永生化角质形成细胞HaCaT细胞表达IL-6mRNA、IL-8mRNA、IL-10mRNA和分泌IL-8、IL-10的作用机制.方法:以HaCaT细胞为研究对象,分别采用RT-PCR技术及ELISA方法观察中药清热利湿饮提取液对经TNF-α诱导活化的HaCaT细胞表达IL-6mRNA、IL-8mRNA、IL-10mRNA和分泌IL-8、IL-10的影响.结果:清热利湿饮对经TNF-α诱导活化的HaCaT细胞IL-6mRNA和IL-8mRNA的表达有下调作用,在药物浓度为10g/L和12.5g/L时,HaCaT细胞IL-10mRNA的表达量增强较为明显,与TNF-α诱导活化组相比,有显著性差异(P<0.05或P<0.01).清热利湿饮对经TNF-α诱导活化的HaCaT细胞IL-8的分泌有不同程度的抑制作用,但对IL-10的影响不明显.结论:清热利湿饮可下调IL-6mRNA、IL-8mRNA的表达,上调IL-10mRNA的表达,且此作用随药物浓度的升高而增强;同时可降低细胞IL-8的分泌,但对IL-10的分泌无明显的作用.

  20. The dynamic monitor critically ill pneumonia patient blood and the bronchial tube pulmonary alveolus fill in the cleaning solution IL-6, IL-8, the IL-10 content and significance%动态监测重症肺炎患者血液和支气管肺泡灌洗液中 IL-6IL-8、IL-10 的含量及其意义

    Institute of Scientific and Technical Information of China (English)

    李国保; 李沛

    2009-01-01

    Objective The dynamic monitor critically ill pneumonia patient blood and in the bronchial tube pulmonary alveolus syringe fluid IL-6, IL-8, the IL-10 density change, discusses its clinical significance. Methods Receives this courtyard ICU the critically ill pneumonia patient, the selected patient in the course the 1st day, CPIS grades >6 to divide into the CPIS high grouping, the CPIS grading ≤6 divides into CPIS the low grouping. In the course 1st, 4, 7 day of extraction circumference venous blood makes the cell factor determination as well as the bronchial tube pulmonary alveolus syringe fluid inspection. Results Regardless in the blood in BALF, CPIS high grouping's IL-6, the IL-8 level is lower than CPIS the grouping obvious markup, the difference has the remarkable significance (P<0.01), CPIS groups the IL-10 level to be lower than high the grouping group CPIS to be slightly high, but not yet reaches the remarkable difference;In blood and BALF IL-6, IL-8 level and CPIS grading present related (P<0.05), in blood and BALF IL-10 level and CPIS grading not obvious relevance.Conclusion The critically ill pneumonia patient blood and in the bronchial tube pulmonary alveolus syringe fluid IL-6, the IL-8 level may reflect that the lung infects the degree, IL-8, the IL-10 level and the change tendency may reflect the patient prognosis situation.%目的 动态监测重症肺炎患者血液和支气管肺泡灌洗液中 IL-6IL-8、IL-10 的浓度变化,探讨其临床意义.方法 收住本院ICU的重症肺炎患者,入选患者在病程的第 1 天,CPIS 评分>6 分为 CPIS高分组,CPIS 评分≤6 分为 CPIS 低分组.在病程的第 1、4、7 天抽取外周静脉血做细胞因子测定以及支气管肺泡灌洗液检查.结果 无论在血液中还是在 BALF 中,CPIS 高分组的 IL-6IL-8水平比 CPIS 低分组明显增高,差异有统计学意义(P<0.01),CPIS 高分组 IL-10 水平比 CPIS 低分组组稍高,但尚未达显著差异;血液和 BALF

  1. Induction of IL-6 and inhibition of IL-8 secretion in the human airway cell line Calu-3 by urban particulate matter collected with a modified method of PM sampling

    Energy Technology Data Exchange (ETDEWEB)

    Alfaro-Moreno, Ernesto, E-mail: ealfaro.incan@gmail.com [Lung Toxicology Unit, Pneumology Section, K.U. Leuven (Belgium); Subdireccion de Investigacion Basica, Instituto Nacional de Cancerologia, Avenida San Fernando 22, C.P. 14080, Mexico D.F. (Mexico); Torres, Victor [Departamento Farmacologia, Facultad de Medicina, U.N.A.M. (Mexico); Miranda, Javier [Departamento de Fisica Experimental, Instituto de Fisca, U.N.A.M. (Mexico); Martinez, Leticia [Deparatmento de Aerobiologia, Centro de Ciencias de la Atmosfera - Facultad de Medicina, U.N.A.M. (Mexico); Garcia-Cuellar, Claudia [Subdireccion de Investigacion Basica, Instituto Nacional de Cancerologia, Avenida San Fernando 22, C.P. 14080, Mexico D.F. (Mexico); Nawrot, Tim S.; Vanaudenaerde, Bart; Hoet, Peter [Lung Toxicology Unit, Pneumology Section, K.U. Leuven (Belgium); Ramirez-Lopez, Pavel [Escuela Superior de Ingenieria Quimica e Industrias Extractivas, I.P.N. (Mexico); Rosas, Irma [Deparatmento de Aerobiologia, Centro de Ciencias de la Atmosfera - Facultad de Medicina, U.N.A.M. (Mexico); Nemery, Benoit [Lung Toxicology Unit, Pneumology Section, K.U. Leuven (Belgium); Osornio-Vargas, Alvaro Roman [Subdireccion de Investigacion Basica, Instituto Nacional de Cancerologia, Avenida San Fernando 22, C.P. 14080, Mexico D.F. (Mexico)

    2009-07-15

    Exposure to particulate matter (PM) induces inflammatory cytokines. In the present study, we evaluated the secretion of IL-6 and IL-8 by an airway cell line exposed to PM with a mean aerodynamic size equal to or less than 10 or 2.5 {mu}m (PM{sub 10} and PM{sub 2.5}, respectively) collected in Mexico City, using a modified high-volume sampling method avoiding the use of solvents or introducing membrane components into the samples. PM was collected on cellulose-nitrate (CN) membranes modified for collection on high-volume samplers. Composition of the particles was evaluated by particle-induced X-ray emission (PIXE) and scanning electron microscopy. The particles (10-160 {mu}g/cm{sup 2}) were tested on Calu-3 cells. Control cultures were exposed to LPS (10 ng/mL to 100 {mu}g/mL) or silica (10-160 {mu}g/cm{sup 2}). IL-6 and IL-8 secretions were evaluated by ELISA. An average of 10 mg of PM was recovered form each cellulose-nitrate filter. No evidence of contamination from the filter was found. Cells exposed to PM{sub 10} presented an increase in the secretion of IL-6 (up to 400%), while IL-8 decreased (from 40% to levels below the detection limit). A similar but weaker effect was observed with PM{sub 2.5}. In conclusion, our modified sampling method provides a large amount of urban PM free of membrane contamination. The urban particles induce a decrease in IL-8 secretion that contrasts with the LPS and silica effects. These results suggest that the regulation of IL-8 expression is different for urban particles (complex mixture containing combustion-related particles, soil and biologic components) than for biogenic compounds or pure mineral particles.

  2. Elevated expression of APE1/Ref-1 and its regulation on IL-6 and IL-8 in bone marrow stromal cells of multiple myeloma.

    Science.gov (United States)

    Xie, Jia-Yin; Li, Meng-Xia; Xiang, De-Bing; Mou, Jiang-Hong; Qing, Yi; Zeng, Lin-Li; Yang, Zhen-Zhou; Guan, Wei; Wang, Dong

    2010-10-01

    A number of growth factors secreted by bone marrow stromal cells (BMSCs), including interleukin-6 and -8 (IL-6/8), are important for the initiation and progression of multiple myeloma (MM). However, the mechanisms that regulate the production of IL-6/8 by BMSC have not yet been well characterized. Human dual functional protein apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) is essential for cell survival and proliferation. Previous studies showed that APE1/Ref-1 was overexpressed in tumor cells, but few studies showed its expression in supportive cells in the tumor microenvironment. We first detected APE1/Ref-1 expression in BMSCs of normal, initial, and recurrent MM patients, and then explore the correlation between APE1/Ref-1 level and IL-6/8 secretion of BMSCs. A marked increase of APE1/Ref-1 expression and abnormal subcellular distribution were observed in MM BMSCs. APE1/Ref-1 overexpression was related to higher secretary level of IL-6/8 by MM BMSCs and the IL-6/8 secretion was blocked significantly by adenovirus-mediated APE1/Ref-1-specific (small interfering RNA) siRNA. Our results also demonstrated that APE1/Ref-1-specific siRNA significantly inhibited DNA binding activity of AP-1 and nuclear factor-κB (NF-κB), 2 important transcription factors in the regulation IL-6/8 secretion in MM BMSCs. The results provided by the present study indicate APE1/Ref-1, which plays a regulatory role in IL-6/8 production by BMSCs, may be a potential therapeutic target of MM.

  3. TLR4介导汉滩病毒引起血管内皮细胞分泌IL-6和TNF-α%Secretion of IL-6,Il-8 and TNF-α from vascular endothelial cells infected by Hantaan virus may be mediated by TLR4

    Institute of Scientific and Technical Information of China (English)

    姜泓; 王平忠; 王丽梅; 张野; 黄长形; 王九平; 徐哲; 孙利; 白雪帆

    2009-01-01

    目的 检测汉滩病毒感染血管内皮细胞后IL-6,IL-8和TNF-α的分泌变化及其与TLR4的关系.方法 用5Lg TCID50/mL的HTNV76-1180.2 mL感染EVC-304细胞(TLR4+)和EVC-304 TS4(TLR4-)分别为实验组,以病毒未感染为阴性对照组,以LPS(2μg/mL)刺激作为阳性对照.48 h后取细胞培养上清,用人IL-6,IL-8和TNF-α定量EIA试剂盒分别检测IL-6,IL-8和TNF-α在两个细胞系感染前后的分泌水平.结果 IL-8在两个细胞系中感染前后的变化不明显,IL-6和TNF-α在EVC-304细胞系中,HTNV感染后升高,而在TLR4表达阴性的EVC-304细胞中,感染前后变化不明显.结论 在TLR4表达阳性的EVC-304细胞中IL-6和TNF-α分泌增加,血管内皮细胞EVC-304在HTNV感染后的IL-6和TNF-α分泌可能是TLR4介导的.

  4. 血清TNF-α、IL-6IL-8、IL-10和IL-13在小儿支原体肺炎诊治中的意义

    Institute of Scientific and Technical Information of China (English)

    邓连瑞

    2013-01-01

    目的:探讨血清中细胞因子TNF-α、IL-6IL-8、IL-10和IL-13在小儿肺炎支原体肺炎发病中的临床意义。方法将90例MPP患儿(轻症52例、重症38例)按采血时间分为治疗前组及治疗后组,对照组85例,采用酶联免疫吸附法(ELISA)检测MPP患儿入院治疗前和抗炎治疗后血清中TNF-α、IL-6IL-8、IL-10和IL-13浓度,并与对照组比较,进行统计学分析。结果 MPP治疗前组TNF-α、IL-6IL-8,IL-13显著高于对照组血清浓度(P0.05),但IL-10治疗后组与对照组比较,浓度升高具有统计学意义(P<0.05);MPP患儿重型组比轻型组比较,TNF-α、IL-6IL-8和IL-13浓度明显升高(P<0.01)。结论 MPP患儿治疗前组较治疗后组及对照组血清TNF-α、IL-6IL-8和IL-13含量升高,提示在MPP 发病机制中起重要作用,并与病情相关;而IL-10在治疗后较治疗前浓度升高,提示与机体恢复期免疫反应相关。

  5. 重症肺炎支原体肺炎肺泡灌洗液中TNF-α、IL-6IL-8、IL-10水平观察

    Institute of Scientific and Technical Information of China (English)

    叶新明; 钱克俭

    2010-01-01

    目的检测重症肺炎支原体肺炎患者支气管肺泡灌洗液(bronchial tube pul monary alveolus syringe fluid,BALF)中肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-8(In-terleukin-8,IL-8)白细胞介素-10(Interleukin-10,IL-10)浓度,探讨其临床意义。方法收住ICU的重症肺炎支原体肺炎患者36例,其CPIS评分〉6分为CPIS高分组共15例,CPIS评分〈6分为CPIS低分组共21例;正常对照组24例。取支气管肺泡灌洗液检测TNF-α、IL-6IL-8、IL-10水平。结果重症肺炎支原体肺炎无论CPIS高分组和CPIS低分组支气管肺泡灌洗液中TNF-α、IL-6IL-8、IL-10水平明显高于对照组,差异有统计学意义(P〈0.01),CPIS高分组TNF-α、IL-6IL-8水平高于CPIS低分组,差异有统计学意义(P〈0.01),CPIS高分组IL-10水平稍高于CPIS低分组,差异无统计学意义(P〉0.05)。2组治疗后恢复期TNF-α、IL-6IL-8、IL-10水平均明显下降(P〈0.01)。结论 TNF-α、IL-6IL-8、IL-10在重症肺炎的发生发展中起重要作用,是重症肺炎支原体肺炎诊断的重要因素之一。利用支气管肺泡灌洗液检测TNF-α、IL-6IL-8、IL-10水平变化对临床诊断治疗及预后有一定的临床价值。

  6. Effect of erythromycin on serum IL-8,MMP-9 and TIMP-1 in children with asthma%依托红霉素对哮喘患儿血清 IL-8、MMP-9、TIMP-1的影响

    Institute of Scientific and Technical Information of China (English)

    任文津; 欧欣; 苏定邦; 梁燕芬

    2014-01-01

    Objective To investigate the effect of erythromycin estolate of serum matrix metalloproteinase -9(MMP-9),matrix metalloproteinase inhibitor-1(TIMP-1) and interleukin -8(IL-8) in treatment of bronchial asthma (asthma) in children.Methods One hundred children with asthma were randomly divided into control group and erythromycin group with 50 cases in each group and were given the global initiative for asthma (GINA) scheme for regular treatment and erythromycin estolate group was given additional e -rythromycin for treatment of 4 weeks.The serum levels of IL-8,MMP-9,TIMP-1 change of the two groups before and after treatment were compared.Results The serum levels of IL-8,MMP-9,TIMP-1 of the two groups were decreased after treatment ( P <0.01), with that of the erythromycin estolate group decreased more significantly than that of the control group ( P <0.01).Conclusion E-rythromycin estolate treatment on the basis of conventional GINA can help to reduce the serum levels of IL -8,MMP-9 and TIMP-1 in children with asthma.%目的:探讨依托红霉素对支气管哮喘(简称哮喘)患儿血清白细胞介素-8(IL-8)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)的影响。方法将100例哮喘患儿随机分为对照组与观察组,各50例,均给予全球哮喘防治创议(GINA)方案正规治疗;观察组加用依托红霉素治疗4周。比较两组治疗前后血清 IL-8、MMP-9、TIMP-1变化。结果两组血清 IL-8、MMP-9、TIMP-1治疗后较治疗前均下降( P <0.01),观察组较对照组下降更为明显( P <0.01)。结论儿童哮喘在常规 GINA 方案治疗基础上给予依托红霉素治疗有利于促使血清 IL-8、MMP-9、TIMP-1水平降低。

  7. The altered expression of inflammation-related molecules and secretion of IL-6 and IL-8 by HUVEC from newborns with maternal inactive systemic lupus erythematosus is modified by estrogens.

    Science.gov (United States)

    Rodriguez, E; Guevara, J; Paez, A; Zapata, E; Collados, M T; Fortoul, T I; Lopez-Marure, R; Masso, F; Montaño, L F

    2008-12-01

    Systemic lupus erythematosus (SLE) predominantly affects women, especially those in reproductive age. Genetic contributions to disease susceptibility as well as immune dysregulation, particularly persistent inflammatory responses, are considered essential features. Our aim was to determine whether human umbilical vein endothelial cells (HUVEC) isolated from healthy newborns to women with inactive SLE show inflammation-related abnormalities that might lead to an early development of SLE in the offsprings. HUVEC isolated from six women with inactive SLE were stimulated with 2.5 ng/mL of TNF-alpha and/or physiological and pharmacological doses of 17-I(2) estradiol (E2). Then the expression of VCAM-1, ICAM-1, E-selectin, toll-like receptor-9 (TLR-9), heat shock protein 70 (HSP70) and HSP90 were measured. The concentrations of IL-6, IL-8, and IL-10 were also determined in maternal serum and in TNF-alpha stimulated and non-stimulated HUVEC culture supernatant. HUVEC from children with no family history of autoimmune disease served as controls. Our results showed that in HUVEC from SLE+ mothers, a constitutively low expression of adhesion molecules was enhanced by TNF-alpha treatment. The E2 (1 ng/mL) increased the expression of adhesion molecules but had no effect upon TNF-alpha-treated cells. IL-6 was constitutively higher in SLE+ HUVEC, whereas IL-8 was lower; E2 treatment diminished the latter. The E2 had no effect upon IL-6 and IL-8 secretions in TNF-alpha-treated cells. SLE+ HUVEC showed a disordered cytoskeleton and overexpressed HSP70, HSP90, and TLR-9. Our results indicate that endothelial cells of newborns to SLE+ mothers are in a proinflammatory condition which can be upregulated by estrogens.

  8. Genome-Wide Association Study of Genetic Variants in LPS-Stimulated IL-6, IL-8, IL-10, IL-1ra and TNF-α Cytokine Response in a Danish Cohort.

    Directory of Open Access Journals (Sweden)

    Margit Hørup Larsen

    Full Text Available Cytokine response plays a vital role in various human lipopolysaccharide (LPS infectious and inflammatory diseases. This study aimed to find genetic variants that might affect the levels of LPS-induced interleukin (IL-6, IL-8, IL-10, IL-1ra and tumor necrosis factor (TNF-α cytokine production.We performed an initial genome-wide association study using Affymetrix Human Mapping 500 K GeneChip® to screen 130 healthy individuals of Danish descent. The levels of IL-6, IL-8, IL-10, IL-1ra and TNF-α in 24-hour LPS-stimulated whole blood samples were compared within different genotypes. The 152 most significant SNPs were replicated using Illumina Golden Gate® GeneChip in an independent cohort of 186 Danish individuals. Next, 9 of the most statistical significant SNPs were replicated using PCR-based genotyping in an independent cohort of 400 Danish individuals. All results were analyzed in a combined study among the 716 Danish individuals.Only one marker of the 500 K Gene Chip in the discovery study showed a significant association with LPS-induced IL-1ra cytokine levels after Bonferroni correction (P<10(-7. However, this SNP was not associated with the IL-1ra cytokine levels in the replication dataset. No SNPs reached genome-wide significance for the five cytokine levels in the combined analysis of all three stages.The associations between the genetic variants and the LPS-induced IL-6, IL-8, IL-10, IL-1ra and TNF-α cytokine levels were not significant in the meta-analysis. This present study does not support a strong genetic effect of LPS-stimulated cytokine production; however, the potential for type II errors should be considered.

  9. 地塞米松联合尿激酶治疗结核性胸膜炎的疗效及对胸腔积液IL-6IL-8和hs-CRP水平的影响%Effect and Impact of IL-6,IL-8 and hs-CRP in Pleural Effusion in Patients with Tuberculous Pleuritis Treated with Dexamethasone and Urokinase

    Institute of Scientific and Technical Information of China (English)

    钟红剑; 刘腊香; 陈文胜; 杨澍

    2016-01-01

    Objective:To discuss the impact of IL-6,IL-8 and hs-CRP in pleural effusion in patients with Tuberculous pleuritis treated with Dexamethasone and Urokinase.Method:A total of 64 patients with tuberculous pleuritis from January 2013 to January 2015 in our hospital were randomly selected and divided into 32 patients of them accepted with conventional oral anti-TB drugs,pleural puncture pumping fluid and intrapleural injection of urokinase were taken as the control group while the other 32 patients of them accepted with intrapleural injection of Dexamethasone were taken as the observation group.The clinical effect and the improvement of clinical symptoms of two group were compared,and the levels of IL-6,IL-8 and hs-CRP before and after 3,7 d treatment were detected.Result:The total effective rate of the observation group was more than that of the control group,differences between two group had statistical significance(P<0.05).The time of hydrothorax disappeared and the pleural thickness of the observation group were more than those of the control group,differences had statistical significance(P<0.05).The incidence of pleural adhesions of the observation group was 9.38%,it was lower than that of the control group,difference between two group had statistical significance(P<0.05).The levels of IL-6,IL-8 and hs-CRP in pleural effusion after 3,7 d treatment of the observation group were notably lower than those of the control group,differences between two groups were statistically significant(P<0.05).Conclusion:Dexamethasone combined with Urokinase in the treatment of tuberculous pleuritis can improve the clinical symptoms and reduce the levels of IL-6, IL-8 and hs-CRP with exact clinical effect,it is worth of clinical use.%目的:探讨地塞米松联合尿激酶治疗结核性胸膜炎的疗效及对胸腔积液IL-6IL-8和hs-CRP水平的影响。方法:选取2013年1月-2015年1月本院收治的结核性胸膜炎患者64例,按照随机数字表法分为对照

  10. Topical application of glycolic acid suppresses the UVB induced IL-6, IL-8, MCP-1 and COX-2 inflammation by modulating NF-κB signaling pathway in keratinocytes and mice skin.

    Science.gov (United States)

    Tang, Sheau-Chung; Liao, Pei-Yun; Hung, Sung-Jen; Ge, Jheng-Siang; Chen, Shiou-Mei; Lai, Ji-Ching; Hsiao, Yu-Ping; Yang, Jen-Hung

    2017-06-01

    Glycolic acid (GA), commonly present in fruits, has been used to treat dermatological diseases. Extensive exposure to solar ultraviolet B (UVB) irradiation plays a crucial role in the induction of skin inflammation. The development of photo prevention from natural materials represents an effective strategy for skin keratinocytes. The aim of this study was to investigate the molecular mechanisms underlying the glycolic acid (GA)-induced reduction of UVB-mediated inflammatory responses. We determined the effects of different concentrations of GA on the inflammatory response of human keratinocytes HaCaT cells and C57BL/6J mice dorsal skin. After GA was topically applied, HaCaT and mice skin were exposed to UVB irradiation. GA reduced the production of UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators [interleukin (IL)-1β, IL-6, IL-8, cyclooxygenase (COX)-2, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP-1)] at both mRNA and protein levels. GA inhibited the UVB-induced promoter activity of NF-κB in HaCaT cells. GA attenuated the elevation of senescence associated with β-galactosidase activity but did not affect the wound migration ability. The topical application of GA inhibited the genes expression of IL-1β, IL-6, IL-8, COX-2, and MCP-1 in UVB-exposed mouse skin. The mice to UVB irradiation after GA was topically applied for 9 consecutive days and reported that 1-1.5% of GA exerted anti-inflammatory effects on mouse skin. We clarified the molecular mechanism of GA protection against UVB-induced inflammation by modulating NF-κB signaling pathways and determined the optimal concentration of GA in mice skin exposed to UVB irradiation. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  11. 参附注射液对肺挫伤患者血浆肿瘤坏死因子及白细胞介素的影响%Effect of shenfu injection on TNF、IL-6IL-8 in patients with pulmonary contusion

    Institute of Scientific and Technical Information of China (English)

    王海文; 宋涛

    2010-01-01

    目的 通过分析参附注射液对肺挫伤患者治疗前后血浆肿瘤坏死因子(TNF)、白细胞介素(IL6IL-8)水平变化,探讨其对肺挫伤的治疗效果.方法 选择肺挫伤患者110例,随机分组.对照组行常规治疗,治疗组在常规治疗基础上加用参附注射液.检测治疗前后患者血浆TNF、IL-6IL-8水平.结果 治疗前两组患者肺挫伤评分差异无统计学意义(P>0.05);治疗后治疗组TNF、IL-6IL-8水平明显降低,与对照组差异有统计学意义(P0.05).Plasma TNF,IL-6,IL-8 levels in the treatnent group significantly reduced compared with control group after treatment(P<0.051.Conclusion Shenfu injection has therapeutic effect on pulmonary contusion,itcan reduce TNF,IL-6,IL-8 levels,antagonize TNF,IL-6,IL-8 of the vasoconstrictive effect,thereby reducing TNF,IL-6,IL-8 caused secondary lung injury,promote the repair of damaged tissue and lung function recovery.

  12. The Effects of Ulinastatin on Oxygen Free Radical and IL-6IL-8、TNF-a During One Lung Ventilation after Chemotherapy to Patients with Lung Cancer%化疗后肺癌病人单肺通气时氧自由基、IL-6IL-8和TNF-α的变化和乌司他丁的保护作用

    Institute of Scientific and Technical Information of China (English)

    马武华; 吴一龙; 李朝霞

    2004-01-01

    目的探讨化疗后肺癌病人单肺通气时氧自由基、IL-6IL-8和TNF-α的变化和乌司他丁的保护作用.方法择期行肺癌手术病人30例,按美国麻醉医师协会(ASA)分级为Ⅱ~Ⅲ级;随机分为乌司他丁组(U组)和对照组(C组),每组各15例.U组给予乌司他丁1万U·kg-1,于麻醉诱导后缓慢静注,C组用等量生理盐水代替.分别于麻醉诱导后(S1)、单肺通气40min(S2)、单肺通气90min(S3)、术毕双肺通气30min(S4)、术后24h(S5)采集外周静脉血样测SOD、MDA、IL-6IL-8和TNF-α.结果 C组SOD在S3、S4时明显降低(P<0.05),U组从S2开始升高,且U组在S3、S4时均明显高于C组(P<0.05);两组MDA于S3、S4时均显著升高(P<0.05),但两组之间无明显差别.两组IL-6于S2后均显著升高(P<0.05),和C组比较,U组S3、S4时均显著降低(P<0.05).两组IL-8于S3、S4、S5时均显著升高(P<0.05),和C组比较,U组S3、S4时均显著降低(P<0.05).两组TNF-α于S2、S3、S4时均显著升高(P<0.05),和C组比较,U组S3时均显著降低(P<0.05).结论乌司他丁可减轻化疗后病人单肺通气期间炎性因子的生成和释放,减少氧自由基的产生,从而减轻病人的炎症反应.

  13. Phospholipase D from Loxosceles laeta Spider Venom Induces IL-6, IL-8, CXCL1/GRO-α, and CCL2/MCP-1 Production in Human Skin Fibroblasts and Stimulates Monocytes Migration

    Directory of Open Access Journals (Sweden)

    José M. Rojas

    2017-04-01

    Full Text Available Cutaneous loxoscelism envenomation by Loxosceles spiders is characterized by the development of a dermonecrotic lesion, strong inflammatory response, the production of pro-inflammatory mediators, and leukocyte migration to the bite site. The role of phospholipase D (PLD from Loxosceles in the recruitment and migration of monocytes to the envenomation site has not yet been described. This study reports on the expression and production profiles of cytokines and chemokines in human skin fibroblasts treated with catalytically active and inactive recombinant PLDs from Loxosceles laeta (rLlPLD and lipid inflammatory mediators ceramide 1-phosphate (C1P and lysophosphatidic acid (LPA, and the evaluation of their roles in monocyte migration. Recombinant rLlPLD1 (active and rLlPLD2 (inactive isoforms induce interleukin (IL-6, IL-8, CXCL1/GRO-α, and CCL2/monocyte chemoattractant protein-1 (MCP-1 expression and secretion in fibroblasts. Meanwhile, C1P and LPA only exhibited a minor effect on the expression and secretion of these cytokines and chemokines. Moreover, neutralization of both enzymes with anti-rLlPLD1 antibodies completely inhibited the secretion of these cytokines and chemokines. Importantly, conditioned media from fibroblasts, treated with rLlPLDs, stimulated the transmigration of THP-1 monocytes. Our data demonstrate the direct role of PLDs in chemotactic mediator synthesis for monocytes in human skin fibroblasts and indicate that inflammatory processes play an important role during loxoscelism.

  14. 急性淋巴细胞白血病患者血清IL-3、IL-6IL-8水平的测定及其临床意义%Significance of Interleukin(IL) - 3,6,8 Levels in Pre - and Post - Treatment of Acute Lymphocytic Leukimia

    Institute of Scientific and Technical Information of China (English)

    张宏; 梁建英; 孙兰云; 李军; 傅晋翔

    2001-01-01

    目的探讨IL-3、IL-6IL-8在急性淋巴细胞白血病(AIL)中的意义。方法采用酶联免疫法(ELISA)测定45例急性淋巴细胞白血病患者血清IL-3、IL-6IL-8水平。结果 AIL初诊患者血清IL-3水平明显低于正常对照组(P<0.05),血清IL-6IL-8水平明显高于正常对照组(P<0.05、P<0.001),经治疗AIL CR期患者IL-3、IL-6IL-8水平恢复正常;AIL NR组与初诊组相比无显著性差异(P>0.05)。结论检测IL-3、IL-6IL-8水平的变化有助于判断AIL患者病情的变化,并可作为监测治疗反应的辅助指标。%Objective To investigate the prognostic significance of interleukin(IL) - 3,6, 8 levels in patients with acute lymphocytic leukemia(AIL). Method ELISA assay were employed to investigate the levels of IL - 3, IL - 6 and IL - 8 in 45 AIL patients. Results The levels of IL - 3 were much lower at the time of diagnosis when compared with controls(P < 0.05), otherwise the levels of IL- 6 and IL- 8 were higher in comparison with controls(P < 0.05,P < 0.001 respectively).The levels returned to normal levels in those who got completely remission(CR). There was no difference between the patients who failed to get CR and denovo patients. Conclusion Dunamic monitoring the levels of IL - 3, IL - 6 and IL - 8 may have prognostic value in clinical outcome and is useful marker treatment of AIL patients.

  15. Clinical Significance of Determination of Changes of Serum IL-6, IL-8, IL-10 and IL-18 Levels After Treatment in Patients with Chronic Renal Diseases%慢性肾病患者细胞因子测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    刘从江; 李芬; 张磊; 刘剑华

    2008-01-01

    目的:探讨了慢性肾病患者血清IL-6IL-8、IL-10和IL-18水平的变化及意义.方法:分别应用放射免疫分析和酶联法对32例慢性肾病患者进行了血清IL-6IL-8、IL-10和IL-18测定,并与35名正常健康人作比较.结果:慢性肾病患者血清IL-6IL-8、IL-10和IL-18水平显著地高于正常人组(P<0.01),经治疗6个月后与正常人组比较仍有差异(P<0.05).结论:检测慢性肾病患者血清IL-6IL-8、IL-10和IL-18水平的变化对疾病的预后观察具有重要的临床价值.

  16. IL-6IL-8在不同潮气量单肺通气肺癌根治术中的表达%Effect of One-lung Ventilation of Different Tidal Volume on the Expressions of Interleukin-6 and Interleukin-8 in Lung Cancer Patients during Radical Operation

    Institute of Scientific and Technical Information of China (English)

    林飞; 潘灵辉; 钱卫; 黄宇; 杜学柯; 裴圣林

    2012-01-01

    目的 观察在肺癌根治术中不同潮气量(VT)的单肺通气(OLV)对血IL-6IL-8表达的影响.方法 30例行肺癌根治术患者,用随机数字表法分为3组.行双腔支气管插管麻醉,术中单肺通气期间在保持分钟通气量不变的情况下,A组VT=10 ml/kg,呼吸频率(f)=12次/min,B组VT=8 ml/kg,f=15次/min,C组VT=6 ml/kg,f=20次/min.在OLV前(T1)、OLV后30 min(T2)、60 min(T3)、OLV结束前(T4)检测血IL-6IL-8的表达.结果 3组在T2、T3、T4时点的IL-6IL-8表达均明显高于T1(P<0.05),且随OLV时间延长而逐渐升高;OLV后随设定的潮气量减低,IL-6IL-8表达逐渐降低; A组的IL-6IL-8表达显著高于B、C组(P<0.05).结论 在单肺通气的肺癌根治术中,采用小潮气量的通气模式可减少肺内炎症反应.%Objective To study effect of one-lung ventilation( OLV ) of different tidal volume( VT ) on the expressions of serum interleukin-6( IL-6 ) and interleukin-8( IL-8 ) in lung cancer patients during radical operation. Methods Thirty lung cancer patients undergoing radical operation were enrolled in the study. All the patients received double-lumen endobronchial intubation anesthesia, and were randomly divided into three groups after one-lung ventilation during radical operation: Group A( VT = 10 ml/kg, respiratory frequency( f ) = 12/min ), Group B( VT = 8 ml/kg, f = 12/min ), Group C( VT =6 ml/kg,f = 12/min ). The expressions of serum IL-6,IL-8 were detected before OLV( T1 ),30 min after OLV ( T2 ),60 min after OLV ( T3 ),1 min before OLV ending( T4 ). Results Compared with T1 ,the expressions of IL-6,IL-8 on T2 ,T3 ,T4 significantly increased in three groups( P <0. 05 ),and the increase was in a time-dependent manner. The expressions of IL-6, IL-8 gradually decreased with VT reduction during OLV. The expressions of IL-6, IL-8 in Group A were significantly higher than those in Group B, C( P < 0. 05 ). Conclusion The ventilation mode of low tidal volume can reduce the pulmonary

  17. 食管癌患者血清IL-2、IL-6IL-8、IL-18、slL-2R、slL-6R水平的监测和意义

    Institute of Scientific and Technical Information of China (English)

    杜翠霞

    2012-01-01

    目的 探讨食管癌患者血清IL-2、IL-6IL-8、IL-18、slL-2R、slL-6R水平的监测和意义.方法 我院采用酶联免疫吸附试验方法检测40例食管癌患者和40例健康体检者的血清IL-2、IL-6IL-8、IL-18、slL-2R、slL-6R水平.结果 观察组患者的血清IL-6IL-8、IL-18、slL-2R、slL-6R水平均显著高于对照组,两组比较,差异具有显著性(P<0.05).观察组患者的血清IL-2水平明显低于对照组,两组比较,差异具有显著性(P<0.05).结论 血清IL-2、IL-6IL-8、IL-18、slL-2R、slL-6R水平与食管癌的发生发展有关,可反映食管癌的进展,并可作为食管癌病情监测的重要指标,对肿瘤的临床分期、疗效和预后的判断也有一定的帮助.

  18. 甲型副伤寒沙门氏菌cdtB亚基的原核表达及对巨噬细胞IL-6IL-8、TNF-α分泌的影响%Cloning and expression of recombinant Salmonella paratyphi A cytolethal distending toxin proteins and its effect on cytokine production by human monocyte-derived macrophages

    Institute of Scientific and Technical Information of China (English)

    陈鸿鹄; 吴圆圆; 占利; 梅玲玲

    2016-01-01

    目的 研究甲型副伤寒沙门氏菌感染过程中,cdtB对宿主巨噬细胞分泌促炎细胞因子的影响.NF-κB信号通路阻断剂对cdtB诱导的巨噬细胞分泌细胞因子的影响.方法 对甲型副伤寒沙门氏菌cdtB亚基进行原核表达,制备并模型纯化重组蛋白,建立其刺激人THP-1巨噬细胞模型,ELISA检测THP-1分泌IL-6,IL-8和TNF-α等细胞因子.在共培养体系中加入NF-κB信号通路阻断剂,ELISA检测THP-1分泌IL-6,IL-8和TNF-α等细胞因子.结果 成功构建甲型副伤寒沙门氏菌cdtB原核表达系统,表达并纯化重组cdtB蛋白,与空白对照相比,受到cdtB刺激的THP-1细胞上清中的IL-6,IL-8和TNF-α浓度显著上升,而在THP-1细胞培养基中加入NF-κB信号通路阻断剂SN50可以显著抑制重组cdtB诱导的IL-6IL-8、TNF-α分泌.结论 甲型副伤寒沙门氏菌cdtB能够通过NF-κB信号通路诱导巨噬细胞分泌IL-6IL-8和TNF-α,在甲型副伤寒相关的炎症反应中发挥促进作用.

  19. Influence of Anesthetic Maintence with Intravenous Infusion of Propofol on the Apoptosis of Neutrophils and the Level of Cytokines in Sera of Patients with Biliary Surgery%比较两种麻醉剂对胆道手术患者中性粒细胞凋亡、TNF-α、IL-6IL-8的影响

    Institute of Scientific and Technical Information of China (English)

    张良清; 徐军发; 蔡康荣; 姚华国

    2004-01-01

    探讨TNF-α、IL-6IL-8与异丙酚麻醉下胆道手术患者中性粒细胞凋亡的关系.ASA Ⅰ~Ⅱ级择期行胆道手术的非肿瘤患者43例,随机分为异丙酚麻醉组(P组,n=22)及安氟醚麻醉组(E组,n=21).另选择健康成年人16例作健康对照组.取手术前(T1)、手术开始(T2)、手术开始后3h(T3)、24h(T4)、72h(T5)外周静脉血10ml,检测中性粒细胞凋亡及血浆细胞因子的水平.结果发现胆道手术患者术前中性粒细胞凋亡率明显低于健康对照组;同手术前比,T3、T4、T5时点中性粒细胞的凋亡率均明显降低(P<0.01);而与E组比,P组分别在T3、T4时间点中性粒细胞凋亡率明显升高(P<0.01).胆道手术患者围术期血浆TNF-α变化差异不明显;IL-6在手术创伤后升高,术后1d达峰值,但在组间无明显的差异;围术期血浆IL-8的水平变化同IL-6,但与E组比,P组分别在T3、T4时间IL-8的血浆水平明显降低(P<0.05、P<0.01).本研究认为异丙酚麻醉与安氟醚麻醉相比,具有明显地减轻手术创伤后中性粒细胞凋亡的延迟作用,可能与异丙酚麻醉组创伤后细胞因子IL-8的释放较低有关.

  20. Expression of IL-1, IL-6 and IL-8 in the skin of TCE-sensitized guinea pigs%三氯乙烯致敏豚鼠皮肤组织中白细胞介素-1、-6和-8表达的研究

    Institute of Scientific and Technical Information of China (English)

    朱启星; 戴丹; 冯晓亮; 沈彤; 俞韵

    2010-01-01

    目的 研究白细胞介素(IL)-1、IL-6IL-8在三氯乙烯(TCE)致敏豚鼠皮肤组织中的表达情况,探讨TCE药疹样皮炎发病机制.方法 将白色雌性豚鼠随机分成空白对照组、溶剂对照组、TCE实验组、2,4-二硝基氯苯(DNCB)阳性对照组,根据豚鼠最大值试验(GPMT)方法处理豚鼠,在终末激发后(依据致敏结果以及取材时点的不同,将TCE实验组以及DNCB阳性对照组分为TCE致敏组24 h、TCE致敏组72 h、TCE未致敏组24 h和TCE未致敏组72 h;DNCB组24 h和DNCB组72 h)进行皮肤反应评分,并采取皮肤组织,制成蜡块,采用Elivison二步法免疫组织化学法检测各组皮肤组织中IL-1、IL-6IL-8的表达情况.结果 根据皮肤反应评分≥1判断为致敏阳性,TCE实验组致敏率为62.1%;ICE致敏组24 h和ICE致敏组72 h的IL-1水平要显著高于溶剂对照组,且差异有统计学意义(P0.05).结论 TCE对豚鼠皮肤具有致敏作用,IL-1在TCE致敏过程中具有重要意义,而IL-6IL-8可能不参与TCE致敏作用.

  1. Suplementação de N-acetilcisteína em pacientes infectados pelo HIV submetidos ao primeiro tratamento anti-retroviral: Avaliação do efeito sobre a carga viral, TNF-α, IL-6, IL-8, β2-microglobulina, IgA, IgG e IgM, haptoglobina e α1-glicoproteína ácida N-acetylcysteine supplementation of HIV-infected patients under the first anti-retroviral treatment: Evaluation of the effect on viral load, TNF-α, IL-6, IL-8, β2-microglobulin, IgA, IgG, IgM, haptoglobin and α1-acid glycoprotein

    Directory of Open Access Journals (Sweden)

    Aricio Treitinger

    2002-03-01

    Full Text Available Indivíduos infectados pelo vírus da imunodeficiência humana (HIV- 1 apresentam aumento progressivo da carga viral, da destruição do sistema de defesa imune celular e alterações imunológicas e inflamatórias, incluindo a elevação dos níveis séricos do fator de necrose tumoral alfa (TNF-α, interleucina 8 (IL-8, β2- microglobulina, IgA, IgG e IgM, haptoglobina e α1-glicoproteína ácida.O objetivo deste estudo foi avaliar os níveis séricos destes marcadores em indivíduos submetidos ao primeiro tratamento antiretroviral, suplementados ou não com N-acetilcisteína. Participaram deste estudo, duplo cego controlado por placebo, que teve a duração de 180 dias, 24 indivíduos que iniciaram a terapia antiretroviral O Grupo Estudo foi constituído por 11 indivíduos, que receberam suplementação de 600 mg/dia de Nacetilcisteína enquanto o Grupo Controle foi constituído por 13 indivíduo que receberam placebo. Os níveis dos marcadores avaliados foram determinados no dia anterior ao início do tratamento a que foram submetidos e após 60, 120 e 180 dias. Verificou-se diminuição significativa dos níveis de TNF-α (p=0,0001, IL-6 (p>0,05, IL-8 (p=0,0001, β2-microglobulina (p=0,0005, IgA (p=0,007, IgG (p=0,001, IgM (p=0,0001, haptoglobina (p=0,0001 e α1-glicoproteína ácida (p=0.012 em decorrência do tratamento anti-retroviral. A suplementação com N-acetilcisteína, na dose utilizada neste estudo, não teve efeitos aditivos ou sinérgicos sobre as variáveis analisadas. Em conclusão, a suplementação de pacientes HIV-positivos com 600 mg/dia de N-acetilcisteína não proporcionou benefícios adicionais àqueles decorrentes do tratamento anti-retroviral.Human immunodeficiency virus infection is associated with a progressive elevation of viral load and with a continuous destruction of the immune cellular defense system which is marked by immunological and inflammatory disorders characteristic of HIV-infected individuals. These

  2. Research Advancement on Exercise and IL-6%运动与IL-6的研究进展

    Institute of Scientific and Technical Information of China (English)

    王今越; 丁树哲; 刘伟; 王小虹

    2007-01-01

    通过文献资料调研,总结并分析以往至最新的IL-6研究成果,从运动与肌源性IL-6 、运动与不同类型肌纤维IL-6的生成、运动训练与IL-6IL-6R系统、运动模式与IL-6、糖代谢与IL-6IL-6与抗氧化剂VC、VE、IL-6IL-8IL-6与SOCS-3几个方面论述运动介导下,IL-6的生成特点、影响因素和生物学功能.

  3. 糖皮质激素治疗结核性胸膜炎的疗效分析及其对炎症细胞因子表达的影响%Effects of glucocorticoid in patients with tuberculous pleuriifs and its inlfunce on the expression of ;inlfammatory cytokines IL-6 and IL-8

    Institute of Scientific and Technical Information of China (English)

    王德翠; 王俊玲; 王俊英; 孙希霞

    2016-01-01

    目的:观察糖皮质激素用于结核性胸膜炎的疗效分析及其对胸水炎症细胞因子表达水平的影响。方法选择2012年1月至2015年6月滨州市结核病防治院收治的193例结核性胸膜炎患者,将其分为对照组(95例)和研究组(98例),所有研究对象均给予抗结核药物治疗,其中研究组在此基础上给予胸腔注射地塞米松治疗,抽取两组患者不同治疗时间段的胸水并检测炎症细胞因子表达水平。结果研究组患者治疗有效者89例,无效9例,对照组患者有效74例,无效21例,两组患者疗效比较差异有统计学意义(P0.05)。研究组患者经胸腔注射地塞米松治疗后第3、6、9天胸腔积液IL-6的表达水平显著低于对照组患者[(276.49±27.85)pg/ml vs(350.38±20.01)pg/ml,(195.32±14.35)pg/ml vs(312.51±14.82)pg/ml,(86.74±10.28)pg/ml vs(251.74±16.62)pg/ml],差异有统计学意义(P0.05).The levels of inflammatory cytokines IL-6 level after treatment of 3,6 and 9 d in research group was lower than that in control group [(276.49±27.85) pg/ml vs (350.38±20.01) pg/ml,(195.32±14.35) pg/ml vs (312.51±14.82) pg/ml,(86.74±10.28) pg/ml vs (251.74±16.62) pg/ml,and there was significant difference(P<0.05).and IL-8 level[(576.51±19.79)pg/ml vs(850.64±27.70)pg/ml,(225.30±14.29)pg/ml vs(742.49±15.28) pg/ml,(127.68±11.23)pg/ml vs(443.47±12.63)pg/ml] Conclusions Intrapleural injection of glucocorticoid in the treatment of tuberculous pleurisy, can make the drug directly acts on the chest, better realize the control of inflammatory cytokines, encourage pleural effusion absorption, improve the clinical symptoms early. It is worthy of clinical apphcation.

  4. Study on the Serum Levels of Relevant Cytokines IL-1β, IL-6, IL-8 and Tumor Markers CEA, CA15-3, PRL in Breast Cancer Patients with Bone Metastatic Lesions Shown on SPECT Radio-nuclide Bone Scan%SPECT放射性核素骨显像与血清相关指标协同评价乳腺癌骨转移

    Institute of Scientific and Technical Information of China (English)

    朱宝

    2009-01-01

    目的:评价乳腺癌患者放射性核素骨显像与血清肿瘤指标和细胞因子水平测定的价值.方法:随机选择乳腺浸润性导管癌骨显像示骨转移瘤与骨显像正常患者各20 例,乳腺良性病患者30例及健康体检者35例,分别测定其血清中CEA、CA15-3及PRL; IL-1β、IL-6IL-8的含量.结果:本文结果显示,乳腺癌无骨转移组CEA、CA15-3及PRL三项肿瘤相关标志物水平与对照组比较略有升高,但统计学差异皆无显著性(P均>0.05);有骨转移组上述三项指标水平则升高均非常显著(P均<0.01);乳腺良性病组三项指标水平与对照组比较均无显著差异(P均>0.05).同时>2个骨转移灶组三项指标水平较≤2个转移灶的患者三项肿瘤相关指标升高均非常显著(P均<0.01).三项白介素水平测定结果显示,无骨转移组三项白介素水平与对照组比较差异均无显著性(P均>0.05);而有骨转移组则与对照组比较升高均有显著性(P均<0.05).结论:血清三项肿瘤标志物及IL-1β、IL-6IL-8水平的变化与骨转移发生有一定关系.其检测将有助于乳腺癌骨转移瘤的动态监测.

  5. Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Antonietta Rosella; Mackay, Andrew Reay, E-mail: andrewreay.mackay@univaq.it [Department of Applied Clinical and Biotechnological Sciences, University of L’Aquila, Via Vetoio, Coppito 2, L’Aquila 67100 (Italy)

    2014-01-27

    Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many ways in which gelatinase B/MMP-9 influences tumour biology. Following a brief outline of the gelatinase B/MMP-9 gene and protein, we analyse the role(s) of gelatinase B/MMP-9 in different phases of the tumorigenic process, and compare the importance of gelatinase B/MMP-9 source in the carcinogenic process. What becomes apparent is the importance of inflammatory cell-derived gelatinase B/MMP-9 in tumour promotion, early progression and triggering of the “angiogenic switch”, the integral relationship between inflammatory, stromal and tumour components with respect to gelatinase B/MMP-9 production and activation, and the fundamental role for gelatinase B/MMP-9 in the formation and maintenance of tumour stem cell and metastatic niches. It is also apparent that gelatinase B/MMP-9 plays important tumour suppressing functions, producing endogenous angiogenesis inhibitors, promoting inflammatory anti-tumour activity, and inducing apoptosis. The fundamental roles of gelatinase B/MMP-9 in cancer biology underpins the need for specific therapeutic inhibitors of gelatinase B/MMP-9 function, the use of which must take into account and substitute for tumour-suppressing gelatinase B/MMP-9 activity and also limit inhibition of physiological gelatinase B/MMP-9 function.

  6. Neutrophil and monocyte responses to downhill running: Intracellular contents of MPO, IL-6, IL-10, pstat3, and SOCS3.

    Science.gov (United States)

    van de Vyver, M; Engelbrecht, L; Smith, C; Myburgh, K H

    2016-06-01

    High-intensity exercise results in immune activation. This study determined whether (a) there is concordance between serum MPO and neutrophil and/or monocyte intracellular MPO content; (b) peripheral blood mononuclear cells respond to inflammatory interleukins (ILs) by increasing intracellular signaling. Healthy male (n = 12) volunteers participated in high-intensity running (12 × 5 min, 10% decline, 15 km/h). Blood sample (pre, post, 4 h) analyses included serum concentrations of IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, matrix metalloprotease-9 (MMP-9) and creatine kinase (CK). Intracellular IL-6, IL-10, MPO and STAT3/SOCS3 signaling were assessed in mononuclear cells. CK (1573 ± 756 u/L), MMP-9 (101 ± 27 ng/mL), neutrophil (9.89 ± 0.76 × 10(9) cells/L) and monocyte counts (1 ± 0.08 × 10(9) cells/L) increased at 4 h. At 4 h serum (7.1 ± 1.3 ng/mL) and monocyte MPO (1.7-fold) increased, whereas neutrophil MPO decreased (0.8-fold). Intracellular monocyte IL-10 and IL-6 decreased by 15% and 20-30%, respectively, coinciding with elevations in serum IL-10 of 14.5 ± 4.7 pg/mL and IL-6 of 5.4 ± 2.9 pg/mL, suggesting immune cell cytokine release in response to exercise. Intracellular PBMC p-STAT3 to total STAT3 ratio increased from pre to 4 h. Circulating monocytes are responsive to increased serum IL-6 suggesting a negative feedback loop via STAT3 signaling. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The ERK1/2 Inhibitor U0126 Attenuates Diabetes-Induced Upregulation of MMP-9 and Biomarkers of Inflammation in the Retina

    Directory of Open Access Journals (Sweden)

    Ghulam Mohammad

    2013-01-01

    Full Text Available This study was conducted to determine the expression of matrix metalloproteinase-9 (MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1 in a time-dependent manner and the effect of extracellular-signal-regulated kinases-1/2 (ERK1/2 inhibition on the expressions of MMP-9, TIMP-1, and inflammatory biomarkers in the retinas of diabetic rats. The expression of MMP-9 was quantified by zymography, and the mRNA level of MMP-9 and TIMP-1 was quantified by RT-PCR. The expression of inducible nitric oxide synthase (iNOS, interleukin-6 (IL-6, and tumor necrosis factor-alpha (TNF-α was examined by Western blot analysis. MMP-9 expression was significantly higher in diabetic rat retinas compared to controls at all time points.TIMP-1 expression was nonsignificantly upregulated at 1week of diabetes and was significantly downregulated at 4 and 12 weeks of diabetes. Intravitreal administration of the ERK1/2 inhibitor U0126 prior to induction of diabetes decreased ERK1/2 activation, attenuated diabetes-induced upregulation of MMP-9, iNOS, IL-6, and TNF-α and upregulated TIMP-1 expression. In MMP-9 knockout mice, diabetes had no effect on retinal iNOS expression and its level remained unchanged. These data provide evidence that ERK1/2 signaling pathway is involved in MMP-9, iNOS, IL-6, and TNF-α induction in diabetic retinas and suggest that ERK1/2 can be a novel therapeutic target in diabetic retinopathy.

  8. Polymorphisms of the MMP-9 gene and abdominal aortic aneurysm

    Science.gov (United States)

    Smallwood, Linda; Allcock, Richard; van Bockxmeer, Frank; Warrington, Nicole; Palmer, Lyle J; Iacopetta, Barry; Golledge, Jonathan; Norman, Paul E

    2008-01-01

    Background Increased matrix metalloproteinase-9 (MMP-9) activity has been implicated in the formation of abdominal aortic aneurysms (AAAs). The aim of the present study was to explore the association between potentially functional variants of the MMP-9 gene and AAA. Method The −1562C>T and −1811A>T variants of the MMP-9 gene were genotyped in 678 men with AAAs (>30mm in diameter) and 659 controls (aortic diameter 19−22mm) recruited from a population-based trial of screening for AAAs. The levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed using multivariate logistic regression. Results There was no association between the MMP-9 −1562C>T (OR 0.70 95%CI 0.27, 1.82) or −1811A>T (OR 0.71, 95%CI 0.28, 1.85) genotypes, or the most common haplotype (OR 0.81 95%CI 0.62, 1.05), and AAA. The serum MMP-9 concentration (ng/mL) was higher in cases than controls and in minor allele carriers in cases and controls although the differences were not statistically significant. Conclusion The results suggest that a genetic tendency to have higher levels of circulating MMP-9 is not associated with AAAs. PMID:18763261

  9. Association of MMP-9 gene polymorphisms with nephrolithiasis patients.

    Science.gov (United States)

    Mehde, Atheer Awad; Mehdi, Wesen Adel; Yusof, Faridah; Raus, Raha Ahmed; Zainal Abidin, Zaima Azira; Ghazali, Hamid; Abd Rahman, Azlina

    2017-02-15

    Nephrolithiasis is one of the causes which lead to chronic kidney disease (CKD). Matrix metalloproteinases (MMPs) are endopeptidases degrading extracellular matrix which correlate with the pathogenesis of atherosclerosis. The current study was designed to analyze the association of (R279Q, C1562T) polymorphism of MMP-9 with nephrolithiasis patients. Genotyping of MMP-9/R279Q and of MMP-9/C1562T polymorphism were carried out by PCR-based restriction digestion method. Serum level of MMP-9, oxidative stress marker, MDA, and uric acid were measured in patients and control. Allele frequencies of the MMP-9/C1562T polymorphism for C and T allele were 71.25% and 28.75% in patients, 87.08% and 12.92% in control respectively. The homozygote TT was more frequent in the nephrolithiasis patients group, while T allele frequency was significantly higher in the nephrolithiasis patients group than in the control group. The patients with CT and TT genotype showed a significant increase in serum MMP-9, Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Malondialdehyde (MDA), and uric acid when compared to CC genotype in patients with nephrolithiasis. The R279Q polymorphism site with regard to the relationship with nephrolithiasis was not significant. The result indicates that patients with TT genotype had an increased risk of stones. Also, the results demonstrate that TT allele of the C1562T polymorphism in the MMP-9gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with TT genotype of MMP-9. © 2017 Wiley Periodicals, Inc.

  10. Cervical cancer cell-derived interleukin-6 impairs CCR7-dependent migration of MMP-9-expressing dendritic cells.

    Science.gov (United States)

    Pahne-Zeppenfeld, Jennifer; Schröer, Nadine; Walch-Rückheim, Barbara; Oldak, Monika; Gorter, Arko; Hegde, Subramanya; Smola, Sigrun

    2014-05-01

    Cervical carcinogenesis is a consequence of persistent infection with high-risk human papillomaviruses (HPVs). Recent studies indicate that HPV-transformed cells actively instruct their microenvironment to promote carcinogenesis. Here, we demonstrate that cervical cancer cells activate monocytes to produce their own CCL2 for further monocyte recruitment and reprogram their function during differentiation and maturation to dendritic cells (DCs). Our data show that cervical cancer cells suppress the induction of the chemokine receptor CCR7 in phenotypically mature DCs and impair their migration toward a lymph node homing chemokine, required to initiate adaptive immune responses. We confirmed the presence of CD83(+)CCR7(low) DCs in cancer biopsies. The second factor essential for DC migration, matrix-metalloproteinase MMP-9, which also has vasculogenic and protumorigenic properties, is not suppressed but upregulated in immature as well as mature DCs. We identified interleukin-6 (IL-6) as a crucial cervical cancer cell-derived mediator and nuclear factor kappaB (NF-jB) as the central signaling pathway targeted in DCs. Anti-IL-6 antibodies reverted not only NF-jB inhibition and restored CCR7-dependent migration but also blocked MMP-9 induction. This is the first report demonstrating the dissociation of CCR7 and MMP-9 expression in phenotypically mature CD83(+) DCs by cancer cells. Our results show that cervical cancer cells actively shape the local microenvironment. They induce the accumulation of myeloid cells and skew their function from immune activation to local production of protumorigenic MMP-9. Neutralizing anti-IL-6 antibodies can counteract this functional dysbalance and should therefore be considered for adjuvant cervical cancer therapy.

  11. IL-6/sIL-6R trans-signalling, but not TNF-alpha induced angiogenesis in a HUVEC and synovial cell co-culture system.

    Science.gov (United States)

    Hashizume, Misato; Hayakawa, Naohiko; Suzuki, Miho; Mihara, Masahiko

    2009-10-01

    Angiogenesis in synovia is a characteristic of RA patients. We examined whether IL-6 or TNF-alpha induce tubule formation in a co-culture system of fibroblast-like synovial cells from RA patients (RA-FLS) and human umbilical vein endothelial cells (HUVEC). The effects of IL-6 and TNF-alpha on the expression of angiogenic factors in RA-FLS and HUVEC, and the proliferation of HUVEC were also studied. IL-6 + sIL-6R induced tubule formation, whereas IL-6 alone did not. IL-6/sIL-6R-induced tubule formation was completely suppressed by the addition of either anti-IL-6R or anti-VEGF antibody. TNF-alpha did not induce tubule formation. On the contrary, it decreased CD31-positive area compared with the control. IL-6 + sIL-6R augmented VEGF production in RA-FLS, whereas IL-6 alone did not. Anti-IL-6R antibody suppressed IL-6/sIL-6R-induced VEGF production, but not spontaneous VEGF production. In contrast, TNF-alpha did not induce VEGF production from RA-FLS and HUVEC. IL-6 + sIL-6R stimulation of RA-FLS strongly induced mRNA expression of VEGF, but not of other angiogenic factors, such as EGF, bFGF, TGF-beta, IL-1, TNF-alpha and IL-8. Neither IL-6 nor IL-6/sIL-6R promoted HUVEC proliferation, whereas TNF-alpha significantly inhibited VEGF-induced HUVEC proliferation. In conclusion, IL-6/sIL-6R complex showed angiogenic activity via the production of VEGF from RA-FLS, but TNF-alpha was anti-angiogenic in our experimental system.

  12. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

    Energy Technology Data Exchange (ETDEWEB)

    Bouchet, Sandrine; Bauvois, Brigitte, E-mail: brigitte.bauvois@crc.jussieu.fr [INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris 75006 (France)

    2014-04-04

    Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  13. MEK-dependent IL-8 induction regulates the invasiveness of triple-negative breast cancer cells.

    Science.gov (United States)

    Kim, Sangmin; Lee, Jeongmin; Jeon, Myeongjin; Lee, Jeong Eon; Nam, Seok Jin

    2016-04-01

    Interleukin-8 (IL-8) serves as a prognostic marker for breast cancer, and its expression level correlates with metastatic breast cancer and poor prognosis. Here, we investigated the levels of IL-8 expression in a variety of breast cancer cells and the regulatory mechanism of IL-8 in triple-negative breast cancer (TNBC) cells. Our results showed that IL-8 expression correlated positively with overall survival in basal-type breast cancer patients. The levels of IL-8 mRNA expression and protein secretion were significantly increased in TNBC cells compared with non-TNBC cells. In addition, the invasiveness of the TNBC cells was dramatically increased by IL-8 treatment and then augmented invasion-related proteins such as matrix metalloproteinase (MMP)-2 or MMP-9. We observed that elevated IL-8 mRNA expression and protein secretion were suppressed by a specific MEK1/2 inhibitor, UO126. In contrast, the overexpression of constitutively active MEK significantly increased the level of IL-8 mRNA expression in BT474 non-TNBC cells. Finally, we investigated the effect of UO126 on the tumorigenecity of TNBC cells. Our results showed that anchorage-independent growth, cell invasion, and cell migration were also decreased by UO126 in TNBC cells. As such, we demonstrated that IL-8 expression is regulated through MEK/ERK-dependent pathways in TNBC cells. A diversity of MEK blockers, including UO126, may be promising for treating TNBC patients.

  14. IL-8 as a urinary biomarker for the detection of bladder cancer

    Directory of Open Access Journals (Sweden)

    Urquidi Virginia

    2012-05-01

    Full Text Available Abstract Background Current urine-based assays for bladder cancer (BCa diagnosis lack accuracy, so the search for improved biomarkers continues. Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8, Matrix metallopeptidase 9 (MMP-9 and Syndecan in the diagnosis of BCa through urinalysis. Methods Voided urines from 127 subjects, cancer subjects (n = 64, non-cancer subjects (n = 63 were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA. Data were also compared to a commercial ELISA-based BCa detection assay (BTA-Trak© and urinary cytology. We used the area under the curve of a receiver operating characteristic (AUROC to compare the performance of each biomarker. Results Urinary protein concentrations of IL-8, MMP-9 and BTA were significantly elevated in BCa subjects. Of the experimental markers compared to BTA-Trak©, IL-8 was the most prominent marker (AUC; 0.79; 95% confidence interval [CI], 0.72-0.86. Multivariate regression analysis revealed that only IL-8 (OR; 1.51; 95% CI, 1.16-1.97, p = 0.002 was an independent factor for the detection of BCa. Conclusions These results suggest that the measurement of IL-8 in voided urinary samples may have utility for urine-based detection of BCa. These findings need to be confirmed in a larger, prospective cohort.

  15. Interleukins IL-6, IL-8, IL-10, IL-12 and periimplant disease. An update

    National Research Council Canada - National Science Library

    Candel-Martí, Maria-Eugenia; Flichy-Fernández, Antonio-Juan; Alegre-Domingo, Teresa; Ata-Ali, Javier; Peñarrocha-Diago, Maria A

    2011-01-01

    ... (IL-12)) as markers of periimplant disease (mucositis and periimplantitis). An increase in the levels of these cytokines in dental implant crevicular fluid may give rise to a lack of osteointegration, bone loss or implant failure...

  16. Interleukin-6 (IL-6) production by astrocytes: autocrine regulation by IL-6 and the soluble IL-6 receptor.

    Science.gov (United States)

    Van Wagoner, N J; Oh, J W; Repovic, P; Benveniste, E N

    1999-07-01

    In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). However, the role of IL-6 in its own regulation in astrocytes has not been determined. In this study, we examined the influence of IL-6 alone or in combination with TNF-alpha or IL-1beta on IL-6 expression. IL-6 alone had no effect on IL-6 expression; however, the addition of the soluble IL-6 receptor (sIL-6R) induced IL-6 transcripts. Addition of TNF-alpha or IL-1beta plus IL-6/sIL-6R led to synergistic increases in IL-6 expression. This synergy also occurred in the absence of exogenously added IL-6, attributable to TNF-alpha- or IL-1beta-induced endogenous IL-6 protein production. IL-6 upregulation seen in the presence of TNF-alpha or IL-1beta plus IL-6/sIL-6R was transcriptional, based on nuclear run-on analysis. Experiments were extended to other IL-6 family members to determine their role in IL-6 regulation in astrocytes. Oncostatin M (OSM) induced IL-6 alone and synergized with TNF-alpha for enhanced expression. These results demonstrate that IL-6/sIL-6R and OSM play an important role in the regulation of IL-6 expression within the CNS, particularly in conjunction with the proinflammatory cytokines TNF-alpha and IL-1beta.

  17. The effect of IL-6 on the trophoblast cell line HTR-8/SVneo

    Directory of Open Access Journals (Sweden)

    Jovanović Milica

    2010-01-01

    Full Text Available Embryonic development up to the blastocyst stage, implantation into the uterine wall and the development of the functional placenta are steps crucial for the establishment of normal pregnancy. Specific cells of the placenta, the trophoblast cells, invade the uterine stroma and spiral arteries, adapting them to pregnancy. Interleukin-6 is present in the human endometrium during the receptive phase and early pregnancy. Trophoblasts also produce IL-6, which was found to stimulate trophoblast invasion and migration in vitro. Here we show that the activity of MMP-9 may contribute to the observed increased invasion. In addition, in the HTR-8/SVneo trophoblast cell line IL-6 increases cell proliferation. .

  18. Detection of MMP-2 and MMP-9 in the Lesions of Psoriasis%银屑病皮损中MMP-2 MMP-9的检测

    Institute of Scientific and Technical Information of China (English)

    陈晋广; 任小丽; 胡雅玉; 陈祥恩

    2005-01-01

    目的探讨MMP-2,MMP-9在细胞外基质(ECM)降解和银屑病发病机理中的作用及意义.方法采用免疫组化ABC法检测银屑病患者皮损中MMP-2,MMP-9.结果银屑病皮损中既可检测到MMP-2,又可检测到MMP-9,而在正常皮肤则为阴性.结论MMP-2,MMP-9参与了银屑病的发病过程.

  19. Circulating levels of matrix metalloproteinase-9 (MMP-9, neutrophil gelatinase-associated lipocalin (NGAL and their complex MMP-9/NGAL in breast cancer disease

    Directory of Open Access Journals (Sweden)

    Nonni Afroditi

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9 is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

  20. Neutrophil Gelatinase-Associated Lipocalin (NGAL, Pro-Matrix Metalloproteinase-9 (pro-MMP-9 and Their Complex Pro-MMP-9/NGAL in Leukaemias

    Directory of Open Access Journals (Sweden)

    Sandrine Bouchet

    2014-04-01

    Full Text Available Matrix metalloproteinase (MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9 also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro-MMP-9 (active and latent forms and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  1. Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS.

    Science.gov (United States)

    Ranjbaran, Javad; Farimani, Marzieh; Tavilani, Heidar; Ghorbani, Marzieh; Karimi, Jamshid; Poormonsefi, Faranak; Khodadadi, Iraj

    2016-04-01

    It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.

  2. Study of the relationship of MMP-9 and serum fructosamine levels in diabetic retinopathy patients

    Directory of Open Access Journals (Sweden)

    Chong Wang

    2014-05-01

    Full Text Available AIM: To explore the relationship of MMP-9 and serum fructosamine levels and further illustrate the role of the development in diabetic retinopathy patients.METHODS: Serum MMP-9 levels were measured using enzyme-linkedimmunosorbent assays a in 30 health controls and 30 diabetic retinopathy patients, the relationship of MMP-9 and serum fructosamine levels were analyzed。RESULTS: Compared with healthy controls. The expression levels of MMP-9 indiabetic retinopathy patients were significantly increased \\〖(8.14±2.28pmol/L, vs(2.47±1.41pmol/L\\〗, MMP-9 were positive correlation with fructosamine(r=0.94, PCONCLUSION:The occurrence and progress of diabetic retinopathy might be closely related to the expression level of MMP-9, and the abnormal expression of MMP-9 in patients' serum might be associated with the secretion of fructosamine.

  3. Involvement of TSP1 and MMP9/NGAL in Angiogenesis during Orthodontic Periodontal Remodeling

    Directory of Open Access Journals (Sweden)

    Petra Surlin

    2014-01-01

    Full Text Available In the present study the aim was to measure the levels of Thrombospondin-1 (TSP1 and Lipocalin-2/matrix metalloproteinase 9 (MMP9/NGAL complex in gingival crevicular fluid (GCF at different time points of orthodontic treatment, to determine the relationship between these values and those of total-matrix metalloproteinase 9 (MMP9 and theirs implication in angiogenesis balance, in the situation of a good control of the bacterial plaque, emphasizing the role of TSP1 and MMP9/NGAL complex. GCF samples were collected from 16 young orthodontic patients requiring upper canine distalization (test tooth with first premolar extraction. The contralateral canine (control tooth was free from orthodontic force. For the orthodontic appliance, brackets Roth 0.018 inch with 0.012 inch NiTi archwire and a laceback were used. TSP1, MMP9/NGAL, and MMP9 increased from 1 hour before activation of orthodontic appliance to a maximum at 8 hours for MMP9 and 72 hours for MMP9/NGAL and TSP1. The results show a change in time of TSP1, MMP9/NGAL, and MMP9 levels in GCF of patients with this method of orthodontic treatment. The powerful correlation of MMP9/NGAL with TSP1 suggests their stronger involvement in angiogenesis processes in PDL during orthodontic periodontal remodeling, in the situation of a healthy periodontium and a good control of the bacterial plaque.

  4. Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Cuiyun Sun; Qian Wang; Hongxu Zhou; Shizhu Yu; Alain R.Simard; Chunsheng Kang; Yanyan Li

    2013-01-01

    The matrix-degrading metalloproteinases (MMPs),particularly MMP-9,play important roles in the pathogenesis and development of malignant gliomas.In the present study,the oncogenic role of MMP-9 in malignant glioma cells was investigated via antisense RNA blockade in vitro and in vivo.TJ905 malignant glioma cells were transfected with pcDNA3.0 vector expressing antisense MMP-9 RNA (pcDNA-ASMMP9),which significantly decreased MMP-9 expression,and cell proliferation was assessed.For in vivo studies,U251 cells,a human malignant glioma cell line,were implanted subcutaneously into 4-to 6-week-old BALB/c nude mice.The mice bearing well-established U251 gliomas were treated with intratumoral pcDNA-AS-MMP9-Lipofectamine complex (AS-MMP-9-treated group),subcutaneous injection of endostatin (endostatin-treated group),or both (combined therapy group).Mice treated with pcDNA (empty vector)-Lipofectamine served as the control group.Four or eight weeks later,the volume and weight of tumor,MMP-9 expression,microvessel density and proliferative activity were assayed.We demonstrate that pcDNA-AS-MMP9 significantly decreased MMP-9 expression and inhibited glioma cell proliferation.Volume and weight of tumor,MMP-9 expression,microvessel density and proliferative activity in the antisense-MMP-9-treated and therapeutic alliance groups were significantly lower than those in the control group.The results suggest that MMP-9 not only promotes malignant glioma cell invasiveness,but also affects tumor cell proliferation.Blocking the expression of MMP-9 with antisense RNA substantially suppresses the malignant phenotype of glioma cells,and thus can be used as an effective therapeutic strategy for malignant gliomas.

  5. NDRG1 Controls Gastric Cancer Migration and Invasion through Regulating MMP-9.

    Science.gov (United States)

    Chang, Xiaojing; Xu, Xiaoyang; Xue, Xiaoying; Ma, Jinguo; Li, Zhenhua; Deng, Peng; Chen, Jing; Zhang, Shuanglong; Zhi, Yu; Dai, Dongqiu

    2016-10-01

    The purpose of this study is to detect the clinical significance of NDRG1 and its relationship with MMP-9 in gastric cancer metastatic progression. 101 cases of gastric cancer specimens were utilized to identify the protein expression of NDRG1 and MMP-9 by immunohistochemistry, their clinical significance was also analyzed. The suppression by siRNA-NDRG1 was employed to detect the role of NDRG1 in gastric cancer progression and its relationship with MMP-9. NDRG1 expression was correlated inversely with the degree of tumor cell differentiation (p 0.05). Furthermore, cell proliferation and invasion effect were remarkably enhanced when NDRG1 was silencing, but MMP-9 expression was increased. NDRG1 silencing enhances gastric cancer cells progression through upregulating MMP-9. It suggests that NDRG1 may inhibit the metastasis of gastric cancer via regulating MMP-9.

  6. Combined spectroscopy and molecular modeling studies on the binding of galbanic acid and MMP9.

    Science.gov (United States)

    Kiani, Amir; Almasi, Khadijeh; Shokoohinia, Yalda; Sadrjavadi, Komail; Nowroozi, Amin; Shahlaei, Mohsen

    2015-11-01

    The molecular mechanism of galbanic acid (GBA) binding to matrix metalloproteinase 9 (MMP9) was investigated by fluorescence quenching, absorption spectroscopy, FT-IR, molecular docking and molecular dynamics (MD) simulation procedures. The fluorescence emission of MMP9 was quenched by GBA. The titration of MMP9 by various amount of GBA was also followed by UV-Vis absorption spectroscopy. The results revealed that GBA, as a biologically active sesquiterpene coumarin derivative, has an ability to bind strongly to MMP9. Molecular docking results indicated that the main active binding site for GBA has been located in a hydrophobic cavity in the vicinity of Zn atom. Moreover, MD simulation results suggested that GBA as a coumarin derivative can interact with MMP9, without affecting the secondary structure of MMP9. MD simulations, molecular docking as computational methods from one hand and experimental data from other hand reciprocally supported each other.

  7. Signatures of positive selection at hemopexin (PEX) domain of matrix metalloproteinase-9 (MMP-9) gene

    Indian Academy of Sciences (India)

    Yang Liu; Yang Zhao; Chunlei Lu; Maobin Fu; Tonghai Dou; Xiaoming Tan

    2015-12-01

    Matrix metalloproteinases-9 (MMP-9) is an important cancer-associated, zinc-dependent endopeptidase. To investigate the natural selection hypothesis of MMP-9, the orthologous sequences from 12 vertebrates were compared and a molecular evolution analysis was performed. Results suggest that amino acid residues present in the middle region of the protein are more selectively constrained, whereas amino acid residues in the C-terminal region of the MM~P-9 protein including exon 13 showed lowest conservation level in non-primate species, suggesting that it is an exon with fast evolving rate compared to the others analyzed. InterProScan analysis shows that exon 13 was located in hemopexin (PEX) domain of MM~P-9. Positive selection was detected in PEX domain of MMP-9 protein between human and other species, which indicates that selective pressure may play a role in shaping the function of MM~P-9 in the course of evolution.

  8. MMP-2和MMP-9在肺癌组织中的表达%Expression of MMP-2 and MMP-9 in Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    孙书明; 周妍; 罗金芳; 桂律; 胡志雄; 金盈; 金复生

    2003-01-01

    目的:研究肺癌和正常肺组织中基质金属蛋白酶2 (MMP-2)和MMP-9的表达.方法:采用免疫组织化学EnVision方法, 对71例肺癌标本和31例正常肺组织检测MMP-2和MMP-9的表达.结果:71例肺癌标本中,小细胞肺癌(SCLC)4例,MMP-2表达阳性3例(75.0%),MMP-9表达阳性2例(50.0%);非小细胞肺癌(NSCLC)有67例,年龄40岁以上64例,MMP-2表达阳性39例,阳性率60.9%(39/64);MMP-9表达阳性46例,阳性率71.9%(46/64).正常肺标本31例,年龄40岁以下MMP-2和MMP-9表达均为阴性,年龄在40岁以上26例,MMP-2阳性表达9例,阳性率34.6%(9/26),MMP-9阳性表达10例,阳性率38.5%(10/26);40岁以上NSCLC标本的MMP-2和MMP-9阳性表达与正常肺标本比较,差异均有显著意义.结论:在NSCLC中高表达的MMP-2和MMP-9均是好的肿瘤标记物,但是,MMP-9阳性率比MMP-2更高,因此MMP-9的检测具有更大的临床意义.

  9. Concomitant lack of MMP9 and uPA disturbs physiological tissue remodeling

    DEFF Research Database (Denmark)

    Lund, Ida K; Nielsen, Boye S; Almholt, Kasper

    2011-01-01

    Urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9, gelatinase B) have separately been recognized to play important roles in various tissue remodeling processes. In this study, we demonstrate that deficiency for MMP9 in combination with ablation of either uPA- or tissue...

  10. Expression of MMP-9 and TIMP-1 in Lesions of Systemic Sclerosis and Its Implications

    Institute of Scientific and Technical Information of China (English)

    Chi MENG; Xu'e CHEN; Jiawen LI; Yan WU; Houjun LIU

    2008-01-01

    In order to investigate the role of MMP-9 and TIMP-1 in the pathogenesis of systemic sclerosis, the expression of MMP-9 and TIMP-1 was immunohistochemically detected in skin lesions of the patients with diffuse cutaneous systemic sclerosis, skin lesions of the patients with limited cutaneous systemic sclerosis, and skin tissues of normal subjects. The results showed that the expression of MMP-9 in lesions of diffuse cutaneous systemic sclerosis was significantly lower than that of normal skins (P<0.05). However, no significant difference in the level of MMP-9 in the limited cutaneous systemic sclerosis and normal skin was found. Meanwhile, the expression of TIMP-1 in lesions of diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis were significantly higher than that of normal skins (both P<0.05). It was suggested that the expression of MMP-9 and TIMP-1 might play an important role in the development of systemic sclerosis.

  11. Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells.

    Science.gov (United States)

    Liu, Wen-Hsin; Chen, Ying-Jung; Chien, Jen-Hung; Chang, Long-Sen

    2014-05-01

    This study explores the suppression mechanism of amsacrine (4-(9-Acridinylamino)-N-(methanesulfonyl)-m-anisidine hydrochloride) on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in human leukemia cells. Amsacrine attenuated cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels in U937, Jurkat, HL-60, K562, KU812, and MEG-01 cells. Moreover, amsacrine reduced both MMP-2/MMP-9 promoter luciferase activity and MMP-2/MMP-9 mRNA stability in leukemia cells. Studies on amsacrine-treated U937 cells revealed that amsacrine-elicited ROS generation induced JNK and p38 MAPK activation but reduced the phospho-ERK level. Amsacrine-induced ERK inactivation and p38 MAPK/JNK activation were demonstrated to suppress MMP-2/MMP-9 promoter luciferase activity and promote MMP-2/MMP-9 mRNA decay, respectively. p38 MAPK/JNK activation led to up-regulation of protein phosphatase 2A catalytic subunit α (PP2Acα) in amsacrine-treated U937 cells. Okadaic acid (PP2A inhibitor) treatment increased MMP-2/MMP-9 mRNA stability in amsacrine-treated cells, whereas PP2Acα over-expression increased MMP-2/MMP-9 mRNA decay. Amsacrine-induced MMP-2/MMP-9 down-regulation was also related to PP2Acα up-regulation on Jurkat, HL-60, K562, KU812, and MEG-01 cells. Collectively, our data indicate that amsacrine induces MMP-2/MMP-9 down-regulation via simultaneous suppression of genetic transcription and mRNA stability in human leukemia cells.

  12. Abnormal expression of MMP-9 and imbalance of MMP-9/TIMP-1 is associated with prolonged uterine bleeding after a medical abortion with mifepristone and misoprostol.

    Science.gov (United States)

    Li, Li; Zhou, Zanhua; Huang, Lili

    2009-01-01

    To investigate the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitory of metalloproteinase-1 (TIMP-1) in women who had undergone a medical abortion and explore their possible role in the mechanism of prolonged uterine bleeding after a mifepristone-misoprostol abortion. Cross-sectional study. Tertiary referral university hospital. Forty women were recruited following a medical abortion with mifepristone and misoprostol, 20 with duration of bleeding >14 days and 20 with duration of bleeding 14 days after a medical abortion (bleeding group), whereas each sample of women with duration of bleeding after a medical abortion (control group) showed normal endometrial changes. Immunohistochemistry and semi-quantitative scoring showed a significantly decreased expression level of MMP-9 in the bleeding group, compared with the control group. There was no significant difference of TIMP-1 expression between the bleeding group and the control group. The MMP-9/TIMP-1 ratio value was significantly lower in the bleeding group than in the control group. This study documents that prolonged bleeding after a medical abortion with mifepristone and misoprostol is associated with retained products of conception with inflammatory cell infiltration, abnormal expression of MMP-9 and imbalance of MMP-9/TIMP-1.

  13. MMP-9 directed shRNAs as relevant inhibitors of matrix metalloproteinase 9 activity and signaling

    Directory of Open Access Journals (Sweden)

    Ewa Nowak

    2013-08-01

    Full Text Available Introduction: The main function of matrix metalloproteinases is the degradation of extracellular matrix components, which is related to changes in the proliferation of cells, their differentiation, motility, and death. MMPs play an important role in physiological processes such as embryogenesis, angiogenesis and tissue remodeling. The increase of MMPs activity is also observed in pathological conditions including tumorigenesis where MMP-2 (gelatinase A and MMP-9 (gelatinase B show the ability to degrade the basement membrane of vessels and they are involved in metastasis. The aim of our study was to verify the changes of MMP-9 enzymatic activity and the mobility of cells after inhibition of MMP-9 gene expression.Material and Methods: The oligonucleotide shRNA insert had been designed to silence MMP-9 gene expression and was cloned into the pSUPER.neo expression vector. The construct was introduced into the HeLa (CCL-2 cervical cancer cells by lipotransfection. Simultaneously in control cells MMP-9 were inhibited by doxycycline. Changes in activity of MMP-9 were analyzed by gelatin zymography and wound-healing assay.Results/Conclusions: Gelatin zymography allowed us to confirm that activity of MMP-9 in cells transfected by shRNA-MMP-9 and treated by doxycycline were similar and significantly lower in comparison with control cells. Phenotypic tests of migration in vitro confirm statistically significant (P<0.05 changes in cell migration – control cells healed 3 to 5 times faster in comparison with transfected or doxycycline treated cells. Our studies show the significant role of MMP-9 in mobility and invasiveness of tumor cells, thus indicating a potential target point of interest for gene therapy.

  14. Knocking out IL-6 by vaccination

    DEFF Research Database (Denmark)

    Galle, Pia; Hougs, Lotte; Barington, Torben

    2004-01-01

    Inappropriate expression of IL-6 plays a role in various inflammatory conditions, degenerative diseases, and cancers. Several model systems have been developed that can specifically block IL-6-receptor interactions. Here we present a simple and highly effective approach based on vaccination...

  15. IL-6 Compared to Young Mice

    Directory of Open Access Journals (Sweden)

    Jihyun Park

    2014-01-01

    Full Text Available Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly.

  16. IL-6 and mouse oocyte spindle.

    Directory of Open Access Journals (Sweden)

    Jashoman Banerjee

    Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

  17. Autocrine IL-6 mediates pituitary tumor senescence

    Science.gov (United States)

    Fuertes, Mariana; Ajler, Pablo; Carrizo, Guillermo; Cervio, Andrés; Sevlever, Gustavo; Stalla, Günter K.; Arzt, Eduardo

    2017-01-01

    Cellular senescence is a stable proliferative arrest state. Pituitary adenomas are frequent and mostly benign, but the mechanism for this remains unknown. IL-6 is involved in pituitary tumor progression and is produced by the tumoral cells. In a cell autonomous fashion, IL-6 participates in oncogene-induced senescence in transduced human melanocytes. Here we prove that autocrine IL-6 participates in pituitary tumor senescence. Endogenous IL-6 inhibition in somatotroph MtT/S shRNA stable clones results in decreased SA-β-gal activity and p16INK4a but increased pRb, proliferation and invasion. Nude mice injected with IL-6 silenced clones develop tumors contrary to MtT/S wild type that do not, demonstrating that clones that escape senescence are capable of becoming tumorigenic. When endogenous IL-6 is silenced, cell cultures derived from positive SA-β-gal human tumor samples decrease the expression of the senescence marker. Our results establish that IL-6 contributes to maintain senescence by its autocrine action, providing a natural model of IL-6 mediated benign adenoma senescence. PMID:27902467

  18. MMP-2和MMP-9在食管癌中表达的研究%Expressions of MMP-2 and MMP-9 in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    武志; 潘晓玲; 仲洁

    2013-01-01

    目的 分析基质金属蛋白酶(MMP)-2和MMP-9在食管癌患者血清中的表达与食管癌临床病理因素之间的关系.方法 应用酶联免疫吸附法检测60例食管癌患者血清中MMP-2、MMP-9的含量与患者年龄、性别、组织学类型、临床分期及区域淋巴结转移等临床病理因素之间的关系.结果 对照组血清中MMP-2和MMP-9的浓度均值分别为61.31、87.67 ng/ml,而食管癌患者血清中MMP-2和MMP-9的浓度均值分别121.66、169.73 ng/ml,均高于正常者血清中含量,差异有统计学意义(t=3.015,P=0.007;t=2.037,P=0.04).MMP-2的含量与有无淋巴结转移(t=2.150,P=0.04)及临床分期(t=2.186,P=0.03)有关,MMP-9的含量与有无淋巴结转移(t=2.390,P=0.02)及临床分期(t=2.149,P=0.03)有关.MMP-2和MMP-9的含量均与食管癌患者的年龄、性别、组织学类型无关(均P>0.05).结论 MMP-2和MMP-9可能与食管癌的侵袭转移有关.%Objective To analyze the expression levels of matrix metallo proteinase-2 (MMP-2) and matrix metallo proteinase-9 (MMP-9) in serum of patients with esophageal cancer,and to analyze the interrelations among MMP-2,MMP-9 and clinicopathologic characteristics of esophageal cancer.Methods The levels of serum MMP-2,MMP-9 from 60 patients with esophageal cancer were detected by enzyme linked immunosorbent assay.The interrelations among MMP-2,MMP-9 and clinicopathologic characteristics of esophageal cancer including age,gender,histological type,whether or not lymph nodes metastasis and TNM staging were analyzed.Results The levels of MMP-2 and MMP-9 in control group were 61.31 ng/ml and 87.67 ng/ml,the levels of MMP-2 and MMP-9 in patients with esophageal cancer were 121.66 ng/ml and 169.73 ng/ml.The levels of MMP-2 and MMP-9 were significantly higher in patients with esophageal cancer than that of general population (t =3.015,P =0.007; t =2.037,P =0.04).The level of MMP-2 was significantly associated with whether or not lymph node metastasis (t =2

  19. 尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达在乳腺癌筛查中的意义%The Clinical Significance of Determining Expressions of Urinary MMP-2,MMP-9 and MMP-9/NGAL Complex for Screening Patients with Breast Cancer in High-risk Female Population

    Institute of Scientific and Technical Information of China (English)

    申哲洙; 顾晋; 赵威; 张志谦

    2008-01-01

    目的 检测女性尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达,探讨其在乳腺癌高危发病妇女普查筛选中的意义.方法 采用明胶酶底物电泳法和Western blot方法,检测正常女性(n=60)、乳腺良性疾病患者(n=41)、乳腺癌患者(n=127)尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达情况.结果 MMP-2、MMP-9MMP-9/NGAL复合物的表达在正常女性尿液中分别为23.33%、15%和13.33%;在乳腺良性疾病患者尿液中分别为43.93%、39.02%和36.59%;在乳腺癌患者尿液中分别为64.56%、76.37%和70.08%.乳腺癌患者尿液中MMP-2、MMP-9MMP-9/NGAL复合物的表达与正常女性间差异有统计学意义(P<0.001);与乳腺良性疾病患者比较差异也有统计学意义(P<0.01).乳腺癌患者尿液中MMP-2+MMP-9+MMP-9/NGAL复合物同时表达,与乳腺良性疾病患者比较差异亦有统计学意义(P<0.01).结论 1)乳腺癌、乳腺良性疾病和正常女性尿液中MMP-2、MMP-9MMP-9/NGAL复合物均有表达.但正常女性很少表达MMP-2和MMP-9,极少表达MMP-9/NGAL复合物.2)乳腺癌患者尿液中MMP-2+MMP-9+MMP-9/NGAL复合物的同时表达,对乳腺癌的诊断具有重要意义.对乳腺癌高危发病妇女的普查筛选也具有指导意义.

  20. Implications of MMP9 for Blood Brain Barrier Disruption And Hemorrhagic Transformation Following Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Renee Jade Turner

    2016-03-01

    Full Text Available Numerous studies have documented increases in matrix metalloproteinases (MMPs, specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB, increased risk of hemorrhagic complications and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke.

  1. Implications of MMP9 for Blood Brain Barrier Disruption and Hemorrhagic Transformation Following Ischemic Stroke

    Science.gov (United States)

    Turner, Renée J.; Sharp, Frank R.

    2016-01-01

    Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke. PMID:26973468

  2. Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Sullu, Yurdanur; Demirag, Guzin G; Yildirim, Arzu; Karagoz, Filiz; Kandemir, Bedri

    2011-12-15

    Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p=0.001), triple-negative (ER, PR, HER2 negative) (p=0.006), and ER-negative tumors (p=0.004) and tumors with distant metastases (p=0.028). MMP-9 expression was increased in cases with HER2 over-expression/amplification, but no statistically significant difference was found (p=0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p=0.492 and p=0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p=0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p=0.042 and p=0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.

  3. A nonintrinsic regional basis for increased infrarenal aortic MMP-9 expression and activity.

    Science.gov (United States)

    Ailawadi, Gorav; Knipp, Brian S; Lu, Guanyi; Roelofs, Karen J; Ford, John W; Hannawa, Kevin K; Bishop, Keith; Thanaporn, Porama; Henke, Peter K; Stanley, James C; Upchurch, Gilbert R

    2003-05-01

    This investigation was undertaken to determine whether intrinsic or regional factors at different anatomic sites of the aorta affect expression and activity of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Aortas from Sprague-Dawley rats (n = 22) were divided into arch, descending thoracic, and infrarenal abdominal segments. Specimens were stimulated with interleukin-1beta (IL-1beta) (2 ng/mL) for 72 hours. In separate experiments, syngeneic aortic segments were transplanted from the thoracic or abdominal aortas of donor rats into the infrarenal aortic position of recipient rats (n = 12 each). At 4 weeks, aortas from rats who had received transplants were harvested, sectioned into arch, thoracic, and transplanted thoracic or transplanted abdominal segments, and stimulated with IL-1beta. Reverse transcriptase polymerase chain reaction, zymography, and reverse zymography were performed to assess MMP-9, MMP-2, and TIMP-1 in all aortic segments. Differences were assessed with analysis of variance (ANOVA) and post-hoc Tukey test. In control rats, abdominal segments had significantly higher MMP-9 expression compared with arch and thoracic segments (P <.002). Total MMP-9 activity was also higher in abdominal segments (P <.02). In rats who received transplants, transplanted thoracic (P <.004) and transplanted abdominal (P <.05) segments demonstrated upregulation of MMP-9 expression, compared with control arch and thoracic segments. Zymography documented increased total MMP-9 activity in transplanted thoracic (P <.03) and transplanted abdominal (P <.04) segments versus arch and thoracic segments. No significant difference in MMP-9 expression was found between control abdominal, transplanted thoracic, or transplanted abdominal segments. No significant differences in MMP-2 or TIMP-1 expression or activity were demonstrated in either control or transplanted segments. These data demonstrate that variations in aortic MMP-9 expression and

  4. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae, E-mail: chidkim@pusan.ac.kr

    2012-04-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  5. Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Clausen, Rikke E; Nguyen, Quoc Hai Trieu;

    2012-01-01

    Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part...... are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases....

  6. Serum level of MMP-2, MMP-9 and Ox-LDL in Alzheimer's disease with hyperlipoidemia

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate serum levels of MMP-2,MMP-9, oxidized low density lipoprotein (ox-LDL) in Alzheimer's disease (AD) patients and study the possible pathway and mechanism of AD with abnormal lipid metabolism. Methods: Subjects in this study were divided into 4 groups: normal lipid group without AD (N), hyperlipoidemia group without AD (H), normal group with AD (A), hyperlipoidemia group with AD (AH). There were 15 individuals in each group. MMP-2, MMP-9, ox-LDL was measured by enzyme linked immunosorbent assay (ELISA). Serum lipids levels were measured by biochemical methods. Results: The serum levels of MMP-2, MMP-9, ox-LDL were significantly higher in H, A and AH groups than those in N group. Those of ox LDL in H, AH groups was higher than that of in A group. The serum level of MMP-2, MMP-9 in AH groups were higher than that of in H group. The score of mini-mental state examination (MMSE) in A and AD groups was negatively correlated with the serum level of ox-LDL. Relationship between the score of MMSE and the serum level of ox-LDL in AD groups and non-AD groups had statistical significance. Conclusion: MMP-2, MMP-9, ox-LDL and abnormal lipid metabolism may participate in pathogenesis of AD, in which abnormal lipid metabolism induces expressions of MMP-2,MMP-9 and ox-LDL. Oxidative stress and blood-brain barrier disruption might accelerate the process of AD.

  7. The Biological Behaviors of Rat Dermal Fibroblasts Can Be Inhibited by High Levels of MMP9

    Directory of Open Access Journals (Sweden)

    Sheng-Neng Xue

    2012-01-01

    Full Text Available Aims. To explore the effects of the high expression of MMP9 on biological behaviors of fibroblasts. Methods. High glucose and hyperhomocysteine were used to induce MMP9 expression in skin fibroblasts. Cell proliferation was detected by flow cytometry and cell viability by CCK-8. ELISA assay was used to detect collagen (hydroxyproline secretion. Scratch test was employed to evaluate horizontal migration of cells and transwell method to evaluate vertical migration of cells. Results. The mRNA and protein expressions of MMP9 and its protease activity were significantly higher in cells treated with high glucose and hyperhomocysteine than those in control group. At the same time, the S-phase cell ratio, proliferation index, cell viability, collagen (hydroxyproline secretion, horizontal migration rate, and the number of vertical migration cells decreased in high-glucose and hyperhomocysteine-treated group. Tissue inhibitor of metalloproteinase 1 (TIMP1, which inhibits the activity of MMP9, recovered the above biological behaviors. Conclusions. High expression of MMP9 in skin fibroblasts could be induced by cultureing in high glucose and hyperhomocysteine medium, which inhibited cell biological behaviors. Inhibitions could be reversed by TIMP1. The findings suggested that MMP9 deters the healing of diabetic foot ulcers by inhibiting the biological behaviors of fibroblasts.

  8. IL-8 as antibody therapeutic target in inflammatory diseases

    DEFF Research Database (Denmark)

    Skov, Lone; Beurskens, Frank J; Zachariae, Claus O C

    2008-01-01

    IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependen...

  9. Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

    DEFF Research Database (Denmark)

    Galle, Pia; Jensen, Lene; Andersson, Christina

    2007-01-01

    ; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental...... allergic encephalitis. Furthermore, aAb-IL-6 carrying mice displayed increased plasma TNFalpha concentrations upon challenge with LPS. Taken together, induction of IL-6 autoantibodies was possible in different mouse strains. The autoantibodies influenced experimental inflammation. This immunotherapeutic...

  10. Interplay Between MMP-9 and TIMP-2 Regulates Ameloblastoma Behavior and Tooth Morphogenesis.

    Science.gov (United States)

    Nunia, Kalpana; Urs, Aadithya B; Kumar, Priya

    2016-01-01

    Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been implicated in the local invasiveness of ameloblastoma. This study aims to assess the role of MMP-9 and TIMP-2 in regulating tumor progression in ameloblastomas, taking tooth germs as control. Formalin-fixed, paraffin-embedded tissue sections of 4 tooth germs and 32 ameloblastomas were immunohistochemically examined using antibodies against MMP-9 and TIMP-2. Strong MMP-9 positivity was seen in the epithelial component in both controls and solid multicystic ameloblastoma. Statistically significant difference was observed in the mean stromal MMP-9 immunoscores between follicular, acanthomatous, and granular ameloblastoma when compared with the tooth germ (P=0.004). TIMP-2 expression in the epithelial and mesenchymal components of solid multicystic ameloblastoma and tooth germ was weak as compared with MMP-9 expression. Highest mean epithelial TIMP-2 immunoscore was observed in follicular ameloblastoma and the difference was statistically significant between follicular and granular ameloblastoma (P=0.05). The comparison of mean stromal TIMP-2 immunoscores showed statistically significant difference between follicular subtype and tooth germ (P=0.048), with tooth germ showing least expression among the groups studied. Strong stromal expression of MMP-9 in ameloblastoma compared with tooth germ mesenchyme indicated the possibility of tumor induction with release of growth factors and cytokines, resulting in invasiveness of ameloblastoma. Epithelial TIMP-2 expression was associated with the least and most aggressive behavior of follicular and granular cell ameloblastoma, respectively. Stromal TIMP-2 expression reflected its role in regulating tumor progression in ameloblastoma and in regulating developmental processes in tooth germs by their inhibitory effect on MMP-9.

  11. Coexpression of CXCR4 and MMP9 predicts lung metastasis and poor prognosis in resected osteosarcoma.

    Science.gov (United States)

    Ren, Zhiwu; Liang, Shoulei; Yang, Jilong; Han, Xiuxin; Shan, Luling; Wang, Biying; Mu, Tianyang; Zhang, Yanqin; Yang, Xueli; Xiong, Shunbin; Wang, Guowen

    2016-04-01

    Osteosarcoma is a highly aggressive bone disease with a tendency to metastasize to the lung. The 5-year survival of patients with metastatic osteosarcoma is only 20 %. Many studies have demonstrated SDF-1/CXCR4 and MMP9 play important roles in the metastasis of malignant tumors, including osteosarcoma. The aim of this study was to investigate the association of CXCR4 and MMP9 expression with clinicopathological features and pulmonary metastasis in osteosarcoma. Using tumor tissue microarrays, we analyzed the expression of CXCR4 and MMP9 among 34 primary osteosarcomas with pulmonary metastasis and 62 primary osteosarcomas without metastasis. A median time of 57.5 months (range: 6 to 171 months) follow-up was performed to evaluate tumor metastasis and the patient survival. The prognostic values were determined by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. The accuracy of oncologic outcome prediction was evaluated by receiver-operating characteristics (ROC) curves (AUC). The expression of CXCR4 and MMP9 was significantly correlated in tumor tissues (P = 0.026). Both CXCR4 and MMP9 were independent predictors for overall survival and metastasis-free survival by Cox multivariate analysis, and high expression for both CXCR4 and MMP9 were even more significant and better biomarkers for osteosarcoma metastasis and survival. The combination of CXCR4 and MMP9 high expression is very likely to be a valuable independent predictor of lung metastasis and survival in osteosarcoma patients.

  12. A self-propagating matrix metalloprotease-9 (MMP-9 dependent cycle of chronic neutrophilic inflammation.

    Directory of Open Access Journals (Sweden)

    Xin Xu

    Full Text Available BACKGROUND: Chronic neutrophilic inflammation is a poorly understood feature in a variety of diseases with notable worldwide morbidity and mortality. We have recently characterized N-acetyl Pro-Gly-Pro (Ac-PGP as an important neutrophil (PMN chemoattractant in chronic inflammation generated from the breakdown of collagen by the actions of MMP-9. MMP-9 is present in the granules of PMNs and is differentially released during inflammation but whether Ac-PGP contributes to this ongoing proteolytic activity in chronic neutrophilic inflammation is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing isolated primary blood PMNs from human donors, we found that Ac-PGP induces significant release of MMP-9 and concurrently activates the ERK1/2 MAPK pathway. This MMP-9 release is attenuated by an inhibitor of ERK1/2 MAPK and upstream blockade of CXCR1 and CXCR2 receptors with repertaxin leads to decreased MMP-9 release and ERK 1/2 MAPK activation. Supernatants obtained from PMNs stimulated by Ac-PGP generate more Ac-PGP when incubated with intact collagen ex vivo; this effect is inhibited by an ERK1/2 pathway inhibitor. Finally, clinical samples from individuals with CF demonstrate a notable correlation between Ac-PGP (as measured by liquid chromatography-tandem mass spectrometry and MMP-9 levels even when accounting for total PMN burden. CONCLUSIONS/SIGNIFICANCE: These data indicate that ECM-derived Ac-PGP could result in a feed-forward cycle by releasing MMP-9 from activated PMNs through the ligation of CXCR1 and CXCR2 and subsequent activation of the ERK1/2 MAPK, highlighting for the first time a matrix-derived chemokine (matrikine augmenting its generation through a discrete receptor/intracellular signaling pathway. These findings have notable implications to the development unrelenting chronic PMN inflammation in human disease.

  13. Critical appraisal of four IL-6 immunoassays.

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    Dana K Thompson

    Full Text Available BACKGROUND: Interleukin-6 (IL-6 contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs, with expected rises in IL-6 concentrations, were used to test the face validity of the various assays. METHODS AND FINDINGS: IVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass at time zero, a single infusion of insulin (0.025 U/kg body mass at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD, an Invitrogen Luminex bead-based multiplex panel (LX, an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX, and R&D High Sensitivity ELISA (R&D. IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47-0.94, p<0.0001 but only ULX correlated (r = 0.31, p = 0.0027 with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90 ± 0.48 pg/mL increased significantly as expected by 90 minutes (1.29 ± 0.59 pg/mL, p = 0.049, and continued rising through 3 hours (4.25 ± 3.67 pg/mL, p = 0.0048. CONCLUSION: This study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1

  14. Inflammageing assessed by MMP9 in normal Japanese individuals and the patients with Werner syndrome.

    Science.gov (United States)

    Goto, Makoto; Chiba, Junji; Matsuura, Masaaki; Iwaki-Egawa, Sachiko; Watanabe, Yasuhiro

    2016-05-01

    Age-associated minor inflammation: inflammageing may explain human ageing mechanism(s). Our previous study reported a significant increase in the serum level of highly sensitive C-reactive protein (hsCRP) with normal ageing and the patients with Werner syndrome (WS). To further study the minor inflammatory condition associated with ageing, another possible ageing biomarker: matrix metalloproteinase-9 (MMP9) was examined in the sera from 217 normal Japanese individuals aged between 1 and 100 years and 41 mutation-proven Japanese WS aged between 32 and 70 years. MMP9 was assayed by ELISA. The serum level of MMP9 was elevated significantly (p normal ageing from both sexes as hsCRP. In contrast to normal ageing, the serum MMP9 level in WS decreased significantly with calendar age (p normal adult population aged between 25 and 70 years (109.1 ± 9.4), nor normal elderly population aged between 71 and 100 years (179.9 ± 16.1). Although both normal ageing and WS were associated with minor inflammation, the inflammatory parameters such as serum MMP9 and hsCRP changed differently between normal ageing and WS. The WS-specific chronic inflammation including skin ulcer and diabetes mellitus may contribute the different behavior of both ageing biomarkers from normal ageing.

  15. Serum matrix metalloproteinase 9 (MMP9) as a biochemical marker for wasting marmoset syndrome.

    Science.gov (United States)

    Yoshimoto, Takuro; Niimi, Kimie; Takahashi, Eiki

    2016-06-01

    Use of the common marmoset (Callithrix jacchus) as a non-human primate experimental animal has increased in recent years. Although wasting marmoset syndrome (WMS) is one of the biggest problems in captive marmoset colonies, the molecular mechanisms, biochemical markers for accurate diagnosis and a reliable treatment remain unknown. In this study, as a first step to finding biochemical marker(s) for the accurate diagnosis of WMS, we conducted blood cell counts, including hematocrit, hemoglobin and platelets, and examined serum chemistry values, including albumin, calcium and levels of serum matrix metalloproteinase 9 (MMP9), using a colony of marmosets with and without weight loss. MMP9 is thought to be an enzyme responsible for the degradation of extracellular matrix components and participates in the pathogenesis of inflammatory conditions, such as human and murine inflammatory bowel disease, which, like WMS, are characterized histologically by inflammatory cell infiltrations in the intestines. The values of hematocrit and hemoglobin and levels of serum albumin and calcium in the WMS group were significantly decreased versus the control group. The platelet values and serum MMP9 concentrations were increased significantly in the WMS group compared with the control group. MMP9 could be a new and useful marker for the diagnosis of WMS in addition to hematocrit, hemoglobin, serum albumin and calcium. Our results also indicate that MMP9 could be a useful molecular candidate for treatment.

  16. Correlations between IL6 and the main clinical and biological parameters in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Mihaela Chicu

    2016-09-01

    Full Text Available Introduction: Cytokines are a family of complex peptide with hormone-like activity. They are soluble proteins without enzymatic activity and serves as the main intracellular mediators. Many cytokines achieves its effects by binding to special receptors membrane, and their adjustment is via soluble receptors. Cytokines are characterized by pleiotropism, overlapping and mutual adjustment. Proinflammatory cytokine involved in major rheumatoid arthritis are TNF, IL1α, IL1β, IL8.The biological effects of IL6 overlap in large part over those of TNF. If TNF is involved in induction of apoptosis or programmed cell death, IL6 is specifically associated with angiogenic factors activation and the occurrence of neovascularity to the synovium; favors articular cartilage degradation by increasing the release of MMP, decreasing PG, recruit osteoclasts, apoptosis of osteoblasts, release of degradative enzymes and the inflammatory mediators - iNOS, COX2 - TNF, IL6, IL8.Material and methods: Based on these data we proposed and realized – for the first time in Romania – the measurement of IL6 levels and the correlation with values of DAS28 score, HAQ, ESR, CRP, Hb and the immunological parameters too. The study was conducted on a group of 80 sick diagnosed with RA in various stages of evolution, under treatment with disease-modifying medication , type Methotrexate, Arava.Conclusions: Levels of IL-6 correlate a direct manner with those of acute phase reactants ,ESR, CRP and indirect values of Hb, IgG; the clinical parameters (number of tender and swollen joints, DAS28, HAQ are not influenced by values IL6.

  17. Dihydroavenanthramide D inhibits human breast cancer cell invasion through suppression of MMP-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young-Rae; Noh, Eun-Mi; Oh, Hyun Ju; Hur, Hyun; Kim, Jeong-Mi; Han, Ji-Hey; Hwang, Jin-Ki; Park, Byung-Hyun; Park, Jin-Woo [Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of); Youn, Hyun Jo; Jung, Sung Hoo [Department of Surgery, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of); Kim, Byeong-Soo; Jung, Ji-Youn; Lee, Sung-Ho [Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702 (Korea, Republic of); Park, Chang-Sik [Division of Animal Science and Resources Research Center for Transgenic Cloned Pigs, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Jong-Suk, E-mail: jsukim@jbnu.ac.kr [Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University, Medical School, Jeonju, Jeonbuk 560-182 (Korea, Republic of)

    2011-02-25

    Research highlights: {yields} MMP-9 plays a pivotal role in the invasion of MCF-7 breast cancer cells. {yields} TPA stimulates MMP-9 expression through activation of MAPK/NF-{kappa}B and MAPK/AP-1 pathways. {yields} Dihydroavenanthramide D suppresses MMP-9 expression via inhibition of TPA-induced MAPK/NF-{kappa}B and MAPK/AP-1 activations. {yields} Dihydroavenanthramide D blocks cell invasion of MCF-7 breast cancer cells. -- Abstract: Dihydroavenanthramide D (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the active component of oat. Previous study demonstrates that DHAvD strongly inhibits activation of nuclear factor-kappa B (NF-{kappa}B), which is a major component in cancer cell invasion. The present study investigated whether DHAvD can modulate MMP-9 expression and cell invasion in MCF-7 human breast cancer cells. MMP-9 expression and cell invasion in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) was increased, whereas these inductions were muted by DHAvD. DHAvD also suppressed activation of mitogen-activated protein kinase (MAPK), and MAPK-mediated nuclear factor-kappa B (NF-{kappa}B) and activator protein-1 (AP-1) activations in TPA-treated MCF-7 cells. The results indicate that DHAvD-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the MAPK/NF-{kappa}B and MAPK/AP-1 pathways in MCF-7 cells. DHAvD may have potential value in breast cancer metastasis.

  18. Suppressed MMP-9 Activity in Myocardial Infarction-Related Cardiogenic Shock Implies Diminished Rage Degradation.

    Science.gov (United States)

    Selejan, Simina-Ramona; Hewera, Lisa; Hohl, Matthias; Kazakov, Andrey; Ewen, Sebastian; Kindermann, Ingrid; Böhm, Michael; Link, Andreas

    2017-07-01

    Receptor for advanced glycation end products (RAGE) and its cleavage fragment soluble RAGE (sRAGE) are opposite players in inflammation. Enhanced monocytic RAGE expression and decreased plasma sRAGE levels are associated with higher mortality in infarction-related cardiogenic shock. Active matrix metalloproteinase-9 (MMP-9) has been implied in RAGE ectodomain cleavage and subsequently sRAGE shedding in vitro. We investigated MMP-9 activity in myocardial infarction-induced cardiogenic shock with regard to RAGE/sRAGE regulation. We determined MMP-9 serum activity by zymography and tissue inhibitor of matrix metalloproteinases (TIMP-1) expression by Western blot and correlated it to RAGE/sRAGE data in patients with cardiogenic shock after acute myocardial infarction (CS, n = 30), in patients with acute myocardial infarction without shock (AMI, n = 20) and in healthy volunteers (n = 20).MMP-9 activity is increased in AMI (P = 0.02 versus controls), but significantly decreased in CS with lowest levels in non-survivors (n = 13, P = 0.02 versus AMI). In all patients, MMP-9 activity correlated inversely with RAGE expression on circulating monocytes (r = -0.57; P = 0.0001; n = 50).TIMP-1 levels showed an inverse regulation in comparison to active MMP-9 with significantly decreased levels in AMI as compared with controls (P = 0.02 versus controls) and highest levels in non-survivors of CS (P RAGE-induced deleterious inflammation in cardiogenic shock.

  19. ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

    Science.gov (United States)

    Hsieh, Wen-Yeh; Kuan, Tang-Ching; Cheng, Kun-Shan; Liao, Yan-Chiou; Chen, Mu-Yuan; Lin, Pei-Heng; Hsu, Yuan-Chang; Huang, Chen-Yi; Hsu, Wei-Hua; Yu, Sheng-Yao; Lin, Chih-Sheng

    2012-01-01

    Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates. Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28). Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions. Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy. PMID:23091417

  20. Characterization of quenched fluorescent triple helical peptides for MMP-2 and MMP-9 optical imaging

    Science.gov (United States)

    Cheney, Philip P.; Fields, Gregg B.; Achilefu, Samuel; Edwards, W. Barry

    2009-02-01

    The prevalence of the gelatinases, MMP-2 and MMP-9, in many human tumors, including breast, colorectal, prostate and gastric cancer, make them an attractive target for molecular imaging. A self assembling homotrimeric triple helical peptide (THP), incorporating sequences from type V collagen with high specificity to MMP-2 and MMP-9, was previously developed. To investigate the viability of a THP for gelatinase imaging, we conjugated 5FAM to ..-amino groups of lysine flanking the hydrolysis site and subjected this substrate (THP-5FAM) to vitro analysis. The synthesis and in vitro results was presented.

  1. IFN-gamma Impairs Release of IL-8 by IL-1beta-stimulated A549 Lung Carcinoma Cells

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    Pfeilschifter Josef

    2008-09-01

    Full Text Available Abstract Background Production of interferon (IFN-γ is key to efficient anti-tumor immunity. The present study was set out to investigate effects of IFNγ on the release of the potent pro-angiogenic mediator IL-8 by human A549 lung carcinoma cells. Methods A549 cells were cultured and stimulated with interleukin (IL-1β alone or in combination with IFNγ. IL-8 production by these cells was analyzed with enzyme linked immuno sorbent assay (ELISA. mRNA-expression was analyzed by real-time PCR and RNase protection assay (RPA, respectively. Expression of inhibitor-κ Bα, cellular IL-8, and cyclooxygenase-2 was analyzed by Western blot analysis. Results Here we demonstrate that IFNγ efficiently reduced IL-8 secretion under the influence of IL-1β. Surprisingly, real-time PCR analysis and RPA revealed that the inhibitory effect of IFNγ on IL-8 was not associated with significant changes in mRNA levels. These observations concurred with lack of a modulatory activity of IFNγ on IL-1β-induced NF-κB activation as assessed by cellular IκB levels. Moreover, analysis of intracellular IL-8 suggests that IFNγ modulated IL-8 secretion by action on the posttranslational level. In contrast to IL-8, IL-1β-induced cyclooxygenase-2 expression and release of IL-6 were not affected by IFNγ indicating that modulation of IL-1β action by this cytokine displays specificity. Conclusion Data presented herein agree with an angiostatic role of IFNγ as seen in rodent models of solid tumors and suggest that increasing T helper type 1 (Th1-like functions in lung cancer patients e.g. by local delivery of IFNγ may mediate therapeutic benefit via mechanisms that potentially include modulation of pro-angiogenic IL-8.

  2. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

  3. Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.

    Science.gov (United States)

    Hathaway, Catherine K; Grant, Ruriko; Hagaman, John R; Hiller, Sylvia; Li, Feng; Xu, Longquan; Chang, Albert S; Madden, Victoria J; Bagnell, C Robert; Rojas, Mauricio; Kim, Hyung-Suk; Wu, Bingruo; Zhou, Bin; Smithies, Oliver; Kakoki, Masao

    2015-04-21

    We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction.

  4. MMP-2 and MMP-9 as prognostic factors in ischaemic stroke

    Directory of Open Access Journals (Sweden)

    Justyna Zielińska-Turek

    2016-09-01

    Full Text Available Objectives: No widely available, adequately sensitive diagnostic test to establish prognosis in stroke patients has been developed thus far. The aim of this study was to analyse changes in plasma levels of MMP-9 and MMP-2 as potential prognostic factors in patients with ischaemic stroke. Methods: The study included 56 patients presenting with the signs of ischaemic stroke for less than 24 hours, and 60 healthy controls without a history of neurological and/or inflammatory disorders. Plasma concentrations of MMP-2 and MMP-9 were determined immunoenzymatically at admission (i.e. within 24 hours of the cerebrovascular episode and on the 7th day of hospital stay. Results: Median concentrations of MMP-9 in stroke patients were significantly lower than in the controls, both at admission and on the 7th day of hospital stay. No significant changes in the concentration of MMP-2 in ischaemic stroke patients were observed during the course of hospital stay. No significant association was found between both MMP concentrations and neurological status of patients with cerebrovascular episodes. Conclusions: The lack of significant associations between plasma concentrations of MMP-2/MMP-9 and clinical status suggests that these metalloproteinases should not be used as prognostic factors in patients with ischaemic cerebral episodes.

  5. Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

    NARCIS (Netherlands)

    Kubben, F.J.G.M.; Sier, C.F.M.; Schram, M.; Witte, T.A.M.C.; Veenendaal, R.A.; Duijn, W. van; Verheijen, J.H.; Hanemaaijer, R.; Lamers, C.B.H.W.; Verspaget, H.W.

    2007-01-01

    Background: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. Aim: This study was performed to investigate whether H.

  6. Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline.

    Science.gov (United States)

    Uehara, Osamu; Takimoto, Kousuke; Morikawa, Tetsuro; Harada, Fumiya; Takai, Rie; Adhikari, Bhoj Raj; Itatsu, Ryoko; Nakamura, Tomohisa; Yoshida, Koki; Matsuoka, Hirofumi; Nagayasu, Hiroki; Saito, Ichiro; Muthumala, Malsantha; Chiba, Itsuo; Abiko, Yoshihiro

    2017-07-01

    Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days. The expression levels of the MMPs and TIMPs in the cells stimulated with arecoline were evaluated by reverse transcription-quantitative polymerase chain reaction at 18 and 30 days. The expression of MMP-9 mRNA in the experimental group was significantly increased compared with in the control group (Parecoline. Based on the data, it is hypothesized that MMP-9 activity may be involved in the pathological alterations of oral epithelium induced by betel quid chewing, and that the NF-κB/IκB, MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of MMP-9 induced by betel quid chewing.

  7. Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

    NARCIS (Netherlands)

    Kubben, F.J.G.M.; Sier, C.F.M.; Schram, M.; Witte, T.A.M.C.; Veenendaal, R.A.; Duijn, W. van; Verheijen, J.H.; Hanemaaijer, R.; Lamers, C.B.H.W.; Verspaget, H.W.

    2007-01-01

    Background: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. Aim: This study was performed to investigate whether H. p

  8. Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence.

    Science.gov (United States)

    Ma, Yonggang; Chiao, Ying Ann; Clark, Ryan; Flynn, Elizabeth R; Yabluchanskiy, Andriy; Ghasemi, Omid; Zouein, Fouad; Lindsey, Merry L; Jin, Yu-Fang

    2015-06-01

    Cardiac ageing involves the progressive development of cardiac fibrosis and diastolic dysfunction coordinated by MMP-9. Here, we report a cardiac ageing signature that encompasses macrophage pro-inflammatory signalling in the left ventricle (LV) and distinguishes biological from chronological ageing. Young (6-9 months), middle-aged (12-15 months), old (18-24 months), and senescent (26-34 months) mice of both C57BL/6J wild type (WT) and MMP-9 null were evaluated. Using an identified inflammatory pattern, we were able to define individual mice based on their biological, rather than chronological, age. Bcl6, Ccl24, and Il4 were the strongest inflammatory markers of the cardiac ageing signature. The decline in early-to-late LV filling ratio was most strongly predicted by Bcl6, Il1r1, Ccl24, Crp, and Cxcl13 patterns, whereas LV wall thickness was most predicted by Abcf1, Tollip, Scye1, and Mif patterns. With age, there was a linear increase in cardiac M1 macrophages and a decrease in cardiac M2 macrophages in WT mice; of which, both were prevented by MMP-9 deletion. In vitro, MMP-9 directly activated young macrophage polarization to an M1/M2 mid-transition state. Our results define the cardiac ageing inflammatory signature and assign MMP-9 roles in mediating the inflammaging profile by indirectly and directly modifying macrophage polarization. Our results explain early mechanisms that stimulate ageing-induced cardiac fibrosis and diastolic dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  9. Post-exercise skeletal muscle glycogen related to plasma cytokines and muscle IL-6 protein content, but not muscle cytokine mRNA expression

    Directory of Open Access Journals (Sweden)

    David Christopher Nieman

    2015-09-01

    Full Text Available Objectives: The purpose of this study was to correlate post-exercise muscle glycogen levels with changes in plasma cytokine, and muscle mRNA cytokine expression and protein content. Methods: Twenty-four male runners (age 36.5±1.8 y, VO2max 60.0±1.5 ml.kg.-1min-1 ran twice (separated by 4 weeks on treadmills to exhaustion at 70% VO2max (average time and distance of 2.24±0.09 h and 24.9±1.1 km. Muscle biopsies from the vastus lateralis and blood samples were collected before and after each run, with IL-6, IL-8, and MCP-1 measured in muscle (mRNA and protein and plasma. Data from the two runs were averaged. Results: Participants experienced a 35.3±4.2% decrease (P<0.001 in skeletal muscle glycogen content (67.5±2.8 to 44.3 ±3.7 mmol/kg wet weight. Muscle mRNA expression for IL-6, IL-8, and MCP-1 increased 7.34±0.90-, 13.9±2.3-, and 4.10±0.60- fold, respectively (all, P<0.001. Skeletal muscle IL-6, IL-8, and MCP-1 protein content increased 35.8±10.6%, 80.6±12.1%, and 105±17.9%, respectively (all P≤0.005. Plasma IL-6, IL-8, and MCP-1 increased 47.1±10.0-, 2.6±0.3-, and 1.6±0.1-fold, respectively (all, P<0.001. Post-exercise muscle glycogen concentrations were negatively correlated with run time to exhaustion (r=-0.70, P<0.001, and changes in muscle IL-6 protein content (r=-0.44, P=0.049, plasma IL-6 (r=-0.72, P<0.001, IL-8 (r=-0.60, P=0.002, and MCP-1 (r=-0.589, P=0.002, but not with changes in muscle IL-8 and MCP-1 protein content, or muscle mRNA expression for IL-6, IL-8, and MCP-1. Conclusions: Prolonged and intensive running increased muscle mRNA expression, muscle protein content, and plasma levels for IL-6, IL-8, and MCP-1, and post-run muscle glycogen levels were most strongly related to plasma cytokine levels.

  10. OSAHS患者呼出气冷凝液中MMP-9的变化%Changes of MMP-9 in exhaled breath condensate of patients with obstructive sleep apnea hypopnea syndrome

    Institute of Scientific and Technical Information of China (English)

    徐健; 李一禄; 陈济明; 徐晓妮; 何梦颖

    2014-01-01

    Objective To evaluate the changes of matrix metalloproteases-9(MMP-9)in exhaled breath con-densate( EBC) with Obstructive sleep apnea-hypopnea syndrome ( OSAHS) . Methods Select 40 males and OSAHS patients for the experimental group, 30 healthy subjects matched age and body mass index as a control group. exhaled breath condensate The levels of MMP-9 in EBC were determined by ELISA. Results Compared to the control group, the MMP-9 in OSAHS group was significantly higher ( P<0. 05 ) . MMP-9 was positively correlated with AHI ( P<0. 05), and negative correlated the lowest SaO2(P<0. 05). Conclusion The MMP-9 levels in EBC in OSAHS pa-tients may reflect the severity of OSAHS.%目的:观察阻塞性睡眠呼吸暂停低通气综合征( OSAHS)患者呼出气冷凝液( EBC)中基质金属蛋白酶9(MMP-9)的变化。方法选取男性40例OSAHS患者为实验组,30例年龄、体重指数等均相匹配的健康查体者为对照组,用ELISA检测EBC中MMP-9水平。结果和对照组比较,OSAHS组EBC中MMP-9明显升高,有显著统计学意义(P<0.05)。 MMP-9与AHI呈正相关,与最低SaO2负相关(P均<0.05)。结论OSAHS患者EBC中MMP-9水平可反映OSAHS病情的严重程度。

  11. 骨肉瘤组织中MMP-2、MMP-9的表达及意义

    Institute of Scientific and Technical Information of China (English)

    周钱宏; 刘爱东

    2009-01-01

    目的 探讨骨肉瘤中基质金属蛋白酶(MMP)-2及MMP-9的表达及其在骨肉瘤发生、发展中的作用.方法 采用免疫组织化学技术检测46例骨肉瘤组织及12例良性骨肿瘤组织中MMP-2及MMP-9的表达情况.结果 MMP-2及MMP-9在骨肉瘤中的表达量明显高于良性骨肿瘤组织,MMP-2及MMP-9的表达与Ennecking分期有关.结论 MMP-2及MMP-9可作为预测骨肉瘤预后的重要指标.

  12. Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis.

    Science.gov (United States)

    Sarkar, Jaganmay; Nandy, Suman Kumar; Chowdhury, Animesh; Chakraborti, Tapati; Chakraborti, Sajal

    2016-12-01

    Green tea polyphenolic catechins have been shown to prevent various types of diseases such as pulmonary hypertension (PAH), cancer and cardiac and neurological disorders. Matrix metalloproteinases (MMPs) play an important role in the development of PAH. The present study demonstrated that among the four green tea catechins (EGCG, ECG, EC and EGC), EGCG and ECG inhibit pro-/active MMP-9 activities in pulmonary artery smooth muscle cell culture supernatant. Based on the above, we investigated the interactions of pro-/active MMP-9 with the green tea catechins by computational methods. In silico molecular docking analysis revealed a strong interaction between pro-/active MMP-9 and EGCG/ECG, and galloyl group appears to be responsible for this enhanced interaction. The molecular docking studies corroborate our experimental observation that EGCG and ECG are mainly active in preventing both the proMMP-9 and MMP-9 activities.

  13. Correlation between the severity of coronary artery lesions and levels of estrogen, hs-CRP and MMP-9.

    Science.gov (United States)

    Guo, Changlei; Zhang, Shaoli; Zhang, Junbiao; Liu, Hui; Li, Peicheng; Liu, Hengdao; Wang, Yakun

    2014-05-01

    The aim of this study was to investigate the correlation between the severity of coronary artery lesions in patients with acute coronary syndromes (ACS) and levels of estrogen, high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). A total of 65 patients with ACS, 33 patients with stable angina pectoris (SAP) and 36 healthy controls were randomly enrolled. Patients with ACS were subdivided into two groups: Acute myocardial infarction (AMI; n=30) and unstable angina pectoris (UAP; n=35). Serum levels of estrogen, hs-CRP and MMP-9 were detected in the four groups of subjects. Serum estrogen levels in patients with AMI, UAP and SAP were significantly lower than those in the control group (Phs-CRP and MMP-9, followed in descending order by those with UAP and SAP (Phs-CRP and MMP-9 were also significantly different among the AMI, UAP and SAP groups (Phs-CRP and MMP-9 levels (r=-0.6634 and -0.6878, respectively; both Phs-CRP and MMP-9 levels correlated positively (r=0.7208, Phs-CRP and MMP-9 levels (r=0.6519 and 0.6835, respectively; both Phs-CRP and MMP-9 levels were significantly correlated with the severity of coronary artery lesions. There was also a significant correlation between serum estrogen, hs-CRP and MMP-9 levels. These data indicate that serum estrogen, hs-CRP and MMP-9 have the potential to be used as biomarkers for evaluating the severity of coronary artery lesions and the stability of coronary artery plaques.

  14. Selective Allosteric Inhibition of MMP9 Is Efficacious in Preclinical Models of Ulcerative Colitis and Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Derek C Marshall

    Full Text Available Expression of matrix metalloproteinase 9 (MMP9 is elevated in a variety of inflammatory and oncology indications, including ulcerative colitis and colorectal cancer. MMP9 is a downstream effector and an upstream mediator of pathways involved in growth and inflammation, and has long been viewed as a promising therapeutic target. However, previous efforts to target matrix metalloproteinases (MMPs, including MMP9, have utilized broad-spectrum or semi-selective inhibitors. While some of these drugs showed signs of efficacy in patients, all MMP-targeted inhibitors have been hampered by dose-limiting toxicity or insufficient clinical benefit, likely due to their lack of specificity. Here, we show that selective inhibition of MMP9 did not induce musculoskeletal syndrome (a characteristic toxicity of pan-MMP inhibitors in a rat model, but did reduce disease severity in a dextran sodium sulfate-induced mouse model of ulcerative colitis. We also found that MMP9 inhibition decreased tumor growth and metastases incidence in a surgical orthotopic xenograft model of colorectal carcinoma, and that inhibition of either tumor- or stroma-derived MMP9 was sufficient to reduce primary tumor growth. Collectively, these data suggest that selective MMP9 inhibition is a promising therapeutic strategy for treatment of inflammatory and oncology indications in which MMP9 is upregulated and is associated with disease pathology, such as ulcerative colitis and colorectal cancer. In addition, we report the development of a potent and highly selective allosteric MMP9 inhibitor, the humanized monoclonal antibody GS-5745, which can be used to evaluate the therapeutic potential of MMP9 inhibition in patients.

  15. MMP-9和 TGFβ1在宫颈鳞癌中的表达和意义%The expression and significance of matrixmetalloproteinase-9 (MMP-9) andtransforming growth factorβ1 (TGF-βl) incervical cancer Abstract

    Institute of Scientific and Technical Information of China (English)

    沈浩明; 杨友义; 吴白平; 向延娥

    2015-01-01

    目的:分别检测宫颈分泌物、血液和宫颈病变组织中的基质金属蛋白酶-9(MMP-9)和转化生长因子β1(TGF-βl)的表达情况,探讨其在宫颈病变形成及演进过程中的意义。方法:应用 ELISA 法检测66例病人(其中慢性宫颈炎组织10例、CINcervicalintraepithelialneoplasia 宫颈上皮内瘤变24例,宫颈鳞癌32例)的宫颈分泌物和血清中的 TGF-βl 和 MMP-9的表达水平。应用免疫组织化学 SP 法检测相对应病人石蜡包埋的不同病变宫颈组织中TGF-βl 和 MMP-9的表达。结果:1.在血清和宫颈分泌物中 TGF-βl 和 MMP-9的浓度与宫颈癌密切相关:慢性宫颈炎组、宫颈上皮内瘤变(CIN)组和宫颈鳞癌(CxCa)组的样本中 TGF-βl 和 MMP-9的浓度逐级升高,提示随着宫颈癌恶性程度的增加,TGF-βl 和 MMP-9的表达明显增强。血清和宫颈分泌物中 MMP-9和 TGF-β1与其切片免疫组化结果相吻合。随着 MMP-9在宫颈分泌物和血清中表达的增强,TGF-β1的表达也明显增高,两者呈正相关。2.TGF-βl 和 MMP-9表达与宫颈癌的病理和临床分类的关系:在宫颈癌组织中有淋巴结转移的 MMP-9和 TGFβ1的表达阳性率显著高于无淋巴结转移的。在宫颈癌≥Ⅱ b 期的 MMP-9和 TGF-βl 的表达阳性率显著高于≤Ⅱ a 期的。MMP-9和 TGF-βl 与宫颈癌肿瘤的大小和组织病理学分级无显著性差异。结论:TGF-βl 和 MMP-9在宫颈病变、宫颈分泌物和血清的中表达与病变良恶性有关,TGF-βl 和 MMP-9高表达是宫颈恶性肿瘤的表现之一,并且 TGF-βl和 MMP-9在宫颈分泌物或血清中的表达具有显著相关性。%Objesctive The expression of matrix metalloproteinase-9 (MMP-9) and transforming growth factorβ1 (TGF-βl) were detectedin cervical secretions, blood andcervical lesions, in order to investigate the significance in thedevelopment ofcervical lesions. Methods 66 cases (including 10

  16. ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.

    Science.gov (United States)

    Lin, Li-Fang; Chuang, Chih-Hung; Li, Chien-Feng; Liao, Ching-Chun; Cheng, Chun-Pei; Cheng, Tian-Lu; Shen, Meng-Ru; Tseng, Joseph T; Chang, Wen-Chang; Lee, Wen-Hwa; Wang, Ju-Ming

    2010-01-01

    The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of the metalloproteinase MMP9, which is known to be an important driver of invasion and metastasis, was found to be inversely correlated with ZBRK1 in tumor tissues and a target for repression in tumor cells. Our findings suggest that ZBRK1 acts to inhibit metastasis of cervical carcinoma, perhaps by modulating MMP9 expression.

  17. Angiogenesis in vestibular schwannomas: expression of extracellular matrix factors MMP-2, MMP-9, and TIMP-1

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Werther, Kim; Nalla, Amarnadh;

    2010-01-01

    Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are potent mediators of tumor angiogenesis. It has been demonstrated that vestibular schwannoma VEGF expression correlates with tumor growth pattern, whereas knowledge on the expression of MMPs is lacking. This study t...... targets the angiogenic process by investigation of tumor expression of MMP-2, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1. A possible correlation with gender, patient age, symptom duration, tumor size, and the absolute and relative growth rate is explored....

  18. MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation

    Directory of Open Access Journals (Sweden)

    Donaldson GC

    2005-12-01

    Full Text Available Abstract Background Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood. This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation. Methods Nineteen COPD patients ((median, [IQR] age 69 [63 to 74], forced expiratory volume in one second (FEV1 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2] provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand. Results MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P P = 0.16. MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P P P Conclusion During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline.

  19. Changes of IL-8 and IL-8 mRNA after blast-fragment combined injury in dogs

    Institute of Scientific and Technical Information of China (English)

    YAN Jia-chuan; YANG Zhi-huan; DONG Hong; FENG Gong; LI Xiao-yan; YIN You-guo

    2001-01-01

    To explore the characteristics and the mechanism of the blast-fragment combined injury.Methods: After the dogs were inflicted with high-velocity fragment injury on their left hindlimbs after blast injury,the IL-8 in the plasma and lung tissue supernatants were assayed with ELISA, and the expression of IL-8 mRNA in lung tissue was detected with in situ hybridization. Results: The levels of IL-8 in plasma and lung tissues were increased after blast, high velocity fragment and blast-fragment combined injuries respectively. IL-8 mRNA were upregulated after injuries. Conclusion: IL-8 may play a role in the occurrence and development of lung injury.Detecting the plasma levels of IL-8 may be quite helpful to estimate the injury.

  20. A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells.

    Science.gov (United States)

    Martinez-Nunez, Rocio T; Bondanese, Victor P; Louafi, Fethi; Francisco-Garcia, Ana S; Rupani, Hitasha; Bedke, Nicole; Holgate, Stephen; Howarth, Peter H; Davies, Donna E; Sanchez-Elsner, Tilman

    2014-01-01

    MicroRNAs are short non-coding single stranded RNAs that regulate gene expression. While much is known about the effects of individual microRNAs, there is now growing evidence that they can work in co-operative networks. MicroRNAs are known to be dysregulated in many diseases and affect pathways involved in the pathology. We investigated dysregulation of microRNA networks using asthma as the disease model. Asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness and airway remodelling. The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-β, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons. After performing microRNA arrays, we found that microRNAs -18a, -27a, -128 and -155 are down-regulated in asthmatic bronchial epithelial cells, compared to cells from healthy donors. Interestingly, these microRNAs are predicted in silico to target several components of the TGF-β, IL-6, IL-8 and interferons pathways. Manipulation of the levels of individual microRNAs in bronchial epithelial cells did not have an effect on any of these pathways. Importantly, knock-down of the network of microRNAs miR-18a, -27a, -128 and -155 led to a significant increase of IL-8 and IL-6 expression. Interestingly, despite strong in silico predictions, down-regulation of the pool of microRNAs did not have an effect on the TGF-β and Interferon pathways. In conclusion, using both bioinformatics and experimental tools we found a highly relevant potential role for microRNA dysregulation in the control of IL-6 and IL-8 expression in asthma. Our results suggest that microRNAs may have different roles depending on the presence of other microRNAs. Thus, interpretation of in silico analysis of microRNA function should be confirmed experimentally in the relevant cellular context taking into account interactions with other micro

  1. A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Rocio T Martinez-Nunez

    Full Text Available MicroRNAs are short non-coding single stranded RNAs that regulate gene expression. While much is known about the effects of individual microRNAs, there is now growing evidence that they can work in co-operative networks. MicroRNAs are known to be dysregulated in many diseases and affect pathways involved in the pathology. We investigated dysregulation of microRNA networks using asthma as the disease model. Asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness and airway remodelling. The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-β, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons. After performing microRNA arrays, we found that microRNAs -18a, -27a, -128 and -155 are down-regulated in asthmatic bronchial epithelial cells, compared to cells from healthy donors. Interestingly, these microRNAs are predicted in silico to target several components of the TGF-β, IL-6, IL-8 and interferons pathways. Manipulation of the levels of individual microRNAs in bronchial epithelial cells did not have an effect on any of these pathways. Importantly, knock-down of the network of microRNAs miR-18a, -27a, -128 and -155 led to a significant increase of IL-8 and IL-6 expression. Interestingly, despite strong in silico predictions, down-regulation of the pool of microRNAs did not have an effect on the TGF-β and Interferon pathways. In conclusion, using both bioinformatics and experimental tools we found a highly relevant potential role for microRNA dysregulation in the control of IL-6 and IL-8 expression in asthma. Our results suggest that microRNAs may have different roles depending on the presence of other microRNAs. Thus, interpretation of in silico analysis of microRNA function should be confirmed experimentally in the relevant cellular context taking into account interactions

  2. Matrix metalloproteinase 9 (MMP-9) in osteosarcoma: review and meta-analysis.

    Science.gov (United States)

    Wang, Jing; Shi, Qiong; Yuan, Tai-Xian; Song, Qi-Lin; Zhang, Yan; Wei, Qiang; Zhou, Lan; Luo, Jinyong; Zuo, Guowei; Tang, Min; He, Tong-Chuan; Weng, Yaguang

    2014-06-10

    The aim of this study is to determine the value of matrix metalloproteinase 9 (MMP-9) in diagnosis of osteosarcoma (OS). A systematic review and meta-analysis was conducted using MEDLINE, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, China Biomedical literature Database (CBM) and China National Knowledge Internet (CNKI) from inception through Aug 29, 2013. Articles written in English or Chinese that investigated the accuracy of MMP-9 for the diagnosis of OS were included. Pooled sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) were determined. I(2) was used to test heterogeneity and source of heterogeneity was investigated by meta-regression (tested with Meta-DiSc and STATA 12.0 statistical softwares). A total of 3729 articles were retrieved, of which 18 were included, accounting for 892 patients. Overall, the pooled sensitivity, specificity and AUC were 0.78 (95% CI 0.730-0.83), 0.90 (95% CI 0.79-0.95), and 0.87 (95% CI 0.83-0.89), respectively. The studies had substantial heterogeneity (I(2)=84%, 95% CI 65-100) (96%, 95% CI 94-99). Assay kit subgroup was the main source of the heterogeneity. Although MMP-9 was identified as a potential biomarker for OS, more studies were clearly needed to establish its diagnostic value.

  3. Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression.

    Science.gov (United States)

    He, Bin; Peng, Hua; Zhao, Ying; Zhou, Hui; Zhao, Zhongxin

    2011-12-01

    Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.

  4. MicroRNA-3713 regulates bladder cell invasion via MMP9.

    Science.gov (United States)

    Wu, Wen-Bo; Wang, Wei; Du, Yi-Heng; Li, Hao; Xia, Shu-Jie; Liu, Hai-Tao

    2016-08-31

    Transitional cell carcinoma (TCC) is the most common type of bladder cancer but its carcinogenesis remains not completely elucidated. Dysregulation of microRNAs (miRNAs) is well known to be involved in the development of various cancers, including TCC, whereas a role of miR-3713 in the pathogenesis of TCC has not been appreciated. Here, we reported that significantly higher levels of matrix metallopeptidase 9 (MMP9), and significantly lower levels of miR-3713 were detected in TCC tissue, compared to the adjacent non-tumor tissue, and were inversely correlated. Moreover, the low miR-3713 levels in TCC specimens were associated with poor survival of the patients. In vitro, overexpression of miR-3713 significantly decreased cell invasion, and depletion of miR-3713 increased cell invasion in TCC cells. The effects of miR-3713 on TCC cell growth appeared to result from its modification of MMP9 levels, in which miR-3713 was found to bind to the 3'-UTR of MMP9 mRNA to inhibit its protein translation in TCC cells. This study highlights miR-3713 as a previously unrecognized factor that controls TCC invasiveness, which may be important for developing innovative therapeutic targets for TCC treatment.

  5. Eugenol with antioxidant activity inhibits MMP-9 related to metastasis in human fibrosarcoma cells.

    Science.gov (United States)

    Nam, Hyang; Kim, Moon-Moo

    2013-05-01

    The oxidative damage of lipid, protein and DNA is known to be involved in chronic inflammation as well as metastasis. It has been highlighted for searching natural compounds without toxicity to prevent development of these diseases. Thus, it was investigated whether eugenol can inhibit matrix metalloproteinase (MMP) expression and activity as well as antioxidant effect. Eugenol was contained as a major ingredient in herbs such as clove and Magnoliae Flos. The direct scavenging effects of eugenol on DPPH radical, hydrogen peroxide, reducing power, lipid peroxidation and genomic DNA damage related to oxidative stress were evaluated in cell free system. It was observed that eugenol specifically exhibited higher inhibitory effect on hydrogen peroxide than other reactive oxygen species, and also blocked DNA oxidation and lipid peroxidation induced by hydroxyl radical. In addition, the inhibitory effects of eugenol on the activity and expression of MMP-9 activity related to metastasis were determined using gelatin zymography and western-blot. The data showed that it inhibited MMP-9 activities in PMA-stimulated HT1080 cells. Furthermore, it was found that eugenol exerts inhibitory effects on MMP-9 via inactivation of ERK. Therefore, these results suggest that eugenol could be available as an excellent agent for prevention of metastasis related to oxidative stress.

  6. Phosphorylation of FOXP3 by LCK downregulates MMP9 expression and represses cell invasion.

    Directory of Open Access Journals (Sweden)

    Kumiko Nakahira

    Full Text Available Forkhead Box P3 (FOXP3 is a member of the forkhead/winged helix family of the transcription factors and plays an important role not only as a master gene in T-regulatory cells, but also as a tumor suppressor. In this study, we identified lymphocyte-specific protein tyrosine kinase (LCK, which correlates with cancer malignancy, as a binding partner of FOXP3. FOXP3 downregulated LCK-induced MMP9, SKP2, and VEGF-A expression. We observed that LCK phosphorylated Tyr-342 of FOXP3 by immunoprecipitation and in vitro kinase assay, and the replacement of Tyr-342 with phenylalanine (Y342F abolished the ability to suppress MMP9 expression. Although FOXP3 decreased the invasive ability induced by LCK in MCF-7 cells, Y342F mutation in FOXP3 diminished this suppressive effect. Thus we demonstrate for the first time that LCK upregulates FOXP3 by tyrosine phosphorylation, resulting in decreased MMP9, SKP2, and VEGF-A expression, and suppressed cellular invasion. We consider that further clarification of transcriptional mechanism of FOXP3 may facilitate the development of novel therapeutic approaches to suppress cancer malignancy.

  7. The Expression and Significance of HGF and MMP-9 in Lichen Planus%HGF和MMP-9在扁平苔藓皮损中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    何肖; 白莉

    2011-01-01

    目的 检测扁平苔藓皮损中肝细胞生长因子(HGF)和基质金属蛋白酶-9(MMP-9)的表达情况,探讨其在扁平苔藓发病中的意义.方法 应用免疫组化法和RT-PCR法测定30例扁平苔藓及30例正常皮肤组织中HGF和MMP-9的表达水平.结果 扁平苔藓组中HGF和MMP-9的表达率均高于正常对照组(P<0.01),且二者在扁平苔藓皮损中的表达呈正相关(r1=0.391,P1=0.032;r2=0.375,P2=0.041).结论 HGF和MMP-9的高表达可能参与了扁平苔藓的发病.%Objective To explore the expression of hepatocyte growth factor( HGF ) and metalloproteinase - 9( MMP - 9 ) in lichen planus,and investigate the function in pathogenesis of lichen planus.Methods The expression of HGF and MMP - 9 was assayed by RT - PCR and immunohistochemistry in 30 LP lesions and 30 normal skins.Results The expression of HGF and MMP - 9 in LP lesions was stronger than that in normal skins( P <0.01 ),and HGF was positively related to the expression of MMP -9 in LP lesions ( r1 =0.391 ,P1 = 0.032; r2 = 0.375, P2 = 0.041 ).Conclusion The increased expression of HGF and MMP -9 may contribute to the formation and progression of lichen planus.

  8. IL-6 predicts organ dysfunction and mortality in patients with multiple injuries

    Science.gov (United States)

    Frink, Michael; van Griensven, Martijn; Kobbe, Philipp; Brin, Thomas; Zeckey, Christian; Vaske, Bernhard; Krettek, Christian; Hildebrand, Frank

    2009-01-01

    Background Although therapeutic concepts of patients with major trauma have improved during recent years, organ dysfunction still remains a frequent complication during clinical course in intensive care units. It has previously been shown that cytokines are upregulated under stress conditions such as trauma or sepsis. However, it is still debatable if cytokines are adequate parameters to describe the current state of trauma patients. To elucidate the relevance of cytokines, we investigated if cytokines predict development of multiple organ dysfunction syndrome (MODS) or outcome. Methods A total of 143 patients with an injury severity score ≥ 16, between 16 and 65 years, admitted to the Hannover Medical School Level 1 Trauma Center between January 1997 and December 2001 were prospectively included in this study. Marshall Score for MODS was calculated for at least 14 days and plasma levels of TNF-α, IL-1β, IL-6, IL-8 and IL-10 were measured. To determine the association between cytokine levels and development of MODS the Spearman rank correlation coefficient was calculated and logistic regression and analysis were performed. Results and Discussion Patients with MODS had increased plasma levels of IL-6, IL-8 and IL-10. IL-6 predicted development of MODS with an overall accuracy of 84.7% (specificity: 98.3%, sensitivity: 16.7%). The threshold value for development of MODS was 761.7 pg/ml and 2176.0 pg/ml for mortality during the in patient time. Conclusion We conclude that plasma IL-6 levels predict mortality and that they are a useful tool to identify patients who are at risk for development of MODS. PMID:19781105

  9. Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interference

    Institute of Scientific and Technical Information of China (English)

    Huibi CAO; Anan WANG; Bernard MARTIN; David R.KOEHLER; Pamela L.ZEITLIN; A.Keith TANAWELL; Jim HU

    2005-01-01

    Interleukin (IL)-8 is a potent neutrophil chemotactic factor and a crucial mediator in neutrophil-dependent inflammation.Various cell types produce IL-8, either in response to external stimuli such as cytokines or bacterial infection, or after malignant transformation. Anti-IL-8 strategies have been considered for anti-inflammatory therapy. In this paper we demonstrate that the RNA interference technique can be used to efficiently down-regulate IL-8 protein expression in airway epithelial cells. We used a helper-dependent adenoviral vector to express a small hairpin (sh)RNA targeting human IL-8 in cultured airway epithelial cells (IB3-1, Cftr-/-; C38, Cftr-corrected) stimulated with TNF-α, IL-1 β or heat-inactivated Burkholderia cenocepacia. Stimulated IL-8 expression in IB3-1 and C38 cells was significantly reduced by shRNA expression. The shRNA targeting IL-8 had no effect on the activation of NF-κB, or on the protein levels of Iκ B or IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore may offer potential for the treatment of inflammatory diseases.

  10. Expression and significance of Twist、MMP-2 and MMP -9 in breast cancer%乳腺癌组织中Twist、MMP-2和MMP-9的表达及意义

    Institute of Scientific and Technical Information of China (English)

    艾斯卡尔·阿尤甫; 古力米热·布然江; 欧江华

    2012-01-01

    Objective To investigate the expression and significance of Twist, MMP - 2 and MMP -9 in Breast Cancer . Methods Immunohislochemical SP method was used to examine the levels of Twist protein, MMP - 2, MMP - 9 in Breast Cancer (70 cases) and paracancerous normal tissues (35 cases) . Results The positive rates of Twist, MMP - 2 and MMP - 9 were higher in Breast Cancer than thouse in the tumor - adjacent normal tissues (72. 9% ,55.1% ,67. 1% vs 16.7% ,28. 6% ,37. 1% ,P < 0.05). Their expressions were positively correlated with the tumor differentiation, the depth of invasion lymph node metastasis (P < 0. 05). Expression of MMP - 2 was positively correlated with that of MMP - 9 (P <0.05). Conclusions The aberrant expressions of Twist,MMP -2 and MMP -9 may play a cooperative role in the infiltration and metastasis of Breast Cancer, which may be taken as a reference index for e-valuating the metastasis and prognosis.%目的 探讨乳腺癌组织中Twist、MMP -2和MMP -9表达的相关性.方法 采用SP免疫组化法检测70例乳腺癌组织(35例癌旁组织作为对照)中Twist、MMP -2和MMP -9的表达情况.结果 乳腺癌组织中Twist、MMP -2和MMP-9的阳性表达率分别为72.9%、55.7%和67.1%,均显著高于癌旁正常组织中的16.7%、28.6%和37.10%(P<0.05).Twist、MMP -2和MMP-9与肿瘤的分化程度、浸润深度和淋巴结转移有关(P<0.05).Twist的表达与MMP -2和MMP -9的表达呈正相关.MMP -2的表达与MMP -9的表达呈正相关.结论 Twist、MMP -2和MMP -9在肿瘤细胞发生浸润转移中有协同作用,可作为评估乳腺癌转移及预后的参考指标.

  11. Expression of MMP-2 and MMP-9 in Cutaneous Malignant Melanoma and its Significance%MMP-2和MMP-9在皮肤恶性黑色素瘤中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    宋宁静; 王晓楠; 陈佳; 吴正升; 章楚光

    2011-01-01

    目的 研究明胶酶(MMP-2和MMP-9)在皮肤黑色素瘤和色素痣组织中的蛋白表达及其意义.方法 应用免疫组织化学S-P法检测90例皮肤黑色素瘤和43例皮肤色素痣组织MMP-2和MMP-9的表达情况,分析它们与患者临床病理特征的关系.结果 皮肤黑色素瘤组织MMP-2和MMP-9蛋白表达阳性率分别为50.0%和55.6%,显著高于色素痣的阳性率27.9%和25.6%(P<0.05和P<0.01);黑色素瘤MMP-2和MMP-9蛋白表达均与肿瘤的浸润深度和淋巴结转移呈正相关(均P<0.05).结论 皮肤恶性黑色素瘤MMP-2和MMP-9表达状况与肿瘤侵袭、转移呈密切相关,提示MMP-2和MMP-9可能在黑色素瘤发生发展过程中发挥了重要作用.%Objective To investigate the expression of MMP-2 and MMP-9 protein in cutaneous melanoma and its significance.Methods The expression of MMP-2 and MMP-9 protein was detected in 90 cases of melanoma and 47 cases of nevus by using streptavidin-peroxidase technique. Their correlations with the clinicopathological features were analyzed. Results The positive rates of MMP-2 and MMP-9 protein in the melanomas were 50.0% and 55.6% ,which were significantly higher than those in the nevus. Both t MMP-2 and MMP-9 protein was positively correlated to the depth of tumour invasion and the lymph node metastasis of melanoma( All P < 0.05). Conclusion The expression of MMP-2 and MMP-9 is closely correlated to the tumout invasion and metastasis. The result suggests that MMP-2 and MMP-9 might play an important role in the cutaneous melanoma development and progression.

  12. The expression of HMGB1/MMP9 and its clinical significance in Non-Small Cell Lung Cancer%HMGB1/MMP9在非小细胞肺癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    苏卫民; 毕明宏

    2012-01-01

    Objective To investigate the significance of high mobility group proteinl ( HMCB1 ) and matrix metalloproteinase-9 ( MMP9 ) in the transfering process of Non-Small Cell Lung Caneer through studying their expression levels in human Non-Small Cell Lung Cancer- and the paraoanoerous tissues in order to reveal their roles in the process of the tumors invasion and metastasis. Methods The expression of HMCBI/MMP9 in 69 specimens of NSCLC and 20 specimens of paraoancerous tissues were determined with the immunohisto-chemical S-P method. The related data of the expression of HMCB1/MMP9 and their clinical and pathological features were statistically analyzed. Results 1. In the NSCLC group ,HMCB1/MMP9 expression positive rate were higher than that in the edge of carcinoma ( con-trol group ). 2. The expression of HMCB1 had a positive correlation with MMP9 in NSCLC invasion and metastasis. Conclusion By testing HMCBI /MMP9 in NSCLC and adjacent tissue, we found that both may play a synergistic role in the process of NSCLC invasion and metastasis. So co-examining HMCBI and MMP9 may be providing basis for diagnosis and prognosis of NSCLC.%目的 探讨HMGB1和MMP9在NSCLC转移过程中的作用.方法 应用免疫组化S-P法检测69例非小细胞肺癌(NSCLC)和20例癌旁组织中HMGB1及MMP9的表达情况,结合临床、病理参数进行统计学分析.结果 1、HMGB1/MMP9二者在NSCLC组织的阳性表达率高于癌旁组织;两组之间差异有统计学意义(P<0.05);2、HMGB1和MMP9在非小细胞肺癌及癌旁组织中表达呈正相关.结论 HMGB1/MMP9联合检测,在NSCLC浸润转移过程中可能起协同作用,可为NSCLC诊断及判断预后提供依据.

  13. 慢性心力衰竭患者血清MMP-9和hs-CRP的表达%Expressions of serum MMP-9 and hs-CRP in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    郑利平

    2012-01-01

    Objective To investigate the changes of serum matrix metalloproteinase-9(MMP-9) and high sensitive Creactive protein(hs-CRP) expressions in the patients with chronic heart failure (CHF). Methods A total of 120 CHF patients was divided into 4 groups according to NYHA cardiac function classes of Ⅰ ,Ⅱ , Ⅲ and Ⅳ. The expression levels of MMP-9 and hs-CRP were detected with ELISA and Latex enhanced immunoturbidimetric assay, respectively, and compared among 4 NYHA cardiac cardiac function classes. Results The expression levels of MMP-9 and hs-CRP were increased as the cardiac function became worsen(P<0. 05). The expression of serum MMP-9 was positively correlated to that of hs-CRP(r=0. 716,P<0. 01). Conclusion When the cardiac dysfunction becomes severe in CHF patients,the expressions of MMP-9 and hs-CRP are remarkably increased, which may participate in the myocardial remodeling of CHF.%目的 探讨基质金属蛋白酶9(MMP-9)和高敏C反应蛋白(hs-CRP)在慢性心力衰竭(CHF)患者的表达.方法 CHF患者120例,ELISA检测血清MMP-9表达,乳胶增强免疫比浊法检测血清hs-CRP水平.比较不同NYHA心功能状态患者MMP-9和hs-CRP的表达差异.结果 随着心功能的恶化,MMP-9和hs-CRP的表达水平显著升高(P<0.05).CHF患者外周血MMP-9和hs-CRP的表达水平呈正相关(r=0.716,P<0.01).结论 CHF患者外周血MMP-9和hs-CRP表达水平随着心功能的减低而升高,MMP-9和hs-CRP表达可能参与了CHF心肌重构的病理过程.

  14. Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2.

    LENUS (Irish Health Repository)

    Stevens, Niall T

    2009-03-01

    Staphylococcus epidermidis is an opportunistic biofilm-forming pathogen associated with neurosurgical device-related meningitis. Expression of the polysaccharide intercellular adhesin (PIA) on its surface promotes S. epidermidis biofilm formation. Here we investigated the pro-inflammatory properties of PIA against primary and transformed human astrocytes. PIA induced IL-8 expression in a dose- and\\/or time-dependent manner from U373 MG cells and primary normal human astrocytes. This effect was inhibited by depletion of N-acetyl-beta-d-glucosamine polymer from the PIA preparation with Lycopersicon esculentum lectin or sodium meta-periodate. Expression of dominant-negative versions of the TLR2 and TLR4 adaptor proteins MyD88 and Mal in U373 MG cells inhibited PIA-induced IL-8 production. Blocking IL-1 had no effect. PIA failed to induce IL-8 production from HEK293 cells stably expressing TLR4. However, in U373 MG cells which express TLR2, neutralization of TLR2 impaired PIA-induced IL-8 production. In addition to IL-8, PIA also induced expression of other cytokines from U373 MG cells including IL-6 and MCP-1. These data implicate PIA as an important immunogenic component of the S. epidermidis biofilm that can regulate pro-inflammatory cytokine production from human astrocytes, in part, via TLR2.

  15. CCR5 Blockade Suppresses Melanoma Development Through Inhibition of IL-6-Stat3 Pathway via Upregulation of SOCS3.

    Science.gov (United States)

    Tang, Qiu; Jiang, Jun; Liu, Jian

    2015-12-01

    In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, we found that chemokine receptor 5 (CCR5) neutralization resulted in reduced melanoma tumor size, decreased percentage of CD11b+ Gr-1(+) myeloid-derived suppressor cells (MDSCs), and increased proportion of cluster of differentiation (CD)3+ T cells in tumor tissues. Suppressive activity of MDSCs on CD4+ T cells and CD8+ T cell proliferation is significantly inhibited by anti-CCR5 antibody. CCR5 blockade also suppresses interleukin (IL)-6 induction, which in turn deactivates signal transducer and activator of transcription 3 (Stat3) in tumors. Furthermore, the suppressed B16 tumor growth induced by CCR5 blockade is abolished with additional administration of recombinant IL-6. CCR5 blockade also induces suppressor of cytokine signaling 3 (SOCS3) upregulations, and anti-CCR5 antibody fails to suppress expression of phospho-Stat3 (p-Stat3), matrix metallopeptidase 9 (MMP9), and IL-6 in cells transfected with SOCS3 short-interfering RNA (SiRNA). All these data suggest that CCR5 blockade suppresses melanoma development through inhibition of IL-6-Stat3 pathway via upregulation of SOCS3.

  16. Factors Associated With Plasma IL-6 Levels During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2015-01-01

    BACKGROUND: Elevated interleukin 6 (IL-6) levels have been linked to cardiovascular disease, cancer and death. Persons with human immunodeficiency virus (HIV) infection receiving treatment have higher IL-6 levels, but few data are available on factors associated with circulating IL-6. METHODS......: Participants in 3 trials with IL-6 measured at baseline were included (N = 9864). Factors associated with IL-6 were identified by linear regression. Demographic and HIV variables (nadir/entry CD4(+) cell count, HIV RNA level, antiretroviral therapy regimen) were investigated in all 3 trials. In the SMART...... education, whereas black race was associated with lower IL-6. Higher HIV RNA levels were associated with higher IL-6 levels, and higher nadir CD4(+) cell counts with lower IL-6 levels. Compared with efavirenz, protease inhibitors were associated with higher and nevirapine with lower IL-6 levels. Smoking...

  17. Role of MMP-3 and MMP-9 and their haplotypes in risk of bladder cancer in North Indian cohort.

    Science.gov (United States)

    Srivastava, Priyanka; Mandhani, Anil; Kapoor, Rakesh; Mittal, Rama D

    2010-11-01

    Matrix metalloproteinases (MMPs) play critical roles in cancer development and progression. Nonsynonymous single nucleotide polymorphisms (SNPs) in functional domain of MMP-3 and MMP-9 contribute appreciably to cancer predisposition and aggression. To test this proposition we examined whether six SNPs of the MMP-3 and MMP-9 genes are associated with risk of bladder cancer (BC) in a North Indian population. Six SNPs of MMP-3 and MMP-9 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study including 200 BC patients and 200 age/gender/ethnicity-matched controls. Increased risk for BC susceptibility was observed in MMP-3 (1171) 5A/5A [P = 0.022; odds ratio (OR), 3.46; 95% confidence interval (CI), 1.20-9.98], MMP-9 (Q279R) QQ (P = 0.048; OR, 1.92; 95%CI, 1.01-3.66), MMP-9 (P574R) PR (P BCG)-treated non-muscle-invasive BC (NMIBC) patients (log-rank P = 0.025). Our data suggested that MMP-3-1171 5A/5A and MMP-9 (Q279R) QQ, MMP-9 (P574R) PR, PR + RR, and R allele are associated with high risk of BC.

  18. Serum haptoglobin-matrix metalloproteinase 9 (Hp-MMP 9) complex as a biomarker of systemic inflammation in cattle.

    Science.gov (United States)

    Bannikov, G A; Hinds, C A; Rajala-Schultz, P J; Premanandan, C; Rings, D M; Lakritz, J

    2011-01-01

    A reliable and specific test that discriminates between acute neutrophil activation and chronic inflammatory disease may be useful in clinical decision making in a variety of conditions encountered in veterinary medical practice. An ELISA specific for neutrophil-derived haptoglobin-matrix metalloproteinase 9 (Hp-MMP 9) complexes was used to determine serum concentrations of Hp-MMP 9 and was compared to ELISA assays for Haptoglobin (Hp) and matrix metalloproteinase 9 (MMP 9) in 15 animals with acute sepsis, 10 animals with chronic inflammatory or metabolic disease and 10 healthy cows. Animal disease classifications were completed prior to the determination of serum concentrations of the 3 proteins. Duration of illness, disease process and lesions observed at necropsy were used to place animals into a specific classification. The serum MMP 9 concentrations in healthy cows differed significantly from those measured in sera of acutely septic and chronically ill animals. Serum haptoglobin concentrations in healthy cows were negligible when compared to animals with acute septic or chronic diseases. There was substantial overlap in MMP 9 and Hp concentrations between acute and chronic disease animals. In contrast, serum concentrations of Hp-MMP 9 complexes found almost exclusively in sera from acutely septic animals but not in chronically ill and normal cattle. The Hp-MMP 9 ELISA may be the serological test of choice in the determination of systemic inflammation associated with bacterial sepsis.

  19. Recognition of Streptococcus pneumoniae and muramyl dipeptide by NOD2 results in potent induction of MMP-9, which can be controlled by lipopolysaccharide stimulation.

    Science.gov (United States)

    Vissers, Marloes; Hartman, Yvonne; Groh, Laszlo; de Jong, Dirk J; de Jonge, Marien I; Ferwerda, Gerben

    2014-12-01

    Matrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis during Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved in Streptococcus pneumoniae pathogenesis.

  20. MMP-9 Levels and IMT of Carotid Arteries are Elevated in Obese Children and Adolescents Compared to Non-Obese

    Directory of Open Access Journals (Sweden)

    Claudio Andrade

    Full Text Available Abstract Background: Childhood obesity is associated with increased risk of atherosclerosis and cardiovascular disease in adulthood. Increased intima-media thickness (IMT of the carotid artery is linked to the initiation and progression of the chronic inflammatory processes implicated in cardiovascular disease. Matrix metalloproteinase-9 (MMP-9 plays an important role in the degradation of the extracellular matrix and, consequently, in the development, morphogenesis, repair and remodeling of connective tissues. Objectives: (i to determine and compare the concentrations of MMP-9, tissue inhibitor of metalloproteinase -1 (TIMP-1, and MMP-9/TIMP-1 ratio in obese and non-obese children and adolescents; (ii to investigate the association of these markers with common and internal IMT of carotid arteries. Methods: Cross-sectional study involving 32 obese and 32 non-obese (control individuals between 8 - 18 years of age. Results: Significantly (p < 0.05 higher values of MMP-9 concentration, as well as a higher MMP-9/TIMP-1 ratio were detected in the obese group compared to control counterparts. Common and internal carotid IMT values were significantly higher (p < 0.001 in the obese group compared to the control group. Positive correlations were observed between the common carotid IMT values and MMP-9 concentrations as well as MMP-9/TIMP-1 ratio. Conclusions: Our data demonstrate that obese children and adolescents present higher mean IMT values, plasma MMP-9 and MMP-9/TIMP-1 ratio compared to the non-obese. Thus, these findings indicate that this group presents a risk profile for early atherosclerosis.

  1. MMP-1 and MMP-9 regulate epidermal growth factor-dependent collagen loss in human carotid plaque smooth muscle cells.

    Science.gov (United States)

    Rao, Velidi H; Kansal, Vikash; Stoupa, Samantha; Agrawal, Devendra K

    2014-02-01

    Mechanisms underlying the rupture of atherosclerotic plaque, a crucial factor in the development of myocardial infarction and stroke, are not well defined. Here, we examined the role of epidermal growth factor (EGF)-mediated matrix metalloproteinases (MMP) on the stability of interstitial collagens in vascular smooth muscle cells (VSMCs) isolated from carotid endarterectomy tissues of symptomatic and asymptomatic patients with carotid stenosis. VSMCs isolated from the carotid plaques of both asymptomatic and symptomatic patients were treated with EGF. The MMP-9 activity was quantified by gelatin zymography and the analysis of mRNA transcripts and protein for MMP-9, MMP-1, EGFR and collagen types I, Col I(α1) and collagen type III, Col III(α1) were analyzed by qPCR and immunofluorescence, respectively. The effect of EGF treatment to increase MMP-9 activity and mRNA transcripts for MMP-9, MMP-1, and EGFR and to decrease mRNA transcripts for Col I(α1) and Col III(α1) was threefold to fourfold greater in VSMCs isolated from the carotid plaques of symptomatic than asymptomatic patients. Inhibitors of EGFR (AG1478) and a small molecule inhibitor of MMP-9 decreased the MMP9 expression and upregulated Col I(α1) and Col III(α1) in EGF-treated VSMCs of both groups. Additionally, the magnitude in decreased MMP-9 mRNA and increased Col I(α1) and Col III(α1) due to knockdown of MMP-9 gene with siRNA in EGF-treated VSMCs was significantly greater in the symptomatic group than the asymptomatic group. Thus, a selective blockade of both EGFR and MMP-9 may be a novel strategy and a promising target for stabilizing vulnerable plaques in patients with carotid stenosis.

  2. The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone

    Science.gov (United States)

    Schmidt, E; Reimer, S; Kruse, N; Bröcker, E-B; Zillikens, D

    2001-01-01

    Bullous pemphigoid (BP) is a subepidermal blistering disease associated with autoantibodies to the hemidesmosomal 180 kD BP autoantigen (BP180). However, the binding of autoantibodies to BP180 alone is not sufficient for blister formation in this disease and the infiltration of neutrophils into the skin is required. Dapsone and nicotinamide inhibit neutrophil chemotaxis and are used effectively in treating BP. IL-8 is a known chemoattractant for neutrophils and has been implicated in the inflammatory process of both human and experimental murine BP. We have recently shown that antibodies to BP180 mediate a dose and time-dependent release of IL-6 and IL-8 from cultured normal human epidermal keratinocytes (NHEK). In the present study, we addressed the question whether dapsone or nicotinamide influence this cytokine release. We demonstrate that dapsone, but not nicotinamide, in its pharmacological range, inhibits the IL-8, but not the IL-6 release from NHEK, induced by anti-BP180 IgG, in a dose-dependent fashion as detected by ELISA. IL-8 mRNA levels, as determined by RT-PCR, were the same in cells treated with BP IgG alone compared to cells treated with BP IgG plus dapsone. This observation suggests that dapsone inhibits the BP IgG-induced IL-8 release from cultured NHEK by mechanisms at the post-transcriptional level. Our findings contribute to the understanding how dapsone leads to a reduced influx of neutrophils into BP lesions and, finally, to the cessation of blister formation in this disease. PMID:11359455

  3. An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice

    Science.gov (United States)

    Tieu, Brian C.; Lee, Chang; Sun, Hong; LeJeune, Wanda; Recinos, Adrian; Ju, Xiaoxi; Spratt, Heidi; Guo, Dong-Chuan; Milewicz, Dianna; Tilton, Ronald G.; Brasier, Allan R.

    2009-01-01

    Vascular inflammation contributes to cardiovascular diseases such as aortic aneurysm and dissection. However, the precise inflammatory pathways involved have not been clearly defined. We have shown here that subcutaneous infusion of Ang II, a vasopressor known to promote vascular inflammation, into older C57BL/6J mice induced aortic production of the proinflammatory cytokine IL-6 and the monocyte chemoattractant MCP-1. Production of these factors occurred predominantly in the tunica adventitia, along with macrophage recruitment, adventitial expansion, and development of thoracic and suprarenal aortic dissections. In contrast, a reduced incidence of dissections was observed after Ang II infusion into mice lacking either IL-6 or the MCP-1 receptor CCR2. Further analysis revealed that Ang II induced CCR2+CD14hiCD11bhiF4/80– macrophage accumulation selectively in aortic dissections and not in aortas from Il6–/– mice. Adoptive transfer of Ccr2+/+ monocytes into Ccr2–/– mice resulted in selective monocyte uptake into the ascending and suprarenal aorta in regions of enhanced ROS stress, with restoration of IL-6 secretion and increased incidence of dissection. In vitro, coculture of monocytes and aortic adventitial fibroblasts produced MCP-1– and IL-6–enriched conditioned medium that promoted differentiation of monocytes into macrophages, induced CD14 and CD11b upregulation, and induced MCP-1 and MMP-9 expression. These results suggest that leukocyte-fibroblast interactions in the aortic adventitia potentiate IL-6 production, inducing local monocyte recruitment and activation, thereby promoting MCP-1 secretion, vascular inflammation, ECM remodeling, and aortic destabilization. PMID:19920349

  4. Expression of matrix metalloproteinases (MMP-2 、MMP-9) in the pancreatic carcinoma%胰腺癌组织中MMP-2、MMP-9的表达

    Institute of Scientific and Technical Information of China (English)

    吴俊本; 张洁; 成丕光; 王树静; 巩本刚; 徐怀勇

    2012-01-01

    目的 检测胰腺癌组织基质金属蛋白酶( MMP-2,MMP-9)的表达,分析其与临床病理特征的关系.方法 应用免疫组化SP法检测30例胰腺癌及配对癌旁胰腺组织以及11例慢性胰腺炎、6例正常胰腺组织中MMP-2、MMP-9的表达,运用统计软件SPSS 12.0分析其与临床病理特征的相关性.结果 正常胰腺组织均无MMP-2及MMP-9的表达.慢性胰腺炎组织MMP-2、MMP-9的阳性表达率均为18.2% (2/11).胰腺癌组织MMP-2、MMP-9的阳性表达率分别为63.3% (19/30)和56.7% (17/30);配对癌旁组织的阳性表达率分别为23.3% (7/30)和40.0%( 12/30).胰腺癌组织的MMP-2及MMP-9阳性表达率均显著高于配对癌旁组织(P<0.05);胰腺癌组织及癌旁组织中MMP-2及MMP-9的表达均显著高于慢性胰腺炎组织和正常胰腺组织(P值均<0.05).MMP-2、MMP-9的表达与胰腺癌临床分期、肿瘤大小、分化程度及淋巴结转移相关.结论 胰腺癌组织中MMP-2、MMP-9呈高表达,其高表达与肿瘤的恶性程度相关.%Objective To study the expression of matrix metallopro-teinase-2 (MMP-2),matrix metalloproteinase-9 (MMP-9) in the pancreatic carcinomas. Methods MMP-2,MMP-9 expression were detected by immunohistochemistry in surgically resected specimens ( cancer tissues,cancer-adjacent tissues and normal tissues) from 30 PC patients,11 pancreatitis patients and 6 normal patients.the results were analyzed combined with clinical pathologic characteristics.The data was analyzed by Chi-Square test.Results There was no expression of MMP-2,MMP-9 in normal pancreatic tissues.Both of MMP-2 and MMP-9 expressions were 18.2% in chronic pancreatitis titssues.Expression of MMP-2,MMP-9 were higher in cancer tissues than in cancer-adjacent tissues(63.3% vs 23.3%,56.7% vs 40.0%,P <0.05).There were positive correlation between MMP-2,MMP-9 expression and lymph nodal metastasis,tumor sizes,clinical stage and differentiation of tumor(P <0.05).Conclusions

  5. Twist1,MMP-2和MMP-9在结直肠癌组织中的表达及意义%Expression of Twist1, MMP-2 and MMP-9 in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    杨振忠; 吴正升; 法文; 李守新; 吕永芳

    2011-01-01

    目的:研究Twist1、MMP-2和MMP-9蛋白在结直肠癌组织中的表达及其相互关系.方法:建立组织微阵列平台,应用免疫组织化学方法检测92例结直肠癌组织Twist1、MMP-2和MMP-9蛋白的表达情况.结果:结直肠癌中Twist1的表达率为64.1%,MMP-2和MMP-9阳性率分别为66.3%和67.4%;Twist1的表达与肿瘤淋巴结受累和TNM分期均呈正相关(均P<0.05),并且与患者总生存率和无复发生存率呈负相关(P<0.01,P<0.05);MMP-2、MMP-9蛋白表达与肿瘤淋巴结受累均呈显著正相关(均P<0.01),并且MMP-9蛋白表达与肿瘤大小也呈显著正相关(P<0.01);Twist1表达状况与MMP-9的表达呈显著正相关(r=0.205,P<0.05),而与MMP-2表达无显著相关性.结论:结直肠癌Twist1、MMP-2和MMP-9表达状况与肿瘤侵袭转移有密切关系;MMP-9表达可能在一定水平上受到Twist1调控.%AIM: To investigate the clinical significance of the expression of Twist1, MMP-2 and MMP-9 proteins in colorectal cancer.METHODS: The expression of Twist1, MMP-2 and MMP-9 proteins was examined on tissue chips containing 92 colorectal cancer samples by immunohistochemistry.RESULTS: The positive rates of Twist1, MMP-2 and MMP-9 protein expression in colorectal cancer were 64.1%, 66.3% and 67.4%, respectively.High expression of Twist1 was positively correlated with lymph node metastasis and TNM stage (both P < 0.05) but inversely with patient's overall survival and relapse-free survival (P<0.05 and 0.01, respectively).The expression of MMP-2 and MMP-9 was significantly correlated with lymph node metastasis (both P < 0.01).A positive correlation was also found between MMP-9 expression and tumor size (P < 0.01).The expression of Twist1 was positively correlated with that of MMP-9 (P < 0.05), but not with that of MMP-2 (P >0.05).CONCLUSION: The expression of Twist1, MMP-2 and MMP-9 plays an important role in tumor invasion and metastasis in colorectal cancer.The expression of

  6. Investigation of association between IL-8 serum levels and IL8 polymorphisms in Chinese patients with sepsis.

    Science.gov (United States)

    Hu, Donghai; Wang, Haiyan; Huang, Xia; Jiang, Yujie; Qin, Yueqiu; Xiong, Bin; Qin, Gang; Sooranna, Suren R; Pinhu, Liao

    2016-12-05

    To assess the clinical relevance of IL8 gene polymorphisms in patients with sepsis and its association with systemic IL-8 levels. PCR and DNA sequencing were used to examine the polymorphism of IL8 in 152 patients with sepsis and in 199 healthy volunteers in China. The distribution frequencies of the genotype and allele were compared among different groups. The serum IL-8 was measured by ELISA and analyzed in relation to polymorphisms of IL8. The homozygote TT genotype and T allele of rs4073 (genotype: p=0.01, allele: p=0.002), the homozygote CC genotype and C allele (genotype: p=0.03, allele: p=0.003) of rs2227306, homozygote AA genotype and A allele of re1126647 (genotype: p=0.01, allele: p=0.002) were associated with susceptibility to sepsis in males. Serum IL-8 levels were significantly increased in patients with sepsis but showed no correlation with IL8 rs4073, rs2227306 and rs1126647 polymorphisms. The male population carrying the homozygote TT genotype and T allele of rs4073, the homozygote CC genotype and C allele of rs2227306 and homozygote AA genotype and A allele of rs1126647 are more susceptible to sepsis, suggesting there is a protective effect in females carrying these genotypes and alleles respectively. There was no association between rs4073, rs2227306 and rs1126647 polymorphisms and serum levels of IL-8 in patients with sepsis. Copyright © 2016. Published by Elsevier B.V.

  7. Expression and significance of oral lichen planus in MMP-2 and MMP-9%口腔扁平苔藓中MMP-2和MMP-9的表达及意义

    Institute of Scientific and Technical Information of China (English)

    浦光瑞; 张虹

    2012-01-01

    [目的]探索MMP -2和MMP -9与口腔扁平苔藓(oral lichen planus,OLP)的发生、发展乃至癌变潜能的关系.[方法]采用免疫组化SP法检测MMP -2和MMP -9在22例OLP、11例正常口腔黏膜组织、22例白斑和22例口腔鳞癌组织表达.[结果]在正常口腔黏膜、扁平苔藓、白斑和鳞癌组织中MMP -2和MMP -9的表达依次增加.MMP -2和MMP -9在口腔扁平苔藓和白斑中的表达显著高于正常口腔黏膜(P<0.05),但在口腔扁平苔藓和白斑间的表达差异无显著性意义(P>0.05);在鳞癌中的表达显著高于其他3组(P<0.05).[结论] MMP -2和MMP -9表达与OLP的发生、发展乃至癌变潜能有关.%To Explore the relationshiops of MMP -2 and MMP -9 to the OLP occurrence, the development and even the canceration potential. [Methods] Immunohisto ?chemistry was performed to examine expressions of MMP -2 and MMP -9 in 22 OLP, 11 normal oral mucosa, 22 oral leukoplakia and 22 squamous cell carcinoma. [Results] The expression of MMP -2 and MMP -9 increased in turn from normal oral mucosa to OLP, oral leukoplakia and oral squamous cell carcinoma tissues. The expression of MMP -2 and MMP -9 in OLP and oral leukoplakia was significantly higher than that in normal oral mucosa ( P 0. 05) ; The expression of MMP - 2 and MMP - 9 in squamous cell carcinoma was significantly higher than The other three groups (P < 0. 05 ) , there was significant difference. [ Conclusion ] The expression levels of MMP - 2 and MMP - 9 correlate with the occurrence of oral lichen planus, development and e-ven cancer potential, which may be useful indicator to judge the possibility of malignant change of OLP.

  8. Serum metrix metalloproteinase-9 combined with homocysteine,IL-6,TNF-α,CRP,HbA1c and lipid profile in the incipient diabetic nephropathy with or without macrovascular diseases

    Institute of Scientific and Technical Information of China (English)

    JIA Wei; YUAN Qiang; LIANG Yong-ping; WANG Hui-ming; HAN Xiang-qun; YIN Shu-qiao; ZHU Xiao-mei; LIU Gui-zhi

    2007-01-01

    Objective:To evaluate the changes of serum matrix metalloproteinase-9 (mmp-9) in patients of incipient diabetic nephropathy with or without macrovascular disease and to analyze the factors associated with homocysteine(hcy),interleukin-6(IL-6),tumor necrosis factor-alpha (TNF-α),highly sensitive C-reactive protein (hsCRP),HbA1c and lipid profile in those patients in order to know whether this marker or other factors are more important to induce diabetic macrovascular disease.Methods:Type 2 diabetes mellitus(T2DM) subjects with incipient diabetic nephropathy with or without macrovascular disease were selected for participation and divided into 2 groups.The patients in group 1(n=38) used insulin,and patients in group 2 (n=34) were treated with an oral antidiabetic drug.Then serum mmp-9,hcy,IL-6 and TNF-α in these patients were measured, and compared to the healthy subjects as control (n=16).The resuits were analyzed by SPSS13.Results:Serum romp-9 and hcy of the patients having incipient diabetic nephropathy with macrovaseular disease were higher than that of patients without macrovascular disease (P<0.01).For insulin-injected patients,whether they accompanied with macrovascular diseases or not,the serum levels of mmp-9,hcy,IL-6 and TNF-α were all lower,but no significant statistics compared with non-insulin used patients or the healthy subjects.The serum level of mmp-9 was more correlatedwith the serum hcv in antidiabetic drug used patients.(P<0.000) Conclusion:The serum level of mmp-9 plays an important role of pathogenesis in the macrovascular disease in the incipient diabetic patients,and the serum level of hcy also can reflect the severely degree of macrovascular disease in these patients,insulin can reduce these markers.

  9. VEGF、MMP-2与MMP-9在卵巢癌组织中的表达及其临床意义%Expression and clinical significance of VEGF,MMP-2 and MMP-9 in ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    曾晓林; 彭耀金

    2010-01-01

    目的:探讨VEGF、MMP-2和MMP-9在卵巢癌组织中的表达及其与卵巢癌发生发展的关系.方法:采用免疫组织化学法检测VEGF、MMP-2和MMP-9在正常卵巢组织、卵巢癌组织中的表达,并对三者的相关性进行分析.结果:卵巢癌组织中VEGF、MMP-2和MMP-9蛋白的表达阳性率显著高于正常卵巢组织(P<0.05),且在卵巢癌Ⅲ~Ⅳ期患者标本中阳性率高于Ⅰ~Ⅱ期(P<0.05);VEGF、MMP-2和MMP-9蛋白阳性表达率与卵巢癌临床分期和淋巴结转移有关(P<0.05).结论:正常卵巢组织和卵巢癌组织中VEGF、MMP-2和MMP-9蛋白含量的变化一致;VEGF、MMP-2和MMP-9均参与了卵巢癌的发生发展过程,三者间可能有协同作用.

  10. Comparison of circulating MMP-9, TIMP-1 and CA19-9 in the detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Brünner, Nils; De Muckadell, Ove B Schaffalitzky

    2010-01-01

    Background/Aim: The performance of the circulating tumor markers carbohydrate antigen 19-9 (CA19-9), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were evaluated separately and in combination for their potential value in detecting pancreatic ductal...... adenocarcinoma. PATIENTS AND METHODS: The patients had symptoms of pancreatic cancer. The discriminative strength of MMP-9 and TIMP-1 were compared to that of CA19-9 using receiver operating characteristics curves, area under the curves (AUC), specificity and sensitivity. RESULTS: The sensitivities of MMP-9......, TIMP-1 and CA19-9 in detecting pancreatic ductal adenocarcinoma were 58.82%, 47.1% and 86%, respectively, with specificities of 34.6%, 69.2% and 73%. The AUCs of MMP-9, TIMP-1 and CA19-9 were 0.50, 0.64 and 0.84, respectively. Combining the three markers did not significantly improve detection...

  11. MMP-9和MMP-2基因多态性与原发性肝癌侵袭转移的关系%Correlation of MMP-9 and MMP-2 Gene SNPs with Hepatocellular Carcinoma Invasion and Metastasis

    Institute of Scientific and Technical Information of China (English)

    吴时胜; 邵立华; 李尚日; 张飞; 谢鸿; 张春秀; 刘桂平

    2012-01-01

    Objectlve To investigate the association between MMP-9 and MMP-2 gene SNPs of promoter regions and both infiltration and metastasis in hepatocellular carcinoma. Methods PCR- restriction fragment length polymorphism(PCR-RFLP) technique was applied to detect MMP-2 and MMP-9 promoter SNPs in 28 patients with hepatocellular carcinoma(8 cases with metastasis) and 42 healthy people. Results The risk of early metastasisof MMP-9-1562TT genotype was increased up to 1. 25-fold(95%CI,3. 64 ~ 5. 69),compared with MMP-9-1562CC or CT genotype,and irrelevant to the age or gender of patients. The risk of liver cancer in population harboring MMP-9-1562TT and MMP-2-1306CC or CT genotypes was significantly higher than in those harboring MMP-9-1562TT,MMP-2-t306CC or TT alone. Conclusion MMP-2-1306T/C polymorphism alone is not a risk factor of primary liver cancer,although has syn-ergistic interactions with MMP-9-1562C/T genotype, MMP-2 and MMP-9 gene polymorphism are related to the infiltration and metastasis of primary liver cancer.%目的 探讨原发性肝癌中MMP-9和MMP-2基因多态性表达与原发性肝癌侵袭转移的关系.方法 用聚合酶链反应—限制性片断长度多态性技术,检测MMP-2和MMP-9启动子基因型在28例原发性肝癌患者(其中8例有转移)和42例健康者中的频率.结果 与携带MMP-9- 1562CC和CT基因型相比,携带MMP-9- 1562TT基因型者早期发生侵袭转移的风险增加1.25倍(95%CI:3.64~5.69),且这种风险增高与研究对象的年龄和性别无关,同时携带MMP-9- 1562TT和MMP-2 - 1306CC或CT基因型的个体,惠肝癌的风险性较单一携带的个体显著增高(P<0.5).结论 MMP-2-1306T/C多态性单独与原发性肝癌风险无关,但与MMP-9- 1562C/T多态性可能有基因-基因交互作用.MMP-2和MMP-9基因多态性与原发性肝癌侵袭转移可能相关.

  12. Expression of GPC3, MMP-9 and MMP-14 in Hepatocellular Carcinoma and Their Influence on the Prognosis of Patients

    Directory of Open Access Journals (Sweden)

    Lei CAI

    2016-03-01

    Full Text Available Objective: To explore the expression of glypican-3 (GPC3, metal matrix proteinase (MMP-9 Methods: Totally 112 paraffin-embedded tissue samples of HCC patients were selected as observation group and 70 normal tissue samples were as control group. The expressions of GPC3, MMP-9 and MMP-14 of two groups were detected using immunohistochemistry assay. The positive rates of two groups were calculated. The relationship between the expression of GPC3, MMP-9 and MMP-14 and clinicopathological features, and their influence on the survival time of HCC patients were compared. Results: The positive expression rates of GPC3, MMP-9 and MMP-14 were higher in observation group that those in control group, the differences were statistically significant (P=0.000; P=0.000; P=0.000. The expression of GPC3 had close relationship with tumor volume, differentiated degree, lymphatic metastasis, and PCNA expression. The expression of MMP-9 had close relationship with tumor volume, lymphatic metastasis, and vascular invasion. The expression of GPC3 had close relationship with tumor volume, differentiated degree, lymphatic metastasis, vascular invasion, and proliferating cell nuclear antigen (PCNA expression.Conclusion: GPC3, MMP-9 and MMP-14 are highly expressed in HCC patients, which shows poor prognosis. Therefore, the detection of GPC3, MMP-9 and MMP-14 after surgery has a certain value on assessment of the prognosis of HCC patients.and MMP-14 in hepatocellular carcinoma (HCC, and their influence on the prognosis of HCC patients. There were positive correlations between GPC3 and MMP-9 (r=0.538, P=0.042, MMP-9 and MMP-14 (r=0.430, P=0.024, and GPC3 and MMP-14Kaplan-Meier method showed that the expressions of GPC3, MMP-9 and MMP-14 were associated with the prognosis of HCC patients, and patients with high expressions of GPC3, MMP-9 and MMP-14 had poor prognosis. (r=0.563, P=0.563.

  13. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    Energy Technology Data Exchange (ETDEWEB)

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K. [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil); Moroz, Andrei [Univ Estadual Paulista – UNESP, School of Pharmaceutical Sciences, Department of Bioprocess and Biotechnology, Cell Culture Laboratory, Araraquara, SP (Brazil); Felisbino, Sérgio L., E-mail: felisbin@ibb.unesp.br [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil)

    2015-02-20

    Matrix metalloproteinases (MMPs) are zinc (Zn{sup 2+}) and calcium (Ca{sup 2+}) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd{sup 2+}) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd{sup 2+} intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl{sub 2} diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl{sub 2}) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl{sub 2} intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd{sup 2+} treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl{sub 2}, respectively, even in the presence of 10 mM of CaCl{sub 2} within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its

  14. Expression of MMP-9 in hepatic sinusoidal obstruction syndrome induced by Gynura segetum

    Institute of Scientific and Technical Information of China (English)

    Xia-zhen YU; Tao JI; Xue-li BAI; Liang LIANG; Lin-yan WANG; Wei CHEN; Ting-bo LIANG

    2013-01-01

    Background and objective:Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by painful hepatomegaly,ascites,increased body weight,and jaundice.Gynura segetum (Compositae),a plant widely used in Chinese traditional medicine,often leads to the development of HSOS.However,the mechanism is unclear.The aim was to study the role of matrix metalloproteinase-9 (MMP-9) in the onset of HSOS induced by Gynura segetum.Methods:Twenty-five male Sprague-Dawley rats were randomly divided into two groups.Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone.Liver sections were evaluated by light microscopy with a modified scoring system.Routine transmission electron microscopy (TEM) methods were used to evaluate the ultrastructual features of fixed liver tissue,and blood samples were collected to determine liver enzyme concentrations.MMP-9 expression was assessed by both immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) methods.Results:A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract.The treated rats presented clinical symptoms and the histopathological manifestation of HSOS,including abnormal liver enzyme concentrations (alanine aminotransferase (ALT):(84.8±13.62) vs.(167.0±72.63) U/L,P<0.05; aspartate aminotransferase (AST):(27.6±6.31)vs.(232.8±108.58) U/L,P<0.05).Hematoxylin and eosin (H&E) staining and TEM together revealed deposition of red blood cells,the damage and destruction of hepatic sinusoidal endothelial cells,collapse of hepatic sinusoids,hemorrhage of subendothelial cells,atrophy and destruction of hepatocytes,etc.Compared with controls,the expression of MMP-9 in the blood sample,the lung and liver tissues of HSOS rats was increased.Conclusions:MMP-9 may have an important role in early pathological changes of HSOS,and thus the onset of the disease.

  15. Zoledronate upregulates MMP-9 and -13 in rat vascular smooth muscle cells by inducing oxidative stress

    Directory of Open Access Journals (Sweden)

    Arun MZ

    2016-04-01

    Full Text Available Mehmet Zuhuri Arun,1 Buket Reel,1 Graciela B Sala-Newby,2 Mark Bond,2 Aikaterini Tsaousi,2 Perry Maskell,2 Andrew C Newby21Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 2Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, UK Background: Bisphosphonates, including zoledronate, target osteoclasts and are widely used in the treatment of osteoporosis and other bone resorption diseases, despite side effects that include damaging the stomach epithelium. Beneficial and adverse effects on other organ systems, including the cardiovascular system, have also been described and could impact on the use of bisphosphonates as therapeutic agents. Vascular smooth muscle cells (VSMCs are major constituents of the normal vascular wall and have a key role in intimal thickening and atherosclerosis, in part by secreting MMPs that remodel the extracellular matrix and cleave cell surface proteins or secreted mediators. In this study, we investigated the effects of zoledronate on MMP expression.Methods: Rat VSMCs were stimulated by PDGF (50 ng/mL plus TNF-α (10 ng/mL or left unstimulated for a further 24 hours in serum-free medium. In other series of experiments, cells were pre-treated either with SC-514 (50 µM or with apocynin (20 nM for 2 hours, then zoledronate (100 µM was added into 2% fetal calf serum containing medium for 24 hours.Results and discussion: Using isolated rat VSMCs in culture, zoledronate (100 µM increased MMP-9 and -13 mRNA expressions but inhibited MMP-2 expression. MMP-9 and MMP-13 up-regulation was shown to depend on the NF-κB pathway; and this was activated by zoledronate. Furthermore, zoledronate elevated the levels of reactive oxygen species detected by either dichlorofluorescein in isolated VSMCs or lucigenin enhanced chemiluminescence in rat aortic rings in vitro. Apocynin, an inhibitor of NADPH oxidase, reversed NF-κB activation and MMP-9 and MMP-13 up-regulation by

  16. Role Of MMP-2 and MMP-9 in Resistance to Drug Therapy in Patients with Resistant Hypertension

    Directory of Open Access Journals (Sweden)

    Leandro Lacerda

    2015-01-01

    Full Text Available Background: Despite the increased evidence of the important role of matrix metalloproteinases (MMP-9 and MMP‑2 in the pathophysiology of hypertension, the profile of these molecules in resistant hypertension (RHTN remains unknown. Objectives: To compare the plasma levels of MMP-9 and MMP-2 and of their tissue inhibitors (TIMP-1 and TIMP-2, respectively, as well as their MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios, between patients with controlled RHTN (CRHTN, n=41 and uncontrolled RHTN (UCRHTN, n=35. In addition, the association of those parameters with clinical characteristics, office blood pressure (BP and arterial stiffness (determined by pulse wave velocity was evaluate in those subgroups. Methods: This study included 76 individuals diagnosed with RHTN and submitted to physical examination, electrocardiogram, and laboratory tests to assess biochemical parameters. Results: Similar values of MMP-9, MMP-2, TIMP-1, TIMP-2, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were found in the UCRHTN and CRHTN subgroups (P>0.05. A significant correlation was found between diastolic BP (DBP and MMP-9/TIMP-1 ratio (r=0.37; P=0.02 and DPB and MMP-2 (r=-0.40; P=0.02 in the UCRHTN subgroup. On the other hand, no correlation was observed in the CRHTN subgroup. Logistic regression models demonstrated that MMP-9, MMP-2, TIMP-1, TIMP-2 and their ratios were not associated with the lack of BP control. Conclusion: These findings suggest that neither MMP-2 nor MMP-9 affect BP control in RHTN subjects.

  17. MMP-9 and pulmonary fibrosis%基质金属蛋白酶-9与肺纤维化

    Institute of Scientific and Technical Information of China (English)

    卞秀娟; 郑金旭

    2006-01-01

    基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)是一种金属离子依赖的蛋白酶,通过多种途径参与特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的发病机制,本文就MMP-9的基本特性及其与肺纤维化的关系进行综述.

  18. Group IVA phospholipase A2-associated production of MMP-9 in macrophages and formation of atherosclerotic lesions.

    Science.gov (United States)

    Ii, Hiromi; Hontani, Naoya; Toshida, Issei; Oka, Mayuko; Sato, Takashi; Akiba, Satoshi

    2008-03-01

    Matrix metalloproteinase-9 (MMP-9) is involved in atherogenesis, and the production of MMP-9 in macrophages is considered to be mediated by the arachidonic acid cascade. The present study examined the possible involvement of group IVA phospholipase A2 (IVA-PLA2), a key enzyme in the arachidonic acid cascade, in the production of MMP-9 induced by oxidized low-density lipoprotein (oxLDL) in macrophages and high-fat diet-induced formation of atherosclerotic lesions using IVA-PLA2-deficient mice (C57BL/6 background). In wild-type mouse peritoneal macrophages, oxLDL induced an increase in MMP-9 in the culture medium. The oxLDL-promoted production of MMP-9 was markedly reduced in IVA-PLA2-deficient macrophages compared to wild-type macrophages. Feeding of wild-type mice with a high-fat diet caused the formation of early atherosclerotic lesions in the aortic root with increases in MMP-9 and macrophages in the lesions and with higher serum levels of total cholesterol. Such lesions were apparently less severe in IVA-PLA2-deficient mice fed a high-fat diet, despite higher total cholesterol levels. Under the conditions, a high-fat diet reduced the serum levels of high-density lipoprotein-cholesterol (HDL-C) in wild-type mice. However, IVA-PLA2-deficient mice fed a high-fat diet were protected against the decrease in HDL-C levels. The present results suggest that IVA-PLA2 is involved in the oxLDL-induced production of MMP-9 in macrophages and the high-fat diet-induced formation of early atherosclerotic lesions. The protection against the lesions in IVA-PLA2-deficient mice may be ascribable, in part, to the impaired production of MMP-9 and/or the maintained levels of HDL-C.

  19. Analysis of the Relationship between Expressions of TF and MMP-9 and Prognosis of Breast Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    Jianxin Zhao; Zengmao Lin; Hongwei Yao; Yuanlian Wan

    2008-01-01

    OBJECTIVE To investigate expression of the tissue factor(TF) and matrix metalloproteinase-9 (MMP-9) in breast cancers,and to assess their expression in relation to possible prognostic significance.METHODS The expression of TF and MMP-9 in 71 breast cancer specimens were determined by EnVision immunohistochemistry,and the positive expressions related to the patient clinical outcome.RESULTS Positive rates of TF and MMP-9 staining were respectively 43.7% and 42.3%. K-M monofactorial analysis showed that the 5-year survival rate of the patients with a positive expression of TF and MMP-9 was lower than those with negative expression (P < 0.05). However, the COX multifactorial analysis indicated that TNM staging and lymph node metastasis were the prognostic factors for breast cancer patients, and that TF and MMP-9 could not be used as the independent prognostic factors (P> 0.05).CONCLUSION The positive rates of TF and MMP-9 were considerably high in breast cancers, which could provide useful information for patient prognosis.

  20. Crosstalk between obesity and MMP-9 in cardiac remodelling -a cross-sectional study in apparent treatment-resistant hypertension.

    Science.gov (United States)

    Ritter, Alessandra Mileni Versuti; de Faria, Ana Paula; Barbaro, Natália; Sabbatini, Andréa Rodrigues; Corrêa, Nathália Batista; Brunelli, Veridiana; Amorim, Rivadavio; Modolo, Rodrigo; Moreno, Heitor

    2017-04-01

    The balance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) plays a key role in the development of hypertension and obesity. We aimed to evaluate the levels of MMP-2 and 9 and TIMP-2 and -1 in obese and non-obese apparent treatment-resistant hypertensive subjects (aTRH) and its association with cardiac hypertrophy. This cross-sectional study enrolled 122 subjects and divided into obese aTRH (n = 67) and non-obese (n = 55) group. Clinical and biochemical data were compared between both groups, including office BP, ambulatory BP, plasma MMP-2 and 9, TIMP-2 and 1 and left ventricular mass index (LVMI). We found higher MMP-9 levels and MMP-9/TIMP-1 ratio in obese aTRH subjects but no difference in MMP-2 and TIMP-1 levels. Obesity influenced MMP-9 levels [β = 20.8 SE =8.6, p = 0.02) independently of potential confounders. In addition, we found a positive correlation between MMP-9 and anthropomorphic parameters. Finally, obese aTRH subjects with left ventricular hypertrophy (LVH) had greater MMP-9 levels compared with non-obese with LVH. Our study suggests that MMP-9 levels are influenced by obesity and may directly participate in the progressive LV remodelling process, suggesting a possible role for a higher cardiovascular risk in apparent resistant hypertensive subjects.

  1. EXPRESSION AND CLINICAL SIGNIFICANCE OF HMGB1 AND MMP-9 IN ENDOMETRIAL CARCINOMA%HMGB1、MMP9在子宫内膜癌中的表达和临床意义

    Institute of Scientific and Technical Information of China (English)

    段玉真; 周晓慧; 张玉娟

    2016-01-01

    目的::探讨高迁移率组蛋白1(HMGB1)和基质金属蛋白酶-9(MMP-9)mRNA在子宫内膜癌中的表达水平和临床意义。方法:应用RT-PCR法检测正常子宫、单纯性增生症、非典型增生症和子宫内膜癌子宫内膜组织HMGB1和MMP9 mRNA的表达水平。结果:子宫内膜癌组织HMGB1、MMP-9 mRNA的表达量明显高于正常子宫、单纯性增生症、非典型增生症子宫内膜组织(P<0.05);子宫内膜癌组织HMGB1、MMP-9 mRNA的表达均与FIGO分期、淋巴结转移和浸润深度有关(P<0.05)。结论:HMGB1、MMP-9在子宫内膜癌的发生、发展和转移过程中可能起着重要作用。%[ABSTRACT]Objective:To investigate the expression and clinical signiifcance of high-mobility group box 1 protein (HMGB1) and matrix metalloproteinases-9 (MMP-9) mRNA in endometrial carcinoma. Methods:RT-PCR was used to detect the HMGB1 and MMP-9 mRNA expression level in normal endometrial tissue, endometrial hyperplasia, atypical endometrial hyperplasia and endometrial carcinoma. Results:The HMGB1 and MMP-9 mRNA expression level in endometrial carcinoma were obviously higher than normal endometrial tissue, endometrial hyperplasia and atypical endometrial hyperplasia (P<0.05). In endometrial carcinoma, the expression of HMGB1 and MMP-9 were all related to FIGO stage, lymph node metastasis and inifltration depth (P<0.05). Conclusions:HMGB1 and MMP-9 may play important role in genesis, development and metastasis of endometrial carcinoma.

  2. CCR7上调MMP-9表达促进非小细胞肺癌转移%Chemokine Receptor 7 Induces Metastasis of NSCLC via Upregulating MMP-9 Expression

    Institute of Scientific and Technical Information of China (English)

    李洋; 刘巍; 方莉; 南娟; 张占雀; 周清华

    2010-01-01

    背景与目的 趋化因子激素受体(CC chemokine receptor 7,CCR7)与非小细胞肺癌(non-small celllung cancer,NSCLC)的淋巴结转移密切相关,但CCR7促进其淋巴结转移的机制尚不明了.本研究通过观察CCR7和MMP.9在NSCLC组织中的表达和相互关系.探讨CCR7促进NSCLC淋巴结转移的机制.方法 应用免疫组织化学染色(SP法)检测90例NSCLC组织中CCR7、MMP-9的表达;将BEI细胞经趋化因子CCLl9处理24 hA,应用RT-PCR和Western blot方法检测MMP-9 mRNA和蛋白表达水平.结果 免疫组织化学结果显示:CCR7主要表达于癌细胞胞质和(或)胞膜,MMP-9主要表达于癌细胞胞质,NSCLC中CCR7、MMP.9阳性表达率分别为70%(63/90)和65.5%(59/90),X2检验显示CCR7和MMP-9表达与NSCLC的临床病理分期(P=0.003,P=0.001)和淋巴结转移(P=0.0042 P=0.003)密切相关,而与年龄、组织学类型、分化程度无关(P>0.05).此外,CCR7和MMP-9表达正相关(r=0.342,P=0.001).CCL21处理组BEI细胞后MMP-9 mRNA和蛋白水平均上调(P<0.05).结论 CCR7和MMP-9表达与NSCLC侵袭转移密切相关,CCL19/CCR7通过上调NSCLC中MMP-9表达促进其转移.

  3. MMP-9、TIMP-1和VEGF在牙龈癌中的表达及意义%Expressions of MMP-9, TIMP-1 and VEGF in Gingival Carcinoma and Their Significance

    Institute of Scientific and Technical Information of China (English)

    李芳凝; 李金源

    2011-01-01

    [Objective]To explore the expressions of matrix mcta11oprotcin-9(MMP-9) , tissue inhibitor of mctalloprotcinasc-1 (TIMP-1) and vascular cndothclial growth factor(VKGF) in gingival carcinoma and their correlation. [Mcthods]Thc expression of MMP-9, TIMP-1 and VEGF in 66 gingival carcinoma tissues and 16 normal gum tissues were detected by SP immunohistochemistry method. The correlation of the expressions with clinical pathology and prognosis was analyzed. [Results] There was significant difference in the positive expression of MMP-9 and VEGF among the well-differentiated, moderately-differentiated and poorly-differen tiated gingival carcinomaC P 0. 05). [Conclusion]MMP-9, TIMP-1 and VEGF may be involved in the pathogencsis and development of gingival carcinoma through the pathway of angiogencsis. The combination detection of MMP-9, TIMP-1 and VEGF may be helpful for the diagnosis, treatment and prognostic assessment of gingival carcinoma.%[目的]探讨基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)及血管内皮生长因子(VEGF)在牙龈癌组织中的表达及相关性.[方法]采用免疫组化SP法检测66例牙龈癌和16例正常牙龈组织中MMP-9,TIMP-1和VEGF的表达情况,分析其表达的相关性.[结果]在高分化、中分化及低分化牙龈癌中MMP-9和VEGF的阳性表达差异均有显著性(P0.05),MMP-9与TIMP-1在牙龈癌中的表达存在负相关(P0.05).[结论]MMP-9,TIMP-1和VEGF三者可能通过"血管生成"通路参与了牙龈癌的发生和发展过程,联合检测三项指标的表达状况可能有助于牙龈癌的诊断、治疗和评估预后.

  4. 前列腺癌中MMP-9和VEGF的表达及相关性研究%An Association Study of MMP-9 and VEGF Protein EXpression in Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    牛军

    2014-01-01

    目的:探讨基质金属蛋白酶( MMP-9)和血管内皮生长因子( VEGF)在前列腺癌组织中的表达以及两者的关系。方法:应用免疫组织化学技术检测120例前列腺增生( BPH)和120例前列腺癌( PCa)组织中MMP-9和VEG的表达水平,并分析两者表达与前列腺癌临床病理特征的关系。结果:120例PCa中MMP-9和VEGF阳性表达率分别为85.01%、83.32%,与BPH组织进行比较,差异均有统计学意义( P <0.05)。MMP-9和VEGF与PCa的病理分级和临床分期有关,且二者呈正相关。结论:MMP-9和VEGF蛋白在PCa中高表达,两者与前列腺癌的发生、发展相关,可以作为预后的判断指标。%ObjectiVe:To eXplore the eXpression of matriX metallo proteinases -9( MMP -9 )and Vascular endothelial growth factor( VEGF)in prostatic cancer( PCA)and the relations between them. Methods:The eXpression of VEGF and MMP-9 in 120 cases of prostate cancer and 120 case s of BPH were detected by immunohistochemistry,with the relationship of their eXpression with clinical characteristics of prostatic cancer further analyzed. ResuIts:The positiVe rate of MMP-9 and VEGF eX-pression in 120 cases PCA is 85. 01 % and 83. 32 %,respectiVely,significantly different from that in BPH( P <0. 0 5). The eXpression of MMP-9 and VEGF in prostate cancer was positiVely correlated with pathological grading and clinical staging of PCA. ConcIusion:The oVer eXpression of MMP-9 and VEGF in PCA is correlated to the generation and the deVelopment of the prostatic carcinoma,which can be taken as an indeX of the prognosis of PCA.

  5. Interleukin-6 (IL-6) and receptor (IL6-R) gene haplotypes associate with amniotic fluid protein concentrations in preterm birth.

    Science.gov (United States)

    Velez, Digna R; Fortunato, Stephen J; Williams, Scott M; Menon, Ramkumar

    2008-06-01

    Spontaneous preterm birth (PTB-gestational age rs1800797, rs1800796 and rs1800795; in IL-6R markers rs4075015, rs4601580, rs4645618, rs6687726 and rs7549338 and markers rs4845623, rs4537545 and rs4845625. In conclusion, our results suggest that IL-6 AF concentration, in situations of PTB, result from variation in IL-6 and more importantly IL-6R.

  6. The expression and significance of NF-κB and MMP-9 in cervical carcinoma%NF-κB、MMP-9在宫颈癌组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    赵玉婵; 李莲; 张连梅; 刘晓兰

    2013-01-01

    Objective To investigate the expression and clinical significance of nuclear factor kappa -B ( NF-κB ) and matrix metalloproteinase ( MMP-9 ) in cervical carcinoma .Methods The expression levels of NF-κB and MMP-9 were detected by immunohistochemistry in 80 cases of cervical carcinoma (CSES),70 cases of cervical intraepithelial neoplasm (CIN) and 50 cases of normal cervical tissues (NCE).The correlation between their expression levels and clinical pathological characteristics was analyzed .Results The expression levels of NF-κB and MMP-9 in CSES were significantly higher than those in CIN and NCE ( P <0.05).The expression levels of NF-κB and MMP-9 were correlated to the pathological classification , clinical staging and lymph node metastasis of cervical carcinoma ( P <0.05),however,which were not related to patient ’ s age and histological types,moreover the expression of NF-κB was positively related with that of MMP-9 ( P <0.05).Conclusion The overexpression of NF-κB and MMP-9 exists in patients with cervical carcinoma ,which may play an important role in the pathogenesis ,development ,invasion and metastasis of cervical carcinoma and NF-κB and MMP-9 can be used as the indexes of diagnosis and prognosis evaluation for cervical carcinoma .%目的观察核转录因子-κB (nuclear factor kappa-B,NF-κB)和MMP-9(matrix metalloprotein-ase,MMP-9)在宫颈癌组织中的表达及临床意义。方法采用免疫组织化学 SP 法检测80例宫颈癌(CSES)、70例子宫颈上皮内瘤样变(CIN)及50例正常子宫颈组织(NCE)NF-κB和MMP-9蛋白表达水平,分析其与临床病理特征的关系。结果在CSES、CIN及NCE中, NF-κB蛋白阳性表达率分别为72.5%、18.6%、0%,MMP-9蛋白阳性表达率分别为68.8%、15.7%、0;即CSES中NF-κB和MMP-9蛋白表达显著高于CIN和NCE,差异具有统计学意义( P <0.05)。 NF-κB、MMP-9表达与宫颈癌不同的病理分级、临床分期

  7. Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion

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    Elene Sapharikas

    2015-06-01

    Full Text Available Critical limb ischemia (CLI induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p < 0.05 and a five-fold increase in chemotaxis in Boyden chambers (p < 0.05. Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p < 0.05. MMP9 activity in monocyte supernatants was significantly enhanced by fucoidan (p < 0.05. Finally, Western blot analysis of fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p < 0.01. Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment.

  8. Rosiglitazone regulates IL-6-stimulated lipolysis in porcine adipocytes.

    Science.gov (United States)

    Yang, Yongqing; Yang, Gongshe

    2010-10-01

    Interleukin (IL)-6, a proinflammatory cytokine, stimulates adipocyte lipolysis and induces insulin resistance in obese and diabetic subjects. However, the effects of the anti-diabetic drug rosiglitazone on IL-6-stimulated lipolysis and the underlying molecular mechanism are largely unknown. In this study, we demonstrated that rosiglitazone suppressed IL-6-stimulated lipolysis in differentiated porcine adipocytes by inactivation of extracellular signal-related kinase (ERK). Meanwhile, rosiglitazone enhanced the lipolysis response of adipocytes to isoprenaline. In addition, rosiglitazone significantly reversed IL-6-induced down-regulation of several genes such as perilipin A, peroxisome proliferators activated receptor gamma (PPARγ), and fatty acid synthetase, as well as the up-regulation of IL-6 mRNA. However, mRNA expression of PPARγ coactivator-1 alpha (PCG-1α) was enhanced by rosiglitazone in IL-6-stimulated adipocytes. These results indicate that rosiglitazone suppresses IL-6-stimulated lipolysis in porcine adipocytes through multiple molecular mechanisms.

  9. Prognostic values of ETS-1, MMP-2 and MMP-9 expression and co-expression in breast cancer patients.

    Science.gov (United States)

    Puzovic, V; Brcic, I; Ranogajec, I; Jakic-Razumovic, J

    2014-01-01

    The aim of this study was to analyse expression of ETS-1 protein and two gelatinases (MMP-2 and MMP-9) and their possible prognostic value in breast carcinoma patients, as well as correlation of their expression with other known prognostic factors such as tumor size, grade, vascular invasion, steroid receptor values, HER2 values and proliferative index. The expression of MMP-2, MMP-9 and ETS-1 was immunohistochemicaly analysed in 121 consecutive primary breast carcinoma patients who underwent surgery at the Clinical Hospital Centre Zagreb during 2002. Three representative areas from each tumor paraffin blocks were taken and arranged on a recipient paraffin block with predefined coordinates for simultaneous analyses of multiple tissue samples (TMA). ETS-1, MMP-2 and MMP-9 expression and co-expression were correlated with other clinico-pathological parameters and based on the available clinical follow up data survival analysis was performed. The ETS-1 protein is found to be expressed in tumor cell nuclei and cytoplasm as well as in stromal lymphocytes, fibroblasts and endothelial cells. MMP-2 and MMP-9 were found to be expressed in cytoplasm of both, tumor and stromal cells. For our analysis only tumor cell expression was used for statistical analysis. We found 56,2% ETS-1 positive tumors, 77,7% were MMP-2 positive, and MMP-9 was expressed in 90% of primary breast carcinomas. There were no significant correlations between MMP-s expression and other patohistological prognostic factors, but expression of ETS-1 was significantly correlated with higher tumor size and grade, as well as with negative steroid receptors. Co-expression of MMP-2, MMP-9 and ETS-1 was found in 40,5 % of tumors, and more commonly was found in tumors larger than 2 cm, high grade tumors, and steroid receptor negative tumors. In univariate analysis, statistically significant negative impact on overall survival (OS) had tumor size, nuclear and tumor grade, ETS-1 expression in tumor cells, co

  10. Cytokine measurements in Brazilian postmenopausal osteoporosis patients reveal high levels of IL-8 = Dosagem de citocinas em pacientes brasileiras com osteoporose pós-menopausa revela altos níveis de IL-8

    Directory of Open Access Journals (Sweden)

    Cardoso, Pablo Ramon Gualberto

    2016-01-01

    Conclusões: A IL-8 mostrou-se elevada no soro das pacientes com osteoporose pós-menopausa, talvez por atuar como um gatilho para a ativação dos osteoclastos e desgaste ósseo que ocorre na osteoporose. Níveis mais altos de IFN-γ, IL-6, IL-9, IL-22, IL-27 e IL-35 também estiveram presentes no soro das pacientes do grupo osteoporose e mostraram associações significativas com os parâmetros clínicos na osteoporose pós-menopausa

  11. 子宫内膜腺癌中MMP-2、MMP-9表达的免疫组化研究%Metalloproteinase-9(MMP-9)in Endometrial Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    仲肖静; 颜丽丽

    2014-01-01

    目的:探讨基质金属蛋白酶-2、-9(Matrix metalloproteinases,MMP)在子宫内膜腺癌组织中的表达及其与临床病理关系。方法:应用免疫组化SP法检测MMP-2、MMP-9在不同子宫内膜组织中的表达情况。结果:MMP-2在正常子宫内膜、子宫内膜增生症和子宫内膜腺癌组织中的阳性表达率分别为15.0%、26.7%、88.0%, MMP-9的阳性表达率分别为25.0%、33.3%、95.0%,MMP-2和MMP-9的表达在子宫内膜腺癌中均明显高于正常子宫内膜、子宫内膜增生症,比较差异均有统计学意义(P<0.05)。MMP-2、MMP-9的表达强度与子宫内膜腺癌的手术-病理分期、组织学分级、肌层浸润和淋巴结转移相关,差异均有统计学意义(P<0.05)。结论:MMP-2、MMP-9在子宫内膜腺癌的发生、发展过程中起促进作用,且两者表达与子宫内膜腺癌的浸润深度和转移程度有关,为早期诊断子宫内膜腺癌以及子宫内膜腺癌的预后判断、靶向治疗提供了可靠的依据。%Objective:To investigate the expression of MMP-2 and MMP-9 in endometrial adenocarcinoma tissue and its relation to clinical pathological characteristics.Method:Expression of MMP-2 and MMP-9 was examined by immunohistochemistry(SP method)in three different kinds of endometrium.Result:The results showed that the positive rates of MMP-2 in normal endometria,endometrial hyperplasias and endometrial adenocarcinomas were 15.0%,26.7%and 88.0%respectively,the positive rates of MMP-9 were 25.0%,33.3%and 95.0%respectively.Expression of MMP-2 and MMP-9 were significantly higher in endometrial adenocarcinoma than those in hyperplastic and normal endometria, the differences were statistically significant(P<0.05).In endometrial adenocarcinoma tissue,the positive expression of MMP-2 and MMP-9 was correlated with clinical pathological characteristics,histodifferentiation,myometrial invasion and lymphatic metastasis,the differences were statistically

  12. Higher IL-6 and IL6:IGF Ratio in Patients with Barth Syndrome

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    Wilson Lori D

    2012-06-01

    Full Text Available Abstract Background Barth Syndrome (BTHS is a serious X-linked genetic disorder associated with mutations in the tafazzin gene (TAZ, also called G4.5. The multi-system disorder is primarily characterized by the following pathologies: cardiac and skeletal myopathies, neutropenia, growth delay, and exercise intolerance. Although growth anomalies have been widely reported in BTHS, there is a paucity of research on the role of inflammation and the potential link to alterations in growth factors levels in BTHS patients. Methods Plasma from 36 subjects, 22 patients with Barth Syndrome (0.5 - 24 yrs and 14 healthy control males (8 - 21 yrs was analyzed for two growth factors: IGF-1 (bound and free and Growth Hormone (GH; and two inflammatory cytokines IL-6 and TNF-α using high-sensitivity enzyme-linked immunosorbent assays. Results The average IL-6 and IL6:IGF ratio levels were significantly higher in the BTHS (p = 0.046 and 0.02 respectively. As for GH, there was a significant group by age interaction (p = 0.01, such that GH was lower for BTHS patients under the age of 14.4 years and higher than controls after age 14.4 years. TNF-α levels were not significantly different, however, the TNF-α:GH was lower in BTHS patients than controls (p = 0.01. Conclusions Comparison of two anabolic growth mediators, IGF and GH, and two catabolic cytokines, IL-6 and TNF-α, in BTHS patients and healthy age-matched controls demonstrated a potential imbalance in inflammatory cytokines and anabolic growth factors. Higher rates of IL-6 (all ages and lower GH levels were observed in BTHS patients (under age 14.5 compared to controls. These findings may implicate inflammatory processes in the catabolic nature of Barth Syndrome pathology as well as provide a link to mitochondrial function. Furthermore, interactions between growth factors, testosterone and inflammatory mediators may explain some of the variability in cardiac and skeletal myopathies seen

  13. Correlation Between Th1, Th2 Cells and Levels of Serum MMP-2, MMP-9 in Children with Asthma

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    Xuan WANG

    2015-12-01

    Full Text Available Abstract Objective: To explore the correlation between Th1 and Th2 cells and the levels of serum matrix metalloproteinase-2 (MMP-2 and MMP-9 in children with asthma. Methods: A total of 89 children with asthma were divided into acute group (n=48 and chronic group (n=41 according to the course of disease, and 40 healthy children at the same term were collected as control group. The ratios of Th1 and Th2 cells as well as levels of MMP-2 and MMP-9 were compared in three groups, and the correlation between Th1 and Th2 cells and levels of MMP-2, MMP-9 was analyzed in acute group and chronic group. Results: When compared with control group, the ratios of Th1 and Th2 cells went down in both acute group and chronic group (P<0.01, while the levels of serum MMP-2 and MMP-9 up (P<0.01. The levels of serum MMP-2 and MMP-9 in acute group were dramatically higher than those in chronic group, and there was statistical significance (P<0.01. Pearson correlation analysis revealed that there was no significant correlation between Th1 and Th2 cells and MMP-2 level (r=0.148, P=0.314, r=0.299, P=0.058; r=0.183, P=0.214, r=0.289, P=0.067, whereas both Th1 and Th2 cells were negatively correlated with MMP-9 level in acute group and chronic group (r=-0.489, P=0.000, r=-0.324, P=0.039; r=-0.352, P=0.014, r=-0.357, P=0.022. Conclusion: Aberrant secretion of Th cells can not only damage the immune function of children with asthma, but also decrease the level of serum MMP-9, consequently affecting the collagen degradation and airway remodeling.

  14. 骨桥蛋白和MMP-2、MMP-9在鼻咽癌中的表达%Over Expression of Osteopontin and MMP-2 MMP-9 in Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    赵冬梅; 李彩云; 于庆凯

    2010-01-01

    目的 探讨骨桥蛋白(OPN)和基质金属蛋白酶2、9(MMP-2、MMP-9)在鼻咽癌组织中的表达及其意义.方法 应用免疫组化二步法,分另别检测OPN和MMP-2、MMP-9在正常对照组(7例)和鼻咽癌(45例)组织中的表达,其中鼻咽癌患者发生颈部淋巴结转移有25例.结果 ①鼻咽癌组织中OPN和MMP-2、MMP-9的阳性率明显高于正常对照组(P<0.05),其中淋巴结转移组表达明显增高(P<0.05).②鼻咽癌中OPN和MMP-2、MMP-9的表达与肿瘤的淋巴结转移相关(P<0.05).结论 OPN和MMP-2、MMP-9可能在鼻咽癌的发生发展和突破基底膜向外扩散及淋巴结转移中起到重要作用.

  15. Study on the Role of MMP-2、MMP-9 in the Metastasis of Breast Cancer%MMP-2、MMP-9在乳腺癌转移中作用的研究

    Institute of Scientific and Technical Information of China (English)

    李治; 帅晓明; 黄韬

    2006-01-01

    目的:了解MMP-2、MMP-9与乳腺癌局部侵袭、淋巴结转移情况的相关性,进而探讨MMP-2、MMP-9在乳腺癌转移发生的作用.方法:用免疫组化染色的方法检测不同患者MMP-2、MMP-9的表达情况,然后进行相关性的分析研究.结果:MMP-2的表达情况与乳腺癌的局部侵袭情况存在显著的相关性(P<0.01),MMP-9的表达情况与乳腺癌的淋巴结转移情况存在显著的相关性(P<0.01).结论:我们认为MMP-2、MMP-9作为MMPs(基质金属蛋白酶家族)中的重要成员,在乳腺癌转移发生过程中有促进作用且作用不同.

  16. Expression and Significance of MMP-9 and TIMP-1 in Malignant Peripheral Nerve Sheath Tumours%MMP-9及TIMP-1在恶性外周神经鞘膜瘤中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    齐云飞; 牟英君; 裴丽霞

    2007-01-01

    目的 探讨恶性外周神经鞘膜瘤(malignant peripheral nerve sheath tumours,MPNST)中基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及组织金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)的表达与病理分级、转移及预后的关系.方法 采用免疫组化S-P法检测MPNST中MMP-9及TIMP-1表达.结果 共检测了58例MPNST,其中MMP-9阳性表达率为89.7%(52/58),TIMP-1阳性表达率是60.3%(35/58).MMP-9蛋白酶的表达与病理学分级、转移率呈正相关,与术后生存率呈负相关;而TIMP-1则相反.结论 MMP-9、TIMP-1与MPNST病理学分级、转移及术后生存期有关,可作为判断恶性外周神经鞘膜瘤恶性程度及预后的可靠指标,为其治疗提供参考价值.

  17. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Ricardo C Ferreira

    2013-04-01

    Full Text Available Inflammation, which is directly regulated by interleukin-6 (IL-6 signaling, is implicated in the etiology of several chronic diseases. Although a common, non-synonymous variant in the IL-6 receptor gene (IL6R Asp358Ala; rs2228145 A>C is associated with the risk of several common diseases, with the 358Ala allele conferring protection from coronary heart disease (CHD, rheumatoid arthritis (RA, atrial fibrillation (AF, abdominal aortic aneurysm (AAA, and increased susceptibility to asthma, the variant's effect on IL-6 signaling is not known. Here we provide evidence for the association of this non-synonymous variant with the risk of type 1 diabetes (T1D in two independent populations and confirm that rs2228145 is the major determinant of the concentration of circulating soluble IL-6R (sIL-6R levels (34.6% increase in sIL-6R per copy of the minor allele 358Ala; rs2228145 [C]. To further investigate the molecular mechanism of this variant, we analyzed expression of IL-6R in peripheral blood mononuclear cells (PBMCs in 128 volunteers from the Cambridge BioResource. We demonstrate that, although 358Ala increases transcription of the soluble IL6R isoform (P = 8.3×10⁻²² and not the membrane-bound isoform, 358Ala reduces surface expression of IL-6R on CD4+ T cells and monocytes (up to 28% reduction per allele; P≤5.6×10⁻²². Importantly, reduced expression of membrane-bound IL-6R resulted in impaired IL-6 responsiveness, as measured by decreased phosphorylation of the transcription factors STAT3 and STAT1 following stimulation with IL-6 (P≤5.2×10⁻⁷. Our findings elucidate the regulation of IL-6 signaling by IL-6R, which is causally relevant to several complex diseases, identify mechanisms for new approaches to target the IL-6/IL-6R axis, and anticipate differences in treatment response to IL-6 therapies based on this common IL6R variant.

  18. IL-1β and IL-6 Are Highly Expressed in RF+IgE+ Systemic Lupus Erythematous Subtype

    Science.gov (United States)

    Zhang, Junlong; Shen, Beilei; Huang, Zhuochun; Tan, Chunyu; Baan, Carla C.

    2017-01-01

    Background. Systemic lupus erythematosus (SLE) is an autoimmune disease with great heterogeneity in pathogenesis and clinical symptoms. Rheumatoid factor (RF) is one key indicator for rheumatoid arthritis (RA) while immunoglobulin E (IgE) is associated with type I hypersensitivity. To better categorize SLE subtypes, we determined the dominant cytokines based on familial SLE patients. Methods. RF, IgE, and multiple cytokines (i.e., IL-1β, IL-6, IL-8, IL-10, IL-17, IFN-γ, IP-10, MCP-1, and MIP-1β) were measured in sera of familial SLE patients (n = 3), noninherited SLE patients (n = 108), and healthy controls (n = 80). Results. Three familial SLE patients and 5 noninherited SLE cases are with features of RF+IgE+. These RF+IgE+ SLE patients expressed significantly higher levels of IL-1β and IL-6 than the other SLE patients (P < 0.05). IL-6 correlated with both IgE and IL-1β levels in RF+IgE+ SLE patients (r2 = 0.583, P = 0.027; r2 = 0.847, P = 0.001), and IgE also correlated with IL-1β (r2 = 0.567, P = 0.031). Conclusion. Both IL-1β and IL-6 are highly expressed cytokines in RF+IgE+ SLE subtype which may be related to the pathogenesis of this special SLE subtype and provide accurate treatment strategy by neutralizing IL-1β and IL-6. PMID:28286780

  19. The role of matrix metalloproteinase MMP-9 and TIMP-2 tissue inhibitor of metalloproteinases as serum markers of bladder cancer.

    Science.gov (United States)

    Ramón de Fata, F; Ferruelo, A; Andrés, G; Gimbernat, H; Sánchez-Chapado, M; Angulo, J C

    2013-09-01

    The diagnosis and molecular staging of bladder cancer based on the detection of gelatinases mRNA (MMP-2 and MMP-9) in peripheral blood circulating and mononuclear cells have shown promising results. We analyze if the determination of the corresponding protein synthesis products makes it possible to diagnose and characterize patients with bladder cancer. Quantification of the serum levels of MMP-2, MMP-9 and TIMP-2 in a series of 42 individuals (31 patients with bladder cancer in different stages and 11 healthy controls) using the ELISA technique was carried out. The determinations were compared between cases and controls (Mann-Whitney U) and between different groups of tumors (Mann-Whitney U or Kruskal-Wallis), according to the clinical-pathological characteristics (age, gender, T category, M category or grade). Diagnostic yield of these markers was evaluated by analysis of the ROC curves. There is a correlation between the determinations of MMP-2 and TIMP-2 (R=.699; P>.0001) and MMP-9 and TIMP-2 (R=.305; P=.049). Patients with bladder cancer have higher levels of MMP-9 (p<0.0001) and TIMP-2 (P=.047) than the controls. Furthermore, the MMP-9/TIMP-2 ratio is also superior in cancer patients (P<.001). Differences were not detected between cancer and controls regarding age (P=.64) or gender (P=.64). Differences were also not detected regarding MMP-2 (P=.35) or MMP-2/TIMP-2 rate (P=.45). Within the cancer patient population, the MMP-2 and MMP-9 values differ according to T category (P=.022 and P=.038, respectively) and those of the TIMP-2 according to M category (P=.036). ROC curve analysis showed that both MMP-9 and the MMP-9/TIMP-2 ratio discriminate patients with cancer and controls, with equivalent diagnostic accuracy (ABC 0.953) and cut offs of 3.93 ng/mL (S 90%; Sp 81%) and 0.053 ng/mL (S 96%; Sp 84%), respectively. The results obtained suggest that both serum MMP-9 and TIMP-2 would have an application in the prediction of the development and progression of

  20. 膀胱癌组织中 MMP-2 MMP-9蛋白表达研究

    Institute of Scientific and Technical Information of China (English)

    刘新郑; 杨锦建; 马长路; 贺付成

    2008-01-01

    目的 探讨膀胱癌组织中MMP-2,MMP-9蛋白的表达及其与膀胱肿瘤恶性程度和侵袭性之间的关系.方法 采用免疫组化方法检测47例膀胱癌及10例正常膀胱组织中MMP-2、MMP~9的表达.结果 与正常对照组相比.膀胱癌组织中MMP-2、MMP-9蛋白的表达明显增高.随肿瘤分级、分期的增高MMP-9和MMP-2的高表达率增高(P<0.05),MMP-2、MMP-9的高表达率同肿瘤分级、分期呈正相关.结论 MMP-2、MMP-9的高表达与膀胱癌的恶性程度有关,在膀胱癌的发生发展中起重要作用,可用于判断膀胱癌恶性程度及预后.

  1. SDF-1/CXCR7 axis enhances ovarian cancer cell invasion by MMP-9 expression through p38 MAPK pathway.

    Science.gov (United States)

    Yu, Yuecheng; Li, Hongmei; Xue, Baoyao; Jiang, Xia; Huang, Kan; Ge, Junli; Zhang, Hongju; Chen, Biliang

    2014-08-01

    Ovarian cancer is an aggressive gynecological malignancy with high metastatic potential. Recently, the CXC receptor (CXCR7) has been identified as a new receptor for stromal-derived factor-1 (SDF-1), and exerts important roles in cancer development. However, its effect on ovarian cancer and the underlying mechanism remain unknown. In this study, we detected abundant CXCR7 expression in ovarian cancer tissues and cells. Moreover, SDF-1 induced dramatically upregulation of CXCR7 mRNA and protein levels, indicating that the SDF-1/CXCR7 axis existed in ovarian cancer. Further analysis confirmed that SDF-1 enhanced cell adhesion and subsequent invasion, which were significantly attenuated when pretreated with CXCR7 small interference RNA (siRNA), indicating the critical function of SDF-1/CXCR7 in cell invasion. Further mechanistic analysis indicated that SDF-1/CXCR7 enhanced cell invasion by matrix metalloproteinase (MMP)-9, as pretreatment with MMP-9 siRNA significantly abrogated a number of invading cells. Additionally, SDF-1/CXCR7 induced phosphorylation of the p38 MAPK pathway, which was accounted for MMP-9 expression as preconditioning with the p38 MAPK inhibitor SB203580 obviously decreased MMP-9 expression. Together, our data implied that SDF-1/CXCR7 enhanced ovarian cancer cell invasion by MMP-9 expression through the p38 MAPK pathway. Thus, these findings confirmed the critical role of SDF-1/CXCR7 during the pathological processes of ovarian cancer and supported its potential targets for further development of antiovarian cancer therapy.

  2. Zymographic patterns of MMP-2 and MMP-9 in the CSF and cerebellum of dogs with subacute distemper leukoencephalitis.

    Science.gov (United States)

    Machado, Gisele F; Melo, Guilherme D; Souza, Milena S; Machado, Andressa A; Migliolo, Daniela S; Moraes, Olívia C; Nunes, Cáris M; Ribeiro, Erica S

    2013-07-15

    Distemper leukoencephalitis is a disease caused by the canine distemper virus (CDV) infection. It is a demyelinating disease affecting mainly the white matter of the cerebellum and areas adjacent to the fourth ventricle; the enzymes of the matrix metalloproteinases (MMPs) group, especially MMP-2 and MMP-9 have a key role in the myelin basic protein fragmentation and in demyelination, as well as in leukocyte traffic into the nervous milieu. To evaluate the involvement of MMPs during subacute distemper leukoencephalitis, we measured the levels of MMP-2 and MMP-9 by zymography in the cerebrospinal fluid (CSF) and in the cerebellum of 14 dogs naturally infected with CDV and 10 uninfected dogs. The infected dogs presented high levels of pro-MMP-2 in the CSF and elevated levels of pro-MMP-2 and pro-MMP-9 in the cerebellar tissue. Active MMP-2 was detected in the CSF of some infected dogs. As active MMP-2 and MMP-9 are required for cellular migration across the blood-brain barrier and any interference between MMPs and their inhibitors may result in an amplification of demyelination, this study gives additional support to the involvement of MMPs during subacute distemper leukoencephalitis and suggests that MMP-2 and MMP-9 may take part in the brain inflammatory changes of this disease.

  3. 2-Deoxy glucose regulate MMP-9 in a SIRT-1 dependent and NFkB independent mechanism.

    Science.gov (United States)

    Edatt, Lincy; Haritha, K; Sruthi, T V; Aswini, P; Sameer Kumar, V B

    2016-12-01

    MMP9 is a member of the family of zinc-containing endopeptidases which degrade various components of the extracellular matrix, thereby regulating matrix remodeling. Since matrix remodeling plays an important role during growth and progression of cancer and considering the fact that, tumor cells switch to aerobic glycolysis as its major energy source, this study was designed to analyze if partial inhibition of glycolysis (the major energy pathway during hypoxia) can be used as a means to control matrix remodeling in terms of MMP9 activity and expression. For this, human epithelial carcinoma cells were treated with glycolytic inhibitor, 2-deoxy glucose (2DG) at sub-lethal concentrations followed by analysis of the expression and activity of MMP2 and MMP9. The experimental findings demonstrate that exposure of cancer cells to glycolytic inhibitor at concentration that does not induce ER stress, downregulates the activity and expression of MMP9 without affecting the expression levels and activity of MMP2. Further mechanistic analysis revealed that the regulation of MMP9 was mediated in a SIRT-1 dependent mechanism and did not alter the NFkB signaling pathway. The overall results presented here, therefore suggest that the use of glycolytic inhibitor, 2DG at concentration that do not affect cell viability or induce ER stress can be an effective strategy to control matrix remodeling.

  4. Pro-MMP-9 upregulation in HT1080 cells expressing CD9 is regulated by epidermal growth factor receptor.

    Science.gov (United States)

    Herr, Michael J; Mabry, Scott E; Jameson, Jessica F; Jennings, Lisa K

    2013-12-06

    Degradation of the surrounding extracellular matrix (ECM) by matrix metalloproteinases (MMPs) drives invasion and metastasis of cancer cells. We previously demonstrated that tetraspanin CD9 expression upregulates pro-MMP-9 expression and release and promotes cellular invasion in a human fibrosarcoma cell line (HT1080). These events were dependent upon the highly functional second extracellular loop of CD9. We report here that the epidermal growth factor receptor (EGFR) tyrosine kinase expression and activity are involved in the CD9-mediated increase in pro-MMP-9 release and cellular invasion. Pro-MMP-9 expression was significantly decreased in a dose-dependent manner using first a broad spectrum receptor tyrosine kinase inhibitor and multiple specific EGFR inhibitors in CD9-HT1080 cells. Furthermore, gefitinib treatment of CD9-HT1080 cells reduced invasion through matrigel. EGFR knockdown using short interfering RNA resulted in decreased pro-MMP-9 expression and release into the media and subsequent cellular invasion without affecting CD9 expression or localization. Conclusively, this study points to EGFR as a key mediator between CD9-mediated pro-MMP-9 release and cellular invasion of HT1080 cells. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Adenylyl cyclase-associated protein-1/CAP1 as a biological target substrate of gelatinase B/MMP-9.

    Science.gov (United States)

    Cauwe, Bénédicte; Martens, Erik; Van den Steen, Philippe E; Proost, Paul; Van Aelst, Ilse; Blockmans, Daniel; Opdenakker, Ghislain

    2008-09-10

    Matrix metalloproteinases (MMPs) are classically associated with the turnover of secreted structural and functional proteins. Although MMPs have been shown to process also a kaleidoscope of membrane-associated substrates, little is known about the processing of intracellular proteins by MMPs. Physiological and pathological cell apoptosis, necrosis and tumor lysis by chemotherapy, radiotherapy or immunological cytotoxicity, are examples of conditions in which an overload of intracellular proteins becomes accessible to the action of MMPs. We used a model system of dying human myelomonocytic cells to study the processing of intracellular protein substrates by gelatinase B/MMP-9 in vitro. Adenylyl cyclase-associated protein-1 or CAP1 was identified as a novel and most efficient substrate of gelatinase B/MMP-9. The presence of CAP1 in the extracellular milieu in vivo was documented by analysis of urine of patients with systemic autoimmune diseases. Whereas no active MMP-9 could be detected in urines of healthy controls, all urine samples of patients with clinical parameters of renal failure contained activated MMP-9 and/or MMP-2. In addition, in some of these patients indications of CAP1 cleavage are observed, implying CAP1 degradation in vivo. The high turnover rate of CAP1 by MMP-9, comparable to that of gelatin as the natural extracellular substrate of this enzyme, may be critical to prevent pathological conditions associated with considerable cytolysis.

  6. Association of Matrix Metalloproteinase-9 (MMP9 Variants with Primary Angle Closure and Primary Angle Closure Glaucoma.

    Directory of Open Access Journals (Sweden)

    Xueli Chen

    Full Text Available Shorter axial length observed in patients with primary angle closure glaucoma (PACG might be due to altered matrix metalloproteinase-9 (MMP9 activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC, and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07 or with PAC/PACG subgroups (Pc > 0.18. Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P 0.47. The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG.

  7. Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Hristina Obradović

    2016-01-01

    Full Text Available Interleukin 17 (IL-17 is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP- 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK activation. Our results imply that MMP-9 mediates IL-17’s capacity to inhibit myoblast differentiation during inflammatory diseases and indicate that Doxy can modulate myoblast response to inflammatory induction by IL-17.

  8. Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation.

    Science.gov (United States)

    Obradović, Hristina; Krstić, Jelena; Kukolj, Tamara; Trivanović, Drenka; Đorđević, Ivana Okić; Mojsilović, Slavko; Jauković, Aleksandra; Jovčić, Gordana; Bugarski, Diana; Santibañez, Juan Francisco

    2016-01-01

    Interleukin 17 (IL-17) is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP-) 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy) treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK activation. Our results imply that MMP-9 mediates IL-17's capacity to inhibit myoblast differentiation during inflammatory diseases and indicate that Doxy can modulate myoblast response to inflammatory induction by IL-17.

  9. Expressions of MMP-2 and MMP-9 during wound healing in rat skin%MMP-2、MMP-9在大鼠皮肤创面愈合过程中的表达

    Institute of Scientific and Technical Information of China (English)

    夏云; 张利远; 徐斌; 陈静; 陈淼

    2012-01-01

    Objective To investigate dynamic changes of metalloproteinase-2 (MMP-2) and MMP-9 expressions during wound healing in rat skin and their correlation. Methods Forty-two rats were used to establish dorsal skin wounds model and equally randomized into seven groups according to the times when the biopsies from skin wounds were harvested at 1,12,24 hours and 3,7,14,21 days after wounds formation, respectively. The other 3 rats were taken as the controls. The expressions of MMP-2 and MMP-9 in the samples were detected by immunohistochemistry. Results MMP-2 and MMP-9 were hardly expressed in normal skins of the control rats. The expression of MMP-2 increased gradually after injury and reached the peak on the 14th day,then decreased gradually to a certain level. The expression of MMP-9 increased rapidly and showed a high level from 24 hours to 7 days after injury, then decreased gradually to a low level. The expression level of MMP-2 was positively correlated to that of MMP-9 at 12 hours and 3,7,14,21 days and negatively correlated at 24 hours after injury. Conclusion The MMP-2 and MMP-9 expressions have certain rule and influence each other during wound healing in rats.%目的 探讨基质金属蛋白酶2 (MMP-2)、MMP-9在大鼠皮肤创面愈合过程中表达的动态及其相关性.方法 42只大鼠制作大鼠背部皮肤创面模型后按取创面皮肤时间随机均分为七组,即在创面形成后1、12、24 h及3、7、14、21d切取背部皮肤创面标本,采用免疫组化法检测标本中MMP-2及MMP-9的表达.另取3只正常大鼠背部皮肤标本作为对照.结果 正常大鼠皮肤中MMP-2、MMP-9几无表达;背部皮肤创面形成后,MMP-2逐渐升高,14 d达峰,21 d仍高于正常水平;MMP-9迅速升高,在24 h-7 d呈高水平表达,后逐渐降至较低水平;MMP-2与MMP-9的表达水平在12h,3、7、14、21d时呈正相关,在24 h时呈负相关.结论 在大鼠创面愈合过程中MMP-2和MMP-9的表达有一定规律,并且二者相互影响.

  10. Expression and significance of MMP-2,MMP-3 and MMP-9 in the gastric carcinoma%MMP-2、MMP-3和 MMP-9在胃癌患者中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    杨云鹏; 刘莉; 李慧

    2016-01-01

    目的:研究 MMP-2、MMP-3和 MMP-9在胃癌细胞转移中作用,进一步探讨 MMP-2、MMP-3和 MMP-9的临床意义。方法体外培养 SGC-7901胃癌细胞和 GES-1胃上皮细胞,划痕损伤实验模型和 Transwell 小室模型法检测这2种细胞的迁移, ELISA 法检测培养液中 MMP-2、MMP-3和 MMP-9的含量。免疫组化检测胃癌、胃炎患者和正常人 MMP-3的阳性率,ELISA 检测血清中 MMP-2、MMP-3和 MMP-9的含量。结果细胞划痕实验和 Transwell 实验均显示,SGC-7901细胞迁移能力强于 GES-1;SGC-7901分泌的3种蛋白含量均高于 GES-1;免疫组化结果显示,胃癌患者 MMP-3的阳性率84.4%,高于胃炎患者和正常人。其血清中 MMP-2、MMP-3和 MMP-9也明显高于胃炎患者和正常人。结论胃癌细胞的转移能力与 MMP-2、MMP-3和 MMP-9的含量相关,3种蛋白可用于胃癌的早期诊断。%Objecitive The research was in order to explore the roles of MMP-2,MMP-3 and MMP 9 which played in the gastric cancer cell metastasis,and make a further study of the clinical signifance.Methods Both SGC-7901 and GES-1 were cultured in vivo.The migra-tion were examined by Wound-healing and the Transwell assay.The expression of MMP-2,MMP-3 and MMP 9 in the medium were detected by ELISA.The positive rate of MMP-3 in the gastric cancer,gastritis and normal was used the IHC,and the serum of MMP-2,MMP-3 and MMP-9 were also examined by ELISA.Results Both Wound-healing and Transwell assay showed that the migration of SGC-7901 cells was more quicker than the GES-1.Comparing to GES-1,the MMP-2,MMP-3 and MMP-9 were higher in the SGC-7901.The immunohistochemical results showed that the positive rate of MMP-3 in the gastric cancer patients was 84.4%,it was higher than the latter.The serum levels of MMP-2 MMP-3 and MMP-9 were also significantly higher than others.Conclusion The migration of gastric cancer cells was depended on the MMP-2,MMP-3 and MMP-9.The 3 proteins can be used

  11. IκB-α、MMP-9在食管癌中的表达及其生物学意义%Expressions of IκB-αand MMP-9 in Esophageal Cancer and Its Biological Significance

    Institute of Scientific and Technical Information of China (English)

    刘亮; 王莉; 倪晓辰; 武中林; 王光大; 赵阳; 左静; 王静; 左连富

    2015-01-01

    Objective To detect the expressions of inhibitor of NF-κB α ( IκB-α) and matrix metalloprotein-9 (MMP-9) protein of nuclear factor kappa B (NF-κB) in different esophageal lesion tissues and to explore the relationship between IκB-α and MMP-9 expressions and pathogenesy, development and metastasis of esophageal cancer. Methods The IκB-α and MMP-9 protein expressions in esophagus squamous cell carcinoma, esophageal atypical hyperplasia and normal esophageal tunica mucosa tissues were detected using immunohistochemistry method;the relationship between the IκB-α and MMP-9 protein expressions in tissues of esophagus squamous cell carcinoma and different clinicopathological features were analyzed as well as the relationship between IκB-αand MMP-9 expressions in tissues of esophagus squamous cell carcinoma. Results The IκB-α protein expression in tissues of esophagus squamous cell carcinoma (80. 0%) was significantly higher than 52. 3% in tissues of esophageal atypical hyperplasia and 8. 3% in normal esophageal tissues, and the differences were statistically significant ( P0. 05). Conclusion The abnormal expressions of IκB-αand MMP-9 protein in esopha-geal cancer is involved in the invasion and metastasis of esophageal cancer.%目的 检测核因子κB(NF-κB)的抑制蛋白α(inhibitor of NF-κB α, IκB-α)及基质金属蛋白酶9(matrix metalloprotein-9,MMP-9)在不同食管病变组织中的表达,探讨IκB-α、MMP-9与食管癌发生、发展及转移的关系. 方法通过免疫组织化学检测食管鳞癌、食管不典型增生组织及食管正常黏膜组织中IκB-α、MMP-9蛋白的表达;分析食管鳞癌组织中IκB-α、MMP-9蛋白表达与不同临床病理特征的关系,并对食管鳞癌组织中IκB-α与MMP-9蛋白表达相关性进行分析. 结果 食管鳞癌组织中IκB-α蛋白的表达(80. 0%)明显高于食管不典型增生组织(52. 3%)及食管正常组织(8. 3%),差异有统计学意义(P0. 05). 结论 IκB-α、MMP

  12. Determinants of IL-6 levels during HIV infection

    DEFF Research Database (Denmark)

    Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2014-01-01

    INTRODUCTION: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD), cancer and death. Compared to the general population, treated HIV+ persons have 50-100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist....... MATERIAL AND METHODS: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT) with IL-6 plasma levels measured at baseline were included (N=9864). Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates...... corresponding to fold differences (FDs) in IL-6 were calculated. Demographics (age, gender, race, BMI) and HIV-specific variables (nadir and entry CD4 counts, HIV-RNA, use of different ART regimens) were investigated in all three trials. In SMART (N=4498), smoking, comorbidities (CVD, diabetes, hepatitis B...

  13. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat...... and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...

  14. Expressions of MMP-2 and MMP-9 in the Esophageal Squamous-celled Carcinoma%食管鳞癌组织中MMP-2和MMP-9的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    曹婧

    2016-01-01

    目的 探讨食管鳞癌组织中基质金属蛋白酶-2(MMP-2)和MMP-9的表达及临床意义.方法 采用免疫组化S-P法检测105例食管鳞癌和50例癌旁正常食管黏膜组织中MMP-2和MMP-9的表达.结果 食管鳞癌组织中MMP-2和MMP-9的阳性率分别为76.2%(80/105)、71.4% (75/105),癌旁正常食管黏膜组织中分别为6.0% (3/50)、8.0%(4/50),比较差异均有统计学意义( P均<0.05).食管鳞癌组织中MMP-2和MMP-9的表达与分化程度、浸润纤维膜与否、临床分期、淋巴结转移与否有关(P均<0.05).食管鳞癌组织中MMP-2和MMP-9的表达呈正相关关系(r=0.438,P<0.05).结论 MMP-2和MMP-9在食管鳞癌组织中均存在高表达,这与食管癌的疾病进展关系密切.

  15. Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

    Directory of Open Access Journals (Sweden)

    Angela P. Bastidas-Coral

    2016-01-01

    Full Text Available During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs. hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold, as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair.

  16. 肺癌患者血清MMP-9和TIMP-1检测的临床意义%The clinical significance of the measurement of serum MMP-9 and TIMP-1 in patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    王小军; 火云霞; 刘华; 李伟华; 潘辉; 蔡曦光

    2013-01-01

    Objective To investigate the serum expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of matrix metalloproteinase-l(TIMP-l) in lung cancer patients and healthy people,and its relationship with clinical pathological features, including staging, the degree of tumor differentiation, the size of tumor, the lymph node metastasis status and distant metastasis, etc. Methods The serum expression of MMP-9 and TIMP-1 in lung caner patients and healthy people were tested by ELISA and analyzed statistically. Results The serum expression of MMP-9 and TIMP-1 in lung caner patients were significantly higher than that of healthy people (P0. 05). Conclusion MMP-9 and TIMP-1 may take part in the progress of lung cancer,and could be used as clinical indicators to monitor the development of disease.%目的 研究基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制剂-1(TIMP-1)在肺癌患者和健康人血清中的含量,及其与分期、肿瘤分化程度、肿瘤大小、淋巴结转移状态、远处转移等病理特征的相关性.方法 通过酶联免疫吸附测定(ELISA)分别检测肺癌患者和健康对照者的血清样本中的MMP-9、TIMP-1的浓度,进行统计学分析.结果 MMP-9和TIMP-1在肺癌患者血清中的含量明显高于健康人群,差异有统计学意义(P<0.01);并与分期、肿瘤大小、淋巴结转移、远处转移呈正相关(P<0.05),与分化程度呈负相关(P<0.05);而与年龄、性别、吸烟史、肿瘤的病理类型无关(P>0.05).结论 MMP-9和TIMP-1参与肺癌的发生、发展、侵袭转移过程,可作为临床监测病情发展的指标.

  17. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer.

    Science.gov (United States)

    Dragutinović, Vesna V; Radonjić, Nevena V; Petronijević, Nataša D; Tatić, Svetislav B; Dimitrijević, Ivan B; Radovanović, Nebojša S; Krivokapić, Zoran V

    2011-09-01

    Colorectal cancer is one of the leading causes of cancer related death in developed countries. One of the reasons is the absence of tumor specific diagnostic and prognostic markers. The aim of this study was to examine the correlation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expressions in serum and clinicopathological features of the colorectal adenocarcinoma. Another aim was to examine expression of MMP-9 in the tissue of the colorectal carcinoma in MMP-9 serum positive patients. In addition, we tried to establish the correlation between preoperative levels of serum markers (CEA and CA 19-9) and presence of MMP-2 or MMP-9. The study was performed on 32 patients with colorectal adenocarcinoma who underwent surgery and 11 patients in a control group who were operated for benign diseases. The samples were analyzed by SDS-PAGE to determine the molecular mass and SDS-PAGE zymography to determine levels of MMP-2 and MMP-9. Expression of MMP-9 was determined immunohistochemically in the tissue of the colorectal carcinoma of MMP-9 serum positive patients. MMP-2 and MMP-9 levels were increased in the serum of the patients with colorectal cancer compared to the control group. There was significant correlation in MMPs levels among the patients with tumor stage I and II and the patients with tumor stage III and IV. Obtained results did not demonstrate correlation between levels of CEA, CA 19-9 and presence of MMP-2 or MMP-9. MMP-9 expression was positive in 85% of MMP-9 serum positive patients with colorectal carcinoma. The overexpression of MMP-2 and MMP-9 strongly suggests its association with colorectal adenocarcinoma. Detection of MMP-2 and MMP-9 in serum might be useful for identification of patients with higher risk for colorectal cancer recurrence.

  18. The effect of captopril on the expression of MMP-9 and the prognosis of neurological function in herpes simplex encephalitis mice.

    Science.gov (United States)

    Zhou, Yu; Zeng, Yan-Ping; Zhou, Qin; Guan, Jing-Xia; Lu, Zu-Neng

    2016-08-01

    Early increased matrix metalloproteinase-9 (MMP-9) expression is involved in the evolution of herpes simplex encephalitis (HSE) by facilitating the development of cerebrovascular complications. However, the molecular mechanism underlying the detrimental effects of MMP-9 in HSE has not been elucidated. Recent research finds angiotensin II plays an important role in regulation of MMP-9 activity. The aim of this work was to identify the influence of angiotensin-converting enzyme inhibitor (ACEI) captopril on MMP-9 activation after herpes simplex virus 1 (HSV-1) infection. Animal models of HSE were established by intracerebral inoculation of HSV-1 into mice. Brain tissue ROS levels were measured by staining with dihydroethidium. MMP-9 protein expression was detected by immunofluorescence and brain water content was measured with dry-wet weight method. Neurological function score was quantified 5 d after HSV-1 infection. Microglial cells were treated with various concentrations of captopril. MMP-9 gelatinolytic activity in the supematant of the cell cultures was assessed by zymography. RT-PCR was used to detect the mRNA expressions of p47phox and MMP-9. Immunofluorescence showed that expression of MMP-9 in brain tissue was mainly presented in OX-42 positive microglia. Quantification of gelatinolytic activity by densitometry showed that expression of MMP-9 in microglia was significantly increased after HSV-1 infection and inhibited by captopril treatment. NADPH oxidase subunit p47phox and MMP-9 mRNA expression were significantly increased 6 h after HSV-1 infection, and were seen reduced after captopril treatment in dose dependence. Captopril also downregulated ROS and MMP-9 protein expression following encephalitis in vivo, and attenuated brain edema, and improved neurological function. This compelling evidence suggests that MMP-9 is a key pathogenic factor within HSE. ACEI captopril could reduce the expression of MMP-9 mediated by ROS, then relieve cerebral edema and

  19. Loss of keratinocyte focal adhesion kinase stimulates dermal proteolysis through upregulation of MMP9 in wound healing.

    Science.gov (United States)

    Wong, Victor W; Garg, Ravi K; Sorkin, Michael; Rustad, Kristine C; Akaishi, Satoshi; Levi, Kemal; Nelson, Emily R; Tran, Misha; Rennert, Robert; Liu, Wei; Longaker, Michael T; Dauskardt, Reinhold H; Gurtner, Geoffrey C

    2014-12-01

    To investigate how epithelial mechanotransduction pathways impact wound repair. Mechanical forces are increasingly recognized to influence tissue repair, but their role in chronic wound pathophysiology remains unknown. Studies have shown that chronic wounds exhibit high levels of matrix metalloproteinase 9 (MMP9), a key proteolytic enzyme that regulates wound remodeling. We hypothesized that epithelial mechanosensory pathways regulated by keratinocyte-specific focal adhesion kinase (FAK) control dermal remodeling via MMP9. A standard wound model was applied to keratinocyte-specific FAK knockout (KO) and control mice. Rates of wound healing were measured and tissue was obtained for histologic and molecular analyses. Transcriptional and immunoblot assays were used to assess the activation of FAK, intracellular kinases, and MMP9 in vitro. A cell suspension model was designed to validate the importance of FAK mechanosensing, p38, and MMP9 secretion in human cells. Biomechanical testing was utilized to evaluate matrix tensile properties in FAK KO and control wounds. Wound healing in FAK KO mice was significantly delayed compared with controls (closure at 15 days compared with 20 days, P = 0.0003). FAK KO wounds demonstrated decreased dermal thickness and collagen density. FAK KO keratinocytes exhibited overactive p38 and MMP9 signaling in vitro, findings recapitulated in human keratinocytes via the deactivation of FAK in the cell suspension model. Functionally, FAK KO wounds were significantly weaker and more brittle than control wounds, results consistent with the histologic and molecular analyses. Keratinocyte FAK is highly responsive to mechanical cues and may play a critical role in matrix remodeling via regulation of p38 and MMP9. These findings suggest that aberrant epithelial mechanosensory pathways may contribute to pathologic dermal proteolysis and wound chronicity.

  20. Effect of fluvastatin on inflammatory factors, MMP-9, mAlb, Hcy and APN in patients with early diabetic nephropathy

    Institute of Scientific and Technical Information of China (English)

    Peng Ye; Dan Li; Li Chen; Xing Chen

    2016-01-01

    Objective:To investigate the effect of fluvastatin on inflammatory factors, MMP-9, mAlb, Hcy and APN in patients with early diabetic nephropathy.Methods:A total of 80 patients with early diabetic nephropathy were randomly divided into diet group (n=40) and fluvastatin group (n=40), and 40 healthy people were regarded as control group. The two groups both received low protein diet, and the fluvastatin group was additionally given fluvastatin. The treatment time of the two groups was 2 months. The levels of inflammatory factors, MMP-9, mAlb, Hcy and APN in the three groups before treatment, after treatment for 1 month, after treatment for 2 months were detected and compared, respectively.Results:Before treatment, the levels of hs-CRP, TNF-α, mAlb, Hcy and MMP-9 in diet and fluvastatin group were significantly higher while the level of APN was significantly lower than that in control group (P0.05), and there was significant difference of all indexes between diet and fluvastatin group (P0.05), while the level of mAlb decreased significantly than that before treatment and after treatment for 1 month in diet group (P<0.05), there were significant differences of the indexes (hs-CRP, TNF-α, MMP-9, Hcy and APN) between diet and fluvastatin group (P<0.05).Conclusions: Early diabetic nephropathy can lead to abnormal the levels of inflammatory factors, MMP-9, mAlb, Hcy and APN, fluvastatin can significantly improve inflammatory factors and the levels of MMP-9, mAlb, Hcy and APN in patients with early diabetic nephropathy.

  1. Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    BACKGROUND: Propofol  is  one  of  the  extensively  and commonly  used  intravenous  anesthetics  and  has  the  ability to  influence  the  proliferation,  motility,  and  invasiveness  of many  cancer  cells.  In  this  study,  the  effects  of  propofol  on hepatocellular carcinoma cells invasion ability were examined. METHODS: We assessed the invasion ability of HepG2 cells in vitro  by  determining  enzyme  activity  and  protein  expression of  MMP-9  using  gelatin  zymography  assay  and  Western  blot. The real-time PCR was used to evaluate the effect of propofol on  microRNA-199a  (miR-199a)  expression,  and  miR-199a-2 precursor  to  evaluate  whether  over-expression  of  miR-199a can affect MMP-9 expression. Finally, the effect of miR-199a on propofol-induced anti-tumor activity using anti-miR-199a was assessed. RESULTS: Propofol  significantly  elevated  the  expression of  miR-199a  and  inhibited  the  invasiveness  of  HepG2  cells. Propofol  also  efficiently  decreased  enzyme  activity  and protein  expression  of  MMP-9.  Moreover,  the  over-expression of miR-199a decreased MMP-9 protein level. Interestingly, the neutralization of miR-199a by anti-miR-199a antibody reversed the effect of propofol on alleviation of tumor invasiveness and inhibition of MMP-9 activity in HepG2 cells. CONCLUSION: Propofol  decreases  hepatocellular  carcinoma cell invasiveness, which is partly due to the down-regulation of MMP-9 expression by miR-199a.

  2. MMP-2、MMP-9及EMMPRIN在子宫内膜异位症中的表达及临床意义%Expression and significance of MMP-2, MMP-9 and VEGF in endometriosis

    Institute of Scientific and Technical Information of China (English)

    车建华; 潘文婧; 刘倩; 谭文华

    2011-01-01

    Objective: To investigate the expression and significance of EMMPRIN, MMP - 2 and MMP - 9 in endometriosis (Ems). Methods: The expression of MMP - 2, MMP - 9 and EMMPRIN in 42 cases of ectopic endometrium, 42 cases of eutopic en-dometrial and 20 cases of normal endometrium were detected by two - step immunohistochemical method, then the correlation of the expression of them was evaluated. Results: The MMP - 2, MMP - 9 and EMMPRIN positive expression rate was 95. 24%、 92. 86% and 90. 48% respectively in the ectopic endometrium group, which were significantly higher than their counterparts in the eutopic endorae-trial group and the normal endometrium group ( P < 0. 05 ) ; there was not significant difference between the eutopic endometrial group and the normal endometrium group. The expression of EMMPRIN protein was positively correlated with MMP - 2, 9 in the ectopic endometrium group (P <0. 01). Conclusion; EMMPRIN, MMP - 2 and MMP -9 are all involved in the process of invasionand tissue remodeling, which is supposed to be part of pathogenesis of endometriosis and EMMPRIN protein plays its role probably through activating MMP - 2, 9 synthesis and secretion.%目的 研究基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、细胞外基质金属蛋白酶诱导因子(EMMPRIN)在子宫内膜异位症(EMs)的表达和意义.方法 应用免疫组化二步法检测EMs患者异位内膜42例、在位内膜42例及正常内膜20例中的MMP-2、MMP-9、EMMPRIN的表达情况,并对它们的EMMPRIN、MMP-2、MMP-9蛋白表达水平进行相关性分析.结果 MMP-2、MMP-9、EMMPRIN在异位内膜组中阳性表达率分别为95.24%、92.86%和90.48%,显著高于在位内膜组、正常内膜组(P<0.05);而在位内膜组和正常内膜组差异无统计学意义(P>0.05).异位内膜组中,EMMPRIN分别和MMP-2,MMP-9呈正相关性(P<0.01).结论 MMP-2、MMP-9、EMMPRIN共同参与了子宫内膜异位症的发生

  3. MMP-2、MMP-9在乳腺导管癌中表达及意义%Expression and significance of MMP-2, MMP-9 in breast carcinoma

    Institute of Scientific and Technical Information of China (English)

    苏书娟; 邢鲁奇; 陈登庭; 邓淼

    2011-01-01

    Objective To research the expression and relationship of matrix metalloproteinase-2 ( MMP-2), metrix metalloproteinase-9(MMP-9) and collagen Ⅳ in breast ductal carcinoma. Methods Immunohistochemistry double staining was used to detect the expression of MMP-2, MMP-9 and collagen Ⅳ in 60 cases of breast ductal carcinoma and analyze their correlation. The relations between MMP-2, MMP-9 and breast ductal carcinoma tumor size, lymph node metastasis, and C-erbB-2 were analyzed. Results The positive expression rate of MMP-2 ,MMP-9 in breast ductal carcinoma was 75% and 80% ,respectively,which were significantly higher than the rate of 10% in normal breast tissues. MMP-2 and MMP-9 were expressed more strongly in the cancer cells approaching the basement membrane or breaking through the basement membrane. The positive expressions of MMP-2 and MMp-9 in the tumor diameter > 2em, with lymph node metastasis, and C-erbB-2 positive group were 83.9% and 90. 3% ,87.0% and 91.3% ,and 80. 9% and 85. 1% ,which were significantly higher than 58.6% and 65.5% ,64. 9% and 67. 6% ,and 46. 2% and 53. 8% of the correponding control groups. Collagen Ⅳ expression and the expression of MMP-2, MMP-9 was negatively correlated. Conclusion The degradation of collagen Ⅳ related to MMP-2 and MMP-9 may play an important role in local invasive and distant metastasis of breast ductal carcinoma. The expressions of MMP-2 ,MMP-9 and collagen Ⅳ may have reference value in determining the invasive and metastatic potential of breast carcinoma and evaluating prognosis.%目的 研究乳腺导管癌中基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达及与Ⅳ型胶原(collagenⅣ)的关系.方法 免疫组化双染法检测60例乳腺导管癌中MMP-2、MMP-9和Ⅳ型胶原的表达并分析其相关性及与肿瘤大小、淋巴结转移及人类表皮生长因子受体-2(C-erbB-2)的关系.结果 MMP-2、MMP-9在乳腺导管癌中

  4. Serum IL-6 level and associated factors: hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Seifi S, Mokhtari A

    2008-07-01

    Full Text Available "nBackground: The annual amount of mortality in ESRD exceeds the expectation and represents the recent evidences of the inflammation as its etiology. The etiology of inflammation is not clearly known. Chronic inflammation is a dominant occurrence of ESRD which increases the risk of atherosclerosis, malnutrition and peripheral vascular disease. Inflammatory responses are orchestrated by cytokines. Some of the proinflammatory cytokines like IL-6 have a crucial role in this phenomenon. The IL-6 and its receptor activity is up regulated in ESRD patients and the increased level of IL-6 predicts cardiovascular mortality and morbidity in normal and CRF patients. This study devotes itself to determining the serum level of IL-6 and factors affecting it in patients undergoing chronic hemodialysis in Imam Khomeini Hospital which can represent the Iranian Society. By identifying factors affecting the serum level of IL-6 and high-risk patients we can provide treatment possibilities, a decrease in mortality and an improvement in its prognosis. "n"nMethods: In this study 42 patients in Imam Dialysis Center were chosen and their serum IL-6 levels were measured at 2 times at three month interval and at the same time blood sample analysis were done for the following: Alb CPR, Ca, P, PTH, TIBC, Ferritin, TG, Chol, LDL, HDL, Uric Acid, Hb, WBC and urea."n"nResults: The mean serum level of IL-6 in hemodialysis patients was 6.35±4.47pg/ml (minimum: 0.55, maximum: 18.25 with the normal range of 1.3±3.2pg/ml."n"nConclusions: The IL-6 level was higher than normal range in the 52% of the patients. The serum IL-6 level had a significant correlations with CPR, Ferritin, TIBC, WBC and their serum IL-6 level was significantly higher in patients with hypertension, but no significant correlation was observed between other parameters and IL-6

  5. Recent advances in neutralizing the IL-6 pathway in arthritis

    Directory of Open Access Journals (Sweden)

    Charles J Malemud

    2009-10-01

    Full Text Available Charles J MalemudDivision of Rheumatic Diseases, Case Western Reserve University, School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio, USAAbstract: Recent advances in understanding the mechanism(s of how IL-6 trans-signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. Serum and/or synovial fluid (SF IL-6 is markedly elevated in adult and juvenile rheumatoid arthritis (RA, psoriatic arthritis (PsA, ankylosing spondylitis (AS and osteoarthritis (OA. IL-6, in concert with IL-17, determines the fate of CD4+ lymphocytes and therefore TH17 cell differentiation. IL-6 also plays a critical role in modulating B-lymphocyte activity. The recognition that IL-6 trans-signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R. Significant clinical benefit was demonstrated as well as reduced serum IL-6 levels with suppression of X-ray progression of disease in several clinical trials in which juvenile or adult RA patients were treated with tocilizumab monotherapy or tocilizumab plus methotrexate. However, levels of serum and/or SF IL-6 cytokine protein superfamily members, adiponectin, oncostatin M, pre-B-cell colony enhancing factor/visfatin and leukemia inhibitory factor are also elevated in RA. Additional studies will be required to determine if anti-IL-6 trans-signaling inhibition strategies with tocilizumab or recombinant soluble IL-6R reduce the level of these cytokines.Keywords: interleukin-6, interleukin-6/interleukin-6 receptor/glycoprotein 130, JAK/STAT pathway, SAP/MAPK pathway, osteoarthritis, rheumatoid arthritis

  6. IL-6 Potentiates Tumor Resistance to Photodynamic Therapy (PDT)

    Science.gov (United States)

    Brackett, Craig M.; Owczarczak, Barbara; Ramsey, Kimberley; Maier, Patricia G.; Gollnick, Sandra O.

    2013-01-01

    Background and Objective Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy. Study Design/Materials and Methods In the current study we used mice deficient for IL-6, Il6−/−, to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity. Results Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murine colon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6−/− mice 24 hours following PDT. Conclusions The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered. PMID:22057495

  7. 166 Assessment of Chronic Spontaneous Urticaria by Serum-Induced TNF & ALPHA; and MMP-9 Release

    OpenAIRE

    Falkencronec, Sidsel; Poulsen, Lars; Maurer, Marcus; Bindslev-Jensen, Carsten; Skov, Per Stahl

    2012-01-01

    Background Previous studies from our group have demonstrated that IgE-mediated basophil activation leads to release of TNFα that in turn can induce matrix metallo-proteinase-9 (MMP-9) release from monocytes. We wished to investigate if serum from chronic spontaneous urticaria-patients with auto-antibodies against IgE/IgE-receptor could induce TNFα and MMP-9 release from donor PBMCs, and if release levels could be used to assess severity and activity of chronic spontaneous urticaria (CSU). Met...

  8. Effect of Cerium on Expression and Activity of MMP-9 from Human Carcinoma of Bladder Cell Line

    Institute of Scientific and Technical Information of China (English)

    李瑾; 胡国武; 欧阳砥; 牛瑞芳; 周永洽; 申泮文

    2004-01-01

    The effects of Ce4+ on cell survival,expression and activity of matrix metalloproteinase-9(MMP-9)with MTT colorimetry and gelatin zymography assays in human bladder carcinoma cell line was studied.The results indicate that the lower concentration of Ce4+(0.01 mmol*L-1)has no influence on cell growth,but inhibits extremely expression of MMP-9 and increases its activity,whereas the higher concentration of Ce4+(1.0 mmol*L-1)can inhibit all of them.The results raise the possibility that Ce4+ may have beneficial effects in attenuating invasion and metastasis of malignant tumors.

  9. Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells.

    Science.gov (United States)

    Li, Xiang; Zhao, Shu-Juan; Shi, Hai-Lian; Qiu, Shui-Ping; Xie, Jian-Qun; Wu, Hui; Zhang, Bei-Bei; Wang, Zheng-Tao; Yuan, Jian-Ye; Wu, Xiao-Jun

    2014-12-01

    Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-κB and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin. In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8‑independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-κB. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of Jak2/PI3K/NF-κB/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.

  10. Expression and Clinical Significance of MMP-9 and CD147 in Salivary Adenoid Cystic Carcinoma%MMP-9、CD147在涎腺腺样囊性癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    任洁琼; 赵艳琴; 范熙明; 南欣荣

    2012-01-01

    目的:联合检测人涎腺腺样囊性癌组织中MMP-9、CD147的表达并分析其相关性,探讨其与临床病理参数间的关系,为腺样囊性癌的临床治疗和预后判断提供理论依据.方法:选择山西医科大学第一医院病理科存档的腺样囊性癌组织标本21例(癌组),正常涎腺组织6例(对照组).21例腺样囊性癌分别依据临床分期、有无侵犯神经进行分组.运用免疫组织化学PV-9000二步法检测MMP-9、CD147,结果用SPSS 13.0软件分析.结果:MMP-9及CD147在腺样囊性癌组中的阳性表达率(分别为76.2%和81.0%)明显高于在对照组中的阳性表达率(分别为16.7%和16.7%),差异有统计学意义(分别为P<0.05和P<0.01).Ⅲ+Ⅳ期腺样囊性癌病例MMP-9及CD147的阳性表达率(均为100.0%),明显高于Ⅰ+Ⅱ期病例(分别为44.4%和55.6%),差异有统计学意义(分别为P<0.01和P<0.05).有无侵犯神经的病例组间比较,MMP-9及CD147的表达差异没有统计学意义(P>0.05).MMP-9和CD147在腺样囊性癌组织中均呈阴性、弱阳性、阳性、强阳性表达者分别为4、5、7和3例,表达一致率为90.5%,Kappa值为0.870.结论:MMP-9和CD147均可作为反映腺样囊性癌细胞生物学行为的客观参考指标,其表达与临床分期密切相关,且二者之间的表达有正相关.%Objective: To investigate the expression of matrix metalloproteinase (MMP)-9 and CD147 in human salivary adenoid cystic carcinoma (SACC) tissues and their correlations. Methods: 21 cases of human SACC tissues and 6 cases of normal human salivary tissues were examined by immunohistochemical method. The relationship between the expression and clinical-pathological behaviors was also analyzed. Follow-up data were statistically analyzed. Results: The expression of MMP-9 and CD 147 in SACC tissues was higher than those in normal salivary tissues. Positive expression rate of MMP-9 and CD147 in SACC tissues was 76.2% and 81.0% respectively

  11. IL6 gene promoter polymorphisms and type 2 diabetes

    DEFF Research Database (Denmark)

    Huth, Cornelia; Heid, Iris M; Vollmert, Caren;

    2006-01-01

    Several lines of evidence indicate a causal role of the cytokine interleukin (IL)-6 in the development of type 2 diabetes in humans. Two common polymorphisms in the promoter of the IL-6 encoding gene IL6, -174G>C (rs1800795) and -573G>C (rs1800796), have been investigated for association with type...... 2 diabetes in numerous studies but with results that have been largely equivocal. To clarify the relationship between the two IL6 variants and type 2 diabetes, we analyzed individual data on >20,000 participants from 21 published and unpublished studies. Collected data represent eight different...... countries, making this the largest association analysis for type 2 diabetes reported to date. The GC and CC genotypes of IL6 -174G>C were associated with a decreased risk of type 2 diabetes (odds ratio 0.91, P = 0.037), corresponding to a risk modification of nearly 9%. No evidence for association was found...

  12. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  13. IL-6 selectively stimulates fat metabolism in human skeletal muscle

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2010-01-01

    and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ~40 and ~1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed...... in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis...... in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein...

  14. Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in Gambians

    Directory of Open Access Journals (Sweden)

    Joof Hassan

    2009-12-01

    Full Text Available Abstract Background Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring leading to in-turning of eyelashes (trichiasis and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population. Methods Linkage disequilibrium (LD mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR analyses. Results LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8 and granulocyte-macrophage colony stimulatory factor (CSF2 loci. The IL8-251 rare allele (IL8-251 TT was associated with protection from scarring trachoma (OR = 0.29 p = 0.027. The intronic CSF2_27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005. There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade. Conclusion innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma.

  15. Expression of MMP-9 and TIMP-1 in juvenile rats with chronic heart failure%MMP-9、TIMP-1在心力衰竭幼鼠心肌中的表达

    Institute of Scientific and Technical Information of China (English)

    梅峻; 谷丽; 陆凤凤; 杨蓉

    2012-01-01

    Objective To investigate the expression of MMP-9 and TIMP-1 in juvenile rats with chronic heart failure. Methods Male Wistar juvenile rats were randomly assigned to sham operation group and model group. The CHF animal model was induced by Massart PE method. The left ventricular end-diastolic pressure (LVEDP) were monitored by multiple channels electrophysiological apparatus; the expression of MMP-9 and TIMP-1 in myocardium was evaluated by qualitative and semiquantitative immunohistochemical staining; the collagen in left ventricular interstitial tissue was examined by Masson staining. Collagen volume fraction (CVF) and peri vascular collagen area(PVCA) were measured by image analysis. Results Compared with the sham-group, the ventricular mass index(LVMI), CVF, PVCA and the expression of MMP-9 and MMP-9/TIMP-1 in left ventricle increased in model group(P <0.05). Compared with the sham-group, the expression of TIMP-1 in left ventricle decreased in model group. Conclusion The results indicate that disturbed expression of MMP-9/TEMP-1 system may be associated with the development of myocardial remodeling in juvenile rats with congestive heart failure.%目的 探讨基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子(TIMP-1)在心力衰竭幼鼠心室重塑中的作用.方法 雄性Wistar幼鼠随机分为二组,对照组(sham)和心力衰竭组(model).采用腹主动脉缩窄法(Massart PE法)[1]对模型组幼鼠制作充血性心力衰竭动物模型,用免疫组化法检测两组幼鼠心室肌中MMP-9、TIMP-1的表达;用多道电生理仪监测2组幼鼠左室舒张末压(LVEDP),用MASSON染色法观察血管周围胶原面积(PVCA),图像分析测量胶原容积分数(CVF).结果 左室舒张末压(LVEDP)、图像分析测量胶原容积分数(CVF)、血管周围胶原面积(PVCA)、MMP-9MMP-9/TIMP-1比值在模型组幼鼠明显高于对照组幼鼠,差别有统计学意义(P<0.01);TIMP-1在模型组幼鼠心肌表达较对照组明显

  16. 二至丸对诱发性乳腺癌组织中VEGF和MMP-9表达的影响%Effect of Erzhi Pills on Expressions of VEGF and MMP-9 in Induced Rat Brest Cancer

    Institute of Scientific and Technical Information of China (English)

    尚广彬; 曾莉萍; 赵益; 张启云; 董伟; 汤喜兰; 徐国良; 朱卫丰; 刘红宁

    2013-01-01

    目的:研究滋阴方二至丸对二甲基苯蒽(DMBA)诱发性乳腺癌大鼠肿瘤组织中血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)表达的影响.方法:60只雌性SD大鼠随机分为空白对照组、DMBA模型组、二至丸高、中、低(6.4,3.2,1.6 g·kg-1)剂量组和三苯氧胺(TAM)组.除空白对照组外,每只大鼠均以致癌剂DMBA诱导(剂量100 mg·kg-1,2次,间隔1周)乳腺癌.诱导第2天开始给予药物干预,每周触诊所有大鼠乳腺肿瘤发生情况并记录体重变化;15周后处死动物,统计各组大鼠乳腺肿瘤的发病率,并采用SP免疫组化法检测各组动物肿瘤组织中VEGF,MMP-9的表达情况.结果:与DMBA模型组比较,二至丸中剂量组和TAM组大鼠乳腺肿瘤平均潜伏期延长(P<0.05),平均肿瘤直径、平均肿瘤体积、平均瘤重显著降低(P<0.05);二至丸中、高剂量组VEGF和MMP-9强阳性率显著性降低(P<0.05),且VEGF与MMP-9的表达呈正相关.结论:滋阴方药二至丸可能通过干预乳腺癌组织中VEGF和MMP-9的表达,抑制乳腺癌生长恶化.%Objective:To explore the effect of Erzhi pills on expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in brest cancer induced by 7,12-dimethylbenz (a) anthrancene (DMBA) in rats.Method:Sixty female SD rats were randomly divided into 6 groups:the blank control group,the DMBA model group,the high,middle,low dose (6.4,3.2,1.6 g ·kg-1,respectively) Erzhi Pills group and tamoxifen (TAM) group.All model rats were induced by DMBA (100 mg ·kg-1,twice,every two weeks),palpated weekly to monitor the progress of the tumor and body weight were also recorded weekly.At the end of trial,the incidence of breast tumors in each group was calculated.And the expressions of VEGF and MMP-9 in breast cancer tissues were detected using immunohistochemical SP method.Result:Comparing with the DMBA model group,the breast cancer incidence,number and volume of

  17. MMP-9和 Fascin 蛋白在口腔扁平苔藓中的表达及相关性研究%Expression and correlation of MMP-9 and Fascin in oral lichen planus

    Institute of Scientific and Technical Information of China (English)

    刘长欢; 金玲; 丁丽娜; 陈英新

    2016-01-01

    Objective To examine the expression and correlation of MMP-9 and Fascin in oral lichen planus(OLP). Methods The expression of MMP-9 and Fascin in 35 cases of normal oral mucosa,45 cases of oral lichen planus and 46 cases of oral squamous cell carcinoma(OSCC)was examined by immunohistochemical technique.The data was analyzed by SPSS,a exact test using software package.Results the expression of MMP-9 in normal oral mucosa,oral lichen pla-nus and oral squamous cell carcinoma rises in turn.The positive rate respectively is 11.4%(4/35)、66.7%(30/45)、89. 1%(41/46),the comparison among groups is statistically significant(P <0.05);The expression of Fascin in normal o-ral mucosa,oral lichen planus and oral squamous cell carcinoma rises in turn.The positive rate respectively is 0%(0/35)、15.6%(7/45)、69.6%(32/46),the comparison among groups is statistically significant(P <0.05);In oral lichen planus,the expression of MMP-9 is positively correlative with that of Fascin(P <0.05).Conclusion MMP-9 and Fas-cin not only respectively paly an important role in cancerous progress of oral lichen planus but also the two factor work together to promote the cancerous progress.%目的:检测 MMP-9和 Fascin 蛋白在口腔扁平苔藓中的表达情况,探讨两者在扁平苔藓发病机制中的作用及相关性。方法采用免疫组化技术检测 MMP-9和 Fascin 蛋白在35例口腔正常黏膜组织、45例口腔扁平苔藓和46例口腔鳞状细胞癌组织中的表达。应用 SPPSS 软件对实验结果进行卡方检验和 Spearman 相关分析。结果MMP-9在口腔正常黏膜组织、口腔扁平苔藓和口腔鳞状细胞癌组织中的表达依次增高,表达率分别为11.4%(4/35)、66.7%(30/45)、89.1%(41/46),组间差别有统计学意义(P <0.05);Fascin 在口腔正常黏膜组织、口腔扁平苔藓和口腔鳞状细胞癌组织中的表达率依次增高表达率分别为0%(0/35)、15.6%(7/45

  18. Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

    NARCIS (Netherlands)

    de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

    1999-01-01

    The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma

  19. Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia

    NARCIS (Netherlands)

    de Bont, ESJM; Vellenga, E; Swaanenburg, JCJM; Fidler, [No Value; Visser-van Brummen, PJ; Kamps, WA

    1999-01-01

    The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. Ih this study plasma interleukin

  20. Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Abdul-Hussien, H.; Schaapherder, A.F.M.; Bockel, J.H. van; Thüsen, J.H. vonder; Roelen, D.L.; Kleemann, R.

    2008-01-01

    Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in

  1. Serum IL-1β, sIL-2R, IL-6, IL-8 and TNF-α in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment

    Directory of Open Access Journals (Sweden)

    Ayşe Binnur Erbağci

    2001-01-01

    Full Text Available Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation.

  2. CIL-102 induces matrix metalloproteinase-2 (MMP-2)/MMP-9 down-regulation via simultaneous suppression of genetic transcription and mRNA stability.

    Science.gov (United States)

    Liu, Wen-Hsin; Chen, Yeh-Long; Chang, Long-Sen

    2012-12-01

    This study explores the CIL-102 suppression mechanism on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in human leukemia K562 cells. CIL-102 attenuated K562 cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels. Moreover, CIL-102 reduced luciferase activity of MMP-2/MMP-9 promoter constructs and MMP-2/MMP-9 mRNA stability. CIL-102 treatment induced JNK and p38 MAPK activation but reduced the phospho-ERK level. Transfection of constitutively active MEK1 restored MMP-2 and MMP-9 promoter activity in CIL-102-treated cells, while suppression of p38 MAPK/JNK activation abolished CIL-102-induced MMP-2/MMP-9 mRNA decay. CIL-102-induced p38 MAPK/JNK activation led to protein phosphatase 2A-mediated tristetraprolin (TTP) down-regulation. The reduction in TTP-KH-type splicing regulatory protein (KSRP) complexes formation promoted KSRP-mediated MMP-2/MMP-9 mRNA decay in CIL-102-treated K562 cells. Moreover, CIL-102 reduced invasion and MMP-2/MMP-9 expression in breast and liver cancer cells. Taken together, our data indicate that CIL-102 induces MMP-2/MMP-2 down-regulation via simultaneous suppression of genetic transcription and mRNA stability, and suggest a potential utility for CIL-102 in reducing MMP-2/MMP-9-mediated cancer progression.

  3. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  4. Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening

    Directory of Open Access Journals (Sweden)

    John J. O'Leary

    2013-01-01

    Full Text Available Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9 as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant and A2780 (cisplatin-sensitive ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R-2-[(4-Biphenylsulfonyl amino]-3 phenylpropionic acid (C21H19NO4S resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.

  5. Purification and characterization of recombinant full-length and protease domain of murine MMP-9 expressed in Drosophila S2 cells

    DEFF Research Database (Denmark)

    Rasch, Morten G; Lund, Ida K.; Illemann, Martin

    2010-01-01

    . No immunoreactivity was observed when the antibody was probed against skin wound material from MMP-9 deficient mice. In conclusion, we have generated and purified two proteolytically active recombinant murine MMP-9 protein constructs, which are critical reagents for future cancer drug discovery studies....... MMP-9. Constructs encoding zymogens of full-length murine MMP-9 and a version lacking the O-glycosylated linker region and hemopexin domains were therefore generated and expressed in stably transfected Drosophila S2 insect cells. After 7 days of induction the expression levels of the full...

  6. Matrix Metalloproteinase-3 (MMP-3 Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Directory of Open Access Journals (Sweden)

    Arturo Flores-Pliego

    Full Text Available The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9 it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation.Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence.Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05, when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05 and up to 72 h (P≤0.001, when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005 when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells.In this work we confirm that placental leukocytes from

  7. A Common Variant of IL-6R is Associated with Elevated IL-6 Pathway Activity in Alzheimer's Disease Brains.

    Science.gov (United States)

    Haddick, Patrick C G; Larson, Jessica L; Rathore, Nisha; Bhangale, Tushar R; Phung, Qui T; Srinivasan, Karpagam; Hansen, David V; Lill, Jennie R; Pericak-Vance, Margaret A; Haines, Jonathan; Farrer, Lindsay A; Kauwe, John S; Schellenberg, Gerard D; Cruchaga, Carlos; Goate, Alison M; Behrens, Timothy W; Watts, Ryan J; Graham, Robert R; Kaminker, Joshua S; van der Brug, Marcel

    2017-01-01

    The common p.D358A variant (rs2228145) in IL-6R is associated with risk for multiple diseases and with increased levels of soluble IL-6R in the periphery and central nervous system (CNS). Here, we show that the p.D358A allele leads to increased proteolysis of membrane bound IL-6R and demonstrate that IL-6R peptides with A358 are more susceptible to cleavage by ADAM10 and ADAM17. IL-6 responsive genes were identified in primary astrocytes and microglia and an IL-6 gene signature was increased in the CNS of late onset Alzheimer's disease subjects in an IL6R allele dependent manner. We conducted a screen to identify variants associated with the age of onset of Alzheimer's disease in APOE ɛ4 carriers. Across five datasets, p.D358A had a meta P = 3 ×10-4 and an odds ratio = 1.3, 95% confidence interval 1.12 -1.48. Our study suggests that a common coding region variant of the IL-6 receptor results in neuroinflammatory changes that may influence the age of onset of Alzheimer's disease in APOE ɛ4 carriers.

  8. Expression of CD147 protein and MMP-9 and the significance in patients with adenomyosis%CD147蛋白和MMP-9在子宫腺肌病中的表达和意义

    Institute of Scientific and Technical Information of China (English)

    邹宁; 任云青; 李培莉; 薛丽萍

    2011-01-01

    Objective:To study the expression of CD147 and MMP-9 protein in patients with adenomyosis as well as their serun levels of soluble CD 147 in order to investigate their roles in the pathogenesis of adenomyosis. Methods: Immunohistochemistry was performed to dezect the expression of CD147 and MMP-9 protein in ectopic endometrium and eutopic endometrial tissues of 37 patients with adenomyosis(AM group) and endometrial tissues of 20 patients only with hysteromyoma( control group). The correlation between the expressions of CD147 and MMP-9 protein was evaluated. ELISA was used to detect the level of soluble CD147 proteins in the peripheral blood of AM group (37 cases with adenomyosis)and control groups(20 cases with hysteromyoma and 20 healthy cases). Results:The expression of CD147 and MMP-9 proteins in glandular and stromal cells in ectopic and eutopic endometrium of the patients with AM were significantly higher than in control group( P < 0.01 ), and the expression of CD147 and MMP-9 protein was much higher in ectopic endometrium than in eutopic endometrium of the patients with AM.The expression of CD147 protein was positively correlated with MMP-9 in patient with AM.The serum levels of soluble CD147 was much higher in AM groups than in both control group with hysteromyoma ( P > 0.05) and healthy group ( P < 0.05). Conclusion: The higher expression of CD147 protein and MMP-9 in ectopic and eutopic endometrium and serum levels of sCD147 may play an important role in the pathogenesis of AM,and CD147 protein plays its role probably through activating MMP-9 synthesis and secretion.%目的:研究CD147蛋白、MMP-9在子宫腺肌病患者组织中的表达及血清中可溶性CD147(sCD147)蛋白水平,探讨其在子宫腺肌病中的作用机制.方法:采用免疫组织化学SP法检测37例子宫腺肌病患者(子宫腺肌病组)子宫异位内膜、在位内膜及20例子宫肌瘤患者(对照组)子宫内膜组织中CD147蛋白和MMP-9的表达,并对其蛋

  9. Concentration Kinetics of Serum MMP-9 and TIMP-1 after Blunt Multiple Injuries in the Early Posttraumatic Period

    Directory of Open Access Journals (Sweden)

    M. Brumann

    2012-01-01

    Full Text Available Metalloproteinases are secreted in response to a variety of inflammatory mediators and inhibited by tissue inhibitors of matrixmetalloproteinases (TIMPs. Two members of these families, MMP-9 and TIMP-1, were differentially expressed depending on clinical parameters in a previous genomewide mRNA analysis. The aim of this paper was now to evaluate the posttraumatic serum levels and the time course of both proteins depending on distinct clinical parameters. 60 multiple traumatized patients (ISS > 16 were included. Blood samples were drawn on admission and 6 h, 12 h, 24 h, 48 h, and 72 h after trauma. Serum levels were quantified by ELISA. MMP-9 levels significantly decreased in the early posttraumatic period (P<0.05 whereas TIMP-1 levels significantly increased in all patients (P<0.05. MMP-9 and TIMP-1 serum concentration kinetics became manifest in an inversely proportional balance. Furthermore, MMP-9 presented a stronger decrease in patients with severe trauma and non-survivors in contrast to minor traumatized patients (ISS ≤ 33 and survivors, initially after trauma.

  10. A novel ameloblastoma cell line (AM-3) secretes MMP-9 in response to Wnt-3a and induces osteoclastogenesis.

    Science.gov (United States)

    Kibe, Toshiro; Fuchigami, Takao; Kishida, Michiko; Iijima, Mikio; Ishihata, Kiyohide; Hijioka, Hiroshi; Miyawaki, Akihiko; Semba, Ichiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Shosei

    2013-06-01

    Ameloblastoma has a high risk of bone invasion and local recurrence. However, the mechanisms of bone invasion in ameloblastoma remain unclear. In this study, we established an experimental model for matrix metalloproteinase (MMP) induction and osteoclastogenesis using ameloblastoma-derived cells. We established an ameloblastoma-derived cell line without viral genes and analyzed the expression of all Wnt and Frizzled members and MMPs by real-time reverse transcription-polymerase chain reaction, and analyzed the activity of MMP-2 and MMP-9 by the in-gel-gelatinase assay. AM-3, newly established ameloblastoma-derived cells retained the morphology of primary-cultured ameloblastoma cells. AM-3 cells overexpressed the messenger RNA of Wnt-5a, Frizzled-2, MMP-2, and MMP-9 and showed the potential of osteoclastogenesis. In addition, Wnt-3a-treatment induced expression and activation of MMP-9 in AM-3 cells. Our study suggests that AM-3 cells retained the characteristics of ameloblastoma, without acquiring typical features of cancer cells. Furthermore, Wnt signaling induced MMP-9 in ameloblastoma cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. X-ray imaging of differential vascular density in MMP-9-/-, PAR-1-/+, hyperhomocysteinemic (CBS-/+) and diabetic (Ins2-/+) mice.

    Science.gov (United States)

    Givvimani, S; Sen, U; Tyagi, N; Munjal, C; Tyagi, S C

    2011-02-01

    Although protease activated receptor-1 (PAR-1) and matrix metalloproteinase-9 (MMP-9) play significant role in vascular remodelling in hyperhomocysteinemia (HHcy due to cystathionine beta synthase deficiency, CBS-/+) and diabetes, mechanism remains nebulous. We hypothesized that differential vascular density and remodelling in different vascular beds in HHcy and diabetes were responsible for an adaptive metabolic homeostasis during the pathogenesis. To test this hypothesis, vascular density in mice lacking PAR-1, MMP-9, CBS and Insulin-2 gene mutant (Ins2-/+, Akita) was measured and compared with wild type (WT, C57BL/6J) mice. The vascular density was detected by x-ray angiography using KODAK 4000 MM image station, using barium sulphate as contrasting agent. The % vascular density in the hearts of WT, CBS-/+ (HHcy), MMP-9-/-, PAR-1-/+ and Ins2-/+ (type-1 diabetes) was 100 ± 2.8, 85 ± 3.3, 90 ± 3.3, 95 ± 3.8 and 73 ± 1.7, respectively. The vascular density in CBS-/+ and Akita hearts decreased while it was increased in lungs of CBS-/+ and MMP-9-/-.There was decreased vascular density in liver and kidney of Akita mice. Vascular density in brain, kidney and mesentery was decreased in CBS-/+ mice. These findings support the notation that metabolic derangement in diabetes and HHcy causes the chronic decline and/or rarefaction in vascular density.

  12. An ex vivo study on immunohistochemical localization of MMP-7 and MMP-9 in temporomandibular joint discs with internal derangement

    Directory of Open Access Journals (Sweden)

    C. Loreto

    2013-04-01

    Full Text Available Internal derangement (ID is among the most common disorders of the temporomandibular joint (TMJ. Previous research by our group highlighted a correlation between apoptosis and TMJ ID. Metalloproteinases (MMP-7 and -9 have been shown to play an important role in extracellular matrix ECM homeostasis and, through it, in joint disc remodelling. The immunohistochemical expression of MMP-7 and -9 was investigated in discs from patients with TMJ ID and from healthy donors and compared with the degree of histological tissue degeneration. The collagen fibre arrangement in pathological discs exhibited varying degrees of disruption. New vessels were consistently detected; endothelial cells from these vessels were immunolabelled with both MMP-7 and MMP-9. More or less intense MMP-7 and MMP-9 immunolabelling was detected in the cytoplasm of disc cells from all patients. MMP-7 and MMP-9 immunostaining was significantly different between pathological and normal discs and correlated with the extent of histopathological degeneration. MMP-7 and MMP-9 upregulation in discs from patients with TMJ ID demonstrates their involvement in disc damage in this disorder. A greater understanding of these processes could help identify ways to curb MMP overproduction without affecting their tissue remodelling action. The design of specific inhibitors for these MMPs would not only help to gain insights into the biological roles of MMPs, but would also aid in developing therapeutic interventions for diseases associated with abnormal ECM degradation.

  13. Matrix metalloproteinase (MMP)-2 and MMP-9 as inflammation markers of Trichinella spiralis and Trichinella pseudospiralis infections in mice.

    Science.gov (United States)

    Bruschi, F; Bianchi, C; Fornaro, M; Naccarato, G; Menicagli, M; Gomez-Morales, M A; Pozio, E; Pinto, B

    2014-10-01

    Trichinella spiralis and Trichinella pseudospiralis exhibit differences in the host-parasite relationship such as the inflammatory response in parasitized muscles. Several studies indicate that matrix metalloproteinases (MMPs) represent a marker of inflammation since they regulate inflammation and immunity. The aim of this study was to evaluate the serum levels of gelatinases (MMP-9 and MMP-2) in mice experimentally infected with T. spiralis or T. pseudospiralis, to elucidate the involvement of these molecules during the inflammatory response to these parasites. Gelatin zymography on SDS polyacrilamide gels was used to assess the serum levels and in situ zymography on muscle histological sections to show the gelatinase-positive cells. In T. spiralis infected mice, the total MMP-9 serum level increased 6 days post-infection whereas, the total MMP-2 serum level increased onward. A similar trend was observed in T. pseudospiralis infected mice but the MMP-9 level was lower than that detected in T. spiralis infected mice. Significant differences were also observed in MMP-2 levels between the two experimental groups. The number of gelatinase positive cells was higher in T. spiralis than in T. pseudospiralis infected muscles. We conclude that MMP-9 and MMP-2 are markers of the inflammatory response for both T. spiralis and T. pseudospiralis infections.

  14. Oxygen-Loaded Nanodroplets Effectively Abrogate Hypoxia Dysregulating Effects on Secretion of MMP-9 and TIMP-1 by Human Monocytes

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    Giulia Rossana Gulino

    2015-01-01

    Full Text Available Monocytes play a key role in the inflammatory stage of the healing process. To allow monocyte migration to injured tissues, the balances between secreted matrix metalloproteinases (MMPs and their inhibitors (TIMPs must be finely modulated. However, a reduction of blood supply and local oxygen tension can modify the phenotype of immune cells. Intriguingly, hypoxia might be targeted by new effective oxygenating devices such as 2H,3H-decafluoropentane- (DFP- based oxygen-loaded nanodroplets (OLNs. Here, hypoxia effects on gelatinase/TIMP release from human peripheral monocytes were investigated, and the therapeutic potential of dextran-shelled OLNs was evaluated. Normoxic monocytes constitutively released ~500 ng/mL MMP-9, ~1.3 ng/mL TIMP-1, and ~0.6 ng/mL TIMP-2 proteins. MMP-2 was not detected. After 24 hours, hypoxia significantly altered MMP-9/TIMP-1 balance by reducing MMP-9 and increasing TIMP-1, without affecting TIMP-2 secretion. Interestingly OLNs, not displaying toxicity to human monocytes after cell internalization, effectively counteracted hypoxia, restoring a normoxia-like MMP-9/TIMP-1 ratio. The action of OLNs was specifically dependent on time-sustained oxygen diffusion up to 24 h from their DFP-based core. Therefore, OLNs appear as innovative, nonconventional, cost-effective, and nontoxic therapeutic tools, to be potentially employed to restore the physiological invasive phenotype of immune cells in hypoxia-associated inflammation.

  15. Regulation of MMP-9 by a WIN-binding site in the monocyte-macrophage system independent from cannabinoid receptors.

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    Svantje Tauber

    Full Text Available The cannabinoid system is known to be involved in the regulation of inflammatory processes. Therefore, drugs targeting cannabinoid receptors are considered as candidates for anti-inflammatory and tissue protective therapy. We demonstrated that the prototypical cannabinoid agonist R(+WIN55,212-2 (WIN reduced the secretion of matrix metalloproteinase-9 (MMP-9 in a murine model of cigarette-smoke induced lung inflammation. In experiments using primary cells and cell lines of the monocyte-macrophage-system we found that binding of the cannabinoid-receptor agonist WIN to a stereo-selective, specific binding site in cells of the monocyte-macrophage-system induced a significant down-regulation of MMP-9 secretion and disturbance of intracellular processing, which subsequently down-regulated MMP-9 mRNA expression via a ERK1/2-phosphorylation-dependent pathway. Surprisingly, the anti-inflammatory effect was independent from classical cannabinoid receptors. Our experiments supposed an involvement of TRPV1, but other yet unidentified sites are also possible. We conclude that cannabinoid-induced control of MMP-9 in the monocyte-macrophage system via a cannabinoid-receptor independent pathway represents a general option for tissue protection during inflammation, such as during lung inflammation and other diseases associated with inflammatory tissue damage.

  16. MMP-9 and MMP-2 gelatinases and TIMP-1 and TIMP-2 inhibitors in breast cancer: correlations with prognostic factors.

    Science.gov (United States)

    Jinga, D C; Blidaru, A; Condrea, Ileana; Ardeleanu, Carmen; Dragomir, Cristina; Szegli, G; Stefanescu, Maria; Matache, Cristiana

    2006-01-01

    The goal of our study was to analyse the prognostic values for some matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in breast cancer. We evaluated the activity and the expression levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 in malignant versus benign fresh breast tumor extracts. For this purpose, gelatinzymography, immunoblotting and ELISA were used to analyse the activity and expression of MMPs and TIMPs. We found that MMP-9 expression level and activity are increased in malignant tumors. In addition, MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio values obtained by us were significantly different in malignant tumors compared to benign tumors. We suggest that the abnormal MMP-9/TIMP-1 balance plays a role in the configuration of breast invasive carcinoma of no special type and also in tumor growth, while altered MMP-2/TIMP-2 ratio value could be associated with lymph node invasion and used as a prognostic marker in correlation with Nottingham Prognostic Index. Finally, we showed that in malignant tumors high expression of estrogen receptors is associated with enhanced activity of MMP-2 and increased bcl- 2 levels, while high expression of progesterone receptors is correlated with low TIMP-1 protein levels.

  17. Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion.

    Science.gov (United States)

    Sapharikas, Elene; Lokajczyk, Anna; Fischer, Anne-Marie; Boisson-Vidal, Catherine

    2015-06-30

    Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate. Monocytes negatively isolated with magnetic beads from peripheral blood of healthy donors were treated with fucoidan. Fucoidan induced a 1.5-fold increase in monocyte adhesion to gelatin (p Fucoidan also enhanced migration 2.5-fold in a transmigration assay (p fucoidan (p fucoidan-treated monocytes showed upregulation of ERK/p38 phosphorylation. Inhibition of ERK/p38 phosphorylation abrogated fucoidan enhancement of migration (p Fucoidan displays striking biological effects, notably promoting monocyte adhesion and migration. These effects involve the ERK and p38 pathways, and increased MMP9 activity. Fucoidan could improve critical limb ischemia by promoting monocyte recruitment.

  18. Preoperative, high IL-6 blood level is a risk factor of postoperative delirium onset in old patients

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    Miriam eCapri

    2014-10-01

    Full Text Available Background: Postoperative delirium (POD is a common complication in elderly patients undergoing surgery, but the underpinning causes are not clear. We hypothesized that inflammaging, the subclinical low and chronic grade inflammation characteristic of old people, can contribute to POD onset. Accordingly, we investigated the association of preoperative and circulating cytokines in elderly patients (>65 yrs, admitted for elective and emergence surgery.Methods: This is secondary analysis of a sub-cohort of patients belonging to a previous large case-control study, where 351 patients were clinically and cognitively thoroughly characterized, together with the assessment of POD (47 patients by Confusion Assessment Method (CAM and Delirium Rating Scale (DRS. 74 preoperative plasma samples were selected from a larger bio-bank and they included 37 subjects with POD and 37 without POD. Inflammaging related cytokines, i.e. IL-1 β, IL-2, IL-6, IL-8, IL-10 and TNF-α were assayed by ELISA in pre-operative blood samples; univariate and multivariable analyses have been applied to identify cytokines independently associated to POD. Associations of cytokine levels with functional status, cognitive decline, intra-hospital mortality and comorbidity were also analyzed independently of POD onset.Results:. High IL-6 and low IL-2 levels were significantly associated with POD. After adjustment for potential confounders in multivariate analysis, high level of preoperative IL-6 was confirmed to be significantly associated with risk of POD onset.. High level of IL-6 was also associated with several baseline features (including poor functional status, cognitive impairment, emergency admission and higher comorbidity burden and intra-hospital mortality.Conclusions: Preoperative, high plasma level of IL-6 ( ≥ 9 pg/mL was significantly associated with POD onset. We propose IL-6 as an additional risk factor of POD onset together with the previously identified factors

  19. HBV replication is significantly reduced by IL-6

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    Jeng King-Song

    2009-04-01

    Full Text Available Abstract Interleukin-6 (IL-6 is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection.

  20. TGF superfamily and MMP2, MMP9, TIMP1 genes expression in the endometrium of women with impaired reproduction.

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    Przemysław Wirstlein

    2008-04-01

    Full Text Available During the putative "implantation window", a period of maximal endometrial receptivity that spans 7-9 days after ovulation, a series of changes on the structural and molecular level occur that render the endometrium susceptible to implantation for the human embryo. Many members of the TGFbetas are expressed by human endometrium at different stages of menstrual cycle. Also studies regarding the MMP2 gene expression and activity of MMP2 in the implantation window have shown a higher expression and activity of MMP2 in women with impaired fertility. We have examined by RT-PCR the expression of TGFbeta2 and MMP2, MMP9 and TIMP1 in 28 patients with idiopathic infertility, 16 patients with unexplained recurrent miscarriage and 16 control women were enrolled in this study. Seven to nine days after ovulation endometrial biopsy by Pipelle or hysteroscopy was performed to assess the expression of TGFbeta2 , MMP2, MMP9 and TIMP1. We found that in endometria from women with idiopathic infertility TGFbeta2 expression was 2.8 fold higher than in endometria from control group and 2.1 fold higher in endometrial samples from women with unexplained recurrent miscarriage compared to the control group. The MMP2, MMP9 and TIMP1 expression in endometrial samples revealed no significant differences between the study groups and control group. There was a statistically significant negative correlation between TGFbeta2 and MMP9 expression in endometria from women in control group. The present investigations suggest that dysregulated TGFbeta2, MMP2, MMP9 and TIMP1 expression are associated with infertility and early pregnancy loss. However the exact mechanism of how overexpression of endometrial TGFbetaand MMPs interferes with implantation may be more complex.

  1. An IL-6 link between obesity and cancer.

    Science.gov (United States)

    Ghosh, Sagar; Ashcraft, Keith

    2013-01-01

    Obesity is a growing epidemic all over the world that by virtue of inducation of a chronic, low-grade, and systemic inflammation leads to an increased risk of a number of diseases, including cancer. IL-6 an important cytokine in the increased risk to cancer in obese patients mainly because of its pro-inflammatory activity. Some data suggest that IL-6 might increase the risk of certain cancers such as those that originate from breast, liver, prostate, colon, and esophagus. A better understanding of the regulation and role of IL-6 in obesity-associated cancer is required to develop effective therapeutic approaches.

  2. Liposomal Nanoparticles Carrying anti-IL6R Antibody to the Tumour Microenvironment Inhibit Metastasis in Two Molecular Subtypes of Breast Cancer Mouse Models

    Science.gov (United States)

    Guo, Chunlei; Chen, Yanan; Gao, Wenjuan; Chang, Antao; Ye, Yujie; Shen, Wenzhi; Luo, Yunping; Yang, Shengyong; Sun, Peiqing; Xiang, Rong; Li, Na

    2017-01-01

    Tumour microenvironment (TME) contributes significantly towards potentiating the stemness and metastasis properties of cancer cells. IL6-Stat3 is one of the important cell signaling pathways in mediating the communication between tumour and immune cells. Here, we have systematically developed a novel anti-CD44 antibody-mediated liposomal nanoparticle delivery system loaded with anti-IL6R antibody, which could specifically target the TME of CD44+ breast cancer cells in different mouse models for triple negative and luminal breast cancer. This nanoparticle had an enhanced and specific tumour targeting efficacy with dramatic anti-tumour metastasis effects in syngeneic BALB/c mice bearing 4T1 cells as was in the syngeneic MMTV-PyMT mice. It inhibited IL6R-Stat3 signaling and moderated the TME, characterized by the reduced expression of genes encoding Stat3, Sox2, VEGFA, MMP-9 and CD206 in the breast tissues. Furthermore, this nanoparticle reduced the subgroups of Sox2+ and CD206+ cells in the lung metastatic foci, demonstrating its inhibitory effect on the lung metastatic niche for breast cancer stem cells. Taken together, the CD44 targeted liposomal nanoparticles encapsulating anti-IL6R antibody achieved a significant effect to inhibit the metastasis of breast cancer in different molecular subtypes of breast cancer mouse models. Our results shed light on the application of nanoparticle mediated cancer immune-therapy through targeting TME. PMID:28255366

  3. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  4. Spatio-temporal expression of MMP-2, MMP-9 and tissue kallikrein in uteroplacental units of the pregnant guinea-pig (Cavia porcellus

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    Rey Sergio

    2007-07-01

    Full Text Available Abstract Background In humans trophoblast invasion and vascular remodeling are critical to determine the fate of pregnancy. Since guinea-pigs share with women an extensive migration of the trophoblasts through the decidua and uterine arteries, and a haemomonochorial placenta, this species was used to evaluate the spatio-temporal expression of three enzymes that have been associated to trophoblast invasion, MMP-2, MMP-9 and tissue kallikrein (K1. Methods Uteroplacental units were collected from early to term pregnancy. MMP-2, MMP-9 and K1 were analysed by immunohistochemistry and Western blot. The activities of MMP-2 and MMP-9 were assessed by gelatin zymography. Results Immunoreactive MMP-2, MMP-9 and K1 were detected in the subplacenta, interlobar and labyrinthine placenta, syncytial sprouts and syncytial streamers throughout pregnancy. In late pregnancy, perivascular or intramural trophoblasts expressed the three enzymes. The intensity of the signal in syncytial streamers was increased in mid and late pregnancy for MMP-2, decreased in late pregnancy for MMP-9, and remained stable for K1. Western blots of placental homogenates at days 20, 40 and 60 of pregnancy identified bands with the molecular weights of MMP-2, MMP-9 and K1. MMP-2 expression remained constant throughout gestation. In contrast, MMP-9 and K1 attained their highest expression during midgestation. Placental homogenates of 20, 40 and 60 days yielded bands of gelatinase activity that were compatible with MMP-2 and MMP-9 activities. ProMMP-2 and MMP-9 activities did not vary along pregnancy, while MMP-2 and MMP-9 increased at 40 and 40–60 days respectively. Conclusion The spatio-temporal expression of MMPs and K1 supports a relevant role of these proteins in trophoblast invasion, vascular remodeling and placental angiogenesis, and suggests a functional association between K1 and MMP-9 activation.

  5. 胃癌DNA倍体分析及TIMP-2和MMP-9的表达%ANALYSIS OF DNA PLOIDY AND EXPRESSIONS OF TIMP-2 AND MMP-9 IN PATIENTS WITH GASTRIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张景芳; 张原平; 苗芳; 纪祥瑞

    2007-01-01

    目的 检测胃癌DNA倍体及基质金属蛋白酶抑制因子-2(TIMP-2)和基质金属蛋白酶-9(MMP-9)在胃癌中的表达,以探讨胃癌侵袭转移的分子基础和机制.方法 采用免疫组织化学方法检测MMP-9和TIMP-2在99例胃癌、16例癌周黏膜、16例胃癌远处转移灶和25例胃癌淋巴结转移灶标本中的表达情况;采用流式细胞术检测其中47例胃癌、6例癌周黏膜及4例胃癌远处转移灶标本的DNA倍体及S期分数.结果 MMP-9的表达与LAUREN分型、BORRMANN分型、淋巴结转移、转移部位、浸润深度和肿瘤TNM分期有关(χ2=6.65~8.03,P<0.05、0.01);TIMP-2表达与BORRMANN分型、淋巴结转移和浸润深度有关(χ2=5.01~7.05,P<0.05);DNA异倍体率与分化和淋巴结转移有关(χ2=5.083、11.750,P<0.05),S期分数与肿瘤大小、分化和淋巴结转移有关(χ2=4.931~6.299,P<0.05);MMP-9和TIMP-2间存在正相关关系(r=0.22,P<0.05);MMP-9表达、DNA异倍体率和S期分数在胃癌与癌周非癌黏膜间表达的差异具有统计学意义.结论 MMP-9和TIMP-2的异常表达尤其二者间的失衡及DNA异倍体和高S期分数参与了肿瘤的演进和异质化过程.

  6. 牙周病大鼠正畸源性牙根吸收和MMP-9表达的观察%Expression of MMP-9 and root resorption by orthodontic force in rats with periodontal disease

    Institute of Scientific and Technical Information of China (English)

    王月; 王明洁; 常悦; 崔淑霞

    2015-01-01

    目的:探讨牙周病大鼠不同正畸条件下牙根吸收情况与牙组织中基质金属蛋白酶9(MMP-9)表达水平的变化.方法:取108只大鼠,54只制作大鼠牙周病模型,模型制备成功后分别给予0、50和80 g正畸力牵拉1、7、14 d,每个条件下6只大鼠;另54只给予相同正畸处理但不制备牙周病模型(对照组).以上颌切牙为支抗,分别牵拉左侧上颌第一磨牙向近中移动.取各组大鼠实验牙制作组织切片,观察牙根吸收情况,应用免疫组化染色观察MMP-9的表达.结果:50或80 g正畸力牵拉7d后,两组大鼠牙周膜均排列紊乱,可见明显的牙根吸收现象,牙周病组大鼠牙根吸收情况较对照组严重;牵拉14 d后牙根吸收活动基本停止.随着正畸力的增加,MMP-9表达水平逐渐升高;牵拉7d后MMP-9表达水平最高,14 d后下降;牙周病组牙组织中MMP-9表达水平高于对照组(F组别=3.031,P=0.022;F正畸力=6.634,P=0.014;F时间=4.820,P=0.009;F交互=0.890,P=0.514).结论:牙组织中MMP-9表达水平可能能反映牙周病大鼠牙根吸收的程度.

  7. Determinants of IL-6 levels during HIV infection

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    Álvaro H Borges

    2014-11-01

    Full Text Available Introduction: Elevated IL-6 levels have been linked to increased risk of cardiovascular disease (CVD, cancer and death. Compared to the general population, treated HIV+ persons have 50–100% higher IL-6 levels, but few data on the determinants of IL-6 levels during HIV infection currently exist. Material and Methods: Participants in three international HIV trials (SMART, ESPRIT and SILCAAT with IL-6 plasma levels measured at baseline were included (N=9864. Factors independently associated with log2-transformed IL-6 level were identified by multivariate linear regression; exponentiated estimates corresponding to fold differences (FDs in IL-6 were calculated. Demographics (age, gender, race, BMI and HIV-specific variables (nadir and entry CD4 counts, HIV-RNA, use of different ART regimens were investigated in all three trials. In SMART (N=4498, smoking, comorbidities (CVD, diabetes, hepatitis B/C [HBV/HCV], HDL-cholesterol, renal function (eGFR and educational level were also assessed. Results: Demographics associated with higher IL-6 were older age (FD [95% CI]: 1.09 [1.08–1.11] per 10 yr and higher BMI (1.02 [1.01–1.04] per 5 kg/m2, whereas black race was associated with reduced IL-6 (0.96 [0.93–0.99]. As for HIV variables, patients not receiving ART (1.36 [1.29–1.43] and with higher HIV-RNA (1.24 [1.01–1.52] for >100,000 vs. ≤500 copies/mL had increased IL-6. Participants taking protease inhibitors (PI had higher IL-6 (1.14[1.09–1.19]. Higher nadir CD4 count (0.98 [0.97–0.99]/100 cells/µL was related to lower IL-6. All evaluated comorbidities were related to higher IL-6; FDs in IL-6 were 1.08 [1.04–1.12] for smoking, 1.12 [1.02–1.24] for CVD, 1.07 [1.00–1.16] for diabetes and 1.12 [1.02–1.24] for HBV (1.15 [1.02–1.30] and 1.53 [1.45–1.62] for HCV. IL-6 increased with decreasing eGFR (0.98 [0.97–1.00]/10 mL/min and HDL-cholesterol (0.98 [0.96–0.99]/10 mg/mL. Lower education was related to higher IL-6 (1.09 [1

  8. Bacterial flagellin induces IL-6 expression in human basophils.

    Science.gov (United States)

    Jeon, Jun Ho; Ahn, Ki Bum; Kim, Sun Kyung; Im, Jintaek; Yun, Cheol-Heui; Han, Seung Hyun

    2015-05-01

    Binding of allergen to IgE on basophils positively affects allergic inflammation by releasing inflammatory mediators. Recently, basophils were shown to express pattern-recognition receptors, such as toll-like receptors (TLRs), for recognizing microbe-associated molecular patterns (MAMPs) that are independent of allergen-IgE binding. In this study, we investigated whether MAMP alone can induce IL-6 production in a human basophil cell line, KU812. Stimulation with flagellin in the absence of allergen-IgE association induced IL-6 expression in KU812 cells, while stimulation with lipoteichoic acid, peptidoglycan, or poly I:C did not under the same condition. Flagellin-induced IL-6 expression was also observed in human primary basophils. Flow cytometric analysis showed that KU812 cells expressed flagellin-recognizing TLR5 both on the cell surface and in the cytoplasm while TLR2 and TLR3 were observed only in the cytoplasm. We further demonstrated that although flagellin augmented the phosphorylation of mitogen-activated protein kinases including p38 kinase, ERK, and JNK, flagellin-induced IL-6 production was attenuated by inhibitors for p38 kinase and ERK, but not by JNK inhibitors. In addition, flagellin enhanced phosphorylation of signaling molecules including CREB, PKCδ, and AKT. The inhibitors for PKA and PKC also showed inhibitory effects. Interestingly, flagellin-induced IL-6 production was further enhanced by pretreatment with inhibitors for PI3K, implying that PI3K negatively affects the flagellin-induced IL-6 production. Furthermore, DNA binding activities of NF-κB, AP-1, and CREB, which play pivotal roles in the induction of IL-6 gene expression, were increased by flagellin. These results suggest that flagellin alone is sufficient to induce IL-6 gene expression via TLR5 signaling pathways in human basophils.

  9. pVHL co-ordinately regulates CXCR4/CXCL12 and MMP2/MMP9 expression in human clear-cell renal cell carcinoma

    DEFF Research Database (Denmark)

    Struckmann, K; Mertz, Kd; Steu, S;

    2008-01-01

    Loss of pVHL function, characteristic for clear-cell renal cell carcinoma (ccRCC), causes increased expression of CXCR4 chemokine receptor, which triggers expression of metastasis-associated MMP2/MMP9 in different human cancers. The impact of pVHL on MMP2/MMP9 expression and their relationship...

  10. Purification and characterization of recombinant full-length and protease domain of murine MMP-9 expressed in Drosophila S2 cells

    DEFF Research Database (Denmark)

    Rasch, Morten G; Lund, Ida K; Illemann, Martin;

    2010-01-01

    MMP-9. Constructs encoding zymogens of full-length murine MMP-9 and a version lacking the O-glycosylated linker region and hemopexin domains were therefore generated and expressed in stably transfected Drosophila S2 insect cells. After 7 days of induction the expression levels of the full...

  11. The Pathological and Physiological Roles of IL-6 Amplifier Activation

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    Masaaki Murakami, Toshio Hirano

    2012-01-01

    Full Text Available The NFκB-triggered positive feedback loop for IL-6 signaling in type 1 collagen+ non-immune cells (IL-6 amplifier was first discovered to be a synergistic signal that is activated following IL-17A and IL-6 stimulation in type 1 collagen+ non-immune cells. Subsequent disease models have shown that it can also be stimulated by the simultaneous activation of NFκB and STAT3, functions as a local chemokine inducer, and acts as a mechanism for local inflammation, particularly chronic ones like rheumatoid arthritis and a multiple sclerosis. Moreover, we have recently shown that hyper activation of the IL-6 amplifier via regional neural activation establishes a gateway for immune cells including autoreactive T cells to pass the blood-brain barrier at dorsal vessels in 5th lumbar cord. Here we review how the IL-6 amplifier is activated by neural activation and the physiological relevance of the gateway to the central nervous system. Accumulating evidences continues to suggest that the IL-6 amplifier offers a potential molecular mechanism for the relationship between neural activation and the development of inflammatory diseases, which could establish a new interdisciplinary field that fuses neurology and immunology.

  12. 下肢曲张静脉壁MMP-2、MMP-9和胶原含量的临床研究%Clinical study of MMP-2, MMP-9 and collagen in lower limb varicose veins

    Institute of Scientific and Technical Information of China (English)

    邵拥军; 朱化刚; 周静

    2012-01-01

    目的研究曲张大隐静脉管壁基质金属蛋白酶(MMP)-2、MMP-9的表达及其与临床症状和体征分期的关系,并检测曲张静脉壁总的胶原含量,探讨MMP-2、MMP-9和胶原在曲张静脉重塑时的作用.方法采用免疫组化SP法检测曲张静脉壁和正常大隐静脉壁MMP-2和MMP-9的表达,采用Masson染色法检测曲张静脉壁和正常对照组总的胶原含量,采用χ2检验和t检验进行统计学分析处理.结果 MMP-2和MMP-9在正常静脉壁和曲张静脉壁均有表达,但曲张静脉壁MMP-2和MMP-9的阳性率明显升高(P<0.05);C4-C6期MMP-2和MMP-9的阳性率明显高于C1-C3期(P<0.05);曲张静脉壁总的胶原含量显著高于正常对照组(P<0.05).结论 MMP-2、MMP-9的异常表达导致了静脉壁总的胶原含量增加,参与了曲张静脉的重塑.%Objective To investigate the expression of matrix metalloproteinase -2 and -9 in varicose veins, and their relationships with clinical stages , and to discuss the changes of total collagen in varicose veins, and their significance. Methods The expression of MMP-2 and MMP-9 was examined by immunohistochemistry SP methods in varicose veins (VV) and normal veins (NVV), the total collagen was detected using Masson staining in varicose veins and normal veins, and chi-square test and T- test was used for statistical analysis. Results MMP-2 and -9 were both expressed in NVV and VV, and the positive expression rate in VV was significantly higher than that in NVV (P< 0.05). The positive expression of MMP-2 and -9 was significantly higher in C4-C6 stages than in C1-C3 stages (P <0.05), and the collagen was significantly increased in varicose veins (P <0.05). Conclusion The abnormal expression of MMP-2 and -9 leads to collagen increasing in varicose veins, which may participate in vascular remodeling in varicose veins.

  13. The regulating role of mutant IκBα in expression of TIMP-2 and MMP-9 in human glioblastoma multiform

    Institute of Scientific and Technical Information of China (English)

    HU Yu-hua; YU Li-Jie; SHAO En-de; WU Jian-liang; JI Jian-wen

    2009-01-01

    Background Our previous studies demonstrated that mutant IκBα (IκBαM) inhibited the occurrence, growth and angiogenesis of human glioblastoma multiform (GBM). However, the specific mechanism by which IKBαM regulates protein-degrading enzymes secreted from GBM to inhibit invasion and metastasis has remained unclear. The aim of the present study was to investigate the regulatory role and significance of IκBαM genes in the expression of tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in human GBM. Methods We established the following four GBM cell lines stably expressing IκBαM by plasmid construction, gene transfection and screening for IκBαM protein expression: mutant IκBα-transfected cells (G36△-M), wild-type IκBα-transfected cells (G36△-W), empty plasmid transfected cells (G36△-P) and untransfected cells (G36△). The TIMP-2 and MMP-9 expression was detected by RT-PCR and Western blotting. Tumor cells were then implanted subcutaneously into nude mice to establish an animal model of ectopic tumor growth, and TIMP-2 and MMP-9 expression was determined by immunohistochemical methods. Results The results showed that there was a significant increase in TIMP-2 expression and a significant decrease in MMP-9 expression in the G36A-M group at both the RNA and protein levels compared with the G36A-W group, G36△-P group and G36△ group. Similar results were observed in the immunohistochemical staining analysis of tumor tissues. In the G36A-M group, TIMP-2 expression was significantly higher while MMP-9 expression was significantly lower than in the other three groups. Conclusions Our findings indicate that IκBαM inhibits the activation of NF-κB. It significantly up-regulates TIMP-2 expression in human malignant glioma cells and down-regulates the expression of MMP-9. Thus, IκBαM maintains the integrity of the extracellular matrix and further inhibits the growth and metastasis of tumor tissues.

  14. A novel cantharidin analog N-Benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji-Yeon; Chung, Tae-Wook; Choi, Hee-Jung [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Lee, Chang Hyun [Department of Anatomy, College of Korean Medicine, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Eun, Jae Soon; Han, Young Taek [College of Pharmacy, Woosuk University, Wanju-gun, Jeonbuk (Korea, Republic of); Choi, Jun-Yong [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Kim, So-Yeon; Han, Chang-Woo [Department of Internal Medicine, Korean Medicine Hospital, School of Korean Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of); Jeong, Han-Sol, E-mail: jhsol33@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Ha, Ki-Tae, E-mail: hagis@pusan.ac.kr [Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of); Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongnam (Korea, Republic of)

    2014-05-02

    Highlights: • We examined the inhibition of N-Benzylcantharidinamide on MMP-9-mediated invasion. • Unlike cantharidin, N-Benzylcantharidinamide has very low toxicity on Hep3B cells. • The reduced MMP-9 expression was due to HuR-mediated decrease of mRNA stability. • We suggest N-Benzylcantharidinamide as a novel inhibitor of MMP-9-related invasion. - Abstract: Invasion and metastasis are major causes of malignant tumor-associated mortality. The present study aimed to investigate the molecular events underlying inhibitory effect of N-Benzylcantharidinamide, a novel synthetic analog of cantharidin, on matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of cantharidin, only N-Benzylcantharidinamide has the inhibitory action on MMP-9 expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells were significantly suppressed by treatment of N-Benzylcantharidinamide in a dose-dependent manner. On the other hand, the transcriptional activity of MMP-9 promoter and nuclear levels of NF-κB and AP-1 as the main transcriptional factors inducing MMP-9 expression were not affected by it although the level of MMP-9 mRNA was reduced by treatment of N-Benzylcantharidinamide. Interestingly, the stability of MMP-9 mRNA was significantly reduced by N-Benzylcantharidinamide-treatment. In addition, the cytosolic translocation of human antigen R (HuR), which results in the increase of MMP-9 mRNA stability through interaction of HuR with 3′-untranslated region of MMP-9 mRNA, was suppressed by treatment of N-Benzylcantharidinamide, in a dose-dependent manner. Taken together, it was demonstrated, for the first time, that N-Benzylcantharidinamide suppresses MMP-9 expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of invasive potential in highly metastatic Hep3B cells.

  15. IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis

    DEFF Research Database (Denmark)

    Skov, L.; Beurskens, F.J.; Reitamo, S.;

    2008-01-01

    IL-8 is a chemokine that has been implicated in a number of inflammatory diseases involving neutrophil activation. HuMab 10F8 is a novel fully human mAb against IL-8, which binds a discontinuous epitope on IL-8 overlapping the receptor binding site, and which effectively neutralizes IL-8-dependen...... pathological conditions associated with IL-8 overproduction Udgivelsesdato: 2008/7/1...

  16. Late Progresses in Research of ECM1,MMP-9 and Gastric Cancer%ECM1、MMP-9与胃癌的研究新进展

    Institute of Scientific and Technical Information of China (English)

    李晓虹; 吴秋婉

    2011-01-01

    Extracellular matrix protein-1 ( ECM1 ) is a kind of secreted glycoprotein,which can promote endothelial cells proliferation and angiogenesis. ECM1 expression is significantly elevated in gastric cancer tissues and other malignant epithelial tumors, which gives rise to its potential correlation with tumor infiltration and metastasis. Matrix metalloproteinase-9( MMP-9 ) can degrade the basement membrane and the extracellular matrix, promote vascularization and enhance the invasiveness and metastasis of gastric cancer cells. Thus,to discuss the roles of ECM1 and MMP-9 in the carcinogenesis and development of gastric cancer will help further realize the interaction of cancer cells and their surrounding microenvironment, and provide theoretical basis for early diagnosis and treatment of gastric cancer.%细胞外基质蛋白-1(ECM1)是一种分泌型糖蛋白,可刺激内皮细胞增殖,促进血管形成.在胃癌组织和其他恶性上皮肿瘤中高表达,与恶性肿瘤的浸润和转移相关.基质金属蛋白酶9(MMP-9)可降解基底膜和细胞外基质,促进脉管形成而增强胃癌细胞的侵袭和转移能力.探讨ECM1与MMP-9在胃癌发生发展中的作用将有助于人们进一步认识肿瘤与其周围微环境相互作用的机制,为胃癌的早期诊断和治疗提供理论依据.

  17. Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma.

    Science.gov (United States)

    Zhou, Dong-Ni; Deng, Yan-Fei; Li, Rong-Hua; Yin, Ping; Ye, Chun-Sheng

    2014-01-01

    This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were upregulated. We further found that RECK expression level was inversely correlated with MMP9 expression level in NPC, whereas RAGE expression level was positively correlated with MMP9 expression level. Moreover, aberrant expressions of these proteins had a positive correlation with the titers of EBVCA-IgA, lymphatic metastasis, recurrence and survival. Together, these findings suggest that dysregulations of RECK and RAGE expressions may be collectively involved in tumor progression of NPC by regulating MMP9 expression and that they may be a good prognostic predictors for NPC.

  18. Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-β, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

    Science.gov (United States)

    Sepehri, Zahra; Masoumi, Mohammad; Ebrahimi, Nazanin; Kiani, Zohre; Nasiri, Ali Akbar; Kohan, Farhad; Sheikh Fathollahi, Mahmood; Kazemi Arababadi, Mohammad; Asadikaram, Gholamreza

    2016-01-01

    Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-β and TNF-α. This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-β and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique. With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-β and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-β were also increased in females in comparison to males in the group 4. According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-β.

  19. Effect of human osteopontin on proliferation, transmigration and expression of MMP-2 and MMP-9 in osteosarcoma cells

    Institute of Scientific and Technical Information of China (English)

    刘思金; 胡国法; 刘亚军; 刘思国; 高虹; 张传生; 魏影允; 薛延; 劳为德

    2004-01-01

    Background To explore the effect of human osteopontin (hOPN) on the proliferation, transmigration and expression of matrix metallproteinase-2 (MMP-2) and matrix metallproteinase-9 (MMP-9) in osteosarcoma (OS) cells in vitro. Methods The prokaryotic-expression vector of hOPN was produced, hOPN was then subcloned into E. coli BL21 (DE3) cells and purified with ProBondTM Columns. The proliferation, cell cycle and the expression of cyclin A in OS cells were investigated by using MTT assay, flow cytometry and Western blot respectively. The transmigration of OS cells was checked by using transwell cell culture chamber. The micro-pore-filter-membrane system was used to study the chemiotaxis of hOPN to OS cells. The levels of total protein were examined according to Coomassie Brilliant Blue manuals. The expression of MMP-2 and MMP-9 were evaluated by detecting the volume of degradation of gelatin on SDS-PAGE gel.Results The prokaryotic-expression vector of hOPN and purified hOPN protein were achieved hOPN promoted OS cells proliferation in a dose-dependent manner, and stimulated cyclin A expression in OS cells to accelerate cell division cycle, hOPN facilitated the trans-membrane migration of OS cells. hOPN also enhanced the secretion of MMP-2 and MMP-9 in OS cells. Conclusion hOPN could stimulate cyclin A expression in OS cells, hOPN has chemiotaxis to OS cells and increases their transmigration, hOPN enhances the secretion of MMP-2 and MMP-9 in OS cells.

  20. MMP9 expression in oesophageal adenocarcinoma is upregulated with visceral obesity and is associated with poor tumour differentiation.

    LENUS (Irish Health Repository)

    Allott, Emma H

    2011-11-28

    Overweight and obesity is linked to increased incidence and mortality of many cancer types. Of all cancers, oesophageal adenocarcinoma (OAC) displays one of the strongest epidemiological links with obesity, accounting for up to 40% of cases, but molecular pathways driving this association remain largely unknown. This study aimed to elucidate mechanisms underpinning the association of obesity and cancer, and to determine if visceral obesity is associated with aggressive tumour biology in OAC. Following co-culture with visceral adipose tissue explants, expression of genes involved in tumour cell invasion and metastasis (matrix metalloproteinase (MMP)2 and MMP9) were upregulated between 10-fold (MMP2) and 5000-fold (MMP9), and expression of tumour suppressor p53 was downregulated 2-fold in OAC cell lines. Western blotting confirmed these results at the protein level, while zymographic analysis detected increased activity of MMPs in OAC cell lines following co-culture with adipose tissue explants. When OAC cell lines were cultured with adipose tissue conditioned media (ACM) from visceral adipose tissue, increased proliferative, migratory and invasive capacity of tumour cells was observed. In OAC patient tumour biopsies, elevated gene expression of MMP9 was associated with visceral obesity, measured by visceral fat area, while increased gene expression of MMP9 and decreased gene expression of tumour suppressor p53 was associated with poor tumour differentiation. These novel data highlight an important role for visceral obesity in upregulation of pro-tumour pathways contributing to aggressive tumour biology, and may ultimately lead to development of stratified treatment for viscerally obese OAC patients. © 2011 Wiley Periodicals, Inc.

  1. Serum IL-10, MMP-7, MMP-9 Levels in Helicobacter pylori Infection and Correlation with Degree of Gastritis

    OpenAIRE

    Gontar Siregar; Sahat Halim; Ricky Sitepu

    2016-01-01

    AIM: Helicobacter pylori causes gastric mucosal inflammation and immune reaction. However, the increase of IL-10, MMP-7, and MMP-7 levels in the serum is still controversial. The objective of this study was to investigate the serum levels of IL-10, MMP-7 & MMP-9 in gastritis patients with H. pylori infection. MATERIALS AND METHODS: A cross-sectional study was done on seventy gastritis patients that consecutive admitted to endoscopy units. The diagnosis of gastritis was made based on histo...

  2. Serum IL-10, MMP-7, MMP-9 Levels in Helicobacter pylori Infection and Correlation with Degree of Gastritis

    OpenAIRE

    Siregar, Gontar; Halim, Sahat; Sitepu, Ricky

    2016-01-01

    AIM: Helicobacter pylori causes gastric mucosal inflammation and immune reaction. However, the increase of IL-10, MMP-7, and MMP-7 levels in the serum is still controversial. The objective of this study was to investigate the serum levels of IL-10, MMP-7 & MMP-9 in gastritis patients with H. pylori infection.MATERIALS AND METHODS: A cross-sectional study was done on seventy gastritis patients that consecutive admitted to endoscopy units. The diagnosis of gastritis was made based on histopatho...

  3. Elevation of MMP-3 and MMP-9 in CSF and Blood in Patients with Severe Traumatic Brain Injury

    Science.gov (United States)

    Grossetete, Mark; Phelps, Jeremy; Arko, Leopold; Yonas, Howard; Rosenberg, Gary A.

    2009-01-01

    OBJECTIVE Traumatic brain injury (TBI) causes elevation of matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier (BBB) disruption, hemorrhage and cell death. We hypothesized that patients with TBI have an increase in MMPs in the ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement, and 24 and 72 hrs after admission. Seven TBI patients were entered into the study with six having complete data for analysis. Only patients that had a known time of insult that fell within a six hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus (NPH). Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblotting. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kDa) in the CSF obtained at the time of arrival (TOA) (p<0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly elevated in the CSF, indicating endogenous MMP production. Western immunoblots showed increased levels of MMP-3 in CSF at all times measured, while MMP-3 was not detected in the CSF of NPH. CONCLUSIONS We show that MMPs are elevated in CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated elevations of MMP-3 and MMP-9 in ventricular CSF in TBI patients compared to controls. While these preliminary results will need to be replicated, we propose that MMPs may be important in BBB opening and hemorrhage secondary to brain injury in patients. PMID:19834375

  4. Stomach Cancer: Interconnection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth.

    Science.gov (United States)

    Burlaka, Anatoly P; Ganusevich, Irina I; Gafurov, Marat R; Lukin, Sergey M; Sidorik, Evgeny P

    2016-04-01

    High levels of reactive oxygen (ROS) and nitrogen (RNS) species can lead to the destruction of extracellular matrix facilitating tumor progression. ROS can activate matrix metalloproteinases (MMP), damage DNA and RNA. Therefore, the levels of MMP, ROS and RNS can serve as additional prognostic markers and for the estimation of the effectiveness of tumor therapy. Concerning gastric cancer, the prognostic role of MMP, its connection with the cancer staging remains controversial and correlations between the activity of MMP with the ROS and RNS levels are insufficiently confirmed. Superoxide generation rates, nitric oxide (NO) levels, concentrations of active forms of matrix metalloproteinases MMP-2 and MMP-9 in tumor and adjacent tissues of patients with stomach cancer at different disease stages were measured by electron spin resonance (ESR) including spin-trapping and polyacrylamide gel zymography. It is shown that the activity of MMP-2 and MMP-9 in tumor tissue correlate with the superoxide radicals generation rate and NO levels (r = 0.48÷0.67, p < 0.05). The activity of MMP-2 and MMP-9 in tumor tissues and superoxide radical generation rates correlate positively with the stage of regional dissemination (r = 0.45 and 0.37, correspondingly, p < 0.05), but MMP-2 and MMP-9 activity inversely depends on distant metastatic degree of stomach cancer (r = 0.58; p < 0.05). Additionally, the feasibility of ESR to locally determine oxidative stress is demonstrated.

  5. Hematopoietic Stem Cell Mobilization and Homing after Transplantation: The Role of MMP-2, MMP-9, and MT1-MMP

    Directory of Open Access Journals (Sweden)

    Neeta Shirvaikar

    2012-01-01

    Full Text Available Hematopoietic stem/progenitor cells (HSPCs are used in clinical transplantation to restore hematopoietic function. Here we review the role of the soluble matrix metalloproteinases MMP-2 and MMP-9, and membrane type (MT1-MMP in modulating processes critical to successful transplantation of HSPC, such as mobilization and homing. Growth factors and cytokines which are employed as mobilizing agents upregulate MMP-2 and MMP-9. Recently we demonstrated that MT1-MMP enhances HSPC migration across reconstituted basement membrane, activates proMMP-2, and contributes to a highly proteolytic bone marrow microenvironment that facilitates egress of HSPC. On the other hand, we reported that molecules secreted during HSPC mobilization and collection, such as hyaluronic acid and thrombin, increase MT1-MMP expression in cord blood HSPC and enhance (prime their homing-related responses. We suggest that modulation of MMP-2, MMP-9, and MT1-MMP expression has potential for development of new therapies for more efficient mobilization, homing, and engraftment of HSPC, which could lead to improved transplantation outcomes.

  6. ATP6V1H Deficiency Impairs Bone Development through Activation of MMP9 and MMP13

    Science.gov (United States)

    Zhao, Gexin; Yokoyama, Tadafumi; Huang, Yan; Bishop, Kevin; Maduro, Valerie; Accardi, John; Toro, Camilo; Boerkoel, Cornelius F.; Gahl, William A.; Duan, Xiaohong; Malicdan, May Christine V.; Lin, Shuo

    2017-01-01

    ATP6V1H is a component of a large protein complex with vacuolar ATPase (V-ATPase) activity. We identified two generations of individuals in which short stature and osteoporosis co-segregated with a mutation in ATP6V1H. Since V-ATPases are highly conserved between human and zebrafish, we generated loss-of-function mutants in atp6v1h in zebrafish through CRISPR/Cas9-mediated gene knockout. Homozygous mutant atp6v1h zebrafish exhibited a severe reduction in the number of mature calcified bone cells and a dramatic increase in the expression of mmp9 and mmp13. Heterozygous adults showed curved vertebra that lack calcified centrum structure and reduced bone mass and density. Treatment of mutant embryos with small molecule inhibitors of MMP9 and MMP13 significantly restored bone mass in the atp6v1h mutants. These studies have uncovered a new, ATP6V1H-mediated pathway that regulates bone formation, and defines a new mechanism of disease that leads to bone loss. We propose that MMP9/MMP13 could be therapeutic targets for patients with this rare genetic disease. PMID:28158191

  7. Largescale Transcriptomics Analysis Suggests Over-Expression of BGH3, MMP9 and PDIA3 in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    He, Yuan; Shao, Fangyang; Pi, Weidong; Shi, Cong; Chen, Yujia; Gong, Diping; Wang, Bingjie; Cao, Zhiwei; Tang, Kailin

    2016-01-01

    Oral squamous cell carcinoma (OSCC) has been reported as the most prevalent cancer of the head and neck region, while early diagnosis remains challenging. Here we took a comprehensive bioinformatics study on microarray data of 326 OSCC clinical samples with control of 165 normal tissues. The cell interaction pathways of ECM-receptor interaction and focal adhesion were found to be significantly regulated in OSCC samples. Further analysis of the topological properties and expression consistency identified that three hub genes in the gene interaction network, MMP9, PDIA3 and BGH3, were consistently up-expressed in OSCC samples. When being validated on additional microarray datasets of 41 OSCC samples, the validation rate of over-expressed BGH3, MMP9, and PDIA3 reached 90%, 90% and 84% respectively. At last, immuno-histochemical assays were done to test the protein expression of the three genes on newly collected clinical samples of 35 OSCC, 20 samples of pre-OSCC stage, and 12 normal oral mucosa specimens. Their protein expression levels were also found to progressively increase from normal mucosa to pre-OSCC stage and further to OSCC (ANOVA p = 0.000), suggesting their key roles in OSCC pathogenesis. Based on above solid validation, we propose BGH3, MMP9 and PDIA3 might be further explored as potential biomarkers to aid OSCC diagnosis.

  8. Largescale Transcriptomics Analysis Suggests Over-Expression of BGH3, MMP9 and PDIA3 in Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yuan He

    Full Text Available Oral squamous cell carcinoma (OSCC has been reported as the most prevalent cancer of the head and neck region, while early diagnosis remains challenging. Here we took a comprehensive bioinformatics study on microarray data of 326 OSCC clinical samples with control of 165 normal tissues. The cell interaction pathways of ECM-receptor interaction and focal adhesion were found to be significantly regulated in OSCC samples. Further analysis of the topological properties and expression consistency identified that three hub genes in the gene interaction network, MMP9, PDIA3 and BGH3, were consistently up-expressed in OSCC samples. When being validated on additional microarray datasets of 41 OSCC samples, the validation rate of over-expressed BGH3, MMP9, and PDIA3 reached 90%, 90% and 84% respectively. At last, immuno-histochemical assays were done to test the protein expression of the three genes on newly collected clinical samples of 35 OSCC, 20 samples of pre-OSCC stage, and 12 normal oral mucosa specimens. Their protein expression levels were also found to progressively increase from normal mucosa to pre-OSCC stage and further to OSCC (ANOVA p = 0.000, suggesting their key roles in OSCC pathogenesis. Based on above solid validation, we propose BGH3, MMP9 and PDIA3 might be further explored as potential biomarkers to aid OSCC diagnosis.

  9. 罗格列酮对DM2患者血清MMP-9和TIMP-1影响的研究%The Effects of Rosiglitazone on the Serum MMP-9 and TIMP-1 in Type 2 Diabetic

    Institute of Scientific and Technical Information of China (English)

    倪强; 张健; 姚永良

    2012-01-01

    Objective To explore the change of rosiglitazone on type 2 diabetic patients and the impact on the expressions of MMP-9 and TIMP-1. Methods The clinical observation using randomized controlled method, 100 patients with DM2 were selected in our stud-y,and 50 healthy adults served as normal control. 100 cases of type 2 diabetics were divided into A and B group. The group A was treated only with conventional therapy. Tne group B was given rosiglitazone besides conventional therapy. And the concentrations of MMP-9 and TIMP-1 in serum were detected before and after therapy. Results Tne DM2 diabetics group serum MMP-9,TIMP-1 and MMP-9/TTMP-1 levels were obvious higher than the healthy control group(P0.05). There was a positive correlation be-tween MMP-9/TTMP-1 and expression level of MMP-9 and TTMP-1 in DM2 diabetics(r =0.631 ,r = 0.558,all P0.05);且MMP-9与TIMP-1之间,MMP-9/TIMP-1与MMP-9、TIMP-1之间均呈正相关.结论:血清MMP-9与TIMP-1可能与DM2发生、发展有关,罗格列酮能显著降低DM2患者MMP-9与TIMP-1水平,纠正MMP-9/TIMP-1比值,以期达到早期诊治,防止DM2大血管病变的目的.

  10. IL-6 RESPONSES TO GLYCAEMIC INDEX DURING RECOVERY FROM EXERCISE

    Directory of Open Access Journals (Sweden)

    Hasani S.H.

    2015-06-01

    Full Text Available Purpose: This study examined the effect of meal with different glycaemic index (GI on plasma IL-6 concentration and glucose metabolism after maximal lengthening contractions of the knee extensors. Using a cross-over design, Material : 10 healthy males completed 5 sets of 10 lengthening (eccentric contractions at 120% 1 repetition-maximum. Subjects were randomized to consume the GI beverage (high-GI, low-GI (15% weight per volume; 3 g/kg BM or placebo in three times within 10 min following exercise, and again at 50 and 110 min during recovery time. Blood samples were collected before exercise and after 0.60, 180 min and 24 h of recovery. Results: Concentration of plasma IL-6 in HGI group was less than LGI and Pla groups. IL-6 tended to significantly increase after exercise in recovery time in 3 groups (all P < 0.05, except for 24 hours (P = 1.00, furthermore there was significant difference for IL-6 between placebo and high glycemic groups in 3hours after exercise (P=.016. Concentration of serum CK in HGI group was less than LGI and Pla groups, CK was significantly elevated at all times points during recovery in 3 groups (all P < 0.05, except for 1 hour after exercise in HGI group (P = 0.31, but there was no significant difference for CK between groups. Conclusion: In summary, consuming HGI carbohydrate during recovery from exercise attenuate plasma IL-6 concentration.

  11. The social environment and IL-6 in rats and humans.

    Science.gov (United States)

    Saxton, Katherine B; John-Henderson, Neha; Reid, Matthew W; Francis, Darlene D

    2011-11-01

    Inflammatory cytokine levels predict a wide range of human diseases including depression, cardiovascular disease, type 2 diabetes, autoimmune disease, general morbidity, and mortality. Stress and social experiences throughout the lifecourse have been associated with inflammatory processes. We conducted studies in humans and laboratory rats to examine the effect of early life experience and adult social position in predicting IL-6 levels. Human participants reported family homeownership during their childhood and current subjective social status. Interleukin-6 (IL-6) was measured from oral mucosal transudate. Rats were housed in groups of three, matched for quality of maternal care received. Social status was assessed via competition for resources, and plasma IL-6 was assessed in adulthood. In both humans and rats, we identified an interaction effect; early social experience moderated the effect of adult social status on IL-6 levels. Rats that experienced low levels of maternal care and people with low childhood socioeconomic status represented both the highest and lowest levels of IL-6 in adulthood, depending on their social status as young adults. The predicted interaction held for non-Hispanic people, but did not occur among Hispanic individuals. Adversity early in life may not have a monotonically negative effect on adult health, but may alter biological sensitivity to later social experiences.

  12. Correlation between IL-6 levels and the systemic inflammatory response score: can an IL-6 cutoff predict a SIRS state?

    Science.gov (United States)

    Giannoudis, Peter V; Harwood, Paul John; Loughenbury, Peter; Van Griensven, Martijn; Krettek, Christian; Pape, Hans-Christoph

    2008-09-01

    Recently, increasing emphasis is being placed upon assessment of the inflammatory status of the patient. Serum inflammatory cytokines, particularly IL-6, have been used as an adjunct to this assessment. Another method uses a combination of simple laboratory and clinical data to provide an assessment of the patient's current level of systemic inflammation, the SIRS. The aim of this study was to investigate, in a group of adult trauma patients, the relationship between the interleukin-6 (IL-6) concentration, the systemic inflammatory response score (SIRS) and outcome. In patients with femoral shaft fracture, serum IL-6 levels and clinical parameters were recorded prospectively on admission and on days 1, 3, 5, and 7. Clinical course, the SIRS score and complications were documented. Nonparametric tests were used to assess relationships between variables and receiver operator characteristic (ROC) curves were used to examine their predictive values. Significance was assumed at the p SIRS state" detected early (day 1 and 3) positively correlated with the IL-6 measurement from the same period (p SIRS state (p SIRS state with an 83% sensitivity and a 75% specificity (area under ROC curve 0.76, p SIRS state and an IL-6 > 300 pg/mL was associated with a significantly increased risk of complication (pneumonia, MOF, death). Both systems were found to be significantly diagnostic of these complications using ROC curve analysis. The IL-6 concentration and SIRS score are useful adjuncts to clinical evaluation of the injured patient. In the early phase, they are closely correlated with the NISS and each other. A cutoff value of 200 pg/dL was shown to be significantly diagnostic of a SIRS state. Significant correlations between adverse events and both the IL-6 level and SIRS state are demonstrated.

  13. 急性脑梗死患者血清MMP-2、MMP-9和hs-CRP检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王清峰

    2010-01-01

    目的 检测急性脑梗死(ACI)患者血清中基质金属蛋白酶-2(MMP-2)、MMP-9和超敏C反应蛋白(hs-CRP)的表达,探讨其临床意义.方法 选取102例ACI患者作为观察组,40例健康查体者作为对照组,检测两组血清MMP-2、MMP-9和hs-CRP水平.结果 观察组MMP-2、MMP-9和hs-CRP表达显著高于对照组,且随梗死范围的增大而升高(P<0.05);观察组MMP-9与hs-CRP的表达呈正相关(r=0.402,P<0.05). 结论 MMP-2、MMP-9和hs-CRP在ACI的发生发展中可能起重要作用;MMP-9和hs-CRP可能具有协同作用,早期联合检测MMP-2、MMP-9和hs-CRP有助于判断脑梗死病变程度.

  14. Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

    Science.gov (United States)

    Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

    2013-11-27

    Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia.

  15. Interleukin-6 receptor expression in contracting human skeletal muscle: regulating role of IL-6

    DEFF Research Database (Denmark)

    Keller, Pernille; Penkowa, Milena; Keller, Charlotte

    2005-01-01

    . Therefore, we investigated IL-6 receptor regulation in response to exercise and IL-6 infusion in humans. Furthermore, using IL-6-deficient mice, we investigated the role of IL-6 in the IL-6 receptor response to exercise. Human skeletal muscle biopsies were obtained in relation to: 3 h of bicycle exercise...

  16. Prognostic value of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase N/CD13 in breast cancer patients.

    Science.gov (United States)

    Ranogajec, Irena; Jakić-Razumović, Jasminka; Puzović, Velibor; Gabrilovac, Jelka

    2012-06-01

    The aim of this study was to analyse the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase APN/CD13 in breast carcinoma samples, and their possible prognostic value in breast cancer patients. The expression of MMP-2, MMP-9 and APN/CD13 in tumor cells was analysed in 138 breast carcinomas by immunohistochemical staining of tumor cells using the semiquantitative method for the detection of cytoplasmic and membrane reaction in tumor cells as well as stromal cells positivity. MMP-2 was positive in tumor cells of 52.9% patients and in stromal cells of 74.6% patients, while MMP-9 positive tumor and stromal cells were found in 84.8 and 63.8% patients, respectively. Tumor cell APN/CD13 expression was found in 36.2% patients. Stromal cell MMP-2 expression correlated significantly with tumor size and neoangiogenesis. A positive correlation was also observed between tumor cell MMP-9 expression and hormone receptor status. Stromal cell coexpression of MMP-2/MMP-9 correlated significantly with tumor size. APN/CD13 expression in tumor cells significantly correlated with tumor type and neoangiogenesis. Overall survival was significantly shorter in patients with MMP-2, MMP-2/MMP-9 positive tumor cells, and tended to be shorter in patients with APN/CD13 positive tumor cells. Coexpression of MMP-2/MMP-9 in tumor cells was an independent risk factor for patient survival (OD = 13.9). Our results suggest that MMP-2, MMP-9, APN/CD13 expression and MMP-2/MMP-9 coexpression in combination with other standard prognostic factors can serve as a poor prognostic factor in the evaluation of breast cancer prognosis.

  17. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages

    Directory of Open Access Journals (Sweden)

    Qi-Ming Wang

    2016-11-01

    Full Text Available Background/Aims: It is well documented that overexpression of EMMPRIN (extracellular matrix metalloproteinase inducer and MMPs (matrix metalloproteinases by monocytes/macrophages plays an important role in atherosclerotic plaque rupture. Green tea polyphenol epigallocatechin-3-gallate (EGCG has a variety of pharmacological properties and exerts cardiovascular protective effects. Recently, the 67-kD laminin receptor (67LR has been identified as a cell surface receptor of EGCG. The aim of the present study was to evaluate the effects of EGCG on the expression of EMMPRIN and MMP-9 in PMA-induced macrophages, and the potential mechanisms underlying its effects. Methods: Human monocytic THP-1 cells were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA. Protein expression and MMP-9 activity were assayed by Western blot and Gelatin zymography, respectively. Real-time PCR was used to examine EMMPRIN and MMP-9 mRNA expression. Results: We showed that EGCG (10-50µmol/L significantly inhibited the expression of EMMPRIN and MMP-9 and activation of extracellular signal-regulated kinase 1/2 (ERK1/2, p38 and c-Jun N-terminal kinase (JNK in PMA-induced macrophages. Downregulation of EMMPRIN by gene silencing hindered PMA-induced MMP-9 secretion and expression, indicating an important role of EMMPRIN in the inhibition of MMP-9 by EGCG. Moreover, 67LR was involved in EGCG-mediated suppression of EMMPRIN and MMP-9 expression. Anti-67LR antibody treatment led to abrogation of the inhibitory action of EGCG on the expression of EMMPRIN and MMP-9 and activation of ERK1/2, p38, and JNK. Conclusion: Our results indicate that EGCG restrains EMMPRIN and MMP-9 expression via 67LR in PMA-induced macrophages, which also suggests that EGCG may be a possible therapeutic agent for stabilizing atherosclerotic plaque.

  18. Therapy with plasma purified alpha1-antitrypsin (Prolastin® induces time-dependent changes in plasma levels of MMP-9 and MPO.

    Directory of Open Access Journals (Sweden)

    Janine Koepke

    Full Text Available The common Z mutation (Glu342Lys of α1-antitrypsin (A1AT results in the polymerization and intracellular retention of A1AT protein. The concomitant deficiency of functional A1AT predisposes PiZZ subjects to early onset emphysema. Clinical studies have implied that, among the biomarkers associated with emphysema, matrix metalloproteinase 9 (MMP-9 is of particular importance. Increased plasma MMP-9 levels are proposed to predict the decline of lung function as well as greater COPD exacerbations in A1AT deficiency-associated emphysema. The aim of the present study was to investigate the effect of A1AT therapy (Prolastin on plasma MMP-9 and myeloperoxidase (MPO levels. In total 34 PiZZ emphysema patients were recruited: 12 patients without and 22 with weekly intravenous (60 mg/kg body weight A1AT therapy. The quantitative analysis of A1AT, MMP-9 and MPO was performed in serum and in supernatants of blood neutrophils isolated from patients before and after therapy. Patients with Prolastin therapy showed significantly lower serum MMP-9 and MPO levels than those without therapy. However, parallel analysis revealed that a rapid infusion of Prolastin is accompanied by a transient elevation of plasma MMP-9 and MPO levels. Experiments with freshly isolated blood neutrophils confirmed that therapy with Prolastin causes transient MMP-9 and MPO release. Prolastin induced the rapid release of MMP-9 and MPO when added directly to neutrophil cultures and this reaction was associated with the presence of IgA in A1AT preparation. Our data support the conclusion that changes in plasma levels of MMP-9 and MPO mirror the effect of Prolastin on blood neutrophils.

  19. IL-8 CHEMOTACTIC FACTOR IN PATIENTS WITH COMMUNITY-ACQUIRED PNEUMONIA AND FEATURES OF IL-8 GENE POLYMORPHISM (251 T/А

    Directory of Open Access Journals (Sweden)

    L. F. Aznabaeva

    2010-01-01

    Full Text Available Fifty-four patients with different clinical course (acute and protracted forms of community-acquired pneumonia (CAP, were studied for interleukin-8 (IL-8 contents in blood serum and its production levels (spontaneous and PHA-stimulated, depending on the IL-8 gene polymorphism at the 251 T → A locus. Employing the data about immunogenetic differences, we have shown some associations between IL-8 production, depending on clinical outcome (adequate responders vs poor response to medication in acute pneumonia. Both in acute and chronic forms of pneumonia, poor response to therapy was associated with decreased reserve capacity of IL-8 production, and a downward trend of cytokine concentration in blood serum. It was revealed that the CAP patients with poor response to treatment exhibit deficient production of IL-8 associated with homozygous AA genotype at the -251 T/A locus of IL-8 gene.

  20. TLR4 induces CREB-mediated IL-6 production via upregulation of F-spondin to promote vascular smooth muscle cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Guan-Lin [Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (China); Graduate Institutes of Life Sciences, National Defense Medical Center, Taipei, Taiwan (China); Wu, Jing-Yiing [Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (China); Yeh, Chang-Ching [Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (China); Graduate Institutes of Life Sciences, National Defense Medical Center, Taipei, Taiwan (China); Kuo, Cheng-Chin, E-mail: kuocc@nhri.org.tw [Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan (China); Graduate Institutes of Life Sciences, National Defense Medical Center, Taipei, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China)

    2016-05-13

    Toll-like receptor 4 (TLR4) is important in promoting inflammation and vascular smooth muscle cell (VSMC) migration, both of which contribute to atherosclerosis development and progression. But the mechanism underlying the regulation of TLR4 in VSMC migration remains unclear. Stimulation of VSMCs with LPS increased the cellular level of F-spondin which is associated with the regulation of proinflammatory cytokine production. The LPS-induced F-spondin expression depended on TLR4-mediated PI3K/Akt pathway. Suppression of F-spondin level by siRNA inhibited not only F-spondin expression but also LPS-induced phosphorylation of cAMP response element binding protein (CREB) and IL-6 expression, VSMC migration and proliferation as well as MMP9 expression. Moreover, suppression of CREB level by siRNA inhibited TLR4-induced IL-6 production and VSMC migration. Inhibition of F-spondin siRNA on LPS-induced migration was restored by addition of exogenous recombinant mouse IL-6. We conclude that upon ligand binding, TLR4 activates PI3K/Akt signaling to induce F-spondin expression, subsequently control CREB-mediated IL-6 production to promote VSMC migration. These findings provide vital insights into the essential role of F-spondin in VSMC function and will be valuable for developing new therapeutic strategies against atherosclerosis. -- Highlights: •LPS-induced F-spondin expression of VSMCs is via a TLR4/PI3K/Akt signaling. •F-spondin is pivotal for LPS-induced CREB-mediated IL-6 production. •F-spondin is required for LPS-induced VSMC migration and proliferation.

  1. 强力霉素对胃癌细胞增殖及Notch1、MMP-9表达的影响%Effect of Doxycycline on Gastric Cancer Cell Proliferation and Notch1, MMP-9 Expression

    Institute of Scientific and Technical Information of China (English)

    许敏; 李红

    2014-01-01

    Objective To investigate the effect of Doxycycline on gastric cancer cell line BGC-823 proliferation and Notch1, Matrix metalloproteinase-9(MMP-9)expression in order to shine a light on new anticancer drugs. Methods Final concentration of 0, 5, 10, 20, 40 mg/L doxycycline were added into human gastric cancer cell line BGC-823. Cell pro-liferation was detected by MTT;Cell cycle distribution was assessed by flow cytometry;Notch1, MMP-9 protein expression was revealed by Immunoblot. Results Doxycycline can inhibit proliferation of human gastric cancer cells line BGC-823, and its effect is dose and time-dependent(P<0.01). Doxycycline alters distribution of gastric cancer cell line BGC-823. With increasing drug concentration, the proportion of cells in S phase dropped(P<0.01). Notch1 expression rose and MMP-9 expression decreased(P<0.01). Conclusion Doxycyclinecan inhibited gastric cancer cell line BGC-823 prolif-eration and up-regulating Notch1 might be one mechanisms.%目的:研究强力霉素对胃癌细胞BGC-823细胞的增殖及Notch1、基质金属蛋白酶-9(MMP-9)蛋白表达的影响,为胃癌的治疗提供新的抗肿瘤药物。方法分别以0、5、10、20、40 mg/L终浓度的强力霉素作用于人胃癌细胞系BGC-823,运用MTT法检测细胞增殖程度;流式细胞仪检测细胞周期分布的影响;Western Blot检测Notch1、MMP-9蛋白水平的表达。结果强力霉素能够抑制人胃癌细胞BGC-823细胞的增殖,且有剂量及时间依赖性(P<0.01);强力霉素能够改变胃癌细胞BGC-823周期的分布,随着浓度的增加,S期所占比例降低;并且随着浓度的增加,Notch1的表达增强,MMP-9的表达降低(P<0.01)。结论强力霉素能够抑制胃癌细胞BGC-823的增殖,促进Notch1上调为可能的机制之一。

  2. Value of serum IL-32,IL-6 and IL-8 in predicting prognosis of patients with acute-on-chronic liver failure by hepatitis B virus%血清 IL-32、IL-6IL-8水平预测慢加急性乙型肝炎肝衰竭患者預后的价值

    Institute of Scientific and Technical Information of China (English)

    吴丛霞; 邹美银; 朱勇根

    2015-01-01

    Objective To explore the value of serum IL‐32 ,IL‐6 and IL‐8 in predicting the prognosis of the patients with acute‐on‐chronic liver failure by hepatitis B virus (HBV‐ACLF ) . Methods Serum levels of IL‐32 ,IL‐6 and IL‐8 were detected by ELISA in 62 patients with chronic hepatitis B(group A) ,68 patients with HBV‐ACLF(group B) and 20 healthy controls(group C) . ALT ,AST ,TBil ,Alb and PT were examined as well .The correlation of serum IL‐32 ,IL‐6 and IL‐8 levels and the prognosis of the patients with HBV‐ACLF was analyzed .Results Serum levels of IL‐32 and IL‐8 were higher ,but serum IL‐6 level was lower ,in groups of A and B than those in group C (P<0 .01) .Serum levels of IL‐32 and IL‐6 were higher ,but serum IL‐8 level was lower ,in group B than those in group A ( P<0 .01 ) .Taking 910.8 pg/ml as the cutoff value of serum IL‐32 ,the sensitivity and specificity were 88.77% and 78.00% ,respectively .Conclusion Serum levels of IL‐32 , IL‐6 and IL‐8 can reflect the severity of liver inflammation injury and illness in the patients with chronic hepatitis B and HBV‐ACLF .But only serum level of IL‐32 has a certain value in predicting the prognosis of the patients with HBV‐ACLF .%目的:探讨IL‐32、IL‐6和IL‐8水平预测慢加急性乙型肝炎肝衰竭(HBV‐ACLF)患者预后的价值。方法采用ELISA法检测62例慢性乙型肝炎(A组)、68例HBV‐ACLF(B组)及20例健康对照(C组)血清IL‐32、IL‐6和IL‐8水平,分析其与ALT、AST、TBil、Alb、PT 的相关性,探讨其预测HBV‐ACLF患者预后的价值。结果 A、B组血清IL‐32和IL‐8水平均高于C组,而血清IL‐6水平低于C组(P<0.01);B组血清IL‐32和IL‐6水平高于A组,而血清IL‐8水平低于A组(P<0.01);取910.8 pg/ml作为血清IL‐32最佳界值时,其预测B组患者短期预后的灵敏度为88.77%,特异性为78.00%。结论 IL‐32、IL‐6、IL‐8均能反映慢性乙型肝炎和 HBV‐ACLF患者肝脏炎症损伤和病情严重程度,但在对HBV‐ACLF患者预后评估方面,仅IL‐32有一定的预测价值。

  3. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2011-06-01

    Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking.

  4. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-02-01

    RATIONALE: Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking. OBJECTIVES: To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8. METHODS: Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline). MEASUREMENTS AND MAIN RESULTS: In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency. CONCLUSIONS: Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.

  5. Inhibitory effect of the carnosine-gallic acid synthetic peptide on MMP-2 and MMP-9 in human fibrosarcoma HT1080 cells.

    Science.gov (United States)

    Kim, Sung-Rae; Eom, Tae-Kil; Byun, Hee-Guk

    2014-09-01

    Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade extracellular matrix components and play important roles in a variety of biological and pathological processes such as malignant tumor metastasis and invasion. In this study, we constructed carnosine-gallic acid peptide (CGP) to identify a better MMP inhibitor than carnosine. The inhibitory effects of CGP on MMP-2 and MMP-9 were investigated in the human fibrosarcoma (HT1080) cell line. As a result, CGP significantly decreased MMP-2 and MMP-9 expression levels without a cytotoxic effect. Moreover, CGP may inhibit migration and invasion in HT1080 cells through the urokinase plasminogen activator (uPA)-uPA receptor signaling pathways to inhibit MMP-2 and MMP-9. Based on these results, it appears that CGP may play an important role in preventing and treating several MMP-2 and MMP-9-mediated health problems such as metastasis.

  6. 人参皂甙Rg3对乳腺癌细胞表达MMP-2和MMP-9的影响

    Institute of Scientific and Technical Information of China (English)

    李博; 杨威; 郑永晨; 杨艳秋

    2005-01-01

    目的研究人参皂甙Rg3对乳腺癌细胞(MCF-7细胞)分泌的基质金属蛋白酶(MMP-2,MMP-9)表达的影响.方法采用酶谱法测定了人参皂甙Rg3对乳腺癌细胞(MCF-7)细胞分泌基质金属蛋白酶(MMP-2,MMP-9)的影响.结果酶谱分析表明人参皂甙Rg3能减少MCF-7细胞分泌MMP-2,MMP-9(P<0.05).结论人参皂甙Rg3能抑制MMP-2和MMP-9的分泌.

  7. Bone mineral density, Bone mineral contents, MMP-8 and MMP-9 levels in Human Mandible and alveolar bone: Simulated microgravity

    Science.gov (United States)

    Rai, Balwant; Kaur, Jasdeep; Catalina, Maria

    Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. It has been reported that head-down tilt bed-rest studies mimic many of the observations seen in flights. There is no study on the correlation on effects of mandibular bone and alveolar bone loss in both sex in simulating microgravity. This study was designed to determine the Bone mineral density and GCF MMP-8 MMP-9 in normal healthy subject of both sexes in simulated microgravity condition of -6 head-down-tilt (HDT) bed rest. The subjects of this investigation were 10 male and 10 female volunteers participated in three weeks 6 HDT bed-rest exposure. The Bone density and bone mineral contents were measured by dual energy X-ray absorptiometry before and in simulated microgravity. The GCF MMP-8 MMP-8 were measured by Enzyme-linked immunosorbent assays (Human Quantikine MMP-8,-9 ELISA kit). The bone mineral density and bone mineral contents levels were significantly decreased in simulated microgravity condition in both genders, although insignificantly loss was higher in females as compared to males. MMP-8 MMP-9 levels were significantly increased in simulated microgravity as compared to normal condition although insignificantly higher in females as compared to males. Further study is required on large samples size including all factors effecting in simulated microgravity and microgravity. Keys words-Simulated microgravity condition, head-down-tilt, Bone loss, MMP-8, MMP-9, Bone density, Bone mineral contents.

  8. Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

    Science.gov (United States)

    Zeng, Rong; Huang, Jun-Peng; Li, Xu Feng; Xiong, Wei-Bin; Wu, Gang; Jiang, Zhao-Jing; Song, Shu-Jie; Li, Ji-Qiang; Zheng, Yan-Fang; Zhang, Ji-Ren

    2016-04-01

    EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.

  9. 大鼠骨骼肌缺血后MMP-9的变化与骨骼肌损伤和重塑的关系%The modification of MMP-9 in rat skeletal muscle ischemia and the relationship between MMP-9 and muscular injury and remolding

    Institute of Scientific and Technical Information of China (English)

    李国华; 刘德群; 刘会仁

    2012-01-01

    目的 建立单一骨骼肌部分缺血损害动物模型,并观察骨骼肌缺血后基质蛋白酶9(MMP-9)的表达与骨骼肌重塑的关系.方法 解剖组:解剖新鲜Wistar大鼠后肢20只20侧,进行血管灌注,观测肌肉血管及神经走行.实验组:Wistar大鼠40只,随机均分为5组,正常对照组(A组)不经缺血处理;缺血1 d组(B组);缺血3 d组(C组);缺血5 d组(D组);缺血7 d组(E组).观察肌纤维横截面和肌细胞坏死程度,测定腓肠肌肌肉重量、毛细血管密度,Western blot法检测MMP-9的表达.结果 大鼠小腿三头肌血供丰富,腓肠肌内侧头血管相对独立.与A组比较,B组肌纤维横切面直径无明显变化,C、D、E组显著减小.肌肉毛细血管密度呈时间依赖性,随时间延长肌肉毛细血管密度明显下降,后逐渐增加.与A组比较,B组肌肉重量无明显变化,C组明显减轻,D组重量显著增加,E组重量下降到A组水平.细胞因子MMP-9变化呈时间依赖性,其表达与毛细血管密度变化平行.骨骼肌缺血导致MMP-9水平下降,而修复时MMP-9升高.结论 大鼠小腿三头肌血供丰富,为腓肠肌缺血后损害的评价提供了解剖学基础.骨骼肌缺血后,肌纤维功能损伤呈时间依赖性加重,缺血一定时间后肌纤维逐渐修复.骨骼肌修复和新毛细血管生成有关.%Objective To observe the changes of matrix metalloproteinase-9 in early stage of skeletal muscle ischemia and to analyze its correlation with skeletal muscle injury and remodeling by creating a single skeletal muscle ischemia animal model with dissecting triceps surae of rats. Methods 60 Wistar rats were divided into anatomic group and experimental group. 20 sides of fresh hindlimbs of 20 Wistar rats in the anatomic group were dessected and vascular arterial perfusion were given, then the following items were observed: muscle shape, blood vessel, nerve shape, muscle fiber shape. The other 40 Wistar rats were divided into 5 groups ( n = 8

  10. Calmodulin kinase II-dependent transactivation of PDGF receptors mediates astrocytic MMP-9 expression and cell motility induced by lipoteichoic acid

    Directory of Open Access Journals (Sweden)

    Hsieh Hsi-Lung

    2010-11-01

    Full Text Available Abstract Background Lipoteichoic acid (LTA is a component of Gram-positive bacterial cell walls, which has been found to be elevated in cerebrospinal fluid of patients suffering from meningitis. Moreover, matrix metalloproteinases (MMPs, MMP-9 especially, have been observed in patients with brain inflammatory diseases and may contribute to brain disease pathology. However, the molecular mechanisms underlying LTA-induced MMP-9 expression in brain astrocytes remain unclear. Objective The goal of this study was to examine whether LTA-induced cell migration is mediated by calcium/calmodulin (CaM/CaM kinase II (CaMKII-dependent transactivation of the PDGFR pathway in rat brain astrocytes (RBA-1 cells. Methods Expression and activity of MMP-9 induced by LTA was evaluated by zymographic, western blotting, and RT-PCR analyses. MMP-9 regulatory signaling pathways were investigated by treatment with pharmacological inhibitors or using dominant negative mutants or short hairpin RNA (shRNA transfection, and chromatin immunoprecipitation (ChIP-PCR and promoter activity reporter assays. Finally, we determined the cell functional changes by cell migration assay. Results The data show that c-Jun/AP-1 mediates LTA-induced MMP-9 expression in RBA-1 cells. Next, we demonstrated that LTA induces MMP-9 expression via a calcium/CaM/CaMKII-dependent transactivation of PDGFR pathway. Transactivation of PDGFR led to activation of PI3K/Akt and JNK1/2 and then activated c-Jun/AP-1 signaling. Activated-c-Jun bound to the AP-1-binding site of the MMP-9 promoter, and thereby turned on transcription of MMP-9. Eventually, up-regulation of MMP-9 by LTA enhanced cell migration of astrocytes. Conclusions These results demonstrate that in RBA-1 cells, activation of c-Jun/AP-1 by a CaMKII-dependent PI3K/Akt-JNK activation mediated through transactivation of PDGFR is essential for up-regulation of MMP-9 and cell migration induced by LTA. Understanding the regulatory mechanisms

  11. Rac1/β-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9

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    Minghua Fan

    2016-03-01

    Full Text Available Background/Aims: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs. Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. Methods: We measured the activity of Rac1 and its downstream targets, β-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the β-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and β-catenin on trophoblast invasion. Results: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the β-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down

  12. Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma

    OpenAIRE

    2014-01-01

    This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were u...

  13. Evidence For A Macromolecular Complex In Poor Prognosis CLL That Contains CD38, CD49d, CD44 and MMP-9.

    OpenAIRE

    Buggins, Andrea Gail Sherman; Levi, Ana; Gohil, Satyen; Fishlock, Keith; Patten, Piers E.M.; Calle, Yolanda; Yallop, Deborah; Devereux, Stephen

    2011-01-01

    Abstract Progressive chronic lymphocytic leukaemia is characterised by the accumulation of neoplastic B-cells in the tissues and correlates with the expression of prognostic biomarkers such as CD38, CD49d and matrix metalloproteinase-9 (MMP9), which are involved in migration and tissue invasion. In this study we investigated the physical relationship between these molecules and demonstrate that CD38, CD49d, MMP9 and CD44 are physically associated in a supramolecular cell surface co...

  14. Comparative Analysis of Matrix Metalloproteinase Family Members Reveals That MMP9 Predicts Survival and Response to Temozolomide in Patients with Primary Glioblastoma

    Science.gov (United States)

    Cai, Jinquan; Sun, Ying; Wang, Guangzhi; Li, Yongli; Li, Ruiyan; Feng, Yan; Han, Bo; Li, Jianlong; Tian, Yu; Yi, Liye; Jiang, Chuanlu

    2016-01-01

    Background Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Radiotherapy plus concomitant and adjuvant TMZ chemotherapy is the current standard of care for patients with GBM. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, are key modulators of tumor invasion and metastasis due to their ECM degradation capacity. The aim of the present study was to identify the most informative MMP member in terms of prognostic and predictive ability for patients with primary GBM. Method The mRNA expression profiles of all MMP genes were obtained from the Chinese Glioma Genome Atlas (CGGA), the Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the GSE16011 dataset. MGMT methylation status was also examined by pyrosequencing. The correlation of MMP9 expression with tumor progression was explored in glioma specimens of all grades. Kaplan–Meier analysis and Cox proportional hazards regression models were used to investigate the association of MMP9 expression with survival and response to temozolomide. Results MMP9 was the only significant prognostic factor in three datasets for primary glioblastoma patients. Our results indicated that MMP9 expression is correlated with glioma grade (p<0.0001). Additionally, low expression of MMP9 was correlated with better survival outcome (OS: p = 0.0012 and PFS: p = 0.0066), and MMP9 was an independent prognostic factor in primary GBM (OS: p = 0.027 and PFS: p = 0.032). Additionally, the GBM patients with low MMP9 expression benefited from temozolomide (TMZ) chemotherapy regardless of the MGMT methylation status. Conclusions Patients with primary GBMs with low MMP9 expression may have longer survival and may benefit from temozolomide chemotherapy. PMID:27022952

  15. IVIG inhibits TNF-α-induced MMP9 expression and activity in monocytes by suppressing NF-κB and P38 MAPK activation.

    Science.gov (United States)

    Zhou, Cuizhen; Huang, Min; Xie, Lijian; Shen, Jie; Xiao, Tingting; Wang, Renjian

    2015-01-01

    Matrix metalloproteinase-9 (MMP9) has been involved in inflammatory and pathologic processes of coronary artery lesions (CAL) in Kawasaki disease (KD). Intravenous immunoglobulin (IVIG), a traditional treatment for Kawasaki disease, could decrease the expressions of MMP9. The purpose of this study was to investigate the protective effect of IVIG in chemotactic migration of monocyte and the regulation of MMP9 induced by tumor necrosis factor-α (TNF-α) in U937s. Studies were carried out with real time polymerase chain reaction (RT-PCR), zymographic, Western blotting and immunofluorescence. U937s' migration was enhanced by TNF-α stimulation, while was inhibited by IVIG pretreatment. MMP9 expression and activity in U937s were also significantly enhanced by TNF-α and inhibited by IVIVG pretreatment. During inflammatory stimulus, nuclear factor kappa B (NF-κB) and P38 Mitogenactivated protein kinase (P38 MAPK) pathways play a significant role in regulating MMP9 gene expression. TNF-α induced nuclear translocation of NF-κB and P38 MAPK activation in U937s were inhibited significantly by IVIG. Furthermore, we clarified that nuclear NF-κB and P38 MAPK pathways play pivotal roles in regulating U937s' migration and MMP9 expressions using PDTC and SB203580, which were specific inhibitors of NF-κB and p38 MAPK pathways. IVIG displays striking biological effects, notably promoting monocyte migration. These effects involve the NF-κB and p38 pathways, and increased MMP9 activity. It might be a crucial mechanism of IVIG reducing the occurrence of CAL that IVIG inhibited monocytes expressing MMP9 and decreased chemotactic migration of monocyte.

  16. The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors

    DEFF Research Database (Denmark)

    Van den Steen, Philippe E; Van Aelst, Ilse; Hvidberg, Vibeke;

    2006-01-01

    with a compact three-dimensional structure. The OG and hemopexin domains have no influence on the cleavage efficiency of MMP-9 substrates. In contrast, the hemopexin domain contains a binding site for the cargo receptor low density lipoprotein receptor-related protein-1 (LRP-1). Furthermore, megalin/LRP-2...... domains down-regulate the bioavailability of active MMP-9 and the interactions with the cargo receptors are proposed to be the original function of hemopexin domains in MMPs....

  17. FSL-1 Induces MMP-9 Production through TLR-2 and NF-κB /AP-1 Signaling Pathways in Monocytic THP-1 Cells

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    Rasheed Ahmad

    2014-08-01

    Full Text Available Background: Matrix metalloproteinase-9 (MMP-9 is known to be implicated in the pathogenesis of many inflammatory disorders. FSL-1 (fibroblast-stimulating lipopeptide-1 induces cytokine production by monocytes/macrophages. However, it is unclear whether FSL-1 is also able to induce MMP-9 production. Herein, we determined whether FSL-1 could induce MMP-9 production, and if so, which signal transduction pathway(s were involved. Methods: MMP-9 expression was assessed with real-time qPCR and ELISA. Signaling pathways were studied by using THP1-XBlue™ cells, THP1-XBlue™-defMyD cells, anti-TLR2 mAb and pharmacological inhibitors. Phospho and total proteins were determined by Western blotting. Results: FSL-1 induces MMP-9 expression (PP-/- THP-1 cells did not express MMP-9 in response to FSL-1 treatment. By small interfering RNA-mediated knockdown, we also show that FSL-1-induced up-regulation of MMP-9 requires MyD88. Pre-treatment of THP-1 cells with inhibitors of JNK (SP600125, MEK/ERK (U0126; PD98056; XMD 8-92, p38 MAPK (SB203580 and NF-κB (BAY11-7085, Triptolide, Resveratrol significantly suppressed (PConclusion: These findings provide the first evidence that FSL-1 induces TLR-2-dependent MMP-9 gene expression which requires the recruitment of MyD88 and leads to activation of MEK1/2 /ERK 1/2, MEK5/ERK5, JNK, p38 MAPK and NF-κB/AP-1.

  18. Plasminogen activator inhibitor-1 controls bone marrow-derived cells therapeutic effect through MMP9 signaling: role in physiological and pathological wound healing.

    Science.gov (United States)

    Ebrahimian, Teni G; Squiban, Claire; Roque, Telma; Lugo-Martinez, Haydee; Hneino, Mohamad; Buard, Valerie; Gourmelon, Patrick; Benderitter, Marc; Milliat, Fabien; Tamarat, Radia

    2012-07-01

    We assessed the role of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase 9 (MMP9) in wound healing process and in the bone marrow mononuclear cells (BMMNC)-related effects on physiological and pathological wound healing. A full thickness excision wound was created by removal of the skin on the midback of irradiated and nonirradiated animals. Angiogenesis and re-epithelialization were markedly increased in PAI-1-/- mice compared to wild-type (WT) animals. We revealed high MMP activity in tissue of PAI-1-/- animals. Of interest, the wound healing process was reduced in PAI-1-/-:MMP9-/- animals compared to PAI-1-/- mice, suggesting a key role of MMP9 in beneficial effect of PAI-1 deficiency on wound closure. To unravel the role of PAI-1 in BMMNC relative effects, mice were treated with or without local injection of BMMNC isolated from WT, PAI-1-/-, and PAI-1-/-: MMP9-/- animals for 14 days (10(6) cells, n = 6 per group). In WT nonirradiated mice, transplantation of BMMNC isolated from PAI-1-/- animals enhanced wound formation when compared with WT BMMNC. BMMNC differentiation into cells with endothelial phenotype was enhanced by PAI-1 deficiency. These effects were abrogated in PAI-1-/-:MMP9-/- and MMP9-/- BMMNC. In addition, using chimeric mice, we demonstrated that PAI-1 deficiency environment increased the BMMNC-GFP recruitment to the wound site, whereas this effect was abrogated when using PAI-1-/-:MMP9-/- BMMNC. PAI-1 deficiency, at least through MMP9 upregulation, enhanced wound healing and BMMNC therapeutic potential in irradiated and nonirradiated animals.

  19. Brief discussion of the action of MMP-9 and TIMP-1 in pulmonary fibrosis%MMP-9和TIMP-1及其在肺纤维化中的作用

    Institute of Scientific and Technical Information of China (English)

    李芳

    2011-01-01

    肺纤维化是一类以弥漫性肺泡炎和肺泡结构紊乱并最终以瘢痕组织取代正常肺组织为特征的疾病.其发生包括早期的肺泡炎阶段和后期的肺纤维化阶段.肺纤维化的发病机理至今尚未清楚.近年来研究发现,基质金属蛋白酶(MMPS)及其抑制剂(TIMPS)与肺纤维化关系密切.本文就MMP-9和TIMP-1与肺纤维化的关系讲行了综述.%Pulmonary fibrosis encompasses a heterogeneous group of diseases characterized by diffuse alveolar inflam-mation , disruption of alveolar structures, and ultimately replacement of the lung parenchyma with scar tissue. This group of diseases features an early stage of alveolar inflammation and late stage of pulmonary fibrosis. The precise mechanisms of pulmonary fibrosis are poorly understood. Previous research has indicated that matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are closely associated with the development of pulmonary fibrosis. This paper reviews the rela-tionship between MMP-9, TIMP-1 , and pulmonary fibrosis.

  20. 血清MMP-2、MMP-9水平与非小细胞肺癌转移关系的研究%Correlation of serum total MMP-2,MMP-9 levels with human non-small cell lung cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    雷建灵; 赵全年; 刘利; 高德荣

    2010-01-01

    目的 探讨非小细胞肺癌(NSCLC)患者血清MMP-2、MMP-9水平与非小细胞肺癌的关系.方法 采用ELISA法检测70例非小细胞肺癌患者及26例健康志愿者血清MMP-2和MMP-9水平.结果 NSCLC患者血清MMP-2和MMP-9含量显著高于正常对照组.NSCLC有转移组血清MMP-2和MMP-9水平显著高于 NSCLC无转移组.结论 血清MMP-2和MMP-9的水平可作为预测非小细胞肺癌转移的指标.

  1. Gene Expression Analysis of an EGFR Indirectly Related Pathway Identified PTEN and MMP9 as Reliable Diagnostic Markers for Human Glial Tumor Specimens

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    Sergio Comincini

    2009-01-01

    Full Text Available In this study the mRNA levels of five EGFR indirectly related genes, EGFR, HB-EGF, ADAM17, PTEN, and MMP9, have been assessed by Real-time PCR in a panel of 37 glioblastoma multiforme specimens and in 5 normal brain samples; as a result, in glioblastoma, ADAM17 and PTEN expression was significantly lower than in normal brain samples, and, in particular, a statistically significant inverse correlation was found between PTEN and MMP9 mRNA levels. To verify if this correlation was conserved in gliomas, PTEN and MMP9 expression was further investigated in an additional panel of 16 anaplastic astrocytoma specimens and, in parallel, in different human normal and astrocytic tumor cell lines. In anaplastic astrocytomas PTEN expression was significantly higher than in glioblastoma multiforme, but no significant correlation was found between PTEN and MMP9 expression. PTEN and MMP9 mRNA levels were also employed to identify subgroups of specimens within the different glioma malignancy grades and to define a gene expression-based diagnostic classification scheme. In conclusion, this gene expression survey highlighted that the combined measurement of PTEN and MMP9 transcripts might represent a novel reliable tool for the differential diagnosis of high-grade gliomas, and it also suggested a functional link involving these genes in glial tumors.

  2. Pertussis toxin B-oligomer suppresses IL-6 induced HIV-1 and chemokine expression in chronically infected U1 cells via inhibition of activator protein 1.

    Science.gov (United States)

    Rizzi, Chiara; Crippa, Massimo P; Jeeninga, Rienk E; Berkhout, Ben; Blasi, Francesco; Poli, Guido; Alfano, Massimo

    2006-01-15

    Pertussis toxin B-oligomer (PTX-B) inhibits HIV replication in T lymphocytes and monocyte-derived macrophages by interfering with multiple steps of the HIV life cycle. PTX-B prevents CCR5-dependent (R5) virus entry in a noncompetitive manner, and it also exerts suppressive effects on both R5- and CXCR4-dependent HIV expression at a less-characterized postentry level. We demonstrate in this study that PTX-B profoundly inhibits HIV expression in chronically infected promonocytic U1 cells stimulated with several cytokines and, particularly, the IL-6-mediated effect, a cytokine that triggers viral production in these cells independently of NF-kappaB activation. From U1 cells we have subcloned a cell line, named U1-CR1, with increased responsiveness to IL-6. In these cells, PTX-B neither down-regulated the IL-6R nor prevented IL-6 induced signaling in terms of STAT3 phosphorylation and DNA binding. In contrast, PTX-B inhibited AP-1 binding to target DNA and modified its composition with a proportional increases in FosB, Fra2, and ATF2. PTX-B inhibited IL-6-induced HIV-1 long-terminal repeat-driven transcription from A, C, E, and F viral subtypes, which contain functional AP-1 binding sites, but failed to inhibit transcription from subtypes B and D LTR devoid of these sites. In addition, PTX-B inhibited the secretion of IL-6-induced, AP-1-dependent genes, including urokinase-type plasminogen activator, CXCL8/IL-8, and CCL2/monocyte chemotactic protein-1. Thus, PTX-B suppression of IL-6 induced expression of HIV and cellular genes in chronically infected promonocytic cells is strongly correlated to inhibition of AP-1.

  3. 脑室出血早产儿血浆MMP-2和MMP-9测定的临床意义%Significance of detection of plasma MMP-2 and MMP-9 in diagnosis of the periventricular hemorrhage intraventricular hemorrhage premature infants

    Institute of Scientific and Technical Information of China (English)

    江明荣; 黄循斌; 谢晓彬; 周曙明

    2012-01-01

    Objective To investigate the clinical significance of detection of plasma MMP-2 and MMP-9 in dangosis of the periventricular hemorrhage-intraventricular hemorrhage (PVH-IVH) premature infants. Methods ELISA method was to determine the contents of MMP-2 and MMP-9 in blood plasma of 40 premature infants and 20 controls premature infants without the complication of intracranial hemorrhage,etc. Results The contents of MMP-2 and MMP-9 in premature infants with PVH-IVH was significantly higher than those of the control group (P < 0.01 )and the contents of MMP-2 and MMP-9 increaed ohviously with the bleeding degree aggravation. Conclusion The change of contents of MMP-2 and MMP-9 in blood plasma disclose tge early occurrence and injury extent of PVH-IVH.%目的 探讨血浆基质金属蛋白酶-2和9(MMP-2、MMP-9)在早产儿脑室周围-脑室内出血(PVH-IVH)时的临床意义.方法 采用ELISA法测定早产儿脑室周围-脑室内出血患儿及20例对照组早产儿(无颅内出血等并发症)血浆MMP-2、MMP-9含量.结果 PVH-IVH患儿MMP-2、MMP-9比对照组早产儿显著升高(均P<0.01),随着出血程度加重,血浆MMP-2、MMP-9均明显升高(均P<0.01).结论 血浆MMP-2和MMP-9含量的变化,可客观早期的判断PVH-IVH的发生、损伤程度.

  4. Blockade of P2X4 Receptors Inhibits Neuropathic Pain-Related Behavior by Preventing MMP-9 Activation and, Consequently, Pronociceptive Interleukin Release in a Rat Model

    Science.gov (United States)

    Jurga, Agnieszka M.; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2017-01-01

    Neuropathic pain is still an extremely important problem in today’s medicine because opioids, which are commonly used to reduce pain, have limited efficacy in this type of pathology. Therefore, complementary therapy is needed. Our experiments were performed in rats to evaluate the contribution of the purinergic system, especially P2X4 receptor (P2X4R), in the modulation of glia activation and, consequently, the levels of nociceptive interleukins after chronic constriction injury (CCI) of the right sciatic nerve, a rat model of neuropathic pain. Moreover, we studied how intrathecal (ith.) injection of a P2X4R antagonist Tricarbonyldichlororuthenium (II) dimer (CORM-2) modulates nociceptive transmission and opioid effectiveness in the CCI model. Our results demonstrate that repeated ith. administration of CORM-2 once daily (20 μg/5 μl, 16 and 1 h before CCI and then daily) for eight consecutive days significantly reduced pain-related behavior and activation of both spinal microglia and/or astroglia induced by CCI. Moreover, even a single administration of CORM-2 on day 7 after CCI attenuated mechanical and thermal hypersensitivity as efficiently as morphine and buprenorphine. In addition, using Western blot, we have shown that repeated ith. administration of CORM-2 lowers the CCI-elevated level of MMP-9 and pronociceptive interleukins (IL-1β, IL-18, IL-6) in the dorsal L4-L6 spinal cord and/or DRG. Furthermore, in parallel, CORM-2 upregulates spinal IL-1Ra; however, it does not influence other antinociceptive factors, IL-10 and IL-18BP. Additionally, based on our biochemical results, we hypothesize that p38MAPK, ERK1/2 and PI3K/Akt but not the NLRP3/Caspase-1 pathway are partly involved in the CORM-2 analgesic effects in rat neuropathic pain. Our data provide new evidence that P2X4R may indeed play a significant role in neuropathic pain development by modulating neuroimmune interactions in the spinal cord and DRG, suggesting that its blockade may have potential

  5. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

    Directory of Open Access Journals (Sweden)

    Rosseau Simone

    2006-07-01

    Full Text Available Abstract Background Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH2-terminal kinase (JNK Methods Human bronchial epithelial cells (BEAS-2B or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP. JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. Results S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1. We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser63/73-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. Conclusion S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c

  6. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1 Virus Infection in the Mexican Population.

    Directory of Open Access Journals (Sweden)

    Román Alejandro García-Ramírez

    Full Text Available Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1 virus infections. Most patients infected with the influenza A (H1N1 pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α. We propose that single-nucleotide polymorphisms (SNPs in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1 pdm09 virus infection.145 patients with influenza A (H1N1 (pA/H1N1, 133 patients with influenza-like illness (ILI, and 360 asymptomatic healthy contacts (AHCs were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8 using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4 were measured on a Luminex 100.The IL6 rs1818879 (GA heterozygous genotype was associated with severe influenza A (H1N1 virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05-11.56, and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively. Genetic susceptibility was determined (pA/H1N1 vs. AHC: the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9, and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89. Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007. Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001 and IL-6 (p  =  0.007 levels.The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were associated with influenza A (H1N1 virus

  7. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population

    Science.gov (United States)

    García-Ramírez, Román Alejandro; Ramírez-Venegas, Alejandra; Quintana-Carrillo, Roger; Camarena, Ángel Eduardo; Falfán-Valencia, Ramcés; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection. Methods 145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100. Results The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05–11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p  =  0.007) levels. Conclusions The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were

  8. Genetic and bibliographic information: IL6ST [GenLibi

    Lifescience Database Archive (English)

    Full Text Available IL6ST interleukin 6 signal transducer (gp130, oncostatin M receptor) human Periodontitis...iodontal Diseases (C07.465.714) > Periodontitis (C07.465.714.533) Stomatognathic Diseases (C07) > Mouth Dise...ases (C07.465) > Periodontal Diseases (C07.465.714) > Periodontitis (C07.465.714.533) > Aggressive Periodontitis (C07.465.714.533.161) 04A0389761 ...

  9. BRD4 Phosphorylation Regulates HPV E2-Mediated Viral Transcription, Origin Replication, and Cellular MMP-9 Expression

    Directory of Open Access Journals (Sweden)

    Shwu-Yuan Wu

    2016-08-01

    Full Text Available Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4, a transcription co-factor and chromatin regulator, uses a phosphorylation-induced switch mechanism to recruit E2 protein encoded by cancer-associated human papillomavirus (HPV to viral early gene and cellular matrix metalloproteinase-9 (MMP-9 promoters. Enhanced MMP-9 expression, induced upon keratinocyte differentiation, occurs via BRD4-dependent recruitment of active AP-1 and NF-κB to their target sequences. This is triggered by replacement of AP-1 family members JunB and JunD by c-Jun and by re-localization of NF-κB from the cytoplasm to the nucleus. In addition, BRD4 phosphorylation is critical for E2- and origin-dependent HPV DNA replication. A class of phospho-BRD4-targeting compounds, distinct from the BET bromodomain inhibitors, effectively blocks BRD4 phosphorylation-specific functions in transcription and factor recruitment.

  10. Anti-inflammatory activities of Physalis alkekengi var. franchetii extract through the inhibition of MMP-9 and AP-1 activation.

    Science.gov (United States)

    Hong, Ju-Mi; Kwon, Ok-Kyoung; Shin, In-Sik; Song, Hyuck-Hwan; Shin, Na-Rae; Jeon, Chan-Mi; Oh, Sei-Ryang; Han, Sang-Bae; Ahn, Kyung-Seop

    2015-01-01

    Physalis alkekengi has been traditionally used for the treatment of coughs, middle ear infections, and sore throats in Korea, Europe, and China. It exhibits a variety of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-cancer effects. The anti-inflammatory effects of the P. alkekengi methanol extract (PA) and its molecular mechanisms have not yet been fully investigated. In the present study, the chromatogram of PA was established by UPLC analysis. The anti-inflammatory effects of PA were also investigated using murine microphage cell lines, RAW 264.7 cells, and a murine model of OVA induced asthma. In LPS-stimulated RAW264.7 cells, PA reduced the MMP-9 expression with decreases in the production of nitric oxide, inteleukin-6, and tumor necrosis factor-α. Furthermore, PA suppressed the phosphorylation of MAPKs, which resulted in the inhibition of AP-1 activation. These effects of PA were consistent with the results of the in vivo experiment. PA-treated mice significantly inhibited inflammatory cell counts and cytokine production in bronchoalveolar lavage fluids and airway-hyperresponsiveness in OVA-induced asthmatic mice. PA treated mice also showed a marked inhibition of inducible nitric oxide synthase and MMP-9 expression. In conclusion, our results suggest that PA may be a valuable therapeutic material in treating various inflammatory diseases, including allergic asthma.

  11. Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation.

    Science.gov (United States)

    Nascimento, G C; Rizzi, E; Gerlach, R F; Leite-Panissi, C R A

    2013-11-18

    Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs). This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs). TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs), have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX). TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test) and infiltration of polymorphonuclear neutrophils into the synovial fluid (myeloperoxidase enzyme quantification). MMP expression in the trigeminal ganglion was shown to vary during the phases of the inflammatory process. MMP-9 regulated the early phase and MMP-2 participated in the late phase of this process. Furthermore, increases in plasma extravasation in periarticular tissue and myeloperoxidase activity in the joint tissue, which occurred throughout the inflammation process, were diminished by treatment with DOX, a nonspecific MMP inhibitor. Additionally, the increases of mechanical allodynia and orofacial hyperalgesia were attenuated by the same treatment.

  12. Expression of MMP-2 and MMP-9 in the rat trigeminal ganglion during the development of temporomandibular joint inflammation

    Directory of Open Access Journals (Sweden)

    G.C. Nascimento

    2013-11-01

    Full Text Available Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs. This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs. TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs, have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX. TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test and infiltration of po