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Sample records for cells recruits vcam-1

  1. ICAM-1 Clustering on Endothelial Cells Recruits VCAM-1

    NARCIS (Netherlands)

    J.D. van Buul; J. van Rijssel; F.P.J. van Alphen; A.M. van Stalborch; E.P.J. Mul; P.L. Hordijk

    2010-01-01

    In the initial stages of transendothelial migration, leukocytes use the endothelial integrin ligands ICAM-1 and VCAM-1 for strong adhesion. Upon adhesion of the leukocyte to endothelial ICAM-1, ICAM-1 is clustered and recruited to the adhered leukocyte, promoting strong adhesion. In this study, we p

  2. THE ROLE OF VCAM-1/VLA-4 IN THE ACTIVATION OF ALLOGENIC T CELLS BY MURINE MACROPHAGES

    Institute of Scientific and Technical Information of China (English)

    He Long; Cao Xuetao; Zhang Weiping; Chen Guoyou; Zhu Xuejun; Yu Yizhi

    1998-01-01

    Vascular cell adhesion molecule 1 (VCAM-1) is a member of immunoglobulin superfamily. The principal ligand for VCAM-1 is integrin α4β1/VLA-4 (very late antigen 4). It was reported that VCAM-1 was expressed on macrophages and dendritic cells, but little is known about its function on these professional antigen presenting cells (APC). The present study was performed to investigate the expression of VCAM-1 on macrophages and the role of VCAM-1/VLA-4 in the activation of allogenic T cells by murine macrophages. We analyzed VCAM-1 expression on peritoneal macrophages and macrophage cell line J774A.1 by fluorescence-activated cell sorting (FACS). Using neutralizing antibodies, we further analyzed the role of VCAM-1/VLA-4 interaction in macrophage and allogenic T cell mixed lymphocyte reaction (MLR). We found that VCAM-1 was constitutively expressed on macrophages and its expression level was upregulated by soluble tumor associated antigen (freeze-thaw lysates of FBL-3 leukemia cells) and TNF-α.In MLR assays, we observed that blocking VCAM-1/VLA-4 interaction with anti-VCAM-1 or anti-VLA-4mAbs caused significant inhibition of the proliferative response and IL-2 production. These results suggest that VCAM-1on macrophages not only facilitates the cell-tocell contact through adhesive interaction but also plays a role in the costimulation of T cells via its interaction with VLA-4 on the T cells.

  3. Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as a Biomarker in the Mouse Model of Experimental Autoimmune Myocarditis (EAM)

    Science.gov (United States)

    Grabmaier, U.; Kania, G.; Kreiner, J.; Grabmeier, J.; Uhl, A.; Huber, B. C.; Lackermair, K.; Herbach, N.; Todica, A.; Eriksson, U.; Weckbach, L. T.; Brunner, S.

    2016-01-01

    Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of mice with coxsackie virus-induced as well as in patients with viral infection-triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a biomarker in inflammatory heart diseases remains unclear. Therefore, we investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly correlated with disease activity and progression of cardiac dysfunction in the mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide together with complete Freund`s adjuvant. ELISA revealed strong expression of cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized compared to control mice at acute and chronic stages of the disease. sVCAM-1 did not correlate with the degree of acute cardiac inflammation analyzed by histology or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM. Cardiac systolic dysfunction studied with positron emission tomography indicated a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages of the disease but showed no strong correlation with the severity of EAM. PMID:27501319

  4. Angiotensin-(1-7) regulates Angiotensin II-induced VCAM-1 expression on vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Feng [Department of Cardiology, Peking University People' s Hospital, Beijing (China); William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London (United Kingdom); Ren, Jingyi [Department of Cardiology, Peking University People' s Hospital, Beijing (China); Chan, Kenneth [William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London (United Kingdom); Chen, Hong, E-mail: chenhongbj@medmail.com.cn [Department of Cardiology, Peking University People' s Hospital, Beijing (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer We for the first time found that Ang-(1-7) inhibits Ang II-induced VCAM-1 expression. Black-Right-Pointing-Pointer The inhibitory effect of Ang-(1-7) on VCAM-1 is mediated by MAS receptor. Black-Right-Pointing-Pointer The effect of Ang-(1-7) is due to the suppression of NF-kappaB translocation. -- Abstract: Angiotensin II (Ang II) and Angiotensin-(1-7) (Ang-(1-7)) are key effector peptides in the renin-angiotensin system. Increased circulatory Ang II level is associated with the development of hypertension and atherosclerosis, whereas Ang-(1-7) is a counter-regulatory mediator of Ang II which appears to be protective against cardiovascular disease. However, whether Ang-(1-7) regulates the action of Ang II on vascular endothelial cells (EC) remains unclear. We investigated the effects of Ang II and Ang-(1-7) in the context of atherogenesis, specifically endothelial cell VCAM-1 expression that is implicated in early plaque formation. The results show that Ang II increased VCAM-1 mRNA expression and protein displayed on EC surface, while Ang-(1-7) alone exerted no effects. However, Ang-(1-7) significantly suppressed Ang II-induced VCAM-1 expression. Ang-(1-7) also inhibited the Ang II-induced VCAM-1 promoter activity driven by transcription factor NF-KappaB. Furthermore, immunofluorescence assay and ELISA showed that Ang II facilitated the nuclear translocation of NF-kappaB in ECs, and this was attenuated by the presence of Ang-(1-7). The inhibitory effects of Ang-(1-7) on Ang II-induced VCAM-1 promoter activity and NF-kappaB nuclear translocation were all reversed by the competitive antagonist of Ang-(1-7) at the Mas receptor. Our results suggest that Ang-(1-7) mediates its affects on ECs through the Mas receptor, and negatively regulates Ang II-induced VCAM-1 expression by attenuating nuclear translocation of NF-kappaB.

  5. Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells

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    Pei-Chen Wang

    2014-02-01

    Full Text Available VCAM-1 (CD106, a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1. In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGFβ1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.

  6. Serum vascular cell adhesion molecule-1 (VCAM1 level is elevated in colorectal cancer regardless of the tumor stage

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    Rumeysa Ciftci

    2016-06-01

    Full Text Available Purpose: Vascular cell adhesion molecule-1 (VCAM1 is a transmembrane glycoprotein, which is expressed on endothelium and plays role in inflammation. It is over-expressed on colorectal cancer (CRC cells and plays role in metastasis development and angiogenesis. We aimed to compare serum VCAM1 levels of CRC patients with heathy controls and evaluate its relationship with clinicopathological parameters, treatment response and overall survival (OS.Methods: The study enrolled 111 patients with histopathologically confirmed CRC followed-up in our clinic and 30 sex- and age-matched healthy controls. Pre-treatment serum VCAM1 levels were determined by the solid-phase sandwich ELISA method.Results: Metastatic disease was present in 57 patients. Forty percent of 40 metastatic patients receiving systemic therapy had partial or complete response. The median serum VCAM1 level was significantly higher in CRC patients than controls (p<0.001. In addition, serum VCAM1 level was significantly higher in diabetic CRC patients than those without diabetes (p = 0.03. There was no significant relationship between VCAM1 and other clinicopathological parameters including stage and response to systemic therapy. The median follow-up period was 12 (±8.2 months. Twenty patients were dead at the time of analysis. The presence of metastasis (p < 0.001 and elevated CEA level (p < 0.001 were factors affecting OS significantly. However, serum VCAM1 did not have a significant impact on OS (p = 0.55.Conclusion: Serum VCAM1 level is significantly elevated in CRC patients regardless of the tumor stage. However, it has no prognostic or predictive role for response to systemic therapy.

  7. JNK signaling-mediated up-regulation of VCAM-1 by TNF-α in human aortic endothelial cells%JNK信号介导TNF-α对内皮细胞VCAM-1的诱导表达

    Institute of Scientific and Technical Information of China (English)

    黄春; 吴文伟; 徐春平; 窦萍

    2009-01-01

    目的 探讨肿瘤坏死因子(TNF)-α对内皮细胞血管细胞黏附分子-1(VCAM-1)表达和分泌的影响,及其可能的细胞内信号途径.方法 用10ng/ml TNF-α与人主动脉内皮细胞(HAEC)共培养不同时间,蛋白印迹法检测细胞VCAM-1蛋白表达和丝裂原活化蛋白激酶ERK1/2、INK的磷酸化水平,ELISA法测定条件培养液中可溶性VCAM-1(sVCAM-1)含量;分别用MEK-ERK1/2抑制剂PD98059和JNK抑制剂SP600125预处理HAEC 1h,观察TNF-α对VCAM-1表达和分泌的影响.结果 TNF-α以时问依赖方式诱导HAEC VCAM-1蛋白表达,4 h达最大诱导表达,为对照组的(5.80±0.44)倍,条件培养液中sVCAM-1的含量与其蛋白表达呈平行变化;SP600125(而非PD98059)显著抑制上述诱导效应.结论 TNF-α诱导HAEC VCAM-1的表达和分泌至少部分是通过JNK信号介导的.%Objective To investigate the effect of TNF-α on vascular cell adhesion molecule-1 (VCAM-1) expression and secretion in human aortic endothelial cell (HAEC), and the probable intraeeilular signaling pathway. Methods HAECs were incubated with 1O ng/ml TNF-α for various periods, VCAM-1 protein expression, phosphorylation of ERK1/2 and JNK were detected by Western blot. Sol-uble VCAM-1 (sVCAM-1) in the conditioned media was detected by ELISA. HAECs were pre-incubated with PD98059 (MEK-ERK1/2 in-hibitor) or SP600125 (JNK inhibitor) for 1 h, subsequently with TNF-α for 4 h, expression and secretion of VCAM-1 were assessed. Re-stilts TNF-α induced expression of VCAM-1 protein in a time-dependent manner, with a peak at 4 h (5.80 0. 44 folds vs control group).The level of sVCAM-1 in the conditioned media was parallel to the protein expression. SP600125, but not PD98059, reduced TNF-α-induced expression of VCAM-1. Conclusions TNF-α-induced expression of VCAM-1 in HAECs is mediated by JNK signaling at least partly.

  8. Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice

    International Nuclear Information System (INIS)

    Exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of cardiovascular diseases such as atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) is a critical mediator for adhesion and uptake of monocytes across the endothelium in the early stages of atherosclerosis development. The upregulation of VCAM-1 by PCBs may be dependent on functional membrane domains called caveolae. Caveolae are particularly abundant in endothelial cell membranes and involved in trafficking and signal transduction. The objective of this study was to investigate the role of caveolae in PCB-induced endothelial cell dysfunction. Primary mouse aortic endothelial cells (MAECs) isolated from caveolin-1-deficient mice and background C57BL/6 mice were treated with coplanar PCBs, such as PCB77 and PCB126. In addition, siRNA gene silencing technique was used to knockdown caveolin-1 in porcine vascular endothelial cells. In MAECs with functional caveolae, VCAM-1 protein levels were increased after exposure to both coplanar PCBs, whereas expression levels of VCAM-1 were not significantly altered in cells deficient of caveolin-1. Furthermore, PCB-induced monocyte adhesion was attenuated in caveolin-1-deficient MAECs. Similarly, siRNA silencing of caveolin-1 in porcine endothelial cells confirmed the caveolin-1-dependent VCAM-1 expression. Treatment of cells with PCB77 and PCB126 resulted in phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), and pharmacological inhibition of ERK1/2 diminished the observed PCB-induced increase in monocyte adhesion. These findings suggest that coplanar PCBs induce adhesion molecule expression, such as VCAM-1, in endothelial cells, and that this response is regulated by caveolin-1 and functional caveolae. Our data demonstrate a critical role of functional caveolae in the activation and dysfunction of endothelial cells by coplanar PCBs.

  9. ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion

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    Li Hailing

    2012-06-01

    Full Text Available Abstract Background Previous studies suggested that the RhoA/ROCK pathway may contribute to vascular complications in diabetes. The present study was designed to investigate whether ROCK inhibitor fasudil could prevent high glucose-induced monocyte-endothelial cells adhesion, and whether this was related to fasudil effects on vascular endothelial cell expression of chemotactic factors, vascular cell adhesion molecule-1 (VCAM-1 and monocyte chemoattractant protein-1 (MCP-1. Methods HUVECs were stimulated with high glucose (HG or HG + fasudil in different concentration or different time. Monocyte-endothelial cell adhesion was determined using fluorescence-labeled monocytes. The mRNA and protein expression of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The protein levels of RhoA, ROCKI and p-MYPT were determined using western blot analysis. ELISA was employed to measure the expression of soluble VCAM-1 and MCP-1 in cell supernatants and human serum samples. Results Fasudil significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio, and prevented HG induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment significantly decreased serum MCP-1 level from 27.9 ± 10.6 pg/ml to 13.8 ± 7.0 pg/ml (P P  Conclusions Treatment with the Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. These results suggest inhibition of Rho/ROCK signaling may have therapeutic potential in preventing diabetes associated vascular inflammation and atherogenesis.

  10. Morin, a Flavonoid from Moraceae, Inhibits Cancer Cell Adhesion to Endothelial Cells and EMT by Downregulating VCAM1 and Ncadherin.

    Science.gov (United States)

    Lee, JeongHee; Jin, Hana; Lee, Won Sup; Nagappan, Arulkumar; Choi, Yung Hyun; Kim, Gon Sup; Jung, JinMyung; Ryu, Chung Ho; Shin, Sung Chul; Hong, Soon Chan; Kim, Hye Jung

    2016-01-01

    Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting antioxidant, antiinflammatory and anticarcinogenic effects. Here, we investigated the anticancer activity of morin focusing on antiadhesive influence. We performed experiments with MDAMB231 human breast cancer cells. Morin inhibited TNFinduced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM1 on MDAMB231 cells as well as HUVECs. Morin also decreased the expression of Ncadherin on MDAMB231 cells. In addition, there was apparent antimetastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM1, and EMT by targeting Ncadherin, and that it features antimetastatic activity in vivo. Further investigation of possible antimetastatic activity of morin against human breast cancer cells is warranted.

  11. Triglyceride-rich lipoprotein modulates endothelial vascular cell adhesion molecule (VCAM-1 expression via differential regulation of endoplasmic reticulum stress.

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    Ying I Wang

    Full Text Available Circulating triglyceride-rich lipoproteins (TGRL from hypertriglyceridemic subjects exacerbate endothelial inflammation and promote monocyte infiltration into the arterial wall. We have recently reported that TGRL isolated from human blood after a high-fat meal can elicit a pro- or anti-atherogenic state in human aortic endothelial cells (HAEC, defined as up- or down-regulation of VCAM-1 expression in response to tumor necrosis factor alpha (TNFα stimulation, respectively. A direct correlation was found between subjects categorized at higher risk for cardiovascular disease based upon serum triglycerides and postprandial production of TGRL particles that increased VCAM-1-dependent monocyte adhesion to inflamed endothelium. To establish how TGRL metabolism is linked to VCAM-1 regulation, we examined endoplasmic reticulum (ER stress and the unfolded protein response (UPR pathways. Regardless of its atherogenicity, the rate and extent of TGRL internalization and lipid droplet formation by HAEC were uniform. However, pro-atherogenic TGRL exacerbated ER membrane expansion and stress following TNFα stimulation, whereas anti-atherogenic TGRL ameliorated such effects. Inhibition of ER stress with a chemical chaperone 4-phenylbutyric acid decreased TNFα-induced VCAM-1 expression and abrogated TGRL's atherogenic effect. Activation of ER stress sensors PKR-like ER-regulated kinase (PERK and inositol requiring protein 1α (IRE1α, and downstream effectors including eukaryotic initiation factor-2α (eIF2α, spliced X-box-binding protein 1 (sXBP1 and C/EBP homologous protein (CHOP, directly correlated with the atherogenic activity of an individual's TGRL. Modulation of ER stress sensors also correlated with changes in expression of interferon regulatory factor 1 (IRF-1, a transcription factor of Vcam-1 responsible for regulation of its expression. Moreover, knockdown studies using siRNA defined a causal relationship between the PERK/eIF2α/CHOP pathway and

  12. Cytokine induction of VCAM-1 but not IL13Rα2 on glioma cells: a tale of two antibodies.

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    Vaidehi Mahadev

    Full Text Available The interleukin-13 receptor alpha2 (IL13Rα2 is a cell surface receptor that is over-expressed by a subset of high-grade gliomas, but not expressed at significant levels by normal brain tissue. For both malignant and non-malignant cells, IL13Rα2 surface expression is reported to be induced by various cytokines such as IL-4 or IL-13 and tumor necrosis factor (TNF. Our group has developed a therapeutic platform to target IL13Rα2-positive brain tumors by engineering human cytotoxic T lymphocytes (CTLs to express the IL13-zetakine chimeric antigen receptor. We therefore sought to investigate the potential of cytokine stimulation to induce IL13Rα2 cell surface expression, and thereby increase susceptibility to IL13Rα2-specific T cell killing. In the course of these experiments, we unexpectedly found that the commercially available putative IL13Rα2-specific monoclonal antibody B-D13 recognizes cytokine-induced VCAM-1 on glioblastoma. We provide evidence that the induced receptor is not IL13Rα2, because its expression does not consistently correlate with IL13Rα2 mRNA levels, it does not bind IL-13, and it is not recognized by IL13-zetakine CTL. Instead we demonstrate by immunoprecipitation experiments and mass spectrometry that the antigen recognized by the B-D13 antibody following cytokine stimulation is VCAM-1, and that VCAM-1, but not IL13Rα2, is induced on glioma cells by TNF alone or in combination with IL-13 or IL-4. Further evaluation of several commercial B-D13 antibodies revealed that B-D13 is bi-specific, recognizing both IL13Rα2 and VCAM-1. This binding is non-overlapping based on soluble receptor competition experiments, and mass spectrometry identifies two distinct heavy and light chain species, providing evidence that the B-D13 reagent is di-clonal. PE-conjugation of the B-D13 antibody appears to disrupt IL13Rα2 recognition, while maintaining VCAM-1 specificity. While this work calls into question previous studies that have used

  13. Inhibitory Effects of Atorvastatin on the mRNA Expression of ICAM-1 and VCAM-1 Activated by TNF-α in Cultured Human Umbilical Vein Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    Zhiming Yang; Zhanhai Li; Gaiying Fan; Bin Liang; Ying Ma; Chuanshi Xiao; Yuming Kang

    2007-01-01

    To investigate the effects of atorvastatin on the mRNA expression of intercellular adhesion molecule-1 ( ICAM-1 ) and vascular cell adhesion molecule-1 ( VCAM-1 ) activated by TNF-α in cultured human umbilical vein endothelial cells (HUVEC).Methods and Results Lactic dehydrogenase (LDH) activity in the culture media increased when HUVEC were incubated with TNF-α,suggesting a cytotoxic effect of TNF-α on HUVEC.The mRNA expression of ICAM-1 and VCAM-1 increased in HUVEC incubated with 10μg/L TNF-α and reached peak in HUVEC incubated with 30μg/L TNF-α.The mRNA expression of ICAM-1 and VCAM-1 in HUVEC incubated with 30μg/L TNF-α began to increase at 6 h,reached peak at 48 h,and kept a plateau until 72 h.Atorvastatin dose-dependently inhibited the mRNA expressions of ICAM-1 and VCAM-1 activated by incubating HUVEC with 30μg/L TNF-α for 48 hours.Conclusions Atorvastatin might stabilize plaque and decelerate the process of AS by inhibiting the mRNA expressions of ICAM-1 and VCAM-1.

  14. Glycated LDL increase VCAM-1 expression and secretion in endothelial cells and promote monocyte adhesion through mechanisms involving endoplasmic reticulum stress.

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    Toma, Laura; Sanda, Gabriela M; Deleanu, Mariana; Stancu, Camelia S; Sima, Anca V

    2016-06-01

    Type 2 Diabetes Mellitus is a worldwide epidemic, and its atherosclerotic complications produce morbidity and mortality in affected patients. It is known that the vascular cell adhesion molecule-1 (VCAM-1) levels are increased in the sera of diabetic patients. Our aim was to investigate the impact of the endoplasmic reticulum stress (ERS) in VCAM-1 expression and secretion in human endothelial cells (HEC) exposed to glycated low-density lipoproteins (gLDL). The results showed that 24 h incubation of HEC with gLDL induces (i) stimulation of VCAM-1 expression and secretion, determining increased monocyte adhesion to HEC; (ii) RAGE up-regulation and free cholesterol loading; (iii) ERS activation (increased eIF2α phosphorylation and CHOP mRNA levels, and decreased GRP78 protein expression); and (iv) oxidative stress [increased levels of reactive oxygen species (ROS) and glutamate cysteine ligase catalytic unit gene expression]. Treatment of gLDL-exposed HEC with ERS inhibitors, salubrinal (Sal) and sodium phenylbutyrate (PBA), decreased intracellular ROS. Incubation of gLDL-exposed cells with the anti-oxidant N-acetyl-cysteine (NAC) reduced ERS, revealed by decreased eIF2α phosphorylation and CHOP gene expression and increased GRP78 expression, thus validating the interconnection between ERS and oxidative stress. Sal, PBA, NAC and inhibitors of p38 MAP kinase and NF-kB induced the decrease of VCAM-1 expression and of the ensuing monocyte adhesion induced by gLDL. In conclusion, in HEC, gLDL stimulate the expression of cellular VCAM-1, the secretion of soluble VCAM-1, and the adhesion of monocytes through mechanisms involving p38 MAP kinase and NF-kB signalling pathways activated by RAGE, ERS and oxidative stress, thus contributing to diabetic atherosclerosis. PMID:27206739

  15. Enzymatically quiescent heparanase augments T cell interactions with VCAM-1 and extracellular matrix components under versatile dynamic contexts.

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    Sotnikov, Ilya; Hershkoviz, Rami; Grabovsky, Valentin; Ilan, Neta; Cahalon, Liora; Vlodavsky, Israel; Alon, Ronen; Lider, Ofer

    2004-05-01

    During their migration into inflammatory sites, immune cells, such as T cells, secrete extracellular matrix (ECM)-degrading enzymes, such as heparanase, which, under mildly acidic conditions, degrade heparan sulfate proteoglycans (HSPG). We have previously shown that at pH 7.2, human placental heparanase loses its enzymatic activity, while retaining its ability to bind HSPG and promote T cell adhesion to unfractionated ECM. We now demonstrate that the 65-kDa recombinant human heparanase, which is devoid of enzymatic activity, but can still bind HSPG, captures T cells under shear flow conditions and mediates their rolling and arrest, in the absence or presence of stromal cell-derived factor 1 alpha (SDF-1 alpha; CXCL12), in an alpha(4)beta(1)-VCAM-1-dependent manner. Furthermore, heparanase binds to and induces T cell adhesion to key ECM components, like fibronectin and hyaluronic acid, in beta(1) integrin- and CD44-specific manners, respectively, via the activation of the protein kinase C and phosphatidylinositol 3-kinase intracellular signaling machineries. Although the nature of the putative T cell heparanase-binding moiety is unknown, it appears that heparanase exerts its proadhesive activity by interacting with the T cells' surface HSPG, because pretreatment of the cells with heparinase abolished their subsequent response to heparanase. Also, heparanase augmented the SDF-1 alpha-triggered phosphorylation of Pyk-2 and extracellular signal-regulated kinase-2 implicated in integrin functioning. Moreover, heparanase, which had no chemotactic effect on T cells on its own, augmented the SDF-1 alpha-induced T cell chemotaxis across fibronectin. These findings add another dimension to the known versatility of heparanase as a key regulator of T cell activities during inflammation, both in the context of the vasculature and at extravascular sites. PMID:15100255

  16. Telmisartan attenuates hyperglycemia-exacerbated VCAM-1 expression and monocytes adhesion in TNFα-stimulated endothelial cells by inhibiting IKKβ expression.

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    Song, Kee-Ho; Park, Jung-Hyun; Jo, Inho; Park, Joong-Yeol; Seo, Jungwon; Kim, Soon Ae; Cho, Du-Hyong

    2016-03-01

    Uncontrolled hyperglycemia accelerates endothelial damage and vascular inflammation caused by proinflammatory cytokines including tumor necrosis factor α (TNFα), which leads to arteriosclerotic cardiovascular diseases such as myocardial infarction. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), is prescribed for treatment of hypertensive patients with concurrent diabetes mellitus (DM). Although a few clinical trials have suggested that telmisartan decreases cardiovascular complications in diabetic patients, the molecular mechanism for the beneficial effects remains elusive. Here, we investigated a molecular mechanism and effects of telmisartan on the expression of vascular cell adhesion molecule-1 (VCAM-1) and attachment of monocytes onto endothelial cells induced by TNFα in hyperglycemia-treated bovine aortic endothelial cells (BAEC). Telmisartan dose-dependently decreased hyperglycemia-aggravated IκB kinase β (IKKβ) expression and nuclear factor-κB (NF-κB) p65-Ser(536) phosphorylation, which accompanied a decrease in VCAM-1 expression and THP-1 monocytes adhesion. Among ARBs, including losartan and fimasartan, only telmisartan showed the inhibitory effects on expression of VCAM-1 and IKKβ, and phosphorylation of NF-κB p65-Ser(536). The telmisartan's beneficial effects were not changed by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist, although GW9662 clearly inhibited rosiglitazone-induced CD36 expression. Finally, ectopic expression of wild type (WT)-IKKβ significantly restored telmisartan-attenuated VCAM-1 expression, NF-κB p65-Ser(536) phosphorylation, and THP-1 monocytes adhesion. Taken together, our findings demonstrate that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by decreasing expression of IKKβ and VCAM-1 independently of PPARγ. Telmisartan may be useful for the treatment of DM-associated vascular

  17. Astragalus polysaccharides suppress ICAM-1 and VCAM-1 expression in TNF-α-treated human vascular endothelial cells by blocking NF-KB activation

    Institute of Scientific and Technical Information of China (English)

    Yu-ping ZHU; Tao SHEN; Ya-jun LIN; Bei-dong CHEN; Yang RUAN; Yuan CAO; Yue QIAO

    2013-01-01

    Aim:To investigate the effects ofAstragalus polysaccharides (APS) on tumor necrosis factor (TNF)-α-induced inflammatory reactions in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanisms.Methods:HUVECs were treated with TNF-α for 24 h.The amounts of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) were determined with Western blotting.HUVEC viability and apoptosis were detected using cell viability assay and Hoechst staining,respectively.Reactive oxygen species (ROS) production was measured by DHE staining.Monocyte and HUVEC adhesion assay was used to detect endothelial cell adhesive function.NF-KB activation was detected with immunofluorescence.Results:TNF-α (1-80 ng/mL) caused dose-and time-dependent increases of ICAM-1 and VCAM-1 expression in HUVECs,accompanied by significant augmentation of IKB phosphorylation and NF-KB translocation into the nuclei.Pretreatment with APS (10 and 50 μg/mL)significantly attenuated TNFα-induced upregulation of ICAM-1,VCAM-1,and NF-KB translocation.Moreover,APS significantly reduced apoptosis,ROS generation and adhesion function damage in TNF-α-treated HUVECs.Conclusion:APS suppresses TNFα-induced adhesion molecule expression by blocking NF-KB signaling and inhibiting ROS generation in HUVECs.The results suggest that APS may be used to treat and prevent endothelial cell injury-related diseases.

  18. Genetic variation in CD36, HBA, NOS3 and VCAM1 is associated with chronic haemolysis level in sickle cell anaemia: a longitudinal study.

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    Coelho, Andreia; Dias, Alexandra; Morais, Anabela; Nunes, Baltazar; Ferreira, Emanuel; Picanço, Isabel; Faustino, Paula; Lavinha, João

    2014-03-01

    Chronic haemolysis stands out as one of the hallmarks of sickle cell anaemia, a clinically heterogeneous autosomal recessive monogenic anaemia. However, the genetic architecture of this sub-phenotype is still poorly understood. Here, we report the results of an association study between haemolysis biomarkers (serum LDH, total bilirubin and reticulocyte count) and the inheritance of 41 genetic variants of ten candidate genes in a series of 99 paediatric SS patients (median current age of 9.9 yr) followed up in two general hospitals in Greater Lisboa area (median follow-up per patient of 5.0 yr). Although in a large number of tests a seemingly significant (i.e. P haplotype 7 within VCAM1 gene; (ii) a lower total bilirubin was associated with the 3.7-kb deletion at HBA gene, rs2070744_T allele at NOS3 gene, and haplotype 9 within VCAM1 promoter; and (iii) a diminished reticulocyte count was associated with the 3.7-kb deletion at HBA, whereas an increased count was associated with rs1984112_G allele at CD36 gene. On the whole, our findings suggest a complex genetic architecture for the sickle cell anaemia haemolysis process involving multiple pathways, namely control of vascular cell adhesion, NO synthesis and erythrocyte volume and haemoglobinisation. PMID:24168396

  19. VCAM-1-targeted core/shell nanoparticles for selective adhesion and delivery to endothelial cells with lipopolysaccharide-induced inflammation under shear flow and cellular magnetic resonance imaging in vitro

    Directory of Open Access Journals (Sweden)

    Yang H

    2013-05-01

    Full Text Available Hong Yang,1 Fenglong Zhao,1 Ying Li,1 Mingming Xu,1 Li Li,1 Chunhui Wu,1 Hirokazu Miyoshi,2 Yiyao Liu11Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China; 2Radioisotope Research Center, University of Tokushima, Kuramoto-cho, Tokushima, JapanAbstract: Multifunctional nanomaterials with unique magnetic and luminescent properties have broad potential in biological applications. Because of the overexpression of vascular cell adhesion molecule-1 (VCAM-1 receptors in inflammatory endothelial cells as compared with normal endothelial cells, an anti-VCAM-1 monoclonal antibody can be used as a targeting ligand. Herein we describe the development of multifunctional core-shell Fe3O4@SiO2 nanoparticles with the ability to target inflammatory endothelial cells via VCAM-1, magnetism, and fluorescence imaging, with efficient magnetic resonance imaging contrast characteristics. Superparamagnetic iron oxide and fluorescein isothiocyanate (FITC were loaded successfully inside the nanoparticle core and the silica shell, respectively, creating VCAM-1-targeted Fe3O4@SiO2(FITC nanoparticles that were characterized by scanning electron microscopy, transmission electron microscopy, fluorescence spectrometry, zeta potential assay, and fluorescence microscopy. The VCAM-1-targeted Fe3O4@SiO2(FITC nanoparticles typically had a diameter of 355 ± 37 nm, showed superparamagnetic behavior at room temperature, and cumulative and targeted adhesion to an inflammatory subline of human umbilical vein endothelial cells (HUVEC-CS activated by lipopolysaccharide. Further, our data show that adhesion of VCAM-1-targeted Fe3O4@SiO2(FITC nanoparticles to inflammatory HUVEC-CS depended on both shear stress and duration of exposure to stress. Analysis of internalization into HUVEC-CS showed that the efficiency of delivery of VCAM-1-targeted Fe3O4@SiO2(FITC nanoparticles was

  20. Fut8基因通过促进VLA-4/VCAM-1表达影响B细胞发育%Fut8 gene affects the development of B cells by regulating the core fucosylation of VLA-4/VCAM-1

    Institute of Scientific and Technical Information of China (English)

    焦鑫艳; 马彪; 王旭; 刘庆平; 李文哲

    2012-01-01

    The aim of this study is to explore the role of fucosyltransferase VIII (Fut8) in VLA -4/VCAM-1 expression and B cell development. Firstly, Fut8 -knockdown 70Z/3 cells and Fut8 -knockdown ST2 cells were established by RNA inference using 70Z/3 cells (pre-B cell line) and ST2 cells. Then Fut8 gene-silencing effects were detected by Western blot. In cell adhesion assays and colony forming tests, we found that the loss of a core fucose in both very late antigen 4 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) would lead to a decreased binding between pre-B cells and stromal cells, followed the impaired pre-B cells generation in Fut8+ mice. Flow cytometry analysis revealed that Fut8 expression was extremely required for regulating pre-B cell reproduction. These findings clearly demonstrated that the Fut8 could regulate the VLA-4/VCAM-1 interaction and the proper transition from pro-B to pre-B cells, showing the important role of Fut8 in B cell differentiation and development%目的 探讨核心岩藻糖基化修饰对VLA-4/VCAM-1表达及B细胞发育的影响.方法 通过RNA干扰技术使前B细胞(70Z/3)和基质细胞(ST2)的Fut8基因沉默,免疫沉淀和Western blot检测Fut8基因沉默效率,以细胞黏附实验和克隆形成实验分别研究Fut8基因对VLA-4/VCAM-1之间亲和力和对B细胞分化发育的影响.结果 Fut8基因沉默使VLA-4/VCAM-1之间的亲和力以及前B细胞和基质细胞之间的黏附作用降低,并使前B细胞的克隆形成能力明显下降.流式细胞仪分析结果也表明,Fut8祖B细胞向前B细胞分化过程受阻.结论 本实验揭示了Fut8基因调节VLA-4/VCAM-1之间结合能力以及前B细胞克隆形成的机理,为B细胞分化发育研究提供理论依据.

  1. High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation.

    Science.gov (United States)

    Huang, Xiaoqin; He, Dan; Ming, Jia; He, Yubin; Zhou, Champion; Ren, Hui; He, Xin; Wang, Chenguang; Jin, Jingru; Ji, Liang; Willard, Belinda; Pan, Bing; Zheng, Lemin

    2016-02-01

    Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis

  2. Lauric acid abolishes interferon-gamma (IFN-γ)-induction ofIntercellular AdhesionMolecule-1 (ICAM-1) andVascularCellAdhesionMolecule-1 (VCAM-1) expression in human macrophages

    Institute of Scientific and Technical Information of China (English)

    Wei-Siong Lim; Mary-Shi-Ying Gan; Melissa-Hui-Ling Ong; Choy-Hoong Chew

    2015-01-01

    Objective:To investigate the effect of different concentrations of lauric acid on Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) expression in IFN-γ stimulated human monocytic THP-1 cell line.Methods:THP-1 cell were cultured using Roswell Park Memorial Institute medium supplemented with 10% fetal bovine serum. THP-1 monocytes were firstly differentiated into macrophages by using phorbol-12-myristate-13-acetate. IFN-γ response test was perfomed and total cellular RNA was extracted using TRI Reagent®LS before q-RT-PCR was carried out. Subsequently, IFN-γ treated THP-1 macrophages were stimulated with increasing doses of lauric acid for another 24 hour, before q-RT-PCR. MTT assay was carried out to investigate the effect of lauric acid on undifferentiated and differentiated THP-1 cells.Results:The mRNA expression levels of ICAM-1 and VCAM-1 were normalized toβ-actin and relatived to the untreated cells. The expressions of ICAM-1 and VCAM-1 were significantly induced in cells treated with 10 ng/mL of IFN-γ. This showed that IFN-γ could up-regulate inflammatory process and may cause atheroma formation. Although lauric acid did not have any significant impact on undifferentiated and differentiated THP-1 cell viability, the normalized fold expressions of ICAM-1 and VCAM-1 in IFN-γ-treated THP-1 macrophages were decreased significantly in a dose dependent manner with the presence of increasing doses of lauric acid.Conclusions:This study successfully proved that lauric acid was able to antagonize the up-regulatory effect of IFN-γ on ICAM-1 and VCAM-1 expressions in THP-1 macrophages. This indicates that lauric acid may be an anti-inflammatory therapeutic and prophylaxis agent for atherosclerosis.

  3. The influence of propofol on the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in reoxygenated human umbilical vein endothelial cells.

    LENUS (Irish Health Repository)

    Corcoran, T B

    2012-02-03

    BACKGROUND: Leucocytes are a pivotal component of the inflammatory cascade that results in tissue injury in a large group of disorders. Free radical production and endothelial activation promote leucocyte-endothelium interactions via endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) which augment these processes, particularly in the setting of reperfusion injury. Propofol has antioxidant properties which may attenuate the increased expression of these molecules that is observed. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia, then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg mL(-1) or propofol 5 microg mL(-1), for 4 h after reoxygenation and were examined for ICAM-1 and VCAM-1 expression. RESULTS: Hypoxia did not increase the expression of ICAM-1\\/VCAM-1. ICAM-1 expression peaked 12 h after reoxygenation (21.75(0.6) vs. 9.6(1.3), P = 0.02). Propofol, but not Diprivan, prevented this increase (8.2(2.9) vs. 21.75(0.6), P = 0.009). VCAM-1 expression peaked 24 h after reoxygenation (9.8(0.9) vs. 6.6(0.6), P = 0.03). Propofol and Diprivan prevented this increase, with no difference between the two treatments observed (4.3(0.3) and 6.4(0.5) vs. 9.8(0.9), P = 0.001, 0.02, respectively). CONCLUSION: These effects are likely to be attributable to the antioxidant properties of propofol, and suggest that propofol may have a protective role in disorders where free radical mediated injury promotes leucocyte-endothelium adhesive interactions.

  4. VCAM-1 is a TGF-β1 inducible gene upregulated in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Agassandian, Marianna; Tedrow, John R; Sembrat, John; Kass, Daniel J; Zhang, Yingze; Goncharova, Elena A; Kaminski, Naftali; Mallampalli, Rama K; Vuga, Louis J

    2015-12-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease of unknown etiology. We previously reported that high plasma levels of vascular cell adhesion molecule 1 (VCAM-1) predict mortality in IPF subjects. Here we investigated the cellular origin and potential role of VCAM-1 in regulating primary lung fibroblast behavior. VCAM-1 mRNA was significantly increased in lungs of subjects with IPF compared to lungs from control subjects (p=0.001), and it negatively correlated with two markers of lung function, forced vital capacity (FVC) and pulmonary diffusion capacity for carbon monoxide (DLCO). VCAM-1 protein levels were highly expressed in IPF subjects where it was detected in fibrotic foci and blood vessels of IPF lung. Treatment of human lung fibroblasts with TGF-β1 significantly increased steady-state VCAM1 mRNA and protein levels without affecting VCAM1 mRNA stability. Further, cellular depletion of VCAM-1 inhibited fibroblast cell proliferation and reduced G2/M and S phases of the cell cycle suggestive of cell cycle arrest. These effects on cell cycle progression triggered by VCAM1 depletion were associated with reductions in levels of phosphorylated extracellular regulated kinase 1/2 and cyclin D1. Thus, these observations suggest that VCAM-1 is a TGF-β1 responsive mediator that partakes in fibroblast proliferation in subjects with IPF. PMID:26386411

  5. Influence of artificial CO2 cavity on MMP-2 and VCAM-1, ICAM-1 expression in MDA-MB-231 cell%体外模拟 CO2气腔对乳腺癌细胞 MMP-2和黏附分子 VCAM-1、ICAM-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈琪枫; 蔡清萍; 方晓明; 姚宁; 方旭东; 龚谋春

    2015-01-01

    目的:探讨体外模拟CO2气腔对MDA-MB-231细胞基质金属蛋白酶-2( matrix metalloprotei-nase 2,MMP-2)和黏附分子血管细胞间黏附分子-1( vascular cell adhesion molecule 1,VCAM-1)、细胞间黏附分子-1(intercellular adhesion molecule 1,ICAM-1)表达的影响。方法体外建立人工气腔,MDA-MB-231细胞在7 mmHg(1 mmHg=0.133 kPa)的CO2分压下暴露l、2及4 h,在处理后0、24、48及72 h,酶联免疫吸附法( enzyme linked immunosorbent assay , ELISA )测定细胞培养液中 MMP-2浓度。流式细胞术测定VCAM-1、ICAM-1表达。缺氧组选用0 mmHg的氦气(1 h)。对照组为常规培养条件。结果1、2及4 h的CO2组处理后0 h时MMP-2的表达明显高于对照组(F=15.045,P<0.05);2 h的CO2组处理后24 h时MMP-2的表达也明显高于对照组和1、4 h的CO2组(F=5.976,P<0.05)。1、2及4 h的CO2组处理后0、24 h时VCAM-1的表达显著高于对照组(F1=18.321,F2=20.443,P<0.05);4 h的CO2组处理后72 h时VCAM-1的表达显著低于1、2 h的CO2组(F=15.045,P<0.05)。缺氧组和1、2及4 h的CO2组处理后0 h时ICAM-1的表达显著高于对照组,其中2 h的CO2组表达又高于1、4 h的CO2组(F=73.765,P<0.05);2、4 h的CO2组处理后24 h时ICAM-1的表达显著高于对照组和1 h的CO2组(F=46.322,P<0.05);2 h的CO2组处理后48 h时ICAM-1的表达显著高于对照组和1、4 h的CO2组(F=22.315,P<0.05)。结论模拟7 mmHg的CO2气腔可使MDA-MB-231细胞MMP-2、VCAM-1、ICAM-1的表达增高,乳腔镜CO2气腔可能对乳腺癌细胞的转移具有一定影响力。%Objective To investigate the influence of in vitro artificial CO 2 cavity on matrix metallopro-teinase 2(MMP-2), adhesion molecule vascular cell adhesion molecule 1(VCAM-1), and intercellular adhesion molecule 1(ICAM-1)expression in MDA-MB-231 cell.Methods An in vitro artificial CO2 cavity model was es

  6. Association of VCAM-1 overexpression with oncogenesis, tumor angiogenesis and metastasis of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yong-Bin Ding; Guo-Yu Chen; Jian-Guo Xia; Xi-Wei Zang; Hong-Yu Yang; Li Yang

    2003-01-01

    AIM: To investigate the relationship between the expression of vascular cell adhesion molecule-1 (VCAM-1) and oncogenesis,tumor angiogenesis and metastasis in gastric carcinoma,and to evaluate the clinical significance of serum VCAM-1levels in gastric cancer.METHODS: Specimens from 41 patients with gastric cancer, 8 patients with benign gastric ulcer, and 10 healthy subjects were detected for the expression of VCAM-1 by immunohistochemistry. Microvessel density (MVD) was measured by counting the endothelial cells immunostained with the monoclonal antibody CD34 at x200 magnification.Serum VCAM-1 concentrations were measured by an enzyme linked immunosorbent assay in the 41 gastric cancer patients before surgery, and at 7 days after surgery as well as in 25 healthy controls. The association between preoperative serum VCAM-1 levels and clinicopathological features, and their changes following surgery was evaluated. Tn addition, serum carcinoembryonic antigen (CEA) was also examined.RESULTS: Of the 41 gastric cancer tissues, 31 (75.6 %)were VCAM-1 positive. The VCAM-1 positive gastric cancers were more invasive and classified in the more advanced stage than the VCAM-1 negative ones. The VCAM-1 positive cancers were associated with more lymph node metastases than VCAM-1-negative ones (P<0.05). The expression of VCAM-1 was detected in tissues of two of the eight patients with gastric ulcer and two of the 10 healthy controls. The expression of VCAM-1 in gastric cancer patients was significantly more frequent than that in the healthy controls and ulcer group (both P<0.05). MVD in VCAM-1 expressing tissues was higher than that in VCAM-1 negative tissues (t=2.13,P<0.05). Serum VCAM-1 levels in gastric cancer patients were significantly higher than those in controls (t=3.4, P<0.05). There was a significant association between serum VCAM-1 levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases.The concentrations of serum

  7. Involvement of VCAM1 in the bovine conceptus adhesion to the uterine endometrium.

    Science.gov (United States)

    Bai, Rulan; Bai, Hanako; Kuse, Mariko; Ideta, Atsushi; Aoyagi, Yoshito; Fujiwara, Hiroshi; Okuda, Kiyoshi; Imakawa, Kazuhiko; Sakurai, Toshihiro

    2014-08-01

    Following bidirectional communication, the conceptus and the uterine epithelium must establish a proper cell-cell interaction, resulting in the progression of implantation processes. To clarify the mechanism of conceptus attachment to the uterine endometrium, we studied whether vascular cell adhesion molecule (VCAM1) was expressed in bovine conceptuses or endometrium during the peri-attachment period. Uterine VCAM1 expression was minimal in day 17 (day 0=day of estrus) cyclic and pregnant animals, but increased between days 20 and 22 of pregnancy. In the intercaruncular regions, VCAM1 protein was localized to the luminal and glandular epithelia, whereas in the caruncular regions, VCAM1 protein was detected in the stroma and endothelia of the uterine endometrium. In cultured endometrial epithelial cells (EECs), VCAM1 expression was up-regulated when treated with uterine flushings or growth factor and further increased when EECs were cocultured with bovine trophoblast CT1 cells. VCAM1 expression in CT1 cells was also up-regulated with the use of uterine flushings, and further increased when these cells were cocultured with EECs. Expression of VCAM1 receptor, integrin α 4 (ITGA4) mRNA, increased significantly in day 22 conceptuses. In day 22 pregnant uteri, VCAM1 protein was found in both EECs and conceptuses, but ITGA4 was localized only to trophoblasts. These observations indicate that cell-cell interactions between conceptuses and uterine epithelial cells are required for sufficient VCAM1 and ITGA4 expression in the bovine species and suggest that uterine VCAM1 and conceptus ITGA4 play a role in the establishment of conceptus adhesion to the uterine endometrium. PMID:24803492

  8. Inhibition of VCAM-1 expression on mouse vascular smooth muscle cells by lobastin via downregulation of p38, ERK 1/2 and NF-κB signaling pathways.

    Science.gov (United States)

    Lee, Kyoungran; Yim, Joung-Han; Lee, Hong-Kum; Pyo, Suhkneung

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease, the progression of which is associated with the increased expression of cell adhesion molecules on vascular smooth muscle cells (VSMCs). Lobastin is a new pseudodepsidone isolated from Stereocaulon alpinum, Antarctic lichen, which is known to have antioxidant and antibacterial activities. However, the nature of the biological effects of lobastin still remains unclear. In the present study, we examine the effect of lobastin on the expression of vascular cell adhesion molecules (VCAM-1) induced by TNF-α in the cultured mouse VSMC cell line, MOVAS-1. Pretreatment of VSMCs for 2 h with lobastin (0.1-10 μg/ml) concentration-dependently inhibited TNF-α-induced protein expression of VCAM-1. Lobastin also inhibited TNF-α-induced production of intracellular reactive oxygen species (ROS). Lobastin abrogated TNF-α-induced phosphorylation of p38 and ERK 1/2, but not JNK, and also inhibited TNF-α-induced NK-κB activation. In addition, lobastin suppressed TNF-α-induced IκB kinase activation, subsequent degradation of IκBα and nuclear translocation of p65 NF-κB. Our results indicate that lobastin downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the p38, ERK 1/2 and NF-κB signaling pathways and intracellular ROS generation. Thus, lobastin may be an important regulator of inflammation in the atherosclerotic lesion and a novel therapeutic drug for the treatment of atherosclerosis.

  9. 平阳霉素作用静脉畸形内皮细胞后VCAM-1、ICAM-1、ICAM-3表达%Pingyangmycin- Regulated Expression of Vascular Cell Adhesion Molecule - 1 ( VCAM - 1 ), Intercellular Adhesion Molecule-1 (ICAM - 1 ) and Intercellular Adhesion Molecule-3 (ICAM-3) in Human Venous Malformation Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    贾玉林; 张文峰; 贾俊; 赵怡芳

    2012-01-01

    Objective: To investigate PYM-regulated expressions of VCAM-1, ICAM-1 and ICAM -3 in primary cultured HVMECs. Methods: Expressions of the adhesion molecules VCAM-1, ICAM-1 and ICAM-3 were studied in PYM -regulated HVMECs in vitro by means of ELISA and RT - PCR. Results: Expressions of VCAM-1 and ICAM -3 were induced, and expression of ICAM-1 was up-regulated, both in a time and concentration-dependent fashion after stimulation with PYM. The expression of VCAM - 1 was observed at 2h and ICAM-1 at 6h and ICAM-3 at 12h. The highest expression of VCAM-1, ICAM-1 and ICAM-3 was observed at 8h, 18h and 24h, After exposed for the same time interval, expression of adhesion molecules on HVMECs exposed to lmg/L of PYM was higher than that exposed to other concentration of PYM. mRNA expressions of VCAM-1, ICAM-1 and ICAM -3 started at 2h, 6h and 12h respectively. Maximal synthetic activity was observed at 6 - 8h for VCAM-1, at 12-18h for ICAM-1 and at 18 -24h for ICAM -3. Synthesis activity was greatly suppressed at l0mg/L or higher concentration. Conclusion: Expression of Ig-like adhesion molecules in HVMECs can be induced or up-regulated by lower concentration of PYM in a time and concentration -dependent fashion.%目的:研究平阳霉素(PYM)作用于人静脉畸形内皮细胞(HVMECs)后Ig粘附分子(VCAM-1、ICAM-1、ICAM-3)表达.方法:体外培养HVMECs,采用细胞ELISA和RT- PCR技术检测不同浓度PYM作用人HVMECs后Ig粘附分子表达.结果:PYM作用人HVMECs后粘附分子表达具有时间浓度效应.PYM能诱导VCAM-1在人HVMECs表达,2h后明显增高,8h后达到峰值,12h后下降,48 h后呈阴性表达.PYM能促进ICAM-1在人HVMECs表达,12h后显著增高,18 h最高,24 h逐渐下降.PYM能促进ICAM-3表达,12 h后逐渐增高,24 h达到峰值,72 h后1CAM-3仍高表达.0.01~1 mg/L PYM能诱导或促进粘附分子表达,表达水平与药物浓度成正相关,1 mg/L PYM作用人HVMECs后粘附分子表达较高,10 mg/L PYM

  10. Association of alpha-thalassemia, TNF-alpha (-308G>A) and VCAM-1 (c.1238G>C) gene polymorphisms with cerebrovascular disease in a newborn cohort of 411 children with sickle cell anemia.

    Science.gov (United States)

    Belisário, André Rolim; Nogueira, Frederico Lisboa; Rodrigues, Rahyssa Sales; Toledo, Nayara Evelin; Cattabriga, Ana Luiza Moreira; Velloso-Rodrigues, Cibele; Duarte, Filipe Otávio Chaves; Silva, Célia Maria; Viana, Marcos Borato

    2015-01-01

    Cerebrovascular disease (CVD) is a severe complication associated with sickle cell anemia. Abnormal transcranial Doppler (TCD) identifies some children at high risk, but other markers would be helpful. This cohort study was aimed at evaluating the effects of genetic biomarkers on the risk of developing CVD in children from Minas Gerais, Brazil. Clinical and hematological data were retrieved from children's records. Outcomes studied were overt ischemic stroke and CVD (overt ischemic stroke, transient ischemic attack, abnormal TCD, or abnormal cerebral angiography). Out of 411 children, 386 (93.9%) had SS genotype, 23 (5.6%) had Sβ(0)-thal and two had severe Sβ(+)-thal (0.5%). Frequency of CVD was lower in Sβ-thal group (p=0.05). No effect of VCAM-1 polymorphism on stroke or CVD risks was detected. Cumulative incidence of stroke was significantly higher for children with TNF-α A allele (p=0.02) and lower for children with HBA deletion (p=0.02). However, no association between CVD and TNF-α -308G>A was found. CVD cumulative incidence was significantly lower for children with HBA deletion (p=0.004). This study found no association between VCAM1 c.1238G>C and stroke. An association between stroke and TNF-α -308A allele has been suggested. Our results have confirmed the protective role of HBA deletion against stroke and CVD.

  11. Clematichinenoside inhibits VCAM-1 and ICAM-1 expression in TNF-α-treated endothelial cells via NADPH oxidase-dependent IκB kinase/NF-κB pathway.

    Science.gov (United States)

    Yan, Simin; Zhang, Xu; Zheng, Haili; Hu, Danhong; Zhang, Yongtian; Guan, Qinghua; Liu, Lifang; Ding, Qilong; Li, Yunman

    2015-01-01

    Proinflammatory cytokine TNF-α-induced adhesion of leukocytes to endothelial cells plays a critical role in the early stage of atherosclerosis. Oxidative stress and redox-sensitive transcription factors are implicated in the process. Thus, compounds that mediate intracellular redox status and regulate transcription factors are of great therapeutic interest. Clematichinenoside (AR), a triterpene saponin isolated from the root of Clematis chinensis Osbeck, was previously demonstrated to have anti-inflammatory and antioxidative properties. However, little is known about the exact mechanism underlying these actions. Thus we performed a detailed study on its effect on leukocytes-endothelial cells adhesion with TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) and cell-free systems. First, we found that AR reduced TNF-α-induced VCAM-1 and ICAM-1 expression and their promoter activity, inhibited translocation of p65 and phosphorylation of IκBα, suppressed IκB kinase-β (IKK-β) activity, lowered O2(∙-) and H2O2 levels, tackled p47(phox) translocation, and decreased NOX4 NADPH oxidase expression. Second, we showed that AR exhibited no direct free radical scavenging ability in cell-free systems at concentrations that were used in intact cells. Besides, AR had no direct effect on the activity of IKK-β that was extracted from TNF-α-stimulated HUVECs. We also found that p47 translocation, NOX4 expression, and reactive oxygen species (ROS) levels were up-regulated before IκB phosphorylation in TNF-α-induced HUVECs. Moreover, TNF-α-enhanced IKK-β activity was also inhibited by (polyethylene glycol) PEG-catalase, N-acetylcysteine (NAC), and vitamin E. In conclusion, these results suggest that AR reduces VCAM-1 and ICAM-1 expression through NADPH oxidase-dependent IKK/NF-κB pathways in TNF-α-induced HUVECs, which finally suppress monocyte-HUVECs adhesion. This compound is potentially beneficial for early-stage atherosclerosis. PMID:25463279

  12. Gene expression of LOX-1, VCAM-1, and ICAM-1 in pre-atherosclerotic mice

    DEFF Research Database (Denmark)

    Fisker Hag, Anne Mette; Pedersen, Sune Folke; Kjaer, Andreas

    2008-01-01

    To identify markers of the earliest stage of atherosclerosis, endothelial dysfunction, we evaluated the gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in very young pre......-atherosclerotic mice. Furthermore, the plasma levels of the soluble VCAM-1 and ICAM-1 were compared to the gene expression profiles. Gene expressions of LOX-1 and VCAM-1 were up-regulated in young apoE(-/-) mice, and thus, it seems probable that these genes play a role in pre-atherosclerosis. Contrarily, the gene...... expression profile of ICAM-1 did not show any apparent differences between the groups, questioning the involvement of this molecule in the early development of atherosclerosis. Plasma levels of sVCAM-1 and sICAM-1 were similar in all mice and did not correlate with the vascular gene expression...

  13. Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients

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    Vilas-Boas, Wendell; Cerqueira, Bruno A. V.; Zanette, Angela M. D.; Reis, Mitermayer G.; Barral-Netto, Manoel

    2010-01-01

    Sickle cell anemia (SCA) is characterized by a marked endothelial dysfunction, owing to many factors. Arginine metabolism can be related to the inflammatory chronic state presented by patients, playing a key role in their clinical outcome and vascular endothelium. We investigated the serum arginase levels in 50 SCA patients (22 men and 28 women, mean age of 17 ± 10.5 years) and 28 healthy controls. Serum arginase levels were associated with biochemical hemolysis markers and cytokines involved in Th17 response, as well as levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). Arginase concentrations were higher in SCA patients, compared with controls (p = 0.005), and were significantly and positively associated with total bilirubin (p = 0.004), indirect bilirubin (p = 0.04), and aspartate aminotransferase (AST; p = 0.039) in the SCA patient group. Moreover, arginase was significantly and positively associated with transforming growth factor-beta (TGF-beta; p = 0.008) among SCA patients. sICAM-1 was significantly and positively associated to reticulocytes (p = 0.014) and AST (p = 0.04). sVCAM-1 was likewise associated with lactate dehydrogenase (p = 0.03). These data suggest a new insight into arginase metabolism, as we show here a shift in arginine catabolism, where TGF-beta may induces the arginase pathway instead of the nitric oxide pathway and a possible involvement of the vascular activation and the serum arginase in chronic hemolysis among SCA patients. Additional studies should be carried out in order to investigate the mechanisms by which TGF-beta participates in the metabolism of arginase in SCA patients. PMID:20405289

  14. SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development

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    Rhys J.P. Skelton

    2014-07-01

    Full Text Available The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5GFP was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5GFP/w human embryonic stem cells (hESCs. Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5posCD34pos population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5posSIRPApos to NKX2-5posSIRPAposVCAM1pos. Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.

  15. Increased plasma sVCAM-1 is associated with severity in IgA nephropathy

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    Zhu Li

    2013-01-01

    Full Text Available Abstract Background A considerable proportion of IgAN patients present with histological vasculitic/crescentic lesions in glomeruli, indicating activation of vascular inflammation. Using sVCAM-1, a well-proven marker for endothelial injury under inflammatory processes, we investigated vascular injury and its association with clinical and pathological manifestations in IgAN patients. Methods In this study, 327 biopsy-proven IgAN patients and 55 healthy controls were enrolled. The Oxford classification and two variables, Active Crescentic Lesion Percentage (ACLP and Chronic Glomerular Lesion Percentage (CGLP, were used for evaluating pathological lesions. Human Umbilical Vein Endothelial Cells were treated with 25-400 ug/ml IgA1. sVCAM-1 in plasma and culture supernatant were measured by ELISA. Results Plasma sVCAM-1 in IgAN patients was significantly higher than healthy controls. In patients with IgAN, plasma sVCAM-1 was significantly correlated with eGFR, 24h urine protein excretion, tubular atrophy/interstitial fibrosis lesion and ACLP, but not CGLP. Meanwhile, compared to healthy volunteers, IgA1 from IgAN patients showed a tendency to increase the HUVECs supernatant sVCAM-1 expression. And IgA1 induced the sVCAM-1 increasing from HUVECs in time- and dose-dependent manner. Conclusions We found increased plasma sVCAM-1 in IgAN patients and its association with severe clinical and pathological manifestations, which might be partly resulted from effect of IgA1 to endothelial cells.

  16. Increased circulating VCAM-1 correlates with advanced disease and poor survival in patients with multiple myeloma: reduction by post-bortezomib and lenalidomide treatment.

    Science.gov (United States)

    Terpos, E; Migkou, M; Christoulas, D; Gavriatopoulou, M; Eleutherakis-Papaiakovou, E; Kanellias, N; Iakovaki, M; Panagiotidis, I; Ziogas, D C; Fotiou, D; Kastritis, E; Dimopoulos, M A

    2016-01-01

    Circulating vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and selectins were prospectively measured in 145 newly-diagnosed patients with symptomatic myeloma (NDMM), 61 patients with asymptomatic/smoldering myeloma (SMM), 47 with monoclonal gammopathy of undetermined significance (MGUS) and 87 multiple myeloma (MM) patients at first relapse who received lenalidomide- or bortezomib-based treatment (RD, n=47; or VD, n=40). Patients with NDMM had increased VCAM-1 and ICAM-1 compared with MGUS and SMM patients. Elevated VCAM-1 correlated with ISS-3 and was independently associated with inferior overall survival (OS) (45 months for patients with VCAM-1 >median vs 75 months, P=0.001). MM patients at first relapse had increased levels of ICAM-1 and L-selectin, even compared with NDMM patients and had increased levels of VCAM-1 compared with MGUS and SMM. Both VD and RD reduced dramatically serum VCAM-1 after four cycles of therapy, but only VD reduced serum ICAM-1, irrespective of response to therapy. The reduction of VCAM-1 was more pronounced after RD than after VD. Our study provides evidence for the prognostic value of VCAM-1 in myeloma patients, suggesting that VCAM-1 could be a suitable target for the development of anti-myeloma therapies. Furthermore, the reduction of VCAM-1 and ICAM-1 by RD and VD supports the inhibitory effect of these drugs on the adhesion of MM cells to stromal cells. PMID:27232930

  17. Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies.

    Science.gov (United States)

    Ta, Duy Tien; Guedens, Wanda; Vranken, Tom; Vanschoenbeek, Katrijn; Steen Redeker, Erik; Michiels, Luc; Adriaensens, Peter

    2016-01-01

    Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids) usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1), an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL). Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR), respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets-a must for the development of advanced miniaturized, multi-biomarker biosensor platforms. PMID:27399790

  18. Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies

    Science.gov (United States)

    Ta, Duy Tien; Guedens, Wanda; Vranken, Tom; Vanschoenbeek, Katrijn; Steen Redeker, Erik; Michiels, Luc; Adriaensens, Peter

    2016-01-01

    Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids) usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1), an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL). Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) “click” chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR), respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets—a must for the development of advanced miniaturized, multi-biomarker biosensor platforms. PMID:27399790

  19. Enhanced Biosensor Platforms for Detecting the Atherosclerotic Biomarker VCAM1 Based on Bioconjugation with Uniformly Oriented VCAM1-Targeting Nanobodies

    Directory of Open Access Journals (Sweden)

    Duy Tien Ta

    2016-07-01

    Full Text Available Surface bioconjugation of biomolecules has gained enormous attention for developing advanced biomaterials including biosensors. While conventional immobilization (by physisorption or covalent couplings using the functional groups of the endogenous amino acids usually results in surfaces with low activity, reproducibility and reusability, the application of methods that allow for a covalent and uniformly oriented coupling can circumvent these limitations. In this study, the nanobody targeting Vascular Cell Adhesion Molecule-1 (NbVCAM1, an atherosclerotic biomarker, is engineered with a C-terminal alkyne function via Expressed Protein Ligation (EPL. Conjugation of this nanobody to azidified silicon wafers and Biacore™ C1 sensor chips is achieved via Copper(I-catalyzed azide-alkyne cycloaddition (CuAAC “click” chemistry to detect VCAM1 binding via ellipsometry and surface plasmon resonance (SPR, respectively. The resulting surfaces, covered with uniformly oriented nanobodies, clearly show an increased antigen binding affinity, sensitivity, detection limit, quantitation limit and reusability as compared to surfaces prepared by random conjugation. These findings demonstrate the added value of a combined EPL and CuAAC approach as it results in strong control over the surface orientation of the nanobodies and an improved detecting power of their targets—a must for the development of advanced miniaturized, multi-biomarker biosensor platforms.

  20. Characterization of VCAM-1-binding peptide-functionalized quantum dots for molecular imaging of inflamed endothelium.

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    Yun Chen

    Full Text Available Inflammation-induced activation of endothelium constitutes one of the earliest changes during atherogenesis. New imaging techniques that allow detecting activated endothelial cells can improve the identification of persons at high cardiovascular risk in early stages. Quantum dots (QDs have attractive optical properties such as bright fluorescence and high photostability, and have been increasingly studied and developed for bio-imaging and bio-targeting applications. We report here the development of vascular cell adhesion molecule-1 binding peptide (VCAM-1 binding peptide functionalized QDs (VQDs from amino QDs. It was found that the QD fluorescence signal in tumor necrosis factor [Formula: see text] (TNF-[Formula: see text] treated endothelial cells in vitro was significantly higher when these cells were labeled with VQDs than amino QDs. The VQD labeling of TNF-[Formula: see text]-treated endothelial cells was VCAM-1 specific since pre-incubation with recombinant VCAM-1 blocked cells' uptake of VQDs. Our ex vivo and in vivo experiments showed that in the inflamed endothelium, QD fluorescence signal from VQDs was also much stronger than that of amino QDs. Moreover, we observed that the QD fluorescence peak was significantly blue-shifted after VQDs interacted with aortic endothelial cells in vivo and in vitro. A similar blue-shift was observed after VQDs were incubated with recombinant VCAM-1 in tube. We anticipate that the specific interaction between VQDs and VCAM-1 and the blue-shift of the QD fluorescence peak can be very useful for VCAM-1 detection in vivo.

  1. Evaluation of ICAM-1 and VCAM-1 Gene Polymorphisms in Patients with Periodontal Disease.

    Science.gov (United States)

    Wang, Li; Li, Xiao-Hong; Ning, Wan-Chen

    2016-01-01

    BACKGROUND We aimed to investigate the potential genetic relationships between the polymorphisms of gene rs5498 ICAM-1 and rs1041163 VCAM-1 and chronic periodontitis in a Chinese population within Heilongjiang. MATERIAL AND METHODS Genomic DNA was extracted from oral mucosa cells of 584 periodontal patients and 182 healthy individuals. Genotyping of the rs5498 ICAM-1 and rs1041163 VCAM-1 gene polymorphisms was performed with the Multiplex SNaPshot technique. RESULTS Statistically significant associations were identified between the chronic periodontal patients and the controls in the gene polymorphisms of rs5498 ICAM-1 (P=0.007) and rs1041163 VCAM-1 (P=0.029). The distribution of rs5498 (P=0.029) and rs1041163 (P=0.049) differed significantly across the mild, moderate, and severe groups of periodontitis. CONCLUSIONS Our findings indicate that ICAM-1 rs5498 and VCAM-1 rs1041163 polymorphisms contribute to chronic periodontitis, and ICAM-1 rs5498 and VCAM-1 rs1041163 gene polymorphisms might be associated with periodontitis severity in the Heilongjiang Chinese population. Further studies should be conducted to determine whether these polymorphisms could be used as biomarkers of periodontitis. PMID:27391418

  2. Lauric acid abolishes interferon-gamma (IFN-γ-induction of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 expression in human macrophages

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    Wei-Siong Lim

    2015-09-01

    Conclusions: This study successfully proved that lauric acid was able to antagonize the up-regulatory effect of IFN-γ on ICAM-1 and VCAM-1 expressions in THP-1 macrophages. This indicates that lauric acid may be an anti-inflammatory therapeutic and prophylaxis agent for atherosclerosis.

  3. Effect of hyperlipidemia on endothelial VCAM-1 expression and the protective role of fenofibrate

    Institute of Scientific and Technical Information of China (English)

    WU Jun; LIN Jinchao; HE Zhaochu; OU Biru; GUO Haisen

    2007-01-01

    The effect of hyperlipidemia and inflammation on endothelial functions was studied.The enrolled included control(basic chow),hyperlipidemia and fenofibrate-treated groups(high fat diet).The hyperlipidemia model was set up by four-week atherogenic diet,followed by a 16-week treatment in the fenofibrate-treated group(fenofibrate 40 mg/kg every day)and without treatment in the hypedipidemia group,respectively.In the 20th week,serum lipid level and NO levels were measured,and the expression of vascular cell adhesion molecule-1(VCAM-1)and cell adhesiveness in aortic endothelia observed by computer-aided system.Compared with the control group,hyperlipidemia rats showed lower levels of NO and increases in leukocyte accumulation on the endothelial surface,also stronger and more extensive endothelial expression of VCAM-1.In fenofibrate-treated group,the expression of VCAM-1 and leukocyte accumulation on the endothelial surface was decreased,while serum levels of NO were increased as compared with hyperlipidemia group.Hyperlipidemia can inhibit the NO activity and promote the damage of VACA-1 to aortic endothelia.Fenofibrate can effectively prevent the pathogenesis of atherosclerosis by restoring NO levels and down-regulating the VCAM-1 expression.

  4. Adiponectin and leptin induce VCAM-1 expression in human and murine chondrocytes.

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    Javier Conde

    Full Text Available BACKGROUND: Osteoarthritis (OA and rheumatoid arthritis (RA, the most common rheumatic diseases, are characterized by irreversible degeneration of the joint tissues. There are several factors involved in the pathogenesis of these diseases including pro-inflammatory cytokines, adipokines and adhesion molecules. OBJECTIVE: Up to now, the relationship between adipokines and adhesion molecules at cartilage level was not explored. Thus, the aim of this article was to study the effect of leptin and adiponectin on the expression of VCAM-1 in human and murine chondrocytes. For completeness, intracellular signal transduction pathway was also explored. METHODS: VCAM-1 expression was assessed by quantitative RT-PCR and western blot analysis upon treatment with leptin, adiponectin and other pertinent reagents in cultured human primary chondrocytes. Signal transduction pathways have been explored by using specific pharmacological inhibitors in the adipokine-stimulated human primary chondrocytes and ATDC5 murine chondrocyte cell line. RESULTS: Herein, we demonstrate, for the first time, that leptin and adiponectin increase VCAM-1 expression in human and murine chondrocytes. In addition, both adipokines have additive effect with IL-1β. Finally, we demonstrate that several kinases, including JAK2, PI3K and AMPK are at a play in the intracellular signalling of VCAM-1 induction. CONCLUSIONS: Taken together, our results suggest that leptin and adiponectin could perpetuate cartilage-degrading processes by inducing also factors responsible of leukocyte and monocyte infiltration at inflamed joints.

  5. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation

    Science.gov (United States)

    Cuff, Carolyn A.; Kothapalli, Devashish; Azonobi, Ijeoma; Chun, Sam; Zhang, Yuanming; Belkin, Richard; Yeh, Christine; Secreto, Anthony; Assoian, Richard K.; Rader, Daniel J.; Puré, Ellen

    2001-01-01

    Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null mice to atherosclerosis-prone apoE-deficient mice. We found a 50–70% reduction in aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type littermates. We demonstrate that CD44 promotes the recruitment of macrophages to atherosclerotic lesions. Furthermore, we show that CD44 is required for phenotypic dedifferentiation of medial smooth muscle cells to the “synthetic” state as measured by expression of VCAM-1. Finally, we demonstrate that hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured primary aortic smooth muscle cells, whereas high-molecular-weight forms of hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays a critical role in the progression of atherosclerosis through multiple mechanisms. PMID:11581304

  6. Construction and expression of the eukaryotic expression vector of VCAM-1 extracellular domains%血管内皮细胞黏附分子胞外区基因真核表达载体构建及表达

    Institute of Scientific and Technical Information of China (English)

    朴君; 武翼; 朴敬爱; 李文哲

    2013-01-01

    As we know that the extracellular domains from D1 to D4 of vascular cell adhesion molecule 1 (VCAM-1) play important roles during early B cell differentiation. To express VCAM-1 extracellular domains from D1 to D4 (VCAM-1 D1-D4), the cDNA segments of VCAM-1 were amplified from NIH/3T3 cell line by PCR, and then VCAM-1 cDNA was cloned into eukaryotic expressive vector pIRES2-AcGFP1-Nuc-VCAM-1. With DNA sequencing and restriction endonuclease (Nhe Ⅰ and EcoR Ⅰ ) digestion analysis, it is confirmed that the eukaryotic expression vector pIRES2-AcGFP1 -Nuc -VCAM -1 had been constructed successfully. After transformation of pIRES2-AcGFP1-Nuc-VCAM-1 vector to Raji cells, the expression of VCAM-1 was detected in VCAM-1 transformed Raji cells. In cell binding assay, the expressed VCAM -1 was specially interacted with very late antigen-4 (VLA-4) on 70Z/3 cells. Our results suggested that the expressed VCAM-1 D1 -D4 will provide a experimental basis for further study on B cell differentiation and colony formation.%目的 构建并表达血管内皮细胞黏附分子(VCAM-1)胞外区基因真核表达载体.方法 从小鼠NIH/3T3细胞提取总RNA,以其为模板通过RT-PCR扩增VCAM-1胞外区(D1-D4结构域)cDNA.利用PCR获得VCAM-1胞外区基因,连接pMD19-T载体,进行基因序列测序.将VCAM-1 D1-D4目的片段插入到真核表达载体pIRES2-AcGFP1-Nuc中,构建重组真核表达质粒pIRES2-AcGFP1-Nuc-VCAM-1.经双酶切鉴定VCAM-1胞外区基因真核表达载体构建的成功与否.利用脂质体把pIRES2-AcGFP1-Nuc-VCAM-1导入至人B淋巴性白血病细胞株(Raji)内.结果 基因测序结果表明成功扩增出VCAM-1胞外区基因,双酶切鉴定表明重组的真核表达质粒pIRES2-AcGFP1-Nuc-VCAM-1构建成功.Western blot结果显示导入pIRES2-AcGFP1-Nuc-VCAM-1质粒的Raji细胞中VCAM-1高表达.细胞结合实验表明,表达的VCAM-1与前B细胞(70Z/3)表面的VLA-4特异性结合.结论 VCAM-1真核表达载体构建及表达成

  7. Patients with essential hypertension present higher levels of sE-selectin and sVCAM-1 than normotensive volunteers.

    Science.gov (United States)

    Palomo, Iván; Marín, Patricio; Alarcón, Marcelo; Gubelin, Gilda; Viñambre, Ximena; Mora, Eduardo; Icaza, Gloria

    2003-11-01

    In essential hypertension (EH) patients, blood pressure can modify serum concentrations of some soluble forms of cell adhesion molecules (CAM), e.g., soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1). The objective of this study was to compare the serum levels of these CAMs in compensated (CH) and non-compensated (NCH) EH patients. Our findings show that sE-selectin and sVCAM-1 levels are higher in EH patients than normotensive subjects (sVCAM-1: 796+/-52 vs. 605+/-24 ng/mL, p<0.0001, and sE-selectin: 71+/-21 vs. 48+/-14 ng/mL, p<0.0001). Serum concentrations of both CAMs was higher in NCH patients than CH patients. High arterial blood pressure (ABP) may therefore increase the production of cell adhesion molecules, probably through endothelial activation. PMID:14649309

  8. Aortic VCAM-1: an early marker of vascular inflammation in collagen-induced arthritis.

    Science.gov (United States)

    Denys, Anne; Clavel, Gaëlle; Lemeiter, Delphine; Schischmanoff, Olivier; Boissier, Marie-Christophe; Semerano, Luca

    2016-05-01

    Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA. PMID:26859834

  9. Clopidogrel Protects Endothelium by Hindering TNFα-Induced VCAM-1 Expression through CaMKKβ/AMPK/Nrf2 Pathway.

    Science.gov (United States)

    Yang, Huabing; Zhao, Pengjun; Tian, Shiliu

    2016-01-01

    Clopidogrel (INN), an oral antiplatelet drug, has been revealed to have a number of biological properties, for instance, anti-inflammation and antioxidation. Oxidative stress plays an imperative role in inflammation, diabetes mellitus, atherosclerosis, and cancer. In the present study, human aortic endothelial cells (HAECs) were employed to explore the anti-inflammatory activity of INN. INN reduced TNFα-induced reactive oxygen species (ROS) generation and time-dependently prompted the expression and activity of heme oxygenase 1 (HO-1). Cellular glutathione (GSH) levels were augmented by INN. shHO-1 blocked the INN suppression of TNFα-induced HL-60 cell adhesion. The CaMKKβ/AMPK pathway and Nrf2 transcriptional factor were implicated in the induction of HO-1 by INN. Additionally, TNFα dramatically augmented VCAM-1 expression at protein and mRNA levels. INN treatment strikingly repressed TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Compound C, an AMPK inhibitor, and shNrf2 abolished TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Our data suggest that INN diminishes TNFα-stimulated VCAM-1 expression at least in part via HO-1 induction, which is CaMKKβ/AMPK pathway-dependent. PMID:26824050

  10. Clopidogrel Protects Endothelium by Hindering TNFα-Induced VCAM-1 Expression through CaMKKβ/AMPK/Nrf2 Pathway

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    Huabing Yang

    2016-01-01

    Full Text Available Clopidogrel (INN, an oral antiplatelet drug, has been revealed to have a number of biological properties, for instance, anti-inflammation and antioxidation. Oxidative stress plays an imperative role in inflammation, diabetes mellitus, atherosclerosis, and cancer. In the present study, human aortic endothelial cells (HAECs were employed to explore the anti-inflammatory activity of INN. INN reduced TNFα-induced reactive oxygen species (ROS generation and time-dependently prompted the expression and activity of heme oxygenase 1 (HO-1. Cellular glutathione (GSH levels were augmented by INN. shHO-1 blocked the INN suppression of TNFα-induced HL-60 cell adhesion. The CaMKKβ/AMPK pathway and Nrf2 transcriptional factor were implicated in the induction of HO-1 by INN. Additionally, TNFα dramatically augmented VCAM-1 expression at protein and mRNA levels. INN treatment strikingly repressed TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Compound C, an AMPK inhibitor, and shNrf2 abolished TNFα-induced expression of VCAM-1 and HL-60 cell adhesion. Our data suggest that INN diminishes TNFα-stimulated VCAM-1 expression at least in part via HO-1 induction, which is CaMKKβ/AMPK pathway-dependent.

  11. Interferon-gamma and interleukin-4 differentially regulate ICAM-1 and VCAM-1 expression on human lung fibroblasts

    NARCIS (Netherlands)

    Spoelstra, FM; Postma, DS; Hovenga, H; Noordhoek, JA; Kauffman, HF

    1999-01-01

    The expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and more specifically vascular adhesion molecule-1 (VCAM-1) on lung fibroblasts may be important for migration of inflammatory cells through the submucosa to the airway lumen in the asthmatic inflammatory response. T

  12. Expression of pulmonary mRNA encoding ICAM-1, VCAM-1, and P-selectin following thoracic irradiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tsujino, Kayoko; Kodama, Akihisa; Nanaoka, Noriyoshi; Maruta, Tsutomu; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1999-08-01

    Recent studies have revealed that ionizing radiation induces the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin in vitro. The purpose of this study was to investigate the expression of these adhesion molecules in mouse lung following whole thoracic irradiation. C57BL/6J mice were irradiated with a single dose of 12 Gy to the thoraces and sacrificed at 4, 12, 24, and 48 hours and 1, 2, 4, and 8 weeks after irradiation. Expression of total lung mRNA for ICAM-1, VCAM-1, and P-selectin was quantified by the Northern blot method and normalized to {beta}-actin. There were increases in mRNA for ICAM-1 of 42% at 4 hours (p<0.05), 76% at 24 hours (p<0.01), and 51% at 48 hours (p<0.05) compared with the controls. There returned to the control level at 1 week. The expression of VCAM-1 mRNA was also increased by 49% (p<0.01) at 12 hours and was still increased by 25% at 1 week. P-selectin mRNA was transiently increased by 59% at 12 hours. These early inductions of mRNA for ICAM-1, VCAM-1, and P-selectin in mouse lung following thoracic irradiation were transient but significant, and are one of the most immediate changes reported in vivo. (author)

  13. ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro.

    Science.gov (United States)

    Steffen, B J; Breier, G; Butcher, E C; Schulz, M; Engelhardt, B

    1996-06-01

    The expression of cell adhesion molecules (CAMs) in the choroid plexus was studied in normal brain and during experimental autoimmune encephalomyelitis (EAE) in the SJL/J mouse during inflammation induced by intracerebral injection of killed Corynebacterium parvum in the C3H/He mouse. Both ICAM-1 and VCAM-1, but not MAdCAM-1, were constitutively expressed on choroid plexus epithelium but not on the fenestrated capillary endothelial cells within the choroid plexus. During EAE, we observed an up-regulation of ICAM-1 and VCAM-1 and de novo expression of MAdCAM-1 on choroid plexus epithelial cells. In contrast, endothelial cells in the choroid plexus were not induced to express any of the investigated CAMs. In in situ hybridization analysis we demonstrated that ICAM-1, VCAM-1, and MAdCAM-1 were locally synthesized and that the amount of their mRNAs increased in the inflamed choroid plexus. In vitro, primary choroid plexus epithelial cells could be induced to express ICAM-1, VCAM-1, and MAdCAM-1 on their surface after treatment with proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, interferon-gamma, and lipopolysaccharide. To investigate the functional status of the expressed CAMs we performed Stamper-Woodruff binding assays on frozen sections of inflamed and naive brains. ICAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelial cells mediated binding of lymphocytes via their known ligands LFA-1 and alpha4-integrin, respectively. The expression of ICAM-1, VCAM-1, and MAdCAM-1 on choroid plexus epithelial cells together with the lack of their expression on the fenestrated choroid plexus endothelium raises the possibility that the epithelial blood-cerebrospinal-fluid barrier plays an important role in the immunosurveillance of the central nervous system. PMID:8669469

  14. Expression of TGF-β1 in Placenta of the Patients with Pregnancy-induced Hypertension and Its relationship with Serum VCAM-1

    Institute of Scientific and Technical Information of China (English)

    XIANG Wenpei; XU Xiaoyan; CHEN Hanping

    2005-01-01

    The expression of transforming growth factor-β1 (TGF-β1) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of TGF-β1 and the amount of vascular cell adhesion molecule-1 (VCAM-1) in serum was studied. Immunohistochemistry ABC was used to detect the expression and distribution of TGF-β1 in placental tissues in 40 PIH women and 20 normal pregnancy women. High resolution pathological image analysis system was used to determine the quality of TGF-β1. The VCAM-1 in serum was examined by enzyme linked immunoabsorbent assay (ELISA). The results showed that TGF-β1 could be express in syncytiotrophoblast. The levels of TGF-β1 expression in placental tissues of the patients with moderate and severe PIH were significantly higher (P<0.05), while the serum VCAM-1 was significantly lower than in normal group (P<0.01). There was a significant positive correlation between the expression of TGF-β1 in placental tissues and the serum VCAM-1 (r=0. 969, P<0.01). It was concluded that the level of TGF-β1 expression in PIH was increased and was positively correlated with the amount of serum VCAM-1, indicating that they might be involved in the pathogenesis of PIH.

  15. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Kristoffersen, Ulrik Sloth; Pedersen, Sune Folke;

    2009-01-01

    endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1...... transgenic (HIV-1Tg) rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1...... was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV...

  16. Change of hs-CRP, sVCAM-1, NT-proBNP levels in patients with pregnancy-induced hypertension after therapy with magnesium sulfate and nifudipine

    Institute of Scientific and Technical Information of China (English)

    Li Wang; Zhi-Qiang Liu; Ying-Qian Huo; Li-Juan Yao; Xue-Gong Wei; Yun-Fang Wang

    2013-01-01

    Objective:To investigate the change of the hs-CRP, sVCAM-1,NT-proBNP levels of the patients with pregnancy-induced hypertension(PIH) syndrome.Methods:A total of200 patients withPIH were divided into mild, moderate and severe group, and50 healthy pregnancy patients served as the control group.The serum sVCAM-1 levels were detected by enzyme-linked immunosorbent assay, hs-CRP were detected by immunity transmission turbidity, andNT-proBNP levels were determined by the colloidal gold method.Patients were treated with magnesium sulfate and nifudipine and the contrastive analysis was performed before and after treatment.And the pathological changes in placental ofPIH patients were detected by hematoxylin-eosin staining at the same time.Results:The hs-CRP, sVCAM-1,NT-proBNP levels of patients in the mild, moderate and severePIH group were significantly higher than that in the control group(P<0.05). The hs-CRP, sVCAM-1,NT-proBNP levels in the severe group were significantly higher than the mild group and the moderate group, the difference was statistically significant(P<0.05).The hs-CRP, sVCAM-1,NT-proBNP of the moderate group were significantly higher than the mild group (P<0.05).There was a positive correlation between hs-CRP, sVCAM-1,NT-proBNP expression levels and the degree of thePIH.The expression of hs-CRP, sVCAM-1,NT-proBNP levels of the moderate and the severe group were significantly decreased(P<0.05).The number of placental villi and interstitial blood vessel in the moderate and severePIH group were significantly less than the control group(P<0.05).Conclusions:The increased levels of serum hs-CRP, sVCAM-1, NT-proBNP may be involved in the process of vascular endothelial cell injury of thePIH, and the hs-CRP, sVCAM-1,NT-proBNP can be used as the auxiliary index for diagnosis ofPIH and determination ofPIH severity.

  17. Nicorandil attenuates endothelial VCAM-1 expression via thioredoxin production in diabetic rats induced by streptozotocin.

    Science.gov (United States)

    Liu, Lihua; Liu, Yun; Qi, Benling; Wu, Qinqin; Li, Yuanyuan; Wang, Zhaohui

    2014-06-01

    The anti-angina agent nicorandil has been reported to be beneficial even in patients who have angina with diabetes. However, the mechanism underlying the effect of nicorandil in patients with diabetes remains to be elucidated. In this study, the protective effect of nicorandil on thioredoxin (TRX) protein was investigated, as TRX is a multifunctional endogenous redox regulator that protects cells against various types of cellular and tissue stress. This study was conducted to examine whether nicorandil induces the expression of TRX for the protection against diabetic damage in the vascular tissue of rats. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (STZ) (fasting glucose levels in STZ-induced rats were >14 mmol/l). Diabetic rats were divided into a diabetic control and a nicorandil-treated group. Nicorandil was administered at a dosage of 15 mg/kg/day by gavage feeding. After five weeks of nicorandil administration, blood samples were obtained from the angular vein to measure levels of stress markers, serum superoxide dismutase and malondialdehyde, using the ELISA. The expression of TRX in STZ-induced rat vascular tissue was analyzed by immunohistochemistry, quantitative polymerase chain reaction (qPCR) and western blot analysis. The oral administration of nicorandil induced TRX protein and mRNA expression in the vascular tissue of STZ-induced diabetic rats. In the diabetic control group, the levels of stress were markedly higher than those in the nicorandil-treated group, indicating that nicorandil reduces oxidative stress in serum. In addition to inducing TRX expression, nicorandil attenuated the expression of the vascular cell adhesion molecule-1 (VCAM-1) in diabetic rat vascular endothelial cells. In conclusion, nicorandil attenuates the formation of reactive oxygen species and induces TRX protein expression, consequently resulting in the suppression of VCAM-1 secretion in the vascular endothelial cells of STZ-induced diabetic

  18. The Expression of PLF in Placenta in Pregnancy-Induced Hypertension and the Relationship between the PLF and Serum VCAM-1

    Institute of Scientific and Technical Information of China (English)

    徐晓燕; 相文佩; 陈汉平

    2003-01-01

    Summary: To study the expression of placental isoferritin (PLF) in placental tissue of pregnancy-in-duced hypertension (PIH) and the relationship between the level of expression of PLF and theamount of vascular cell adhesion molecule-1 (VCAM-1) in serum, immunohistochemical techniquewas used to detect the expression of PLF in placenta tissue in 45 PIH patients (PIH group) and 15normal pregnant women (normal group). High resolution pathological image analysis system(HPIAS-100) was employed to determine the quantity of PLF. The VCAM-1 in serum was exam-ined by enzyme linked immunoabsorbent assay (ELISA). The results showed that the levels of PLFexpressions in moderate and severe PIH patients were significantly lower than that of normal group(P<0. 01). The serum VCAM-1 was significantly decreased in PIH group (1310±177 ρ/ng/ml)than that of normal group (609±72 ρ/ng/ml, P<0. 01).The significant negative correlation exist-ed between the expression of PLF in placental tissue and the serum VACM-1 (r=-0. 58, P<0. 01).It was concluded that the level of PLF expression in PIH decreases and is negatively correlated withthe amount of serum VCAM-1, indicating that these may be involved in the pathogenesis of PIH.

  19. Soluble adhesion molecules ICAM-1, VCAM-1, P-selectin in children with Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Elzbieta Maciorkowska; Maciej Kaczmarski; Anatol Panasiuk; Katarzyna Kondej-Muszynska; Andrzej Kemonai

    2005-01-01

    AIM: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children withHelicobacter pylori(H pylori)infection and to evaluate their significance for the morphological changes found in gastric mucosa.METHODS: The study included 106 children: 59children (55.7%) with chronic gastritis and positive IgG against H pylori, 29 children (27.3%) after previous H pylori infection without the bacterium colonization but with positive IgG against H pylori, and 18 children (17%) with functional disorders of the gastrointestinal system but with normal IgG against H pylori. Endoscopic and histopathological evaluation of gastric mucosa was performed based on the Sydney System classification.The evaluation of sP-selectin, sIC AM-1, sVCAM-1 levels in the sera of children was carried out using ELISA test.RESULTS: The assessment of gastritis activity degrees indicated statistically significant values in the antrum and corpus (P<0.001) of children examined. Serum sVCAM-1 levels were higher in group with gastritis due to H pylori infection than in group without infection and differed statistically (P<0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive molecules in infected children and decreased after eradication of H pylori. Serum sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were similar in children with and without H pylori infection.CONCLUSION: Assessment of adhesive molecules (sPselectin, sICAM-1, sVCAM-1) in the sera of children with active H pylori infection can show the participation of sVCAM-1 in the pathogenesis of gastric mucosal inflammation, sP-selectin and sICAM-1 concentrations in the sera of children with H pylori infection after eradication cannot reveal any significant differences as compared to healthy children.

  20. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

    Directory of Open Access Journals (Sweden)

    Anne Mette Fisker Hag

    Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

  1. 病毒性脑炎患儿S100B蛋白、NSE、sVCAM-1和神经肽Y水平变化的临床意义%Clinical significance of the level change of S100B protein, NSE, sVCAM-1 and neuropeptide Y in children with viral encephalitis

    Institute of Scientific and Technical Information of China (English)

    张永英

    2012-01-01

    Objective To explore the clinical significance of the level change of serum S100B protein, neuron enolase (NSE), soluble vascular endothelial cell adhesion molecules (sVCAM-1) and neuropeptide Y (NPY) in children with viral encephalitis. Methods 32 cases of children viral encephalitis with central nervous system infection were selected as the viral encephalitis group, and according to the illness was divided into light disease group and severe disease group, at the same time, 32 cases without central nervous system infection (by lumbar puncture) of children were chose as control group. S100B protein, NSE, sVCAM-1 and NPY level of the serum and cerebrospinal fluid in children were detected, and the results were compared. Results The levels of S100B protein, NSE, sVCAM-1 and neuropeptide Y (NPY) in the viral encephalitis group were obviously higher than those in the control group, there were significant differences (P < 0.05). For the viral encephalitis children, S100B protein, NSE, sVCAM-1 and neuropeptide Y (NPY) level in serum and cerebrospinal fluid were significantly lower in light disease group than those in severe group, there were significant differences (P < 0.05). Conclusion There is a correlation between the change and illness weight of viral encephalitis children cerebrospinal fluid and serum S100B protein, NSE, sVCAM-1 and neuropeptide Y level, which has an important value to judge the illness.%目的 探讨病毒性脑炎患儿脑脊液及血清中S100B蛋白、神经元烯醇化酶(NSE)、可溶性血管内皮细胞黏附分子(sVCAM-1)和神经肽Y(NPY)水平变化的临床意义.方法 选取32例有中枢神经系统感染的病毒性脑炎患儿为病毒性脑炎组,并根据病情分为轻症组和重症组,选择同期住院的经腰椎穿刺确定无中枢神经系统感染的病毒性脑炎患儿32例作为对照组.检测各组患儿血清和脑脊液中S100B蛋白、NSE、sVCAM-1和NPY的水平,并将结果进行比较.结果 病毒性脑炎

  2. Preparation and Stability of VCAM-1-targeted Ultrasound Contrast Agent%血管细胞黏附分子-1靶向超声造影剂制备及稳定性实验

    Institute of Scientific and Technical Information of China (English)

    刘丽云; 古丽齐满·霍加阿布都拉; 穆玉明; 马婷

    2013-01-01

    目的 探讨静电吸附法制备携血管细胞黏附分子-1(VCAM-1)抗体靶向超声造影剂的可行性及体内、外稳定性.方法 根据抗体和微泡的体积比将靶向造影剂分为3组,采用静电吸附法制备并检测微泡大小、形态和荧光亮度,流式细胞仪检测靶向造影剂的体外稳定性.复制兔早期动脉粥样硬化模型,进行靶向微泡的血管造影,采用免疫荧光法检测靶向微泡的体内稳定性.结果 通过静电吸附法可将VCAM-1抗体与SonoVue两者结合,VCAM-1抗体与SonoVue按1∶1比例配制的最佳.体外实验中,流式细胞仪检测显示剧烈震荡前后VCAM-1抗体携带率无明显变化(78.2%±4.2% vs 76.3%±3.6%).体内实验中,可见大量靶向微泡在受损血管内膜处黏附,未见靶向微泡在正常血管内膜处黏附.结论 静电吸附法可以制备VCAM-1抗体靶向微泡,并与受损血管内膜特异性结合,且体内、外均能保持一定的稳定性.%Objective To prepare SonoVue microbubbles carring Vascular Cell Adhesion Molecule-1 (VCAM-1) antibody using a electrostatic attraction way and evaluate its stability in vivo and in vitro.Methods Targeted contrast agent was divided into three groups according to different ratio of VCAM-1/SonoVue microbubbles.The physiochemical properties of microbubbles were evaluated by cell-size instrument,optical and fluorescence microscope.The stability of microbubbles were assessed by flowcytometry test in vitro and by immunofluorescence test in vivo.Results VCAM-1 and SonoVue can be combined by electrostatic attraction.VCAM-1/SonoVue microbubbles ratio of 1:1 was optimum.In vitro flowcytometry test,the binding rate of VCAM-1 before and after shaking was no significant different (78.2%±4.2% vs 76.3%±3.6%,P<0.05).In vivo test,the targeted microbubbles adhered to the damaged endothelium and there was no adhesion in normal endothelium.Conclusions Contrast agent carrying VCAM 1 can be prepared

  3. Largazole, a class I histone deacetylase inhibitor, enhances TNF-α-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Salahuddin, E-mail: Salah.Ahmed@utoledo.edu [Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States); Riegsecker, Sharayah; Beamer, Maria; Rahman, Ayesha; Bellini, Joseph V. [Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States); Bhansali, Pravin; Tillekeratne, L.M. Viranga [Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States)

    2013-07-15

    In the present study, we evaluated the effect of largazole (LAR), a marine-derived class I HDAC inhibitor, on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) activity. LAR (1–5 μM) had no adverse effect on the viability of RA synovial fibroblasts. Among the different class I HDACs screened, LAR (0.5–5 μM) inhibited the constitutive expression of HDAC1 (0–30%). Surprisingly, LAR increased class II HDAC [HDAC6] by ∼ 220% with a concomitant decrease in HDAC5 [30–58%] expression in RA synovial fibroblasts. SAHA (5 μM), a pan-HDAC inhibitor, also induced HDAC6 expression in RA synovial fibroblasts. Pretreatment of RA synovial fibroblasts with LAR further enhanced TNF-α-induced ICAM-1 and VCAM-1 expression. However, LAR inhibited TNF-α-induced MMP-2 activity in RA synovial fibroblasts by 35% when compared to the TNF-α-treated group. Further, the addition of HDAC6 specific inhibitor Tubastatin A with LAR suppressed TNF-α + LAR-induced ICAM-1 and VCAM-1 expression and completely blocked MMP-2 activity, suggesting a role of HDAC6 in LAR-induced ICAM-1 and VCAM-1 expression. LAR also enhanced TNF-α-induced phospho-p38 and phospho-AKT expression, but inhibited the expression of phospho-JNK and nuclear translocation of NF-κBp65 in RA synovial fibroblasts. These results suggest that LAR activates p38 and Akt pathways and influences class II HDACs, in particular HDAC6, to enhance some of the detrimental effects of TNF-α in RA synovial fibroblasts. Understanding the exact role of different HDAC isoenzymes in RA pathogenesis is extremely important in order to develop highly effective HDAC inhibitors for the treatment of RA. - Highlights: • Largazole enhances TNF-α-induced ICAM-1 and VCAM-1. • Largazole upregulates class II HDAC (HDAC6) in RA synovial fibroblasts. • Largazole also induces the expression of phospho-p38

  4. Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or em>P. vivax malaria and association with disease severity

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S; Rønn, A;

    1994-01-01

    Increased serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leucocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were detected in Danish malaria patients infected with sequestering Plasmodium falciparum or n...

  5. The effects of colloids or crystalloids on acute respiratory distress syndrome in swine (Sus scrofa models with severe sepsis: analysis on extravascular lung water, IL-8, and VCAM-1

    Directory of Open Access Journals (Sweden)

    Rismala Dewi

    2016-04-01

    Full Text Available Background: Acute respiratory distress syndrome (ARDS is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW elevation and levels of interleukin-8 (IL-8 and vascular cell adhesion molecule-1 (VCAM-1 have been studied as indicators playing a role in the pathogenesis of ARDS. The aim of the study was to determine the effects of colloid or crystalloid on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.Methods: This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, IPB, using 22 healthy swine models with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Analysis of data using the Wilcoxon test , Kolmogorov-Smirnov test, Mann-Whitney test, unpaired t test.Results: Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. EVLW elevation was lower in the colloid compared to the crystalloid group. There was no significant difference in IL-8 and VCAM-1 levels between the two groups.Conclusion: The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI, but not with IL-8 or VCAM-1 levels.

  6. 罗格列酮对2型糖尿病患者颈动脉内膜中层厚度及血清可溶性血管细胞黏附分子-1水平的影响%Effects of Rosiglitazone on the IMT and Serum sVCAM-1 Levels in Type 2 Diabetic Patients

    Institute of Scientific and Technical Information of China (English)

    赵永才; 李新胜; 张金成; 钱红霞

    2011-01-01

    Objective To investigate the change of carotid intima - media thickness ( IMT ) and serum soluble vascular cell adhesion molecule -1 ( sVCAM -1 ) levels in Type 2 diabetic patients, and to assess the effect of rosiglitazone on IMT and sVCAM - 1 levels.Methods In this study 108 cases of Type 2 diabetic patients were randomly divided into treatment group and control group, every group consisted of 54 numbers.The control group received routine therapy alone.The treatment group was treated with rosightazone 4 mg/d on the basis routine therapy for six months.Serum level of sVCAM - 1, plasma glucose and IMT were measured before and after rosiglitazone intervention on two groups, to observe the differences after treatment between the groups with rosiglitazone treatment and without rosiglitazone treatment Results The level of plasma glucose in Type 2 diabetic patients was significantly lower than that before treatment ( P < 0.05 ).After treatment with rosiglitazone, IMT and serum sVCAM - 1 levels decreased significantly ( P <0.05 ).There was no obvious change in IMT and serum sVCAM - 1 levels in control group before and after the treatment ( P > 0.05 ).Using multile linear stepwise regression analysis, the significant correlation between IMT and sVCAM - 1, BMI, 2 hPG, HOMA -IR were discovered ( P <0.01 ).Conclusion there is closely relationship between serume sVCAM - 1 levels and Type 2 diabetic macrovascular disease.Serum sVCAM - 1 can be reduced significantly in the Type 2 diabetic patients after being treated with rosiglitazone, which may be one of the protective mechanisms of vascular vessels.%目的 观察2型糖尿病(T2DM)患者血清可溶性血管细胞黏附分子-1(sVCAM-1)水平和颈动脉内膜中层厚度(IMT)的变化,以及罗格列酮治疗对二者的影响.方法 将108例T2DM患者随机分为治疗组(54例)和对照组(54例).治疗组在原治疗基础上给予罗格列酮4 mg/d.治疗前和治疗6个月后检测血生化指标、IMT及血清sVCAM

  7. COPD稳定期患者血清CRP、TNF-α与VCAM-1关系的研究

    Institute of Scientific and Technical Information of China (English)

    李磊; 夏熙郑

    2009-01-01

    目的 通过检测CRP、TNF-α及VCAM-1在稳定期COPD患者中的水平,探讨血栓前状态与全身炎症反应关系及其在稳定期COPD中的作用.方法 选取COPD稳定期患者44例,健康对照组26例.测量两组的肺功能,采用ELISA检测两组血浆中CRP、TNF-α、sVCAM-1的水平.结果 COPD组CRP水平显著高于对照组;TNF-α水平显著高于对照组;COPD组sVCAM显著高于对照组水平;COPD组患者血浆CRP、TNF-α、sVCAM-1水平与FEV1.0%预计值呈负相关;COPD组血浆CRP、TNF-α与sVCAM-1呈正相关.结论 COPD稳定期患者存在全身炎症反应和血栓前状态.CRP、TNF-α和sVCAM-1可作为判断COPD病情的指标.COPD的全身炎症反应有助于形成PTS.

  8. Role Of Adhesion Molecules Vcam-1 And Ve-Cadherin In Endothelium Dysfunction Development At Hemorrhagic Fever With Renal Syndrome

    Directory of Open Access Journals (Sweden)

    А.А. Baygildina

    2009-12-01

    Full Text Available The research goal is to determine the changes in concentration of both sVCAM-1 and VE-cadherin in blood serum of patients suffered from hemorrhagic fever with renal syndrome (HFRS. 87 patients aged 15-65 were examined. Concentrations of both sVCAM-1 and VE- cadherin in blood serum by means of "Bender MedSystems" (Austria ELISA test were determined. It was shown that in both medium severe and severe forms of HFRS statistically the significant rise of sVCAM-1 concentration in blood with high indices in oliguric period took place. Complicated form was characterized by high indices of sVCAM-1 level in fever period, extremely decreasing in concentration in oliguric period and tendency to normalizing in clinical convalescence period. VE-cadherin level in blood was predominantly lower than control in all the observed groups with the exception of fever period in group with medium severe disease form. Negative correlation of normal intensity between adhesion molecules levels in blood was revealed. In conclusion it is necessary to point out that high VCAM-1 expression by endotheliocytes evidences the development of an adhesion form of endothelial dysfunction, low VE-cadherin production in a base for development of angiogenic form of endothelial dysfunction and changes in expression of these adhesion molecules that have adaptive metabolic response to macroorganism of HFRS pathogenic action

  9. Effect of Thyrotropin on Osteopontin, Integrin αvβ3, and VCAM-1 in the Endothelium via Activation of Akt

    Science.gov (United States)

    Yan, Yumeng; Jiang, Fengwei; Lai, Yaxin; Wang, Haoyu; Liu, Aihua; Wang, Chuyuan; Zhang, Yuanyuan; Teng, Weiping; Shan, Zhongyan

    2016-01-01

    Numerous epidemiological studies have shown that subclinical hypothyroidism (SCH) can impair endothelial function and cause dyslipidemia. Studies have evaluated the effects of thyroid stimulating hormone (TSH) on endothelial cells, but the mechanism underlying the proatherosclerotic effect of increased TSH levels remains unclear. In the present study, SCH rat models were established in thyroidectomized Wistar rats that were given l-T4 daily. The results showed that in vivo, the expression of osteopontin (OPN) vascular cell adhesion molecule (VCAM-1), and levels of integrin αvβ3 in the aortic tissue in SCH and Hypothyroidism (CH) groups was higher than in the control group. However, the effect in the SCH group was higher than in the CH group. In vitro, results showed that different concentration and time gradients of TSH stimulation could increase the expression of OPN, VCAM-1, and integrin αvβ3, and this was accompanied by extracellular signal regulated kinase 1/2 (Erk1/2) and Akt activation in human umbilical vein endothelial cells (HUVECs). TSH induced elevation of these proatherosclerotic factors was partially suppressed by a specific Akt inhibitor but not by a specific Erk inhibitor. Findings suggested that the endothelial dysfunction caused by SCH was related to increased proatherosclerotic factors induced by TSH via Akt activation. PMID:27657042

  10. Endothelial activation markers (VCAM-1, vWF in patients with chronic hepatitis C and insulin resistance

    Directory of Open Access Journals (Sweden)

    T. V. Antonova

    2012-01-01

    Full Text Available Blood markers of endothelial activation (sVCAM-1, vWF: Ag in patients with chronic hepatitis C in the presence of insulin resistance, metabolic syndrome and its components had been evaluated. The study included 69 patients with chronic hepatitis C with oligosymptomatic the disease. In one third of cases of chronic hepatitis C (33.3% showed improvement in the blood content of sVCAM-1 and / or vWF: Ag. In patients with chronic hepatitis C with insulin resistance, metabolic syndrome significantly more often found signs adhesion of endothelial dysfunction (increased blood concentrations of sVCAM-1 than in patients without these disorders. Found that in patients with severe hepatic fibrosis in patients with chronic hepatitis C blood concentration sVCAM-1 is significantly higher compared to patients with early stages of fibrosis (F0-F2, including those in patients without insulin resistance. These data suggest the multivariate development of endothelial dysfunction in chronic hepatitis C.

  11. The effects of probucol on LOX-1 and VCAM-1 expressing in diabetic nephropathy atherosclerosis rats%LOX-1、VCAM-1在糖尿病肾病动脉粥样硬化大鼠中的表达及普罗布考的影响

    Institute of Scientific and Technical Information of China (English)

    郭亚玲; 陈卫东; 杨萍; 张燕; 刘磊; 张继强

    2014-01-01

    目的 观察普罗布考(PL)对糖尿病肾病动脉粥样硬化大鼠模型肾脏及腹主动脉LOX-1、VCAM-1表达的干预,阐明PL减轻其肾脏及主动脉氧化应激的机制.方法 50只雄性SD大鼠随机分为正常对照组和模型组.对照组予以普通饮食,实验组给予高糖、高脂、高胆固醇饮食.8周后模型组予以腹腔注射链脲佐菌素(STZ) 40mg/kg,将造模成功的大鼠随机分为糖尿病肾病组(DN组)和PL治疗组,PL组经口灌胃PL[500mg·(kg·d)-1].第18周测鼠重,血糖及24h尿蛋白定量,处死大鼠抽取血液观察血清生化指标及SOD和MDA,取肾脏及腹主动脉行组织切片观察其病理改变,免疫组织化学法检测肾脏及腹主动脉内LOX-1、VCAM-1蛋白的表达,RT-PCR方法检测肾脏及腹主动脉内LOX-1、VCAM-1核酸的表达.结果 PL能减轻模型组大鼠蛋白尿,改善血清白蛋白,降低血清肌酐、尿素氮,降低甘油三酯、胆固醇及MDA;下调肾脏及腹主动脉LOX-1、VCAM-1蛋白及核酸的表达.结论 PL可减轻肾脏及主动脉的氧化应激,其机制可能与PL降低LOX-1、VCAM-1的表达相关,进而保护肾脏及主动脉内膜功能.%Objectives To evaluate the effect of probucol on the expression of oxidized low density lipoprotein receptor-1 (LOX-1) and vascular cell adhesion molecule-1 (VCAM-1) in the diabetic nephropathy atherosclerosis rats'kidney and aorta,to explain the mechanism of probucol reduce oxidative stress in its'kidney and aorta.Methods Fifty Sprague-dawlay (SD) rats were randomly divided into normal control group(NC) and model group.The former give ordinary diet,the latter with high-sugar,high-fat and high-cholesterol diet.Eight weeks later,the model rats were injected Streptozotocin (STZ) 40mg · kg-1 into intraperitoneal.The rats of successful model to the following experiment:were randomly divided into diabetic nephropathy group (DN) and probucol group (PL),the latter with probucol500mg · (kg · d)-1 gavage.After 18

  12. Effect of liraglutide on the expressions of NF-κB and VCAM-1 in aorta endothelium of type 2 diabetic rats%利拉鲁肽对2型糖尿病大鼠 NF-κB 及VCAM-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    綦才辉; 金勇君; 杨美子; 徐鑫淼; 张凌云; 曹鹏娟

    2014-01-01

    Objective To investigate the effect of liraglutide on the expressions of nuclear factor-kappa B ( NF-κB) and vascular cell adhesion molecule 1 (VCAM-1) in aorta endothelium of type 2 diabetic rats and the possible mechanism. Methods Forty male SD rats were divided into the normal control group (NC group), diabetic control group (DM group), glibenclamide group (DMG group) and liraglutide group (DML group).The model of type2 diabetic rats was eatablised by injecting with low-dose streptozocin( STZ) into abdominal cavity of SD rats after high-fat and high-sugar diet.Then rats in DMG and DML groups were treated with liraglutide and glibenclamide for 8 weeks.At the end of the twelfth week, blood was taken from abdominal aorta to examine biochemical indexes including fasting blood-glucose (FBG), fasting insulin(FIns), totalcholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C) and high density lipoprotein-cholesterol ( HDL-C) .The thoracic aorta was isolated to observe the histological parame-ters by HE staining.The expressions of NF-κB and VCAM-1 in aorta endothelium were determined by immunohisto-chemical method.Rusults The levels of FIns and HOMA-IR in DMG group and DML group were decreased com-pared with those in DM group (P<0.01).The levels of FIns, HOMA-IR,TG and LDL-C and the expressions of NF-κB and VCAM-1 in in aorta endothelium in DML group were decreased compared with those in DMG group ( P<0.05).Conclusion Liraglutide can decrease the expressions of NF-κB and VCAM-1 in aorta endothelium of type2 di-abetic rats and improve glucolipid metabolism.This may be involved in vascular complications of diabetes.%目的:观察利拉鲁肽对2型糖尿病大鼠主动脉核因子-κB(NF-κB)及血管细胞间黏附因子(VCAM-1)表达的影响及可能机制。方法高脂高糖饲料喂养联合小剂量链脲佐菌素腹腔注射,建立2型糖尿病大鼠模型。40只8周龄雄性SD大鼠分为4组:正常对照组( NC

  13. Stem cell recruitment after injury: lessons for regenerative medicine

    OpenAIRE

    Rennert, Robert C; Sorkin, Michael; Garg, Ravi K; Geoffrey C Gurtner

    2012-01-01

    Tissue repair and regeneration are thought to involve resident cell proliferation as well as the selective recruitment of circulating stem and progenitor cell populations through complex signaling cascades. Many of these recruited cells originate from the bone marrow, and specific subpopulations of bone marrow cells have been isolated and used to augment adult tissue regeneration in preclinical models. Clinical studies of cell-based therapies have reported mixed results, however, and a variet...

  14. Effect and modulation of ICAM-1 and VCAM-1 in the inflammatory mechanisms following cerebral ischemia%ICAM-1、VCAM-1在脑缺血损伤炎症机制中的作用及调控

    Institute of Scientific and Technical Information of China (English)

    张丽慧; 魏尔清

    2005-01-01

    细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)在脑缺血损伤炎症过程中起着重要作用.脑缺血后ICAM-1和VCAM-1表达增加;ICAM-1、VCAM-1介导循环中的白细胞与内皮细胞黏附,进而浸润到血管外脑实质,导致缺血后炎症;抑制ICAM-1、VCAM-1表达及作用可减轻脑缺血损伤.

  15. Recruitment of Mesenchymal Stem Cells Into Prostate Tumors Promotes Metastasis

    OpenAIRE

    Jung, Younghun; Kim, Jin Koo; SHIOZAWA, YUSUKE; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E.; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Paul H Krebsbach

    2013-01-01

    Tumors recruit mesenchymal stem cells (MSCs) to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that the CXCR6 ligand CXCL16 facilitates MSC or Very Small Embryonic-Like (VSEL) cells recruitment into prostate tumors. CXCR6 signaling stimulates the conversion of MSCs into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also kno...

  16. Retinal Endothelial Cell Apoptosis Stimulates Recruitment of Endothelial Progenitor Cells

    Science.gov (United States)

    Bhatwadekar, Ashay D.; Glenn, Josephine V.; Curtis, Tim M.; Grant, Maria B.; Stitt, Alan W.; Gardiner, Tom A.

    2013-01-01

    Purpose Bone marrow–derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair. Methods Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed. Results Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05– 0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-α when compared to control medium; SDF-1 remained unchanged. Conclusions The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment. PMID:19474402

  17. Recruitment of Mesenchymal Stem Cells Into Prostate Tumors Promotes Metastasis

    Science.gov (United States)

    Jung, Younghun; Kim, Jin Koo; Shiozawa, Yusuke; Wang, Jingcheng; Mishra, Anjali; Joseph, Jeena; Berry, Janice E.; McGee, Samantha; Lee, Eunsohl; Sun, Hongli; Wang, Jianhua; Jin, Taocong; Zhang, Honglai; Dai, Jinlu; Krebsbach, Paul H.; Keller, Evan T.; Pienta, Kenneth J.; Taichman, Russell S.

    2013-01-01

    Tumors recruit mesenchymal stem cells (MSCs) to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that the CXCR6 ligand CXCL16 facilitates MSC or Very Small Embryonic-Like (VSEL) cells recruitment into prostate tumors. CXCR6 signaling stimulates the conversion of MSCs into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumor cells and induces an epithelial to mesenchymal transition, which ultimately promotes metastasis to secondary tumor sites. Our results provide the molecular basis for MSC recruitment into tumors and how this process leads to tumor metastasis. PMID:23653207

  18. Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts

    NARCIS (Netherlands)

    Spoelstra, FM; Postma, DS; Hovenga, H; Noordhoek, JA; Kauffman, HF

    2000-01-01

    The glucocorticoid budesonide and the long-acting beta(2)-adrenoceptor agonist formoterol are used in asthma therapy for their anti-inflammatory and bronchodilating effects, respectively. Since expression of adhesion molecules on resident cells in the lung plays an important role in asthmatic inflam

  19. Effects of Tribu Saponin from Tribulus terrestris on Gene Expression of ICAM-1, VCAM-1, PPARα and PPARγ in Artery Vessels of Atherosclerotic Rats%蒺藜皂苷对动脉粥样硬化大鼠动脉壁ICAM-1、VCAM-1、PPARα、PPARγ基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    石昌杰; 瞿伟菁; 高娟

    2009-01-01

    To investigate the effects of tribu saponin from Tribulus terrestris(STT) on the gene expression of ICAM-1, VCAM-1 ,PPARα and PPAR-γ in artery vessels of atherosclerotic rats,the model rats of atherosclerosis were established by feeding with high cholesterol diet and injecting with vitamin D_3. The rats were divided into normal group, model group,simvastatin group and 3 groups with SIT. Semi-quantitative RT-PCR was used to detect ICAM-1, VCAM-1, PPARα and PPARγ gene expression in artery vessels. The changes of gene expression of ICAM-1, VCAM-1 , PPARα and PPARγ in artery vessels in each group were analyzed. The results showed that ICAM-1 and VCAM-1 gene expression levels in the model group were significantly higher than those of normal group (P <0.01) , while the PPARα, PPARγ gene expression in the model group were significantly lower than those of normal group ( P < 0.01); Compared with model group,the ICAM-1 and VCAM-1 gene expression levels in each medicated group were significantly lower (P<0.01-P<0.05) and the PPARα and PPAHγ gene expression levels in each medicated group were significantly higher(P < 0.01). STT can down regulate the gene expression of ICAM-1, VCAM-1 and up regulate the gene expression of PPARα, PPARγ in artery vessels of arterosclerotic rats,which may account for the anti-arteriosclerosis effects of STT.%观察全草蒺藜皂苷(tribu saponln from Tribulus terrestris,STT)对实验性动脉粥样硬化(atherosclerosis,AS)大鼠动脉壁中ICAM-1、VCAM-1、PPARα和PPARγ基因表达的影响,以探讨STT抗AS的机制.应用高脂饲料饮食配合注射维生素D3建立SD大鼠AS模型,并设立正常组、模型组、辛伐他汀组和蒺藜皂苷低、中、高剂量组.采用半定量RT-PCR的方法检测各组动物动脉壁中ICAM-1、VCAM-1、PPARα和PPARγ基因的表达,分析造模及各给药大鼠ICAM-1、VCAM-1、PPARα和PPARγ基因表达的变化.与正常组相比,模型组ICAM-1和VCAM-1

  20. Artemether Combined with shRNA Interference of Vascular Cell Adhesion Molecule-1 Significantly Inhibited the Malignant Biological Behavior of Human Glioma Cells

    OpenAIRE

    Ying-Bin Wang; Yi Hu; Zhen Li; Ping Wang; Yi-Xue Xue; Yi-Long Yao; Bo Yu; Yun-Hui Liu

    2013-01-01

    Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma ...

  1. Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy

    DEFF Research Database (Denmark)

    Clausen, P; Jacobsen, P; Rossing, K;

    2000-01-01

    and diabetic nephropathy are associated with elevated plasma concentrations of soluble vascular adhesion molecule (sVCAM)-1, soluble intercellular adhesion molecule (sICAM)-1, and soluble E-selectin (sE-selectin) aiming to illustrate factors of potential pathogenetic relevance for the excess cardiovascular...... with microalbuminuria (n = 15); group 3-patients with macroalbuminuria and normal serum creatinine (n = 15), group 4-patients with macroalbuminuria and moderately elevated serum creatinine (n = 13). RESULTS: Plasma concentrations of sVCAM-1 and sICAM-1 were similar in healthy controls and normoalbuminuric Type 1...... diabetic patients, but the concentrations were increased by the presence of microalbuminuria and overt nephropathy (P ICAM-1 is elevated in Type 1...

  2. 血清 VCAM-1、 FGF2检测与糖尿病足关系研究%On the Relationship Between Serum VCAM-1, FGF2 and Diabetic Foot

    Institute of Scientific and Technical Information of China (English)

    孙海燕

    2015-01-01

    目的:探讨血管细胞黏附分子-1(VCAM-1)和成纤维细胞生长因子2(FGF2)的检测对糖尿病足的诊治意义。方法将我院血管外科住院治疗的120例糖尿病足(DF)患者参照 Wagner 分级方法随机分为 WagnerⅢ级 A 组(37例)、 WagnerⅣ级 B 组(42例)与 WagnerⅤ级 C 组(41例)。对照3组患者治疗前后 VCAM-1、 FGF2、空腹血糖、糖化血红蛋白(HbAlc)水平变化。结果治疗前3组患者 VCAM-1、 FGF2、空腹血糖、糖化血红蛋白(HbAlc)水平比较 P 均<0.05,差异具有统计学意义。治疗后 VCAM-1、 FGF2、空腹血糖、糖化血红蛋白(HbAlc)水平较治疗前明显好转, P 均<0.05,差异具有统计学意义。 VCAM-1、 FGF2水平与 Wagner 分级呈正相关(r =0.621, P>0.05,差异具有统计学意义)。结论血清 VCAM-1、 FGF2水平直接影响 DF 患者血糖水平及创面愈合,治疗期间对其检测有助于评估本病预后。%Objective To investigate the diagnostic significance of the detection of vascular cell adhesion molecule -1 (VCAM-1) and fibroblast growth factor 2 (FGF2) on diabetic foot.Methods According to Wagner classification method, 120 patients with diabetic foot (DF) in our hospital were randomly divided into three groups, namely group A (Wagner grade III, 37 cases), group B of (Wagner grade IV, 42 cases) and group C (Wagner grade V, 41 cases).VCAM-1, FGF2, fasting blood glucose and glycosylat-ed hemoglobin (HbAlc) levels in three groups were compared before and after treatment.Results Before treatment, levels of VCAM-1, FGF2, fasting blood glucose and glycosylated hemoglobin (HbAlc) of the three groups were compared and there was statistically significant difference (P0.05, with significant difference).Conclusion Serum VCAM-1 and FGF2 levels direct-ly affect the DF blood glucose level and wound healing, the detection during treatment is helpful to b evaluate the prognosis

  3. Strategies for recruitment of stem cells to treat myocardial infarction.

    Science.gov (United States)

    Shafiq, Muhammad; Lee, Sang-Hoon; Jung, Youngmee; Kim, Soo Hyun

    2015-01-01

    Heart failure is one of the most prominent causes of morbidity and mortality worldwide. According to the World Health Organization, coronary artery disease and myocardial infarction (MI) are responsible for 29% of deaths worldwide. MI results in obstruction of the blood supply to the heart and scar formation, and causes substantial death of cardiomyocytes in the infarct zone followed by an inflammatory response. Current treatment methodologies of MI and heart failure include organ transplantation, coronary artery bypass grafting, ventricular remodeling, cardiomyoplasty, and cellular therapy. Each of these methodologies has associated risks and benefits. Cellular cardiomyoplasty is a viable option to decrease the fibrosis of infarct scars, adverse post-ischemic remodeling, and improve heart function. However, the low rate of cell survival, shortage of cell sources and donors, tumorigenesis, and ethical issues hamper full exploitation of cell therapy for MI treatment. Consequently, the mobilization and recruitment of endogenous stem/progenitor cells from bone marrow, peripheral circulation, and cardiac tissues has immense potential through harnessing the host's own reparative capacities that result from interplay among cytokines, chemokines, and adhesion molecules. Therapeutic treatments to enhance the mobilization and homing of stem cells are under development. In this review, we present state-of-the-art approaches that are being pursued for stem cell mobilization and recruitment to regenerate infarcted myocardium. Potential therapeutic interventions and delivery strategies are discussed in detail. PMID:25594408

  4. Strategies for recruitment of stem cells to treat myocardial infarction.

    Science.gov (United States)

    Shafiq, Muhammad; Lee, Sang-Hoon; Jung, Youngmee; Kim, Soo Hyun

    2015-01-01

    Heart failure is one of the most prominent causes of morbidity and mortality worldwide. According to the World Health Organization, coronary artery disease and myocardial infarction (MI) are responsible for 29% of deaths worldwide. MI results in obstruction of the blood supply to the heart and scar formation, and causes substantial death of cardiomyocytes in the infarct zone followed by an inflammatory response. Current treatment methodologies of MI and heart failure include organ transplantation, coronary artery bypass grafting, ventricular remodeling, cardiomyoplasty, and cellular therapy. Each of these methodologies has associated risks and benefits. Cellular cardiomyoplasty is a viable option to decrease the fibrosis of infarct scars, adverse post-ischemic remodeling, and improve heart function. However, the low rate of cell survival, shortage of cell sources and donors, tumorigenesis, and ethical issues hamper full exploitation of cell therapy for MI treatment. Consequently, the mobilization and recruitment of endogenous stem/progenitor cells from bone marrow, peripheral circulation, and cardiac tissues has immense potential through harnessing the host's own reparative capacities that result from interplay among cytokines, chemokines, and adhesion molecules. Therapeutic treatments to enhance the mobilization and homing of stem cells are under development. In this review, we present state-of-the-art approaches that are being pursued for stem cell mobilization and recruitment to regenerate infarcted myocardium. Potential therapeutic interventions and delivery strategies are discussed in detail.

  5. Expression of vascular cell adhesion molecule-1 facilitates angiogenesis in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yongbin Ding; Tianson Xia; Guoyu Chen; Jianguo Xia

    2006-01-01

    Objective: To investigate the relationship between the expression of VCAM-1 and oncogenesis, tumor angiogenesis and metastasis in gastric carcinoma. Methods: Using RT-PCR and immunohistochemistry technique, the expression of VCAM-1 were detected in specimens from 44 patients with gastric cancer, 8 with ulcer. Microvessel density (MVD) was also counted by endothelial cells immunostained with monoclonal antibodies CD34. In addition, Circulating sVCAM-1 concentrations were measured by an enzyme linked immunosorbent assay. Results:Of 44 gastric cancer tumor tissues, 36were detected the ex pressions of VCAM-1 mRNA. The rates of VCAM-1 mRNA in the primary gastric cancer tissues were significantly higher than those in the para-cancerous tissues and benign ulcer tissues (P < 0.05). The VCAM-1 posithoseive isolates had more lymph node metastases than that of VCAM-l-negative ones (P < 0.05). MVD of positive VCAM-1 expression tissues were higher than those of negative VCAM-1 (P < 0.05). Circulating sVCAM-1 levels decreased significantly after operation (P < 0.05). Furthermore, the levels of sVCAM-1 were positively correlated with the expressions of VCAM-1 in the tumor tissues (r = 0.64, P <0.05). Conclusion: Expressions of VCAM-1 mRNA was closely related to oncogenesis, tumor angiogenesis and metastasis in gastric carcinoma. The concentration of sVCAM-1 may be considered as an effective mark of tumor burden of gastric cancer.

  6. Dietary Antioxidants Decrease Serum Soluble Adhesion Molecule (sVCAM-1, sICAM-1 but not Chemokine (JE/MCP-1, KC Concentrations, and Reduce Atherosclerosis in C57BL but Not ApoE*3 Leiden Mice Fed an Atherogenic Diet

    Directory of Open Access Journals (Sweden)

    Nuala Murphy

    2005-01-01

    Full Text Available Dietary antioxidants are reported to suppress cellular expression of chemokines and adhesion molecules that recruit monocytes to the artery wall during atherosclerosis. In the present study we measured the effect of feeding apoE*3 Leiden mice or their non-transgenic (C57BL littermates with atherogenic diets either deficient in, or supplemented with, dietary antioxidants (vitamin E, vitamin C and β-carotene for 12 weeks, on serum levels of CC (JE/MCP-1 and CXC (KC chemokines and soluble adhesion molecules (sVCAM-1, sICAM-1 and atherosclerotic lesion size. ApoE*3 Leiden mice developed gross hypercholesterolaemia, and markedly accelerated (10–20 fold; P < 0.0001 atherogenesis, compared with non-transgenic animals. Antioxidant consumption reduced lesion area in non-transgenic, but not apoE*3 Leiden, mice. Serum sVCAM-1 and sICAM-1 levels were significantly (P < 0.0001 increased (sVCAM-1 up to 3.9 fold; sICAM-1 up to 2.4 fold by 4—8 weeks in all groups, and then declined. The initial increase in the concentration of adhesion molecules was reduced by 38%— 61% (P < 0.05 by antioxidant consumption, particularly in non-transgenic mice. By contrast, serum chemokine levels tended to increase more rapidly from baseline in apoE*3 Leiden mice, compared with non-transgenic animals, but were unaffected by dietary antioxidants. We conclude that dietary antioxidants reduce circulating soluble adhesion molecules and atherosclerosis in C57BL mice.

  7. DMPD: Signals and receptors involved in recruitment of inflammatory cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 7744810 Signals and receptors involved in recruitment of inflammatory cells. Ben-Ba...ow Signals and receptors involved in recruitment of inflammatory cells. PubmedID 7744810 Title Signals and r...eceptors involved in recruitment of inflammatory cells. Authors Ben-Baruch A, Mic

  8. Cilostazol decreases the expression of ICAM-1 and VCAM-1 in the retina via up-regulating PPAR-γ in diabetic rats%西洛他唑对糖尿病大鼠视网膜ICAM-1和VCAM-1的影响及其机制

    Institute of Scientific and Technical Information of China (English)

    胡建廷; 王汝霞; 高聆

    2011-01-01

    目的:观察西洛他唑对糖尿病大鼠视网膜细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)表达的影响,并探讨其可能的作用机制.方法:以链脲佐菌素(STZ)诱发大鼠糖尿病.大鼠被随机分为正常对照组、糖尿病模型对照组、西洛他唑高剂量(27 mg·kg-1·d-1)和低剂量(9 mg·kg-1·d-1)组.西洛他唑治疗12周后测定血糖和糖化血红蛋白(HbAlc);利用RT-PCR和Western blot技术检测视网膜组织中ICAM-1,VCAM-1,过氧化物酶体增殖物激活受体γ(PPAR-γ)mRNA和蛋白质的表达.结果:与糖尿病模型对照组相比,西洛他唑能显著降低ICAM-1和VCAM-1 mRNA以及蛋白表达水平;西洛他唑治疗后,PPAR-γ mRNA和蛋白表达水平明显提高.结论:西洛他唑降低糖尿病大鼠视网膜ICAM-1和VCAM-1表达的作用可能与上调PPAR-γ有关.%Objective: To observe the effect of cilostazol on ICAM-1 and VCAM-1 expression in the retina of diabetic rats and to explore the possible mechanism. Methods: Diabetes was induced by STZ in rats. The rats were randomly divided into four groups, and treated with or without cilostazol (9 and 27 mg·kg -1 ·d -1 ). After 12week treatment, blood glucose and HbAlc were determined in all rats. The mRNA expressions of ICAM-1, VCAM1 and PPAR-γ were detected by RT-PCR; their protein expressions were detected by Western blot. Results: Compared with diabetic control, cilostazol depressed the mRNA and protein expressions of ICAM-1 and VCAM-1, but markedly enhanced the mRNA and protein expression of PPAR-γ. Conclusion: Cilostazol depresses adhesion molecule expression in the retina of diabetic rats; this is probably due to up-regulating PPAR-γ.

  9. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation

    OpenAIRE

    Cuff, Carolyn A.; Kothapalli, Devashish; Azonobi, Ijeoma; Chun, Sam; Zhang, Yuanming; Belkin, Richard; Yeh, Christine; Secreto, Anthony; Richard K Assoian; Rader, Daniel J; Puré, Ellen

    2001-01-01

    Atherosclerosis causes most acute coronary syndromes and strokes. The pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the vessel wall and activation of vascular cells. CD44 is an adhesion protein expressed on inflammatory and vascular cells. CD44 supports the adhesion of activated lymphocytes to endothelium and smooth muscle cells. Furthermore, ligation of CD44 induces activation of both inflammatory and vascular cells. To assess the potential contribution of CD4...

  10. Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1and EL expression via the NF-κB pathway.

    Science.gov (United States)

    Wu, Shan; Xu, Hui; Peng, Jinyong; Wang, Changyuan; Jin, Yue; Liu, Kexin; Sun, Huijun; Qin, Jianhua

    2015-03-01

    The modulation of adhesion molecule expression and the reduction of aberrant leukocyte adhesion to the endothelium are attractive approaches for treating inflammation-related vascular complications, including atherosclerosis. Dioscin has a variety of biological activities including anti-inflammatory activity. However, the molecular mechanisms behind dioscin's anti-inflammatory effects are not fully understood. In this study, we investigated the molecular mechanism involved in the effects of dioscin on inflammatory mediators in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). In vitro, dioscin decreased monocyte adhesion to TNF-α-treated HUVECs by reducing vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression and inhibiting endothelial lipase (EL) expression in TNF-α-treated HUVECs and macrophages by blocking the nuclear factor-κB (NF-κB) pathway. Thus, dioscin might inhibit inflammation by interrupting the NF-κB signaling pathway and could potentially contribute to treatments for inflammatory diseases and atherosclerosis. PMID:25577996

  11. sICAM- 1 and sVCAM- 1 levels in blood serum and gingival tissues in rabbits with periodontitis in analogic high altitude anoxia environment%模拟高原低氧兔牙周炎模型血清和牙龈组织中sICAM-1及sVCAM-1的含量

    Institute of Scientific and Technical Information of China (English)

    武曦; 黄镜静; 张纲; 谭颖徽; 高钰琪

    2012-01-01

    Objective: To investigate the expression of soluble inter-cellular adhesion molecules-1( sICAM-1 ) and soluble vascular adhesion molecular-1( sVCAM-1 ) in blood serum and gingival tissues in rabbits with periodontitis in high altitude anoxia environment. Methods: 40 male rabbits were randomly divided into four groups( n = 10 ): control and periodontitis groups in plain, control and periodontitis groups in plateau. The periodontitis models were established by ligation technique on the two central incisors of mandible and periodontitis diet. The anoxia groups were raised in a established condition of altitude at 5 000 meteres above sea level for eight weeks. sICAM-1 and sVCAM-1 levels in blood serum and gingival tissues were detected by ELISA. The morphology of the periodontal tissues were histologicaly observed. Results: More severe periodontitis was observed in anoxia periodontits groups. The concentrations of sl-CAM-1 and sVCAM-1 in anoxia periodontitis group were significantly higher than those in the other groups( P <0. 05 ), and the levels in gingival tissues were higher in blood serum. Conclusion: Cellular adhesion molecules are upregulated in anoxia environment at high altitude and may promotes the destruction of periodontal tissues and diffusion of inflammation into the peripheral blood vessels.%目的:探讨血清和牙龈组织中可溶性细胞间黏附分子- 1(sICAM- 1)、可溶性血管黏附分子- 1(sVCAM- 1)在高原牙周病炎症反应中的作用.方法:将40 只雄兔随机分为常氧对照组、常氧实验组、低氧对照组、低氧实验组,每组10 只,采用正畸丝结扎下颌中切牙与牙周炎食谱的方法建立牙周炎模型,常氧组和低氧组分别在平原和模拟海拔5 000 m条件下饲养8 周,对牙周组织取材进行组织学观察,用ELISA法检测各组实验动物血清和牙龈组织中sICAM- 1、sVCAM- 1表达情况.结果:低氧实验组sICAM- 1、sVCAM- 1浓度显著高于其余各组(P<0.05),且牙龈组

  12. MCP-1 promotes mural cell recruitment during angiogenesis in the aortic ring model.

    Science.gov (United States)

    Aplin, Alfred C; Fogel, Eric; Nicosia, Roberto F

    2010-09-01

    Rings of rat or mouse aorta embedded in collagen gels produce angiogenic outgrowths in response to the injury of the dissection procedure. Aortic outgrowths are composed of branching endothelial tubes and surrounding mural cells. Mural cells emerge following endothelial sprouting and gradually increase during the maturation of the neovessels. Treatment of aortic cultures with angiopoietin-1 (Ang-1), an angiogenic factor implicated in vascular maturation and remodeling, stimulates the mural cell recruitment process. Ang-1 induces expression of many cytokines and chemokines including monocyte chemotactic protein-1 (MCP-1). Inhibition of p38 MAP kinase, a signaling molecule required for mural cell recruitment, blocks Ang1-induced MCP-1 expression. Recombinant MCP-1 dose-dependently increases mural cell number while an anti-MCP-1 blocking antibody reduces it. In addition, antibody mediated neutralization of MCP-1 abrogates the stimulatory effect of Ang-1 on mural cell recruitment. Aortic rings from genetically modified mice deficient in MCP-1 or its receptor CCR2 have fewer mural cells than controls. MCP-1 deficiency also impairs the mural cell recruitment activity of Ang-1. Our studies indicate that spontaneous and Ang1-induced mural cell recruitment in the aortic ring of model of angiogenesis are in part mediated by MCP-1. These results implicate MCP-1 as one of the mediators of mural cell recruitment in the aortic ring model, and suggest that chemokine pathways may contribute to the assembly of the vessel wall during the angiogenesis response to injury.

  13. Macrophage Recruitment Contributes to Regeneration of Mechanosensory Hair Cells in the Zebrafish Lateral Line.

    Science.gov (United States)

    Carrillo, Simón A; Anguita-Salinas, Consuelo; Peña, Oscar A; Morales, Rodrigo A; Muñoz-Sánchez, Salomé; Muñoz-Montecinos, Carlos; Paredes-Zúñiga, Susana; Tapia, Karina; Allende, Miguel L

    2016-08-01

    In vertebrates, damage to mechanosensory hair cells elicits an inflammatory response, including rapid recruitment of macrophages and neutrophils. While hair cells in amniotes usually become permanently lost, they readily regenerate in lower vertebrates such as fish. Damage to hair cells of the fish lateral line is followed by inflammation and rapid regeneration; however the role of immune cells in this process remains unknown. Here, we show that recruited macrophages are required for normal regeneration of lateral line hair cells after copper damage. We found that genetic ablation or local ablation using clodronate liposomes of macrophages recruited to the site of injury, significantly delays hair cell regeneration. Neutrophils, on the other hand, are not needed for this process. We anticipate our results to be a starting point for a more detailed description of extrinsic signals important for regeneration of mechanosensory cells in vertebrates. J. Cell. Biochem. 117: 1880-1889, 2016. © 2016 Wiley Periodicals, Inc. PMID:26755079

  14. Recruitment of activation receptors at inhibitory NK cell immune synapses.

    Directory of Open Access Journals (Sweden)

    Nicolas Schleinitz

    Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

  15. ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice.

    Science.gov (United States)

    Feng, Lizhao; Wang, Yijing; Cai, Han; Sun, Guanghong; Niu, Wanbao; Xin, Qiliang; Tang, Xiaofang; Zhang, Jiawei; Wang, Chao; Zhang, Hua; Xia, Guoliang

    2016-06-01

    Ovarian follicles are the basic functional units of female reproduction in the mammalian ovary. We show here that the protein a disintegrin and metalloproteinase domain 10 (ADAM10), a cell surface sheddase, plays an indispensable role in controlling primordial follicle formation by regulating the recruitment of follicle supporting cells in mice. We demonstrate that suppressing ADAM10 in vitro or deletion of Adam10 in vivo disrupts germline cyst breakdown and primordial follicle formation. Using a cell lineage tracing approach, we show that ADAM10 governs the recruitment of ovarian follicle cells by regulating the differentiation and proliferation of LGR5-positive follicle supporting progenitor cells. By detecting the development of FOXL2-positive pregranulosa cells, we found that inhibiting ADAM10 reduced the number of FOXL2-positive cells in perinatal ovaries. Furthermore, inhibiting ADAM10 suppressed the activation of Notch signaling, and blocking Notch signaling also disrupted the recruitment of follicle progenitor cells. Taken together, these results show that ADAM10-Notch signaling in ovarian somatic cells governs the primordial follicle formation by controlling the development of ovarian pregranulosa cells. The proper recruitment of ovarian follicle supporting cells is essential for establishment of the ovarian reserve in mice. PMID:27084580

  16. Dynamic observation'the levels of slCAM-1ard sVCAM-1 in the patients with acute ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Xia Bin; Shao Fuyuan; Zhao Zhongxin

    2000-01-01

    Background Adhesion molecules play a role in the ischemic injury. It has been shown that there were changes in the patients with ischemic stroke. Objective To approach the serum level of sICAM-I and sVCAM-i in patients with acute ischemic stroke. Methods sICAM-1 and sVCAM-i were measured by enzyme-lined imunosorbent assay and were serially detemined(within 6 hours and at first. third seventh day) in 16 patients with acute ischemic stroke. Results The result showed the serum sICAM-1 in patient with acute ischemic stroke was higher within 6 hours[ (558. 8±174. 8) ng/ml]. at first day [ (655. 1±89.4) ng/ml]and third day[ (571.4±104. 4) ng/ml] than in the controls[ (435. 3±86.6) ng/ml] (P<0.05), especially within the first day. sVCAM-I was higher within 6 hours[ (930.5.±181.7) mg/ml]、 at first day[(1174. 9±179.1)ng/ml]、 third day[( 1215.4±187.4)mg/mi] and seventh day [(988.5 ± 148. 8) ng/ml] than in the controls [ (704.2:± 125.8) ng/ml ] (P<0. 05), especially wi thin the first and third day. There was no significant correlation betwsen sICAM、 sVCAMt-1 levels and the extent of neurological deficits. (P>0.05). Conclusions Serum level of sICAM-I and sVCAM-1 were elevated in acute ischemic stroke and this changes were correlated with the time after stroke

  17. β-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe(-/- Mice.

    Directory of Open Access Journals (Sweden)

    Kaliappan Gopal

    Full Text Available Abdominal aortic aneurysm (AAA is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and β-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and β-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe(-/- mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II, and were orally administered with α-tocopherol and β-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (P = 0.0002 increased (2.24±0.20 mm in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm. Interestingly, β-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, β-carotene significantly decreased the aortic diameter (1.33±0.12 mm in the aneurysm-induced mice (β-carotene, P = 0.0002. It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of β-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe(-/- mice.

  18. GC-rich sequence elements recruit PRC2 in mammalian ES cells.

    Directory of Open Access Journals (Sweden)

    Eric M Mendenhall

    Full Text Available Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2. However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes.

  19. Recruitment and selection of marginal zone B cells is independent of exogenous antigens

    NARCIS (Netherlands)

    Dammers, PM; Kroese, FGM

    2005-01-01

    Marginal zone B (MZ-B) cells of the spleen contribute significantly to the immunity against invasive infections with polysaccharide-encapsulated bacteria. Recent evidence indicates that recruitment and selection of MZ-B cells occurs on the basis of positive selection constraints that likely operate

  20. IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes.

    Science.gov (United States)

    Watson, C; Whittaker, S; Smith, N; Vora, A J; Dumonde, D C; Brown, K A

    1996-07-01

    Using a quantitative monolayer adhesion assay, the current report shows that treatment of human umbilical vein endothelial cells (HUVEC) with IL-6 increases their adhesiveness for blood lymphocytes, particularly CD4+ cells, but not for polymorphonuclear cells and monocytes. This effect, which was most pronounced when using low concentrations of the cytokine (0.1-1.0 U/ml) and a short incubation period (4h), was also apparent with microvascular endothelial cells and a hybrid endothelial cell line. Skin lesions from patients with mycosis fungoides contain high levels of IL-6, and blood lymphocytes from patients with this disorder also exhibited an enhanced adhesion to IL-6-treated HUVEC. The cytokine enhanced intercellular adhesion molecule-1 (ICAM-1) expression and induced the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on endothelial cells. Antibody blocking studies demonstrated that the vascular adhesion molecules ICAM-1, VCAM-1 and E-selectin and the leucocyte integrin LFA-1 all contributed to lymphocyte binding to endothelium activated by IL-6. It is proposed that IL-6 may be involved in the recruitment of lymphocytes into non-lymphoid tissue.

  1. Human progenitor cell recruitment via SDF-1α coacervate-laden PGS vascular grafts.

    Science.gov (United States)

    Lee, Kee-Won; Johnson, Noah R; Gao, Jin; Wang, Yadong

    2013-12-01

    Host cell recruitment is crucial for vascular graft remodeling and integration into the native blood vessel; it is especially important for cell-free strategies which rely on host remodeling. Controlled release of growth factors from vascular grafts may enhance host cell recruitment. Stromal cell-derived factor (SDF)-1α has been shown to induce host progenitor cell migration and recruitment; however, its potential in regenerative therapies is often limited due to its short half-life in vivo. This report describes a coacervate drug delivery system for enhancing progenitor cell recruitment into an elastomeric vascular graft by conferring protection of SDF-1α. Heparin and a synthetic polycation are used to form a coacervate, which is incorporated into poly(glycerol sebacate) (PGS) scaffolds. In addition to protecting SDF-1α, the coacervate facilitates uniform scaffold coating. Coacervate-laden scaffolds have high SDF-1α loading efficiency and provide sustained release under static and physiologically-relevant flow conditions with minimal initial burst release. In vitro assays showed that coacervate-laden scaffolds enhance migration and infiltration of human endothelial and mesenchymal progenitor cells by maintaining a stable SDF-1α gradient. These results suggest that SDF-1α coacervate-laden scaffolds show great promise for in situ vascular regeneration.

  2. A novel method for monitoring functional lesion-specific recruitment of repair proteins in live cells

    Energy Technology Data Exchange (ETDEWEB)

    Woodrick, Jordan; Gupta, Suhani; Khatkar, Pooja; Dave, Kalpana; Levashova, Darya; Choudhury, Sujata; Elias, Hadi; Saha, Tapas; Mueller, Susette; Roy, Rabindra, E-mail: rr228@georgetown.edu

    2015-05-15

    Highlights: • A method of monitoring lesion-specific recruitment of proteins in vivo is described. • Recruitment of repair enzymes to abasic sites is monitored by co-localization. • Repair protein recruitment is consistent with known protein–protein relationships. • Cells demonstrated complete repair of abasic sites by 90 min. - Abstract: DNA–protein relationships have been studied by numerous methods, but a particular gap in methodology lies in the study of DNA adduct-specific interactions with proteins in vivo, which particularly affects the field of DNA repair. Using the repair of a well-characterized and ubiquitous adduct, the abasic (AP) site, as a model, we have developed a comprehensive method of monitoring DNA lesion-specific recruitment of proteins in vivo over time. We utilized a surrogate system in which a Cy3-labeled plasmid containing a single AP-site was transfected into cells, and the interaction of the labeled DNA with BER enzymes, including APE1, Polβ, LIG1, and FEN1, was monitored by immunofluorescent staining of the enzymes by Alexafluor-488-conjugated secondary antibody. The recruitment of enzymes was characterized by quantification of Cy3-Alexafluor-488 co-localization. To validate the microscopy-based method, repair of the transfected AP-site DNA was also quantified at various time points post-transfection using a real time PCR-based method. Notably, the recruitment time kinetics for each enzyme were consistent with AP-site repair time kinetics. This microscopy-based methodology is reliable in detecting the recruitment of proteins to specific DNA substrates and can be extended to study other in vivo DNA–protein relationships in any DNA sequence and in the context of any DNA structure in transfectable proliferating or quiescent cells. The method may be applied to a variety of disciplines of nucleic acid transaction pathways, including repair, replication, transcription, and recombination.

  3. Model of myosin recruitment to the cell equator for cytokinesis: feedback mechanisms and dynamical regimes

    Science.gov (United States)

    Veksler, Alexander; Vavylonis, Dimitrios

    2011-03-01

    The formation and constriction of the contractile ring during cytokinesis, the final step of cell division, depends on the recruitment of motor protein myosin to the cell's equatorial region. During animal cell cytokinesis, cortical myosin filaments (MF) disassemble at the flanking regions and concentrate in the equator. This recruitment depends on myosin motor activity and the Rho proteins that regulate MF assembly and disassembly. Central spindle and astral microtubules help establish a spatial pattern of differential Rho activity. We propose a reaction-diffusion model for the dynamics of MF recruitment to the equatorial region. In the model, the central spindle and mechanical stress promote self-reinforcing MF assembly. Negative feedback is introduced by MF-induced recruitment of inhibitor myosin phosphatase. Our model yields various dynamical regimes and explains both the recruitment of MF to the cleavage furrow and the observed damped MF oscillations in the flanking regions, as well as steady MF assembly. Space and time parameters of MF oscillations are calculated. We predict oscillatory relaxation of cortical MF upon removal of locally-applied external stress.

  4. NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation.

    Science.gov (United States)

    He, Hao; Geng, Tingting; Chen, Piyun; Wang, Meixiang; Hu, Jingxia; Kang, Li; Song, Wengang; Tang, Hua

    2016-01-01

    Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood-brain barrier, conventional CD11b(+)CD27(+) NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. By in vivo recruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment, and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation. PMID:27270556

  5. Neuropeptide Substance-P-Conjugated Chitosan Nanofibers as an Active Modulator of Stem Cell Recruiting

    Directory of Open Access Journals (Sweden)

    Min Sup Kim

    2016-01-01

    Full Text Available The goal to successful wound healing is essentially to immobilize and recruit appropriate numbers of host stem or progenitor cells to the wound area. In this study, we developed a chitosan nanofiber-immobilized neuropeptide substance-P (SP, which mediates stem cell mobilization and migration, onto the surfaces of nanofibers using a peptide-coupling agent, and evaluated its biological effects on stem cells. The amount of immobilized SP on chitosan nanofibers was modulated over the range of 5.89 ± 3.27 to 75.29 ± 24.31 ng when reacted with 10 to 500 ng SP. In vitro migration assays showed that SP-incorporated nanofibers induced more rapid migration of human mesenchymal stem cells on nanofibers compared to pristine samples. Finally, the conjugated SP evoked a minimal foreign body reaction and recruited a larger number of CD29- and CD44-positive stem cells into nanofibers in a mouse subcutaneous pocket model.

  6. Live Cell Imaging Reveals the Dynamics of Telomerase Recruitment to Telomeres.

    Science.gov (United States)

    Schmidt, Jens C; Zaug, Arthur J; Cech, Thomas R

    2016-08-25

    Telomerase maintains genome integrity by adding repetitive DNA sequences to the chromosome ends in actively dividing cells, including 90% of all cancer cells. Recruitment of human telomerase to telomeres occurs during S-phase of the cell cycle, but the molecular mechanism of the process is only partially understood. Here, we use CRISPR genome editing and single-molecule imaging to track telomerase trafficking in nuclei of living human cells. We demonstrate that telomerase uses three-dimensional diffusion to search for telomeres, probing each telomere thousands of times each S-phase but only rarely forming a stable association. Both the transient and stable association events depend on the direct interaction of the telomerase protein TERT with the telomeric protein TPP1. Our results reveal that telomerase recruitment to telomeres is driven by dynamic interactions between the rapidly diffusing telomerase and the chromosome end. PMID:27523609

  7. Recruitment of natural killer cells in advanced stages of endogenously arising B-cell lymphoma: implications for therapeutic cell transfer.

    Science.gov (United States)

    Przewoznik, Margarethe; Hömberg, Nadine; Naujoks, Marcella; Pötzl, Johann; Münchmeier, Niklas; Brenner, Christoph D; Anz, David; Bourquin, Carole; Nelson, Peter J; Röcken, Martin; Mocikat, Ralph

    2012-04-01

    During inflammation and in transplantable tumor models, natural killer (NK) cells are recruited to pathologic tissues and activated to produce proinflammatory cytokines favoring adaptive immune responses of the T-helper type 1 (Th1) type. Interferon (IFN)-γ is needed to induce chemokines that attract NK cells in transplanted tumors. Nothing, however, is known on NK-cell migration in spontaneous tumors. As effective recruitment is a prerequisite for therapeutic NK-cell transfer, we investigated the cytokine milieu and the mechanisms that are instrumental for NK-cell accumulation in an endogenous tumor model. We make use of λ-myc transgenic mice that harbor the c-myc oncogene and develop spontaneous B-cell lymphoma. In contrast to lymphomas induced by tumor cell injection, virtually no IFN-γ produced by NK or by other cells was present in the tumor environment, particularly in advanced stages. Dendritic cells showed an impaired expression of interleukin-12, which is suggestive of deficient Th1 priming. The IFN-γ-dependent chemokines CXCL9 and CXCL10 were pivotal for NK-cell migration in the endogenous lymphoma model. Although IFN-γ was absent in late tumor stages, there was still expression of CXCL9 and CXCL10 with an ongoing influx of NK cells. The results demonstrate that transplantable tumor models do not reflect the situation as found in endogenously arising neoplasia, because in the latter, effective Th1 and cytotoxic T-lymphocyte responses are presumably not induced because of impaired IFN-γ production. The data also suggest that CXCL9 and CXCL10 production and NK-cell migration become independent of IFN-γ during tumor progression, and therefore support approaches of adoptive NK-cell transfer that hold promise for treatment of cancer. PMID:22421939

  8. Growth hormone increases vascular cell adhesion molecule 1 expression

    DEFF Research Database (Denmark)

    Hansen, Troels Krarup; Fisker, Sanne; Dall, Rolf;

    2004-01-01

    We investigated the impact of GH administration on endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, in vivo and in vitro. Soluble VCAM-1, E-selectin, and C-reactive protein concentrations were measured before and after treatment in 25 healthy subjects...... and 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline...... levels of VCAM-1, but not E-selectin, were significantly lower in GHD patients than in healthy subjects (362 +/- 15 microg/liter vs. 516 +/- 21 microg/liter, P treatment, compared with placebo [net difference between groups 151.8 microg/liter (95...

  9. Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment

    OpenAIRE

    Zhang, Yi; Chen, Liuh-Yow; Han, Xin; XIE, Wei; Kim, Hyeung; Yang, Dong; Liu, Dan; Songyang, Zhou

    2013-01-01

    Telomere maintenance is essential for organisms with linear chromosomes and is carried out by telomerase during cell cycle. The precise mechanism by which cell cycle controls telomeric access of telomerase and telomere elongation in mammals remains largely unknown. Previous work has established oligonucleotide/oligosaccharide binding (OB) fold-containing telomeric protein TPP1, formerly known as TINT1, PTOP, and PIP1, as a key factor that regulates telomerase recruitment and activity. However...

  10. 急性缺血性脑血管病患者血ICAM-1、VCAM-1、CD62p的改变及其临床意义

    Institute of Scientific and Technical Information of China (English)

    顾苏兵; 周永列; 赖小彪; 张剑梅

    2000-01-01

    目的探讨急性缺血性脑血管病患者血中性粒细胞表面细胞间粘附分子(ICAM-1)、血管细胞粘附分子(VCAM-1)和血小板上P选择素(CD62p)的改变及其临床意义.方法应用流式细胞术测定121 例脑缺血患者发病48小时内ICAM-1、VCAM-1、CD62p的改变.结果 (1)各种急性脑缺血患者ICAM-1均较对照组升高,P<0.01;脑血栓形成和腔隙性脑梗死CD62p升高,P<0.05;脑血栓形成VCAM-1升高,P<0.05.(2)脑梗死面积≥1.5 cm2者ICAM-1、CD62p较<1.5 cm2者高.(3)ICAM -1与收缩压呈正相关.结论 3种粘附分子在不同脑缺血患者发病初表达不同,测定ICAM -1和CD62p 有助于脑缺血病情观察.

  11. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules

    OpenAIRE

    1991-01-01

    Cytokines such as interleukin 1 (IL-1) promote adhesiveness in human umbilical vein endothelial cells for leukocytes including basophils, eosinophils, and neutrophils, and induce expression of adherence molecules including ICAM-1 (intercellular adhesion molecule-1), ELAM-1 (endothelial-leukocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1). In the present study, blocking monoclonal antibodies (mAb) recognizing ICAM-1, ELAM-1, and VCAM-1 have been used to compare their ...

  12. REST-mediated recruitment of polycomb repressor complexes in mammalian cells

    DEFF Research Database (Denmark)

    Dietrich, Nikolaj; Lerdrup, Mads; Landt, Eskild;

    2012-01-01

    , and increased gene expression. Genome-wide analysis of Polycomb binding in Rest¿/¿ and Eed¿/¿ mouse embryonic stem (mES) cells showed that Rest was required for PRC1 recruitment to a subset of Polycomb regulated neuronal genes. Furthermore, we found that PRC1 can be recruited to Rest binding sites independently......, and PRC2 and show that RNF2 and REST co-regulate a number of neuronal genes in human teratocarcinoma cells (NT2-D1). Using NT2-D1 cells as a model of neuronal differentiation, we furthermore showed that retinoic-acid stimulation led to displacement of PRC1 at REST binding sites, reduced H3K27Me3......Polycomb Repressive Complex (PRC) 1 and PRC2 regulate genes involved in differentiation and development. However, the mechanism for how PRC1 and PRC2 are recruited to genes in mammalian cells is unclear. Here we present evidence for an interaction between the transcription factor REST, PRC1...

  13. The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production

    DEFF Research Database (Denmark)

    Tinning, Anne Robdrup; Jensen, Boye L; Schweda, Frank;

    2014-01-01

    Processing and release of secretory granules involve water movement across granule membranes. It was hypothesized that the water channel aquaporin-1 (AQP-1) contributes directly to recruitment of renin-positive cells in the afferent arteriole. AQP1(-/-) and (+/+) mice were fed a low NaCl diet (LS...... to (+/+) mice. Tissue renin concentration was higher in AQP1(-/-) mice and renin mRNA level was not different between genotypes. Mean arterial blood pressure was not different at baseline and during low salt diet but decreased significantly in both genotypes after addition of ACEI; the response was faster...... for acutely stimulated renin secretion in vivo and from isolated perfused kidney, whereas recruitment of renin-positive cells in response to chronic stimulation is attenuated or delayed in AQP1(-/-) mice....

  14. s-ICAM-1 and s-VCAM-1 in healthy men are strongly associated with traits of the metabolic syndrome, becoming evident in the postprandial response to a lipid-rich meal

    Directory of Open Access Journals (Sweden)

    Nothnagel Michael

    2008-09-01

    Full Text Available Abstract Background The importance of the postprandial state for the early stages of atherogenesis is increasingly acknowledged. We conducted assessment of association between postprandial triglycerides, insulin and glucose after ingestion of a standardized lipid-rich test meal, and soluble cellular adhesion molecules (sCAM in young healthy subjects. Methods Metabolic parameters and sICAM-1, sVCAM-1 and E-selectin were measured before and hourly until 6 hours after ingestion of a lipid-rich meal in 30 healthy young men with fasting triglycerides 260 mg/dl. Levels of CAM were compared in HR and NR, and correlation with postprandial triglyceride, insulin and glucose response was assessed. Results Fasting sICAM-1 and sVCAM-1 levels were significantly higher in HR as compared to NR (p = 0.046, p = 0.03. For sE-selectin there was such a trend (p = 0.05. There was a strong positive and independent correlation between sICAM-1 and postprandial insulin maxima (r = 0.70, p Conclusion This independent association of postprandial triglycerides with sICAM-1 may indicate a particular impact of postprandial lipid metabolism on endothelial reaction.

  15. A study on the pathogenesis of the radiation pneumonitis. Alterations in pulmonary mRNA encoding adhesion molecules ICAM-1, VCAM-1, and P-selectin following thoracic irradiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tsujino, Kayoko; Kodama, Akihisa; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1997-12-01

    To investigate the role of the adhesion molecules in the pathogenesis of the radiation pneumonitis, we quantified the mRNA expression of the adhesion molecules in the lung by Northern blot method following whole thorax irradiation to C57BL/6J mice. After irradiation of 12 Gy to the whole thorax, there were increase of mRNA for ICAM-1 by 42% at 4 hours (p<0.05), 76% at 24 hours (p<0.01) and 51% at 48 hours (p<0.05) compared with controls. And it returned to control level at 1 week. No significant change was observed thereafter until 8 weeks. The expression of VCAM-1 mRNA were also increased by 49% (p<0.01) at 12 hours and were still increased by 25% at 1 week. P-selectin mRNA as transiently increased by 59% at 12 hours. We examined the relationship between the ICAM-1 induction and the radiation dose, and found that ICAM-1 expression was increased by 3 Gy of irradiation and it was increased in radiation dose dependent manner up to 24 Gy. These early inductions of mRNA for ICAM-1, VCAM-1 and P-selectin in mice lungs following thoracic irradiation were transient but significant, and they were one of the most immediate change reported in vivo. It is suggested that these adhesion molecules are possibly related to the pathogenesis of the radiation pneumonitis. (author)

  16. Clusterin Modulates Allergic Airway Inflammation by Attenuating CCL20-Mediated Dendritic Cell Recruitment.

    Science.gov (United States)

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Moon, Keun-Ai; Park, So Young; Park, Sunjoo; Lee, Kyoung Young; Ha, Eun Hee; Kim, Tae-Bum; Moon, Hee-Bom; Lee, Heung Kyu; Cho, You Sook

    2016-03-01

    Recruitment and activation of dendritic cells (DCs) in the lungs are critical for Th2 responses in asthma, and CCL20 secreted from bronchial epithelial cells (BECs) is known to influence the recruitment of DCs. Because asthma is a disease that is closely associated with oxidative stress, we hypothesized that clusterin, an oxidative stress regulatory molecule, may have a role in the development of allergic airway inflammation. The aim of this study was to examine whether clusterin regulates CCL20 production from the BECs and the subsequent DC recruitment in the lungs. To verify the idea, clusterin knockout (Clu(-/-)), clusterin heterogeneous (Clu(+/-)), and wild-type mice were exposed intranasally to house dust mite (HDM) extract to induce allergic airway inflammation. We found that the total number of immune cells in bronchoalveolar lavage fluid and the lung was increased in Clu(-/-) and Clu(+/-) mice. Of these immune cells, inflammatory DCs (CD11b(+)CD11c(+)) and Ly6C(high) monocyte populations in the lung were significantly increased, which was accompanied by increased levels of various chemokines, including CCL20 in bronchoalveolar lavage fluid, and increased oxidative stress markers in the lung. Moreover, HDM-stimulated human BECs with either up- or downregulated clusterin expression showed that CCL20 secretion was negatively associated with clusterin expression. Interestingly, clusterin also reduced the level of intracellular reactive oxygen species, which is related to induction of CCL20 expression after HDM stimulation. Thus, the antioxidant property of clusterin is suggested to regulate the expression of CCL20 in BECs and the subsequent recruitment of inflammatory DCs in the airway. PMID:26826245

  17. Recruitment of Factor H to the Streptococcus suis Cell Surface is Multifactorial.

    Science.gov (United States)

    Roy, David; Grenier, Daniel; Segura, Mariela; Mathieu-Denoncourt, Annabelle; Gottschalk, Marcelo

    2016-07-07

    Streptococcus suis is an important bacterial swine pathogen and a zoonotic agent. Recently, two surface proteins of S. suis, Fhb and Fhbp, have been described for their capacity to bind factor H-a soluble complement regulatory protein that protects host cells from complement-mediated damages. Results obtained in this study showed an important role of host factor H in the adhesion of S. suis to epithelial and endothelial cells. Both Fhb and Fhbp play, to a certain extent, a role in such increased factor H-dependent adhesion. The capsular polysaccharide (CPS) of S. suis, independently of the presence of its sialic acid moiety, was also shown to be involved in the recruitment of factor H. However, a triple mutant lacking Fhb, Fhbp and CPS was still able to recruit factor H resulting in the degradation of C3b in the presence of factor I. In the presence of complement factors, the double mutant lacking Fhb and Fhbp was similarly phagocytosed by human macrophages and killed by pig blood when compared to the wild-type strain. In conclusion, this study suggests that recruitment of factor H to the S. suis cell surface is multifactorial and redundant.

  18. Recruitment of bone marrow derived cells during anti-angiogenic therapy in GBM : Bone marrow derived cell in GBM

    NARCIS (Netherlands)

    Boer, Jennifer C.; Walenkamp, Annemiek M. E.; den Dunnen, Wilfred F. A.

    2014-01-01

    Glioblastoma (GBM) is a highly vascular tumor characterized by rapid and invasive tumor growth, followed by oxygen depletion, hypoxia and neovascularization, which generate a network of disorganized, tortuous and permeable vessels. Recruitment of bone marrow derived cells (BMDC) is crucial for vascu

  19. Activated human valvular interstitial cells sustain interleukin-17 production to recruit neutrophils in infective endocarditis.

    Science.gov (United States)

    Yeh, Chiou-Yueh; Shun, Chia-Tung; Kuo, Yu-Min; Jung, Chiau-Jing; Hsieh, Song-Chou; Chiu, Yen-Ling; Chen, Jeng-Wei; Hsu, Ron-Bin; Yang, Chia-Ju; Chia, Jean-San

    2015-06-01

    The mechanisms that underlie valvular inflammation in streptococcus-induced infective endocarditis (IE) remain unclear. We previously demonstrated that streptococcal glucosyltransferases (GTFs) can activate human heart valvular interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that activated VIC can enhance neutrophil infiltration through sustained IL-17 production, leading to valvular damage. To monitor cytokine and chemokine production, leukocyte recruitment, and the induction or expansion of CD4(+) CD45RA(-) CD25(-) CCR6(+) Th17 cells, primary human VIC were cultured in vitro and activated by GTFs. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by immunohistochemistry in infected valves from patients with IE. The expression of IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (Rorc) was upregulated in GTF-activated VIC, which may enhance the proliferation of memory Th17 cells in an IL-6-dependent manner. Many chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC, which might recruit neutrophils and CD4(+) T cells. Moreover, CXCL1 production in VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were increased in patients with IE compared to healthy donors. Furthermore, elevated serum IL-21 levels have been significantly associated with severe valvular damage, including rupture of chordae tendineae, in IE patients. Our findings suggest that VIC are activated by bacterial modulins to recruit neutrophils and that such activities might be further enhanced by the production of Th17-associated cytokines. Together, these factors can amplify

  20. Characterization of a distinct population of circulating human non-adherent endothelial forming cells and their recruitment via intercellular adhesion molecule-3.

    Directory of Open Access Journals (Sweden)

    Sarah L Appleby

    Full Text Available Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+ population of non-adherent endothelial forming cells (naEFCs which expressed the hematopoietic progenitor cell markers (CD133, CD34, CD117, CD90 and CD38 together with mature endothelial cell markers (VEGFR2, CD144 and CD31. These cells also expressed low levels of CD45 but did not express the lymphoid markers (CD3, CD4, CD8 or myeloid markers (CD11b and CD14 which distinguishes them from 'early' endothelial progenitor cells (EPCs. Functional studies demonstrated that these naEFCs (i bound Ulex europaeus lectin, (ii demonstrated acetylated-low density lipoprotein uptake, (iii increased vascular cell adhesion molecule (VCAM-1 surface expression in response to tumor necrosis factor and (iv in co-culture with mature endothelial cells increased the number of tubes, tubule branching and loops in a 3-dimensional in vitro matrix. More importantly, naEFCs placed in vivo generated new lumen containing vasculature lined by CD144 expressing human endothelial cells (ECs. Extensive genomic and proteomic analyses of the naEFCs showed that intercellular adhesion molecule (ICAM-3 is expressed on their cell surface but not on mature endothelial cells. Furthermore, functional analysis demonstrated that ICAM-3 mediated the rolling and adhesive events of the naEFCs under shear stress. We suggest that the distinct population of naEFCs identified and characterized here represents a new valuable therapeutic target to control aberrant vasculogenesis.

  1. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

    International Nuclear Information System (INIS)

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

  2. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Brady, Robert T. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); O' Brien, Fergal J. [Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland); Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland); Hoey, David A., E-mail: david.hoey@ul.ie [Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland); Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick (Ireland); The Centre for Applied Biomedical Engineering Research, University of Limerick (Ireland); Materials & Surface Science Institute, University of Limerick (Ireland)

    2015-03-27

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting

  3. Comparative effect of genistein and daidzein on the expression of MCP-1, eNOS, and cell adhesion molecules in TNF-α-stimulated HUVECs

    OpenAIRE

    Cho, Hye Yeon; Park, Chung Mu; Kim, Mi Jeong; Chinzorig, Radnaabazar; Cho, Chung Won; Song, Young Sun

    2011-01-01

    We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-α-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-α exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a do...

  4. Regulation of angiogenesis, mural cell recruitment and adventitial macrophage behavior by Toll-like receptors.

    Science.gov (United States)

    Aplin, Alfred C; Ligresti, Giovanni; Fogel, Eric; Zorzi, Penelope; Smith, Kelly; Nicosia, Roberto F

    2014-01-01

    The angiogenic response to injury can be studied by culturing rat or mouse aortic explants in collagen gels. Gene expression studies show that aortic angiogenesis is preceded by an immune reaction with overexpression of Toll-like receptors (TLRs) and TLR-inducible genes. TLR1, 3, and 6 are transiently upregulated at 24 h whereas TLR2, 4, and 8 expression peaks at 24 h but remains elevated during angiogenesis and vascular regression. Expression of TLR5, 7 and 9 steadily increases over time and is highest during vascular regression. Studies with isolated cells show that TLRs are expressed at higher levels in aortic macrophages compared to endothelial or mural cells with the exception of TLR2 and TLR9 which are more abundant in the aortic endothelium. LPS and other TLR ligands dose dependently stimulate angiogenesis and vascular endothelial growth factor production. TLR9 ligands also influence the behavior of nonendothelial cell types by blocking mural cell recruitment and inducing formation of multinucleated giant cells by macrophages. TLR9-induced mural cell depletion is associated with reduced expression of the mural cell recruiting factor PDGFB. The spontaneous angiogenic response of the aortic rings to injury is reduced in cultures from mice deficient in myeloid differentiation primary response 88 (MyD88), a key adapter molecule of TLRs, and following treatment with an inhibitor of the NFκB pathway. These results suggest that the TLR system participates in the angiogenic response of the vessel wall to injury and may play an important role in the regulation of inflammatory angiogenesis in reactive and pathologic processes.

  5. Cdk4 regulates recruitment of quiescent beta-cells and ductal epithelial progenitors to reconstitute beta-cell mass.

    Directory of Open Access Journals (Sweden)

    Ji-Hyeon Lee

    Full Text Available Insulin-producing pancreatic islet beta cells (beta-cells are destroyed, severely depleted or functionally impaired in diabetes. Therefore, replacing functional beta-cell mass would advance clinical diabetes management. We have previously demonstrated the importance of Cdk4 in regulating beta-cell mass. Cdk4-deficient mice display beta-cell hypoplasia and develop diabetes, whereas beta-cell hyperplasia is observed in mice expressing an active Cdk4R24C kinase. While beta-cell replication appears to be the primary mechanism responsible for beta-cell mass increase, considerable evidence also supports a contribution from the pancreatic ductal epithelium in generation of new beta-cells. Further, while it is believed that majority of beta-cells are in a state of 'dormancy', it is unclear if and to what extent the quiescent cells can be coaxed to participate in the beta-cell regenerative response. Here, we address these queries using a model of partial pancreatectomy (PX in Cdk4 mutant mice. To investigate the kinetics of the regeneration process precisely, we performed DNA analog-based lineage-tracing studies followed by mathematical modeling. Within a week after PX, we observed considerable proliferation of islet beta-cells and ductal epithelial cells. Interestingly, the mathematical model showed that recruitment of quiescent cells into the active cell cycle promotes beta-cell mass reconstitution in the Cdk4R24C pancreas. Moreover, within 24-48 hours post-PX, ductal epithelial cells expressing the transcription factor Pdx-1 dramatically increased. We also detected insulin-positive cells in the ductal epithelium along with a significant increase of islet-like cell clusters in the Cdk4R24C pancreas. We conclude that Cdk4 not only promotes beta-cell replication, but also facilitates the activation of beta-cell progenitors in the ductal epithelium. In addition, we show that Cdk4 controls beta-cell mass by recruiting quiescent cells to enter the cell

  6. Expression of ICAM-1 and VCAM-1 in human chronic renal allograft rejection%细胞间粘附分子-1和血管细胞粘附分子-1在慢性排斥反应中的表达

    Institute of Scientific and Technical Information of China (English)

    潘晓鸣; 陈勇; 邢俊平

    1998-01-01

    To study the mechanism of human chronic renal allograft rejection, kidney tissues were taken from 16 patients with chronic renal allograft rejection and from 5 healthy subjects, and underwent the frazed section staining for ICAM-1 and VCAM-1 to anti-ICAM-1 and anti-VCAM-1 respectively by using immunohistochemistry(ABC).The results showed that there were differ-ent distribution of ICAM-1 and VCAM-1 expression in nomal kidney and renal allograft during chronic rejection.It was suggested that ICAM-1 and VCAM-1 might play an important role in the pathogenesis of human chronic renal allograft rejection.%为了探讨移植肾慢性排斥反应的发病机制,应用免疫组化技术(ABC法)对16例肾移植术后发生慢性排斥反应患者的移植肾组织及5例正常肾组织行细胞间粘附分子-1(ICAM-1)、血管细胞粘附分子-1(VCAM-1)染色及HE染色.结果表明ICAM-1、VCAM-1在正常肾脏和慢性排斥反应移植肾脏上的表达分布不同;结果提示,它们在移植肾慢性排斥反应的发生、发展过程中起重要作用

  7. CD43 deficiency has no impact in competitive in vivo assays of neutrophil or activated T cell recruitment efficiency.

    Science.gov (United States)

    Carlow, Douglas A; Ziltener, Hermann J

    2006-11-01

    Using noncompetitive methodologies comparing CD43(+/+) and CD43(-/-) mice, it has been reported that CD43(-/-) leukocytes exhibit reduced recruitment efficiency to sites of inflammation. More recent analyses demonstrate that CD43 on activated T cells can function as an E-selectin ligand (E-SelL) in vitro, suggesting that CD43 might promote rolling interactions during recruitment of leukocytes and account for the reported recruitment deficits in CD43(-/-) T cells and neutrophils in vivo. Internally controlled competitive in vivo methods using fluorescent tracking dyes were applied to compare recruitment efficiency of CD43(+/+) vs CD43(-/-) activated T cells to inflamed skin and of peripheral blood neutrophils to inflamed peritoneum. A simple CFSE perfusion method was developed to distinguish arterial/venous vasculature and confirm appropriate extravasation through venules in a Con A-induced cutaneous inflammation model. In vivo recruitment of peripheral blood neutrophils to inflamed peritoneum was core 2 GlcNAcT-I dependent, but recruitment efficiency was not influenced by absence of CD43. There were also no significant differences in core 2 GlcNAcT-I-dependent, selectin-dependent, cutaneous recruitment of activated T cells from CD43(+/+) and congenic CD43(-/-) mice in either B6 or P-selectin(-/-) recipients despite biochemical confirmation that a CD43-specific E-SelL was present on activated T cells. We conclude that recruitment of neutrophils and activated T cells in these in vivo models is not influenced by CD43 expression and that if CD43 on activated T cells performs an E-SelL function in vivo, it contributes in a limited physiological context.

  8. Adipose-Derived Stem Cell-Seeded Hydrogels Increase Endogenous Progenitor Cell Recruitment and Neovascularization in Wounds.

    Science.gov (United States)

    Kosaraju, Revanth; Rennert, Robert C; Maan, Zeshaan N; Duscher, Dominik; Barrera, Janos; Whittam, Alexander J; Januszyk, Michael; Rajadas, Jayakumar; Rodrigues, Melanie; Gurtner, Geoffrey C

    2016-02-01

    Adipose-derived mesenchymal stem cells (ASCs) are appealing for cell-based wound therapies because of their accessibility and ease of harvest, but their utility is limited by poor cell survival within the harsh wound microenvironment. In prior work, our laboratory has demonstrated that seeding ASCs within a soft pullulan-collagen hydrogel enhances ASC survival and improves wound healing. To more fully understand the mechanism of this therapy, we examined whether ASC-seeded hydrogels were able to modulate the recruitment and/or functionality of endogenous progenitor cells. Employing a parabiosis model and fluorescence-activated cell sorting analysis, we demonstrate that application of ASC-seeded hydrogels to wounds, when compared with injected ASCs or a noncell control, increased the recruitment of provascular circulating bone marrow-derived mesenchymal progenitor cells (BM-MPCs). BM-MPCs comprised 23.0% of recruited circulating progenitor cells in wounds treated with ASC-seeded hydrogels versus 8.4% and 2.1% in those treated with controls, p functional modulation of BM-MPCs, we demonstrate a statistically significant increase in BM-MPC migration, proliferation, and tubulization when exposed to hydrogel-seeded ASC-conditioned medium versus control ASC-conditioned medium (73.8% vs. 51.4% scratch assay closure; 9.1% vs. 1.4% proliferation rate; 10.2 vs. 5.5 tubules/HPF; p assays). BM-MPC expression of genes related to cell stemness and angiogenesis was also significantly increased following exposure to hydrogel-seeded ASC-conditioned medium (p functionality to effect greater neovascularization. PMID:26871860

  9. Decidual cell regulation of natural killer cell-recruiting chemokines: implications for the pathogenesis and prediction of preeclampsia.

    Science.gov (United States)

    Lockwood, Charles J; Huang, S Joseph; Chen, Chie-Pein; Huang, Yingqun; Xu, Jie; Faramarzi, Saeed; Kayisli, Ozlem; Kayisli, Umit; Koopman, Louise; Smedts, Dineke; Buchwalder, Lynn F; Schatz, Frederick

    2013-09-01

    First trimester human decidua is composed of decidual cells, CD56(bright)CD16(-) decidual natural killer (dNK) cells, and macrophages. Decidual cells incubated with NK cell-derived IFN-γ and either macrophage-derived TNF-α or IL-1β synergistically enhanced mRNA and protein expression of IP-10 and I-TAC. Both chemokines recruit CXCR3-expressing NK cells. This synergy required IFN-γ receptor 1 and 2 mediation via JAK/STAT and NFκB signaling pathways. However, synergy was not observed on neutrophil, monocyte, and NK cell-recruiting chemokines. Immunostaining of first trimester decidua localized IP-10, I-TAC, IFN-γR1, and -R2 to vimentin-positive decidual cells versus cytokeratin-positive interstitial trophoblasts. Flow cytometry identified high CXCR3 levels on dNK cells and minority peripheral CD56(bright)CD16(-) pNK cells and intermediate CXCR3 levels on the majority of CD56(dim)CD16(+) pNK cells. Incubation of pNK cells with either IP-10 or I-TAC elicited concentration-dependent enhanced CXCR3 levels and migration of both pNK cell subsets that peaked at 10 ng/mL, whereas each chemokine at a concentration of 50 ng/mL inhibited CXCR3 expression and pNK cell migration. Deciduae from women with preeclampsia, a leading cause of maternal and fetal morbidity and mortality, displayed significantly lower dNK cell numbers and higher IP-10 and I-TAC levels versus gestational age-matched controls. Significantly elevated IP-10 levels in first trimester sera from women eventually developing preeclampsia compared with controls, identifying IP-10 as a novel, robust early predictor of preeclampsia. PMID:23973270

  10. CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kowarik Markus C

    2012-05-01

    Full Text Available Abstract Background The chemokines and cytokines CXCL13, CXCL12, CCL19, CCL21, BAFF and APRIL are believed to play a role in the recruitment of B cells to the central nervous system (CNS compartment during neuroinflammation. To determine which chemokines/cytokines show the strongest association with a humoral immune response in the cerebrospinal fluid (CSF, we measured their concentrations in the CSF and correlated them with immune cell subsets and antibody levels. Methods Cytokine/chemokine concentrations were measured in CSF and serum by ELISA in patients with non-inflammatory neurological diseases (NIND, n = 20, clinically isolated syndrome (CIS, n = 30, multiple sclerosis (MS, n = 20, Lyme neuroborreliosis (LNB, n = 8 and patients with other inflammatory neurological diseases (OIND, n = 30. Albumin, IgG, IgA and IgM were measured by nephelometry. CSF immune cell subsets were determined by seven-color flow cytometry. Results CXCL13 was significantly elevated in the CSF of all patient groups with inflammatory diseases. BAFF levels were significantly increased in patients with LNB and OIND. CXCL12 was significantly elevated in patients with LNB. B cells and plasmablasts were significantly elevated in the CSF of all patients with inflammatory diseases. CXCL13 showed the most consistent correlation with CSF B cells, plasmablasts and intrathecal Ig synthesis. Conclusions CXCL13 seems to be the major determinant for B cell recruitment to the CNS compartment in different neuroinflammatory diseases. Thus, elevated CSF CXCL13 levels rather reflect a strong humoral immune response in the CNS compartment than being specific for a particular disease entity.

  11. Expression and Function of the Homeostatic Molecule Del-1 in Endothelial Cells and the Periodontal Tissue

    Directory of Open Access Journals (Sweden)

    Jieun Shin

    2013-01-01

    Full Text Available Developmental endothelial locus-1 (Del-1 is an endothelial cell-secreted protein that limits the recruitment of neutrophils by antagonizing the interaction between the LFA-1 integrin on neutrophils and the intercellular adhesion molecule (ICAM-1 on endothelial cells. Mice with genetic or age-associated Del-1 deficiency exhibit increased neutrophil infiltration in the periodontium resulting in inflammatory bone loss. Here we investigated additional novel mechanisms whereby Del-1 could interfere with neutrophil recruitment and inflammation. Treatment of human endothelial cells with Del-1 did not affect the expression of endothelial molecules involved in the leukocyte adhesion cascade (ICAM-1, VCAM-1, and E-selectin. Moreover, genetic or age-associated Del-1 deficiency did not significantly alter the expression of these adhesion molecules in the murine periodontium, further ruling out altered adhesion molecule expression as a mechanism whereby Del-1 regulates leukocyte recruitment. Strikingly, Del-1 inhibited ICAM-1-dependent chemokine release (CXCL2, CCL3 by neutrophils. Therefore, Del-1 could potentially suppress the amplification of inflammatory cell recruitment mediated through chemokine release by infiltrating neutrophils. Interestingly, Del-1 was itself regulated by inflammatory stimuli, which generally exerted opposite effects on adhesion molecule expression. The reciprocal regulation between Del-1 and inflammation may contribute to optimally balance the protective and the potentially harmful effects of inflammatory cell recruitment.

  12. Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment.

    Science.gov (United States)

    Lorquet, Sophie; Berndt, Sarah; Blacher, Silvia; Gengoux, Emily; Peulen, Olivier; Maquoi, Erik; Noël, Agnès; Foidart, Jean-Michel; Munaut, Carine; Péqueux, Christel

    2010-10-01

    Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF agents. Here we report that these soluble receptors contribute to vessel maturation by mediating a dialogue between endothelial cells (ECs) and mural cells that leads to blood vessel stabilization. Through a multidisciplinary approach, we provide evidence that these soluble VEGF receptors promote mural cell migration through a paracrine mechanism involving interplay in ECs between VEGF/VEGFR-2 and sphingosine-1-phosphate type-1 (S1P)/S1P1 pathways that leads to endothelial nitric oxyde synthase (eNOS) activation. This new paradigm is supported by the finding that sVEGFR-1 and -2 perform the following actions: 1) induce an eNOS-dependent outgrowth of a mural cell network in an ex vivo model of angiogenesis, 2) increase the mural cell coverage of neovessels in vitro and in vivo, 3) promote mural cell migration toward ECs, and 4) stimulate endothelial S1P1 overproduction and eNOS activation that promote the migration and the recruitment of neighboring mural cells. These findings provide new insights into mechanisms regulating physiological and pathological angiogenesis and vessel stabilization.

  13. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation.

    Science.gov (United States)

    Brady, Robert T; O'Brien, Fergal J; Hoey, David A

    2015-03-27

    Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24 hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. PMID:25721667

  14. The Molecular Interaction of CAR and JAML Recruits the Central Cell Signal Transducer PI3K

    Energy Technology Data Exchange (ETDEWEB)

    Verdino, Petra; Witherden, Deborah A.; Havran, Wendy L.; Wilson, Ian A. (Scripps)

    2010-11-15

    Coxsackie and adenovirus receptor (CAR) is the primary cellular receptor for group B coxsackieviruses and most adenovirus serotypes and plays a crucial role in adenoviral gene therapy. Recent discovery of the interaction between junctional adhesion molecule-like protein (JAML) and CAR uncovered important functional roles in immunity, inflammation, and tissue homeostasis. Crystal structures of JAML ectodomain (2.2 angstroms) and its complex with CAR (2.8 angstroms) reveal an unusual immunoglobulin-domain assembly for JAML and a charged interface that confers high specificity. Biochemical and mutagenesis studies illustrate how CAR-mediated clustering of JAML recruits phosphoinositide 3-kinase (P13K) to a JAML intracellular sequence motif as delineated for the {alpha}{beta} T cell costimulatory receptor CD28. Thus, CAR and JAML are cell signaling receptors of the immune system with implications for asthma, cancer, and chronic nonhealing wounds.

  15. Virus-activated T cells regulate expression of adhesion molecules on endothelial cells in sites of infection

    DEFF Research Database (Denmark)

    Marker, O; Scheynius, A; Christensen, Jan Pravsgaard;

    1995-01-01

    inflammatory cells were strongly positive for LFA-1, VLA-4, Pgp-1 and ICAM-1. Expression of ICAM-1 and VCAM-1 was upregulated on the endothelial cells in immunocompetent mice, but not in T-cell deficient nude mice. Analysis of mice deficient in either CD4+ or CD8+ T cells, revealed that not only...... was the inflammatory reaction dependent on the presence of CD8+ cells, but these cells also appeared to be required for maximal upregulation of ICAM-1 and VCAM-1 on the endothelial cells. These results indicate that virus-specific CD8+ T cells are crucially involved in regulating the inflammatory reaction through...

  16. Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice

    OpenAIRE

    Ahn, Jeong-Bin; Kang, Shin Ae; Kim, Dong-Hee; Yu, Hak Sun

    2016-01-01

    As most infections by the helminth parasite elicit the recruitment of CD4+CD25+Foxp3+ T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitore...

  17. Luman recruiting factor is involved in stromal cell proliferation during decidualization in mice.

    Science.gov (United States)

    Li, Xiao; Lin, Pengfei; Chen, Fenglei; Wang, Nan; Zhao, Fan; Wang, Aihua; Jin, Yaping

    2016-08-01

    Decidualization is crucial for successful pregnancy in mice and humans. Although many essential molecular modulators have been identified during decidualization, the precise molecular mechanism of uterine decidualization remains largely unknown. Our previous research indicates that luman recruiting factor (LRF) is strongly expressed in decidual uteri of mice on days 6-8 of pregnancy. In this study, our aim is to determine the biological functions of LRF during decidualization in mice. We used the shLRF lentivirus to attenuate the expression of LRF, which significantly reduced the weight and size of implantation sites on days 7-8 of pregnancy. In a stromal cell culture model, LRF mRNA and protein levels increased significantly during stromal cell decidualization induced by estrogen and progesterone. LRF silencing resulted in the decidual markers decidual prolactin-related protein, insulin-like growth factor-binding protein 1 and progesterone receptor being dramatically reduced, and the decidual process was significantly inhibited. Cell-cycle analysis and cell apoptosis analysis revealed that, although no obvious apoptosis occurred in shLRF-lentivirus-infected stromal cells during decidualization, proliferation was inhibited via S-phase cell-cycle arrest, and the mitotic activity of uterine stromal cells was inhibited. An examination of cell-cycle regulatory factors indicated that the mRNA expression levels of cyclin A and cyclin B1 were significantly down-regulated after treatment with shLRF lentivirus. Thus, LRF seems to be involved in the regulation of decidualization during pregnancy by modulating the expression of the key cell-cycle regulatory factors cyclin A and cyclin B1. PMID:27053244

  18. CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver

    OpenAIRE

    Oo, Ye Htun; Banz, Vanessa; Kavanagh, Dean; Liaskou, Evaggelia; Withers, David R; Humphreys, Elizabeth; Reynolds, Gary M; Lee-Turner, Laura; Kalia, Neena; Hubscher, Stefan G.; Klenerman, Paul; Eksteen, Bertus; Adams, David H

    2012-01-01

    Background & Aims IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells have been implicated in immune-mediated liver diseases, but the molecular basis for their recruitment and positioning within the liver is unknown. Methods The phenotype and migratory behaviour of human liver-derived Th17 and Tc17 cells were investigated by flow cytometry and chemotaxis and flow-based adhesion assays. The recruitment of murine Th17 cells to the liver was studied in vivo using intra-vital microscopy. Results IL...

  19. FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells

    Science.gov (United States)

    Fournier, Michèle; Bourriquen, Gaëlle; Lamaze, Fabien C.; Côté, Maxime C.; Fournier, Éric; Joly-Beauparlant, Charles; Caron, Vicky; Gobeil, Stéphane; Droit, Arnaud; Bilodeau, Steve

    2016-01-01

    Controlling the transcriptional program is essential to maintain the identity and the biological functions of a cell. The Mediator and Cohesin complexes have been established as central cofactors controlling the transcriptional program in normal cells. However, the distribution, recruitment and importance of these complexes in cancer cells have not been fully investigated. Here we show that FOXA and master transcription factors are part of the core transcriptional regulatory circuitry of cancer cells and are essential to recruit M ediator and Cohesin. Indeed, Mediator and Cohesin occupied the enhancer and promoter regions of actively transcribed genes and maintained the proliferation and colony forming potential. Through integration of publically available ChIP-Seq datasets, we predicted the core transcriptional regulatory circuitry of each cancer cell. Unexpectedly, for all cells investigated, the pioneer transcription factors FOXA1 and/or FOXA2 were identified in addition to cell-specific master transcription factors. Loss of both types of transcription factors phenocopied the loss of Mediator and Cohesin. Lastly, the master and pioneer transcription factors were essential to recruit Mediator and Cohesin to regulatory regions of actively transcribed genes. Our study proposes that maintenance of the cancer cell state is dependent on recruitment of Mediator and Cohesin through FOXA and master transcription factors. PMID:27739523

  20. GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1.

    Science.gov (United States)

    Thambyrajah, Roshana; Mazan, Milena; Patel, Rahima; Moignard, Victoria; Stefanska, Monika; Marinopoulou, Elli; Li, Yaoyong; Lancrin, Christophe; Clapes, Thomas; Möröy, Tarik; Robin, Catherine; Miller, Crispin; Cowley, Shaun; Göttgens, Berthold; Kouskoff, Valerie; Lacaud, Georges

    2016-01-01

    In vertebrates, the first haematopoietic stem cells (HSCs) with multi-lineage and long-term repopulating potential arise in the AGM (aorta-gonad-mesonephros) region. These HSCs are generated from a rare and transient subset of endothelial cells, called haemogenic endothelium (HE), through an endothelial-to-haematopoietic transition (EHT). Here, we establish the absolute requirement of the transcriptional repressors GFI1 and GFI1B (growth factor independence 1 and 1B) in this unique trans-differentiation process. We first demonstrate that Gfi1 expression specifically defines the rare population of HE that generates emerging HSCs. We further establish that in the absence of GFI1 proteins, HSCs and haematopoietic progenitor cells are not produced in the AGM, revealing the critical requirement for GFI1 proteins in intra-embryonic EHT. Finally, we demonstrate that GFI1 proteins recruit the chromatin-modifying protein LSD1, a member of the CoREST repressive complex, to epigenetically silence the endothelial program in HE and allow the emergence of blood cells. PMID:26619147

  1. Chemokine Transfer by Liver Sinusoidal Endothelial Cells Contributes to the Recruitment of CD4+ T Cells into the Murine Liver.

    Directory of Open Access Journals (Sweden)

    Katrin Neumann

    Full Text Available Leukocyte adhesion and transmigration are central features governing immune surveillance and inflammatory reactions in body tissues. Within the liver sinusoids, chemokines initiate the first crucial step of T-cell migration into the hepatic tissue. We studied molecular mechanisms involved in endothelial chemokine supply during hepatic immune surveillance and liver inflammation and their impact on the recruitment of CD4(+ T cells into the liver. In the murine model of Concanavalin A-induced T cell-mediated hepatitis, we showed that hepatic expression of the inflammatory CXC chemokine ligands (CXCL9 and CXCL10 strongly increased whereas homeostatic CXCL12 significantly decreased. Consistently, CD4(+ T cells expressing the CXC chemokine receptor (CXCR3 accumulated within the inflamed liver tissue. In histology, CXCL9 was associated with liver sinusoidal endothelial cells (LSEC which represent the first contact site for T-cell immigration into the liver. LSEC actively transferred basolaterally internalized CXCL12, CXCL9 and CXCL10 via clathrin-coated vesicles to CD4(+ T cells leading to enhanced transmigration of CXCR4(+ total CD4(+ T cells and CXCR3(+ effector/memory CD4(+ T cells, respectively in vitro. LSEC-expressed CXCR4 mediated CXCL12 transport and blockage of endothelial CXCR4 inhibited CXCL12-dependent CD4(+ T-cell transmigration. In contrast, CXCR3 was not involved in the endothelial transport of its ligands CXCL9 and CXCL10. The clathrin-specific inhibitor chlorpromazine blocked endothelial chemokine internalization and CD4(+ T-cell transmigration in vitro as well as migration of CD4(+ T cells into the inflamed liver in vivo. Moreover, hepatic accumulation of CXCR3(+ CD4(+ T cells during T cell-mediated hepatitis was strongly reduced after administration of chlorpromazine. These data demonstrate that LSEC actively provide perivascularly expressed homeostatic and inflammatory chemokines by CXCR4- and clathrin-dependent intracellular

  2. CCR4+T cell recruitment to the skin in mycosis fungoides: potential contributions by thymic stromal lymphopoietin and interleukin-16.

    Science.gov (United States)

    Tuzova, Marina; Richmond, Jillian; Wolpowitz, Deon; Curiel-Lewandrowski, Clara; Chaney, Keri; Kupper, Thomas; Cruikshank, William

    2015-02-01

    Mycosis fungoides (MF) is characterized by skin accumulation of CCR4+CCR7- effector memory T cells; however the mechanism for their recruitment is not clearly identified. Thymic Stromal Lymphopoietin (TSLP) is a keratinocyte-derived cytokine that triggers Th2 immunity and is associated with T cell recruitment to the skin in atopic dermatitis. Interleukin-16 (IL-16) is a chemoattractant and growth factor for CD4+T cells. We hypothesized that TSLP and IL-16 could contribute to recruitment of malignant T cells in MF. We found elevated TSLP and IL-16 in very early stage patients' plasma and skin biopsies, prior to elevation in CCL22. Both TSLP and IL-16 induced migratory responses of CCR4+TSLPR+CD4+CCR7-CD31+cells, characteristic of malignant T cells in the skin. Co-stimulation also resulted in significant proliferative responses. We conclude that TSLP and IL-16, expressed at early stages of disease, function to recruit malignant T cells to the skin and contribute to their enhanced proliferation.

  3. Influence of rapid atrial pacing on the expression of vascular cell adhesion molecule-1 in canines%心房快速起搏对犬血管细胞黏附分子-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    李佳; 葛海龙; 陈光远; 高倩萍; 孙俊峰; 李元十; 朱立群; 曹君娴; 富路

    2011-01-01

    目的 研究心房快速起搏犬模型血管细胞黏附分子-1(vascular cell adhesion molecule-1,VCAM-1)的表达.方法 选用成年健康杂种犬13条,随机分为两组:快速起搏组7条,假手术组6条.两组均开胸于右心耳缝植AOO型起搏器,快速起搏组以400 bpm起搏6周,假手术组不起搏.应用酶联免疫法测定血清VCAM-1水平,采用逆转录-多聚酶链反应(RT-PCR)测定左房组织的VCAM-1 mRNA表达水平,同时进行左房的病理分析.结果 快速起搏组犬起搏6周后的血清VCAM-1水平明显高于假手术组(t=11.63,P<0.01),左房的VCAM-1 mRNA表达水平明显高于假手术组,增高32.1%(t=2.49,P=0.03);病理结果示快速起搏组犬左房心肌细胞变性.结论 心房快速起搏可引起犬血清VCAM-1及左房VCAM-1 mRNA表达水平增高.VCAM-1可能参与心房损伤时的心肌重构过程.%Objective To invesligale the expression of vascular cell adhesion molecule - 1 (VCAM - 1) in canines who received lasling rapid alrial pacing. Methods 13 canines were randomly divided inlo Lwo groups; sham - operaled group ( n = 6 ) and alrial pacing group ( n = 7) . A pacemaker ( A00) was implanled Lo the right alrial appendage in each of the dogs. The dogs in alrial pacing group were paced at 400 bpm for 6 weeks while those in the sham - operaled group were not paced. Serum VCAM - 1 level was lesled by ELISA kit. VCAM - 1 gene expression in myocardium of left alrium were analyzed al the mRNA by reverse Iranscriplion polymerase chain reaction. The lefl alrium were also analyzed by palhology. Results Compared with the sham - operaled group, lasling alrial pacing rapidly increased the level of serum VCAM - 1 and the expression of VCAM - 1 al mRNA level in lefl alrium significanlly(P < 0. 05 ). Palhology showed that cell degeneralion existed in the lefl alrium in dogs of alrial pacing group. Conclusion Lasling alrial pacing rapidly can significantly increase the expression of serum VCAM - 1 and VCAM - 1 al m

  4. Colonic inflammation in mice is improved by cigarette smoke through iNKT cells recruitment.

    Directory of Open Access Journals (Sweden)

    Muriel Montbarbon

    Full Text Available Cigarette smoke (CS protects against intestinal inflammation during ulcerative colitis. Immunoregulatory mechanisms sustaining this effect remain unknown. The aim of this study was to assess the effects of CS on experimental colitis and to characterize the intestinal inflammatory response at the cellular and molecular levels. Using the InExpose® System, a smoking device accurately reproducing human smoking habit, we pre-exposed C57BL/6 mice for 2 weeks to CS, and then we induced colitis by administration of dextran sodium sulfate (DSS. This system allowed us to demonstrate that CS exposure improved colonic inflammation (significant decrease in clinical score, body weight loss and weight/length colonic ratio. This improvement was associated with a significant decrease in colonic proinflammatory Th1/Th17 cytokine expression, as compared to unexposed mice (TNF (p=0.0169, IFNγ (p<0.0001, and IL-17 (p=0.0008. Smoke exposure also induced an increased expression of IL-10 mRNA (p=0.0035 and a marked recruitment of iNKT (invariant Natural Killer T; CD45+ TCRβ+ CD1d tetramer+ cells in the colon of DSS-untreated mice. Demonstration of the role of iNKT cells in CS-dependent colitis improvement was performed using two different strains of NKT cells deficient mice. Indeed, in Jα18KO and CD1dKO animals, CS exposure failed to induce significant regulation of DSS-induced colitis both at the clinical and molecular levels. Thus, our study demonstrates that iNKT cells are pivotal actors in the CS-dependent protection of the colon. These results highlight the role of intestinal iNKT lymphocytes and their responsiveness to environmental stimuli. Targeting iNKT cells would represent a new therapeutic way for inflammatory bowel diseases.

  5. Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.

    Science.gov (United States)

    Caires, Hugo R; Esteves, Tiago; Quelhas, Pedro; Barbosa, Mário A; Navarro, Melba; Almeida, Catarina R

    2016-09-01

    Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment. PMID:27628173

  6. Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.

    Science.gov (United States)

    Caires, Hugo R; Esteves, Tiago; Quelhas, Pedro; Barbosa, Mário A; Navarro, Melba; Almeida, Catarina R

    2016-09-01

    Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment.

  7. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1.

    NARCIS (Netherlands)

    Nolte-'t Hoen, E.N.; Buschow, S.I.; Anderton, S.M.; Stoorvogel, W.; Wauben, M.H.M.

    2009-01-01

    Dendritic cells (DCs) are known to secrete exosomes that transfer membrane proteins, like major histocompatibility complex class II, to other DCs. Intercellular transfer of membrane proteins is also observed during cognate interactions between DCs and CD4(+) T cells. The acquired proteins are functi

  8. Recruitment of dendritic cells to the cerebrospinal fluid in bacterial neuroinfections.

    Science.gov (United States)

    Pashenkov, Mikhail; Teleshova, Natalia; Kouwenhoven, Mathilde; Smirnova, Tatiana; Jin, Ya Ping; Kostulas, Vasilios; Huang, Yu Min; Pinegin, Boris; Boiko, Alexey; Link, Hans

    2002-01-01

    Dendritic cells (DC) accumulate in the CNS during inflammation and may contribute to local immune responses. Two DC subsets present in human cerebrospinal fluid (CSF) are probably recruited from myeloid (CD11c(+)CD123(dim)) and plasmacytoid (CD11c(-)CD123(high)) blood DC. In bacterial meningitis and especially in Lyme meningoencephalitis, numbers of myeloid and plasmacytoid DC in CSF were increased, compared to non-inflammatory neurological diseases, and correlated with chemotactic activity of CSF for immature monocyte-derived DC (moDC). Multiple DC chemoattractants, including macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-1, MCP-3, RANTES and stromal cell-derived factor (SDF)-1alpha were elevated in CSF in these two neuroinfections. Chemotaxis of immature moDC induced by these CSFs could be partially inhibited by mAbs against CXCR4, the receptor for SDF-1alpha, and CD88, the receptor for C5a. SDF-1alpha present in CSF also chemoattracted mature moDC, which in vivo could correspond to a diminished migration of antigen-bearing DC from the CSF to secondary lymphoid organs. Regulation of DC trafficking to and from the CSF may represent a mechanism of controlling the CNS inflammation.

  9. Molecular mechanisms involved in secretory vesicle recruitment to the plasma membrane in beta-cells.

    Science.gov (United States)

    Varadi, Aniko; Ainscow, E K; Allan, V J; Rutter, G A

    2002-04-01

    Glucose stimulates the release of insulin in part by activating the recruitment of secretory vesicles to the cell surface. While this movement is known to be microtubule-dependent, the molecular motors involved are undefined. Active kinesin was found to be essential for vesicle translocation in live beta-cells, since microinjection of cDNA encoding dominant-negative KHC(mut) (motor domain of kinesin heavy chain containing a Thr(93)-->Asn point mutation) blocked vesicular movements. Moreover, expression of KHC(mut) strongly inhibited the sustained, but not acute, stimulation of secretion by glucose. Thus, vesicles released during the first phase of insulin secretion exist largely within a translocation-independent pool. Kinesin-driven anterograde movement of vesicles is then necessary for the sustained (second phase) of insulin release. Kinesin may, therefore, represent a novel target for increases in intracellular ATP concentrations in response to elevated extracellular glucose and may be involved in the ATP-sensitive K+channel-independent stimulation of secretion by the sugar.

  10. Increased expression of granulocyte colony-stimulating factor mediates mesenchymal stem cells recruitment after vascular injury

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yong; LIU Ying-xi; XIEShuang-lun; DENG Bing-qing; WANG Jing-feng; NIE Ru-qiong

    2011-01-01

    Background Recent studies indicate that bone marrow-derived cells may significantly contribute to atherosclerosis,post-angioplasty restenosis and transplantation-associated vasculopathy.The responsible bone marrow (BM) cells and mechanisms regulating the mobilization of these cells are currently unclear.The purpose of this study was to investigate the expression of granulocyte colony-stimulating factor (G-CSF) on injured arteries and its effects on mesenchymal stem cells (MSCs) differentiation into vascular smooth muscle cells (VSMCs) in the process of vascular remodeling.Methods Balloon-mediated vascular injury was established in female rats (n=1O0) which received radioprotective whole female BM cells by tail vein injection and male MSCs through a tibial BM injection after lethal irradiation.The injured and contralateral carotid arteries were harvested at 3,7,14 and 28 days after treatment.Results Morphometric analysis indicated that intima to media area-ratio (I/M ratio) significantly increased at 28 days,0.899±-0.057 (P <0.01),compared with uninjured arteries.Combining fluorescence in situ hybridization (FISH) and immunohistochemical analysis showed that a significant number of the neointimal cells derived from MSCs,(45.2±8.5)% at 28 days (P=0.01),compared with (23.5±6.3)% at 14 days.G-CSF was induced in carotid arteries subject to balloon angioplasty (fold mRNA change=8.67±0.63 at three days,relative G-CSF protein=0.657±-0.011 at three days,P <0.01,respectively,compared with uninjured arteries).G-CSF was chemotactic for MSCs but did not affect the differentiation of MSCs into smooth-muscle-like cells.Conclusion Increased expression of G-CSF by injured arteries plays an essential role in contribution to recruitment and homing of MSCs to the site of the arterial lesion.

  11. Recruitment of SHP-1 protein tyrosine phosphatase and signalling by a chimeric T-cell receptor-killer inhibitory receptor

    DEFF Research Database (Denmark)

    Christensen, M D; Geisler, C

    2000-01-01

    Receptors expressing the immunoreceptor tyrosine-based inhibitory motif (ITIM) in their cytoplasmic tail play an important role in the negative regulation of natural killer and B-cell activation. A subpopulation of T cells expresses the ITIM containing killer cell inhibitory receptor (KIR), which...... recognize MHC class I molecules. Following coligation of KIR with an activating receptor, the tyrosine in the ITIM is phosphorylated and the cytoplasmic protein tyrosine phosphatase SHP-1 is recruited to the ITIM via its SH2 domains. It is still not clear how SHP-1 affects T-cell receptor (TCR) signalling....... In this study, we constructed a chimeric TCR-KIR receptor. We demonstrated that SHP-1 is recruited to the chimeric TCR-KIR receptor following T-cell stimulation with either anti-TCR monoclonal antibody (MoAb) or superantigen. However, in spite of this we could not detect any effect of SHP-1 on TCR signalling...

  12. GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL)

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Rösner, Heike I; Pedersen, Christina B;

    2012-01-01

    metazoan transcriptional regulator, Germ cell-less (GCL), as an interaction partner of GAGE12I. GCL directly binds LEM-domain proteins (LAP2β, emerin, MAN1) at the nuclear envelope, and we found that GAGE proteins were recruited to the nuclear envelope inner membrane by GCL. Based on yeast two...

  13. Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63

    Science.gov (United States)

    Poeter, Michaela; Brandherm, Ines; Rossaint, Jan; Rosso, Gonzalo; Shahin, Victor; Skryabin, Boris V.; Zarbock, Alexander; Gerke, Volker; Rescher, Ursula

    2014-04-01

    To enable leukocyte adhesion to activated endothelium, the leukocyte receptor P-selectin is released from Weibel-Palade bodies (WPB) to the endothelial cell surface where it is stabilized by CD63. Here we report that loss of annexin A8 (anxA8) in human umbilical vein endothelial cells (HUVEC) strongly decreases cell surface presentation of CD63 and P-selectin, with a concomitant reduction in leukocyte rolling and adhesion. We confirm the compromised leukocyte adhesiveness in inflammatory-activated endothelial venules of anxA8-deficient mice. We find that WPB of anxA8-deficient HUVEC contain less CD63, and that this is caused by improper transport of CD63 from late multivesicular endosomes to WPB, with CD63 being retained in intraluminal vesicles. Consequently, reduced CD63 cell surface levels are seen following WPB exocytosis, resulting in enhanced P-selectin re-internalization. Our data support a model in which anxA8 affects leukocyte recruitment to activated endothelial cells by supplying WPB with sufficient amounts of the P-selectin regulator CD63.

  14. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

    Directory of Open Access Journals (Sweden)

    Abigail Morris

    Full Text Available Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/- mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

  15. The role of heparanase in pulmonary cell recruitment in response to an allergic but not non-allergic stimulus.

    Science.gov (United States)

    Morris, Abigail; Wang, Bo; Waern, Ida; Venkatasamy, Radhakrishnan; Page, Clive; Schmidt, Eric P; Wernersson, Sara; Li, Jin-Ping; Spina, Domenico

    2015-01-01

    Heparanase is an endo-β-glucuronidase that specifically cleaves heparan sulfate proteoglycans in the extracellular matrix. Expression of this enzyme is increased in several pathological conditions including inflammation. We have investigated the role of heparanase in pulmonary inflammation in the context of allergic and non-allergic pulmonary cell recruitment using heparanase knockout (Hpa-/-) mice as a model. Following local delivery of LPS or zymosan, no significant difference was found in the recruitment of neutrophils to the lung between Hpa-/- and wild type (WT) control. Similarly neutrophil recruitment was not inhibited in WT mice treated with a heparanase inhibitor. However, in allergic inflammatory models, Hpa-/- mice displayed a significantly reduced eosinophil (but not neutrophil) recruitment to the airways and this was also associated with a reduction in allergen-induced bronchial hyperresponsiveness, indicating that heparanase expression is associated with allergic reactions. This was further demonstrated by pharmacological treatment with a heparanase inhibitor in the WT allergic mice. Examination of lung specimens from patients with different severity of chronic obstructive pulmonary disease (COPD) found increased heparanase expression. Thus, it is established that heparanase contributes to allergen-induced eosinophil recruitment to the lung and could provide a novel therapeutic target for the development of anti-inflammatory drugs for the treatment of asthma and other allergic diseases.

  16. Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca

    Directory of Open Access Journals (Sweden)

    Stella R. Zamuner

    2002-01-01

    Full Text Available It has been shown that Bothrops jararaca venom (BjV induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1, LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1 on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-α, interleukin (IL-1 and IL-6 have been investigated. Anti-mouse LECAM-1, LFA-1, ICAM-1 and PECAM-1 monoclonal antibody injection resulted in a reduction of 42%, 80%, 66% and 67%, respectively, of neutrophil accumulation induced by BjV (250 μg/kg, intraperitoneal injection in male mice compared with isotype-matched control injected animals. The anti-mouse CD18 monoclonal antibody had no significant effect on venom-induced neutrophil accumulation. Concentrations of LTB4, TXA2, IL-6 and TNF-α were significant increased in the peritoneal exudates of animals injected with venom, whereas no increment in IL-1 was detected. This results suggest that ICAM-1, LECAM-1, LFA-1 and PECAM-1, but not CD18, adhesion molecules are involved in the recruitment of neutrophils into the inflammatory site induced by BjV. This is the first in vivo evidence that snake venom is able to up-regulate the expression of adhesion molecules by both leukocytes and endothelial cells. This venom effect may be indirect, probably through the release of the inflammatory mediators evidenced in the present study.

  17. Decidual Cell Regulation of Natural Killer Cell–Recruiting Chemokines: Implications for the Pathogenesis and Prediction of Preeclampsia

    OpenAIRE

    Lockwood, Charles J.; Huang, S. Joseph; Chen, Chie-Pein; Huang, Yingqun; Xu, Jie; Faramarzi, Saeed; Kayisli, Ozlem; Kayisli, Umit; Koopman, Louise; Smedts, Dineke; Buchwalder, Lynn F.; Schatz, Frederick

    2013-01-01

    First trimester human decidua is composed of decidual cells, CD56brightCD16− decidual natural killer (dNK) cells, and macrophages. Decidual cells incubated with NK cell–derived IFN-γ and either macrophage-derived TNF-α or IL-1β synergistically enhanced mRNA and protein expression of IP-10 and I-TAC. Both chemokines recruit CXCR3-expressing NK cells. This synergy required IFN-γ receptor 1 and 2 mediation via JAK/STAT and NFκB signaling pathways. However, synergy was not observed on neutrophil,...

  18. IL-15 expression on RA synovial fibroblasts promotes B cell survival.

    Directory of Open Access Journals (Sweden)

    Marta Benito-Miguel

    Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

  19. PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia.

    Science.gov (United States)

    Walker, Melissa M; Novak, Lea; Widener, Rebecca; Grubbs, James Aaron; King, Janice; Hale, Joanetha Y; Ochs, Martina M; Myers, Lisa E; Briles, David E; Deshane, Jessy

    2016-03-01

    We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia. PMID:26829988

  20. Tumour cell recruitment of the JB-1 and L 1210 ascites tumour determined directly by double labelling with [14C]- and [3H]-thymidine.

    Science.gov (United States)

    Maurer-Schultze, B; Kondziella, U; Böswald, M

    1988-07-01

    Tumour cell recruitment of the JB-1 and L 1210 ascites tumour has been demonstrated directly by a double-labelling method with [14C]- and [3H]-thymidine (TdR). After [14C]-labelling of all proliferating tumour cells by multiple injections of [14C]TdR, recruitment of resting cells was stimulated by removal of the majority of tumour cells, i.e. by maximum aspiration of ascitic fluid. The number of recruited resting cells in the remaining tumour that re-enter the cell cycle after stimulation was demonstrated directly by a single injection of [3H]TdR given at different times after stimulation. The increase in the percentage of purely [3H]-labelled cells, i.e. recruited cells, with increasing time after stimulation, shows that recruitment is not a synchronous but a continuous process, the maximum of which occurs earlier in the case of the L 1210 than the JB-1 tumour. This suggests that there seems to be a relationship between the time required for maximum recruitment and the corresponding cell cycle parameters of the unperturbed tumour. There is a transitory increase of the growth fraction to about 100% and a considerable shortening of the cycle time at the maximum of recruitment.

  1. Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.

    KAUST Repository

    Foley, Joseph W

    2013-10-20

    BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF\\'s direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF\\'s motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.

  2. Staphylococcus aureus recruits Cdc42GAP through recycling endosomes and the exocyst to invade human endothelial cells.

    Science.gov (United States)

    Rauch, Liane; Hennings, Kirsten; Trasak, Claudia; Röder, Anja; Schröder, Barbara; Koch-Nolte, Friedrich; Rivera-Molina, Felix; Toomre, Derek; Aepfelbacher, Martin

    2016-08-01

    Activation and invasion of the vascular endothelium by Staphylococcus aureus is a major cause of sepsis and endocarditis. For endothelial cell invasion, S. aureus triggers actin polymerization through Cdc42, N-WASp (also known as WASL) and the Arp2/3 complex to assemble a phagocytic cup-like structure. Here, we show that after stimulating actin polymerization staphylococci recruit Cdc42GAP (also known as ARHGAP1) which deactivates Cdc42 and terminates actin polymerization in the phagocytic cups. Cdc42GAP is delivered to the invading bacteria on recycling endocytic vesicles in concert with the exocyst complex. When Cdc42GAP recruitment by staphylococci was prevented by blocking recycling endocytic vesicles or the exocyst complex, or when Cdc42 was constitutively activated, phagocytic cup closure was impaired and endothelial cell invasion was inhibited. Thus, to complete invasion of the endothelium, staphylococci reorient recycling endocytic vesicles to recruit Cdc42GAP, which terminates Cdc42-induced actin polymerization in phagocytic cups. Analogous mechanisms might govern other Cdc42-dependent cell functions.

  3. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Science.gov (United States)

    Das, Anusuya; Barker, Daniel A; Wang, Tiffany; Lau, Cheryl M; Lin, Yong; Botchwey, Edward A

    2014-01-01

    In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  4. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Directory of Open Access Journals (Sweden)

    Anusuya Das

    Full Text Available In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid (PLAGA microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2 improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3 via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1 mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  5. CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression.

    Directory of Open Access Journals (Sweden)

    Aya Matsui

    Full Text Available BACKGROUND: Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1, recruits immature myeloid-derived cells and enhances early tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+Gr1(+ myeloid-derived cells at tumor sites in mice and promoted CD31(+ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+Gr1(highF4/80(- cells (≈ 90% with a neutrophil-like morphology in vitro. Although CXCL17 expression could not increase the number of CD11b(+Gr1(+ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.

  6. Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice.

    Science.gov (United States)

    Ahn, Jeong-Bin; Kang, Shin Ae; Kim, Dong-Hee; Yu, Hak Sun

    2016-04-01

    As most infections by the helminth parasite elicit the recruitment of CD4(+)CD25(+)Foxp3(+) T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated Treg cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of Treg cells in the muscle tissue. PMID:27180574

  7. Non-cysteine linked MUC1 cytoplasmic dimers are required for Src recruitment and ICAM-1 binding induced cell invasion

    Directory of Open Access Journals (Sweden)

    Gunasekara Nirosha

    2011-07-01

    Full Text Available Abstract Background The mucin MUC1, a type I transmembrane glycoprotein, is overexpressed in breast cancer and has been correlated with increased metastasis. We were the first to report binding between MUC1 and Intercellular adhesion molecule-1 (ICAM-1, which is expressed on stromal and endothelial cells throughout the migratory tract of a metastasizing breast cancer cell. Subsequently, we found that MUC1/ICAM-1 binding results in pro-migratory calcium oscillations, cytoskeletal reorganization, and simulated transendothelial migration. These events were found to involve Src kinase, a non-receptor tyrosine kinase also implicated in breast cancer initiation and progression. Here, we further investigated the mechanism of MUC1/ICAM-1 signalling, focusing on the role of MUC1 dimerization in Src recruitment and pro-metastatic signalling. Methods To assay MUC1 dimerization, we used a chemical crosslinker which allowed for the detection of dimers on SDS-PAGE. We then generated MUC1 constructs containing an engineered domain which allowed for manipulation of dimerization status through the addition of ligands to the engineered domain. Following manipulation of dimerization, we immunoprecipitated MUC1 to investigate recruitment of Src, or assayed for our previously observed ICAM-1 binding induced events. To investigate the nature of MUC1 dimers, we used both non-reducing SDS-PAGE and generated a mutant construct lacking cysteine residues. Results We first demonstrate that the previously observed MUC1/ICAM-1signalling events are dependent on the activity of Src kinase. We then report that MUC1 forms constitutive cytoplasmic domain dimers which are necessary for Src recruitment, ICAM-1 induced calcium oscillations and simulated transendothelial migration. The dimers are not covalently linked constitutively or following ICAM-1 binding. In contrast to previously published reports, we found that membrane proximal cysteine residues were not involved in

  8. Checkpoint Antibodies but not T Cell-Recruiting Diabodies Effectively Synergize with TIL-Inducing γ-Irradiation.

    Science.gov (United States)

    Hettich, Michael; Lahoti, Jayashree; Prasad, Shruthi; Niedermann, Gabriele

    2016-08-15

    T cell-recruiting bispecific antibodies (bsAb) show promise in hematologic malignancies and are also being evaluated in solid tumors. In this study, we investigated whether T cell-recruiting bsAbs synergize with hypofractionated tumor radiotherapy (hRT) and/or blockade of the programmed death-1 (PD-1) immune checkpoint, both of which can increase tumor-infiltrating lymphocyte (TIL) numbers. Unexpectedly, large melanomas treated with hRT plus bsAb (AC133×CD3) relapsed faster than those treated with hRT alone, accompanied by massive TIL apoptosis. This fast relapse was delayed by the further addition of anti-PD-1. Mechanistic investigations revealed restimulation-induced cell death mediated by BIM and FAS as an additional cause of bsAb-mediated TIL depletion. In contrast, the double combination of hRT and anti-PD-1 strongly increased TIL numbers, and even very large tumors were completely eradicated. Our study reveals the risk that CD3-engaging bsAbs can induce apoptotic TIL depletion followed by rapid tumor regrowth, reminiscent of tolerance induction by CD3 mAb-mediated T-cell depletion, warranting caution in their use for the treatment of solid tumors. Our findings also argue that combining radiotherapy and anti-PD-1 can be quite potent, including against very large tumors. Cancer Res; 76(16); 4673-83. ©2016 AACR. PMID:27302161

  9. Study of serum soluble vascular cell adhesion molecule-1 levels in type 2 diabetic patients with diabetic retinopathy

    International Nuclear Information System (INIS)

    To study the change and the correlation of serum soluble vascular cell adhesion molecule-1 (sV-CAM-1) levels with diabetic retinopathy in type 2 diabetic patients, serum sVCAM-1 levels were measured in duplicate by ELISA in 85 type 2 diabetic patients; fundus examination was performed by an ophthalmologist using ophthalmoscope or fundus fluorescein angiography, and the findings were graded as: no signs of diabetic retinopathy (NDR), background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). Serum sVCAM-1 levels were significantly higher in the PDR and BDR groups than those in the control and NDR groups respectively (P<0.01). NDR group showed significantly increased serum sVCAM-levels compared with control group (P<0.01). In contrast, serum sVCAM-1 levels were not related to the presence of blood glucose, serum insulin levels or known diabetic duration. Authors' results suggest that serum sVCAM-1 might be implicated in the development of the diabetic retinopathy, and could assess the severity of diabetic retinopathy. The measurement of serum sVCAM-1 levels in 2 type diabetic patients may be clinically useful for early diagnosis or treatment of diabetic retinopathy

  10. Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax malaria.

    Science.gov (United States)

    Ohnishi, K

    1999-02-01

    Elevated plasma or serum levels of thrombomodulin (TM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin have been reported in several diseases. However, plasma or serum levels of TM, ICAM-1, VCAM-1, and E-selectin have not been investigated in the acute phase of Plasmodium vivax malaria. Serum TM, ICAM-1, VCAM-1, E-selectin, and creatinine levels were determined in six Japanese patients in the acute phase of vivax malaria and in seven healthy Japanese controls. Parasitemias of the peripheral blood were Fujirebio units/ml, 709 +/- 397 ng/ml, 2,112 +/- 782 ng/ml, and 99 +/- 28 ng/ml, respectively, and all were significantly greater than those in the controls (TM; P < 0.005, ICAM-1; P < 0.025, VCAM-1; P < 0.005, E-selectin; P < 0.025). However, no significant difference was identified between patients and controls for serum creatinine values. The serum levels of TM and VCAM-1 were not related to parasitemia. The elevation of serum TM levels suggests that endothelial cell damage occurs in the acute phase of vivax malaria.

  11. 疏风通络方对哮喘大鼠嗜酸细胞跨膜迁移相关因子VCAM-1/PI3K/Rac-1/NOX2/NOX4/SHP-2表达影响的研究%Influence of Shufeng Tongluo prescription on expression of VCAM-1/PI3K/Rac-1/NOX2/NOX4/SHP-2 related factors in eosinophils transendothelia migration in lung of rats with asthma

    Institute of Scientific and Technical Information of China (English)

    刘贵颖; 张慧琪; 尹新中; 朱振刚; 刘旻; 乔亚珍; 窦迎婷; 刘文彬; 刘超武

    2013-01-01

    [目的]探讨疏风通络方对哮喘大鼠嗜酸细胞跨膜迁移的影响.[方法]选择SPF级雄性Wistar大鼠70只为研究对象,随机分为正常组、模型组、地塞米松组、DPI组、中药低、中、高剂量组,共7组,每组大鼠10只.第1天致敏:正常组给予生理盐水1 mL腹腔注射致敏,而其他6组给予1 mL造模液(含Ⅴ级卵清蛋白100 mg,氢氧化铝100 mg和灭活百日咳杆菌6×109个)腹腔注射致敏;第15天开始激发:将各组大鼠分别置于相同大小的雾化箱内,正常组给予生理盐水6 mL雾化激发,其他6组给予5%的Ⅴ级卵清蛋白溶液6 mL雾化激发,每次激发前2h正常组给予生理盐水1 mL灌胃,而其他6组给予相应的药物灌胃.各组每天激发1次,每次激发30 min,连续激发10d后处死大鼠,并采集相应标本,并进一步检测影响嗜酸细胞跨膜迁移的相关指标.[结果]模型组肺组织嗜酸细胞跨膜迁移相关调节因子血管内皮黏附分子-Ⅰ(VCAM-1)、磷脂酰肌醇3激酶(PI3K)、Rac-1、NADPH氧化酶2(NOX2)、NADPH氧化酶4(NOX4)、酪氨酸磷酸酶(SHP-2)出现高表达,高于正常组(P<0.001);各治疗组与模型组相比,地塞米松组抑制上述因子表达的效果最好(P<0.001),中药高剂量组的抑制效果略差于地塞米松组,但两者差异无统计学意义(P>0.05),氯化二联苯碘(DPI)组、中药低、中剂量组抑制效果一般.[结论]疏风通络方对哮喘大鼠嗜酸细胞跨膜迁移有一定的阻抑作用,这可能是其平喘作用机制之一.%[Objective] To explore the effect of Shufeng Tongluo decoction on eosinophils transendothelia migration in lung of rats with asthma. [Methods] Seventy Wistar rats (SPF) were randomly divided into seven groups: normal group, model group, dexamethasone group, DPI group, low-dose group of Chinese medicine, medium-dose group of Chinese medicine, and high-dose group of Chinese medicine with 10 rats in each group. The rats in normal group were

  12. Conjugated Linoleic Acid Induces Mast Cell Recruitment during Mouse Mammary Gland Stromal Remodeling12

    OpenAIRE

    Russell, Joshua S.; McGee, Sibel Oflazoglu; Ip, Margot M.; Kuhlmann, Dietrich; Masso-Welch, Patricia A.

    2007-01-01

    Conjugated linoleic acid (CLA) is a dietary chemopreventive agent that induces apoptosis in the mammary adipose vascular endothelium and decreases mammary brown adipose tissue (BAT) and white adipose tissue (WAT). To determine onset and extent of stromal remodeling, we fed CD2F1/Cr mice diets supplemented with 1 or 2 g/100 g mixed CLA isomers for 1–7 wk. BAT loss, collagen deposition, and leukocyte recruitment occurred in the mouse mammary fat pad, coincident with an increase in parenchymal-a...

  13. Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis patients: evidence for new recruitment and cell activation

    Directory of Open Access Journals (Sweden)

    José R Lapa e Silva

    1996-06-01

    Full Text Available Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demostrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12 or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9 or normal healthy volunteers (n = 3 served as control group. Compared to the control group, the tuberculosis group had significantly higher proportion of cells expressing markers of young monocytes (UCHM1 and RFD7, a marker for phagocytic cells, and increased expression of HLA-DR, a marker of cell activation. In addition, tuberculosis group had significantly higher proportion of cells expressing dendritic cell marker (RFD1 and epithelioid cell marker (RFD9. These data suggest that despite recruitment of monocytes probably from the peripheral blood and local cell activation, host defense of the resident lung cells is insufficient to control M. tuberculosis.

  14. How the stimulus defines the dynamics of vesicle pool recruitment, fusion mode, and vesicle recycling in neuroendocrine cells.

    Science.gov (United States)

    Cárdenas, Ana María; Marengo, Fernando D

    2016-06-01

    The pattern of stimulation defines important characteristics of the secretory process in neurons and neuroendocrine cells, including the pool of secretory vesicles being recruited, the type and amount of transmitters released, the mode of membrane retrieval, and the mechanisms associated with vesicle replenishment. This review analyzes the mechanisms that regulate these processes in chromaffin cells, as well as in other neuroendocrine and neuronal models. A common factor in these mechanisms is the spatial and temporal distribution of the Ca(2+) signal generated during cell stimulation. For instance, neurosecretory cells and neurons have pools of vesicles with different locations with respect to Ca(2+) channels, and those pools are therefore differentially recruited following different patterns of stimulation. In this regard, a brief stimulus will induce the exocytosis of a small pool of vesicles that is highly coupled to voltage-dependent Ca(2+) channels, whereas longer or more intense stimulation will provoke a global Ca(2+) increase, promoting exocytosis irrespective of vesicle location. The pattern of stimulation, and therefore the characteristics of the Ca(2+) signal generated by the stimulus also influence the mode of exocytosis and the type of endocytosis. Indeed, low-frequency stimulation favors kiss-and-run exocytosis and clathrin-independent fast endocytosis, whereas higher frequencies promote full fusion and clathrin-dependent endocytosis. This latter type of endocytosis is accelerated at high-frequency stimulation. Synaptotagmins, calcineurin, dynamin, complexin, and actin remodeling, appear to be involved in the mechanisms that determine the response of these processes to Ca(2+) . In chromaffin cells, a brief stimulus induces the exocytosis of a small pool of vesicles that is highly coupled to voltage-dependent Ca(2+) channels (A), whereas longer or high-frequency stimulation provokes a global Ca(2+) increase, promoting exocytosis irrespective of

  15. Aedes aegypti saliva alters leukocyte recruitment and cytokine signaling by antigen-presenting cells during West Nile virus infection.

    Directory of Open Access Journals (Sweden)

    Bradley S Schneider

    Full Text Available West Nile virus (WNV is transmitted during mosquito bloodfeeding. Consequently, the first vertebrate cells to contact WNV are cells in the skin, followed by those in the draining lymph node. Macrophages and dendritic cells are critical early responders in host defense against WNV infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. Antigen-presenting cell (APC signals have a profound effect on host antiviral responses and disease severity. During transmission, WNV is intimately associated with mosquito saliva. Due to the ability of mosquito saliva to affect inflammation and immune responses, and the importance of understanding early events in WNV infection, we investigated whether mosquito saliva alters APC signaling during arbovirus infection, and if alterations in cell recruitment occur when WNV infection is initiated with mosquito saliva. Accordingly, experiments were performed with cultured dendritic cells and macrophages, flow cytometry was used to characterize infiltrating cell types in the skin and lymph nodes during early infection, and real-time RT-PCR was employed to evaluate virus and cytokine levels. Our in vitro results suggest that mosquito saliva significantly decreases the expression of interferon-beta and inducible nitric oxide synthase in macrophages (by as much as 50 and 70%, respectively, whilst transiently enhancing interleukin-10 (IL-10 expression. In vivo results indicate that the predominate effect of mosquito feeding is to significantly reduce the recruitment of T cells, leading the inoculation site of mice exposed to WNV alone to have up to 2.8 fold more t cells as mice infected in the presence of mosquito saliva. These shifts in cell population are associated with significantly elevated IL-10 and WNV (up to 4.0 and 10 fold, respectively in the skin and draining lymph nodes. These results suggest that mosquito

  16. Antigen-specific and non-specific CD4+ T cell recruitment and proliferation during influenza infection

    International Nuclear Information System (INIS)

    To track epitope-specific CD4+ T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA323-339 epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVAII, replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4+ T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4+ T cells were recruited to the infected lung both in the presence and absence of the OVA323-339 epitope. These data show that, when primed, CD4+ T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection

  17. The stromal cell-surface protease fibroblast activation protein-α localizes to lipid rafts and is recruited to invadopodia.

    Science.gov (United States)

    Knopf, Julia D; Tholen, Stefan; Koczorowska, Maria M; De Wever, Olivier; Biniossek, Martin L; Schilling, Oliver

    2015-10-01

    Fibroblast activation protein alpha (FAPα) is a cell surface protease expressed by cancer-associated fibroblasts in the microenvironment of most solid tumors. As there is increasing evidence for proteases having non-catalytic functions, we determined the FAPα interactome in cancer-associated fibroblasts using the quantitative immunoprecipitation combined with knockdown (QUICK) method. Complex formation with adenosin deaminase, erlin-2, stomatin, prohibitin, Thy-1 membrane glycoprotein, and caveolin-1 was further validated by immunoblotting. Co-immunoprecipitation (co-IP) of the known stoichiometric FAPα binding partner dipeptidyl-peptidase IV (DPPIV) corroborated the proteomic strategy. Reverse co-IPs validated the FAPα interaction with caveolin-1, erlin-2, and stomatin while co-IP upon RNA-interference mediated knock-down of DPPIV excluded adenosin deaminase as a direct FAPα interaction partner. Many newly identified FAPα interaction partners localize to lipid rafts, including caveolin-1, a widely-used marker for lipid raft localization. We hypothesized that this indicates a recruitment of FAPα to lipid raft structures. In density gradient centrifugation, FAPα co-fractionates with caveolin-1. Immunofluorescence optical sectioning microscopy of FAPα and lipid raft markers further corroborates recruitment of FAPα to lipid rafts and invadopodia. FAPα is therefore an integral component of stromal lipid rafts in solid tumors. In essence, we provide one of the first interactome analyses of a cell surface protease and translate these results into novel biological aspects of a marker protein for cancer-associated fibroblasts.

  18. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway.

    Science.gov (United States)

    Hsuan, Chin-Feng; Hsu, Hsia-Fen; Tseng, Wei-Kung; Lee, Thung-Lip; Wei, Yu-Feng; Hsu, Kwan-Lih; Wu, Chau-Chung; Houng, Jer-Yiing

    2015-01-01

    Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis. PMID:26393541

  19. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Chin-Feng Hsuan

    2015-09-01

    Full Text Available Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut, luteolin-7-glucoside (lut-7-g, and oleanolic acid (OA on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs. The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB, an indicator of the activation of nuclear factor-kB (NF-kB. In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

  20. Recruitment of quiet cells at the onset of vasomotion in mesenteric arteries

    DEFF Research Database (Denmark)

    Brings Jacobsen, Jens Christian; Aalkjær, Christian; Matchkov, Vladimir;

    2008-01-01

    Introduction: Smooth muscle cells in the wall of endothelium denuded mesenteric arteries display uncoordinated calcium waves when exposed to nor-adrenaline. However, the cell population shows a considerable heterogeneity with some cells displaying waves of variable frequency whilst others remain ...

  1. Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart.

    Science.gov (United States)

    Malliaras, Konstantinos; Zhang, Yiqiang; Seinfeld, Jeffrey; Galang, Giselle; Tseliou, Eleni; Cheng, Ke; Sun, Baiming; Aminzadeh, Mohammad; Marbán, Eduardo

    2013-02-01

    Cardiosphere-derived cells (CDCs) have been shown to regenerate infarcted myocardium in patients after myocardial infarction (MI). However, whether the cells of the newly formed myocardium originate from the proliferation of adult cardiomyocytes or from the differentiation of endogenous stem cells remains unknown. Using genetic fate mapping to mark resident myocytes in combination with long-term BrdU pulsing, we investigated the origins of postnatal cardiomyogenesis in the normal, infarcted and cell-treated adult mammalian heart. In the normal mouse heart, cardiomyocyte turnover occurs predominantly through proliferation of resident cardiomyocytes at a rate of ∼1.3-4%/year. After MI, new cardiomyocytes arise from both progenitors as well as pre-existing cardiomyocytes. Transplantation of CDCs upregulates host cardiomyocyte cycling and recruitment of endogenous progenitors, while boosting heart function and increasing viable myocardium. The observed phenomena cannot be explained by cardiomyocyte polyploidization, bi/multinucleation, cell fusion or DNA repair. Thus, CDCs induce myocardial regeneration by differentially upregulating two mechanisms of endogenous cell proliferation.

  2. Recruiting 9126 Primary Care Patients by Telephone: Characteristics of Participants Reached on Landlines, Basic Cell Phones, and Smartphones.

    Science.gov (United States)

    Serdarevic, Mirsada; Fazzino, Tera L; MacLean, Charles D; Rose, Gail L; Helzer, John E

    2016-06-01

    In primary care, collecting information about patient health behaviors between appointments can be advantageous. Physicians and researchers who embrace phone-based technology may find valuable ways to monitor patient-reported outcome measures of health (PROM). However, the level of phone technology sophistication should be tailored to the phone use of the population of interest. Despite the growing use of telephones as a means to gather PROM, little is known about phone use among primary care patients. As part of an ongoing study, the authors recruited primary care patients (N = 9126) for a health behavior screening study by calling them on the primary contact number listed in their medical record. The current study evaluated the frequency with which individuals were reached on landlines, basic cell phones, and smartphones, and examined participant characteristics. The majority of participants (63%) used landlines as their primary contact. Of the 37% using cell phones on the recruitment call, most (71%) were using smartphones. Landline users were significantly older than cell phone users (61.4 vs. 46.2 years; P = .001). Cell phone use did not differ significantly between participants with a college education and those without (37% vs. 38%; P = .82); however, smartphone use did differ (61% vs. 77%; P = .01). The majority of participants sampled used landlines as their primary telephone contact. Researchers designing phone-based PROM studies for primary care may have the broadest intervention reach using interactive voice response telephone technology, as patients could report health outcomes from any type of phone, including landlines. (Population Health Management 2016;19:212-215). PMID:26348723

  3. ERK1 and ERK2 are involved in recruitment and maturation of human mesenchymal stem cells induced to adipogenic differentiation

    Institute of Scientific and Technical Information of China (English)

    Elisabetta Donzelli; Caterina Lucchini; Elisa Ballarini; Arianna Scuteri; Fabrizio Carini; Giovanni Tredici; Mariarosaria Miloso

    2011-01-01

    Adipocytes' biology and the mechanisms that control adipogenesis have gained importance because of the need to develop therapeutic strategies to control obesity and the related pathologies. Human mesenchymal stem cells (hMSCs), undifferentiated stem cells present in the bone marrow that are physiological precursors of adipocytes, were induced to adipogenic differentiation. The molecular mechanisms on the basis of the adipogenesis were evaluated, focusing on the MAPKinases ERK1 and ERK2, which are involved in many biological and cellular processes. ERK1 and ERK2 phosphorylation was reduced with different timing and intensity for the two isoforms in treated hMSCs in comparison with control cells until day 10 and then at 14-28 days, it reached the level of untreated cultures. The total amount of ERK1 was also decreased up to day 10 and then was induced to the level of untreated cultures, whereas the expression of ERK2 was not changed following adipogenic induction. Treatment with the specific ERK1/2 inhibitor U0126 during the whole differentiation period hampered hMSCs' adipogenic differentiation, as lipid droplets appeared in very few cells and were reduced in number and size. When U0126 was administered only during the initial phase of differentiation, the number of hMSCs recruited to adipogenesis was reduced while, when it was administered later, hMSCs did not acquire a mature adipocytic phenotype. ERK1 and ERK2 are important for hMSC adipogenic differentiation since any alteration to the correct timing of their phosphorylation affects either the recruitment into the differentiation program and the extent of their maturation.

  4. Circulating CD133+CD34+ progenitor cells inversely correlate with soluble ICAM-1 in early ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Frank Joseph

    2011-08-01

    Full Text Available Abstract Background and Purpose Both endothelial progenitor cells (EPC and markers of neuroinflammation are candidate biomarkers for stroke severity and outcome prediction. A relationship between EPC and neuroinflammatory markers in early stroke is not fully elucidated. The objectives were to investigate correlations between EPC and neuroinflammation markers (adhesion molecules ICAM-1, VCAM-1, E-selectin, tumor necrosis factor (TNF-α, interleukin (IL-6, endothelin (ET-1, markers of tissue injury (matrix metalloproteinases (MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP-1 in early stroke patients. Methods We prospectively recruited symptomatic patients with ischemic cerebrovascular disease. We assessed stroke severity by using of acute (diffusion-weighted imaging (DWI and final lesion volumes (fluid attenuated inversion recovery (FLAIR. We measured serum soluble ICAM-1, VCAM-1, E-selectin, MMP-9, TIMP-1 and plasma TNF-α, IL-6, ET-1 by ELISA, and quantified EPC in mononuclear fraction of peripheral blood on days 1 and 3 in 17 patients (mean(SD age 62(14, with admission National Institutes of Health Stroke Scale (NIHSS 10(8 selected from 175 patients with imaging confirmed ischemic stroke. Non-parametric statistics, univariate and multivariate analysis were used. Results Only ICAM-1 inversely correlated with EPC subset CD133+CD34+ on day 1 (Spearman r = -0.6, p Conclusion Our study showed that high ICAM-1 is associated with low CD133+CD34+subset of EPC. Biomarkers of neuroinflammation may predict tissue injury and stroke severity in early ischemia.

  5. Carbon black nanoparticles and vascular dysfunction in cultured endothelial cells and artery segments

    DEFF Research Database (Denmark)

    Vesterdal, Lise K; Mikkelsen, Lone; Folkmann, Janne K;

    2012-01-01

    surface expression of intercellular cell adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1) in HUVECs at 100µg/ml. CB exposure was also associated with increased reactive oxygen species production and damage to the cell membranes in the form of increased lactate dehydrogenase leakage...

  6. HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that recruits T cells and fuels conjugate formation with Langerhans cells.

    Directory of Open Access Journals (Sweden)

    Zhicheng Zhou

    2011-06-01

    Full Text Available Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold and decreased CCL20/MIP-3-alpha (0.62-fold secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site.

  7. The Neurorepellent Slit2 Inhibits Postadhesion Stabilization of Monocytes Tethered to Vascular Endothelial Cells.

    Science.gov (United States)

    Mukovozov, Ilya; Huang, Yi-Wei; Zhang, Qiuwang; Liu, Guang Ying; Siu, Allan; Sokolskyy, Yaroslav; Patel, Sajedabanu; Hyduk, Sharon J; Kutryk, Michael J B; Cybulsky, Myron I; Robinson, Lisa A

    2015-10-01

    The secreted neurorepellent Slit2, acting through its transmembrane receptor, Roundabout (Robo)-1, inhibits chemotaxis of varied cell types, including leukocytes, endothelial cells, and vascular smooth muscle cells, toward diverse attractants. The role of Slit2 in regulating the steps involved in recruitment of monocytes in vascular inflammation is not well understood. In this study, we showed that Slit2 inhibited adhesion of monocytic cells to activated human endothelial cells, as well as to immobilized ICAM-1 and VCAM-1. Microfluidic live cell imaging showed that Slit2 inhibited the ability of monocytes tethered to endothelial cells to stabilize their actin-associated anchors and to resist detachment in response to increasing shear forces. Transfection of constitutively active plasmids revealed that Slit2 inhibited postadhesion stabilization of monocytes on endothelial cells by preventing activation of Rac1. We further found that Slit2 inhibited chemotaxis of monocytes toward CXCL12 and CCL2. To determine whether Slit2 and Robo-1 modulate pathologic monocyte recruitment associated with vascular inflammation and cardiovascular disease, we tested PBMC from patients with coronary artery disease. PBMC from these patients had reduced surface levels of Robo-1 compared with healthy age- and sex-matched subjects, and Slit2 failed to inhibit chemotaxis of PBMC of affected patients, but not healthy control subjects, toward CCL2. Furthermore, administration of Slit2 to atherosclerosis-prone LDL receptor-deficient mice inhibited monocyte recruitment to nascent atherosclerotic lesions. These results demonstrate that Slit2 inhibits chemotaxis of monocytes, as well as their ability to stabilize adhesions and resist detachment forces. Slit2 may represent a powerful new tool to inhibit pathologic monocyte recruitment in vascular inflammation and atherosclerosis.

  8. Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage.

    Science.gov (United States)

    Lu, Chenggang; Fuller, Margaret T

    2015-12-01

    Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages. PMID:26624996

  9. Anti-Mullerian hormone recruits BMPR-IA in immature granulosa cells.

    Directory of Open Access Journals (Sweden)

    Lauriane Sèdes

    Full Text Available Anti-Müllerian hormone (AMH is a member of the TGF-β superfamily secreted by the gonads of both sexes. This hormone is primarily known for its role in the regression of the Müllerian ducts in male fetuses. In females, AMH is expressed in granulosa cells of developing follicles. Like other members of the TGF-β superfamily, AMH transduces its signal through two transmembrane serine/threonine kinase receptors including a well characterized type II receptor, AMHR-II. The complete signalling pathway of AMH involving Smads proteins and the type I receptor is well known in the Müllerian duct and in Sertoli and Leydig cells but not in granulosa cells. In addition, few AMH target genes have been identified in these cells. Finally, while several co-receptors have been reported for members of the TGF-β superfamily, none have been described for AMH. Here, we have shown that none of the Bone Morphogenetic Proteins (BMPs co-receptors, Repulsive guidance molecules (RGMs, were essential for AMH signalling. We also demonstrated that the main Smad proteins used by AMH in granulosa cells were Smad 1 and Smad 5. Like for the other AMH target cells, the most important type I receptor for AMH in these cells was BMPR-IA. Finally, we have identified a new AMH target gene, Id3, which could be involved in the effects of AMH on the differentiation of granulosa cells and its other target cells.

  10. TWIST Represses Estrogen Receptor-alpha Expression by Recruiting the NuRD Protein Complex in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Junjiang Fu, Lianmei Zhang, Tao He, Xiuli Xiao, Xiaoyan Liu, Li Wang, Luquan Yang, Manman Yang, Tiandan Zhang, Rui Chen, Jianming Xu

    2012-01-01

    Full Text Available Loss of estrogen receptor α (ERα expression and gain of TWIST (TWIST1 expression in breast tumors correlate with increased disease recurrence and metastasis and poor disease-free survival. However, the molecular and functional regulatory relationship between TWIST and ERα are unclear. In this study, we found TWIST was associated with a chromatin region in intron 7 of the human ESR1 gene coding for ERα. This association of TWIST efficiently recruited the nucleosome remodeling and deacetylase (NuRD repressor complex to this region, which subsequently decreased histone H3K9 acetylation, increased histone H3K9 methylation and repressed ESR1 expression in breast cancer cells. In agreement with these molecular events, TWIST expression was inversely correlated with ERα expression in both breast cancer cell lines and human breast ductal carcinomas. Forced expression of TWIST in TWIST-negative and ERα-positive breast cancer cells such as T47D and MCF-7 cells reduced ERα expression, while knockdown of TWIST in TWIST-positive and ERα-negative breast cancer cells such as MDA-MB-435 and 4T1 cells increased ERα expression. Furthermore, inhibition of histone deacetylase (HDAC activity including the one in NuRD complex significantly increased ERα expression in MDA-MB-435 and 4T1 cells. HDAC inhibition together with TWIST knockdown did not further increase ERα expression in 4T1 and MDA-MB-435 cells. These results demonstrate that TWIST/NuRD represses ERα expression in breast cancer cells. Therefore, TWIST may serve as a potential molecular target for converting ERα-negative breast cancers to ERα-positive breast cancers, allowing these cancers to restore their sensitivity to endocrine therapy with selective ERα antagonists such as tamoxifen and raloxifene.

  11. Trichosanthin inhibits T cell activation by interfering with the recruitment of ZAP—70 to CD3 chain

    Institute of Scientific and Technical Information of China (English)

    HONGJIAN; SAILIFU; 等

    1998-01-01

    Plant protein Trichosanthin(Tk) has been shown in our previous experiments to suppress antigenic response of T cells.Here we explored its inhibitory mechanisms on the proliferation of human Jurkat leukemia T cell triggered by anti-CD3 McAb,By examination of tyrosine phosphorylation of cell lysate,we were able to show that Tk could interfere with the PTK-related activity in the TCR/CD3-initiated signal transduction in addition to blocking the phosphorylation of PKC.As shown in our experiment the expression intensity of ZAP-70,a kind of protein tyrosine kinase,was not changed but its phosphorylation could be inhibited.When physical link between CD3 ζ chain and ZAP-70 was further examined by using coimmunoprecipitation after pluse-treatment of the cell line with Tk,the anti-CD3 McAb-induced recruitment of ZAP-70 to CD3 ζ chain was observed to be blocked in some extent.This may account for,at least in part,how Trichosanthin was able to inhibit the TCR-triggered T cell proliferation.

  12. Aberrant mural cell recruitment to lymphatic vessels and impaired lymphatic drainage in a murine model of pulmonary fibrosis.

    Science.gov (United States)

    Meinecke, Anna-Katharina; Nagy, Nadine; Lago, Gabriela D'Amico; Kirmse, Santina; Klose, Ralph; Schrödter, Katrin; Zimmermann, Annika; Helfrich, Iris; Rundqvist, Helene; Theegarten, Dirk; Anhenn, Olaf; Orian-Rousseau, Véronique; Johnson, Randall S; Alitalo, Kari; Fischer, Jens W; Fandrey, Joachim; Stockmann, Christian

    2012-06-14

    Pulmonary fibrosis is a progressive disease with unknown etiology that is characterized by extensive remodeling of the lung parenchyma, ultimately resulting in respiratory failure. Lymphatic vessels have been implicated with the development of pulmonary fibrosis, but the role of the lymphatic vasculature in the pathogenesis of pulmonary fibrosis remains enigmatic. Here we show in a murine model of pulmonary fibrosis that lymphatic vessels exhibit ectopic mural coverage and that this occurs early during the disease. The abnormal lymphatic vascular patterning in fibrotic lungs was driven by expression of platelet-derived growth factor B (PDGF-B) in lymphatic endothelial cells and signaling through platelet-derived growth factor receptor (PDGFR)-β in associated mural cells. Because of impaired lymphatic drainage, aberrant mural cell coverage fostered the accumulation of fibrogenic molecules and the attraction of fibroblasts to the perilymphatic space. Pharmacologic inhibition of the PDGF-B/PDGFR-β signaling axis disrupted the association of mural cells and lymphatic vessels, improved lymphatic drainage of the lung, and prevented the attraction of fibroblasts to the perilymphatic space. Our results implicate aberrant mural cell recruitment to lymphatic vessels in the pathogenesis of pulmonary fibrosis and that the drainage capacity of pulmonary lymphatics is a critical mediator of fibroproliferative changes.

  13. Epidermal Notch1 recruits RORγ + group 3 innate lymphoid cells to orchestrate normal skin repair

    NARCIS (Netherlands)

    Z. Li (Zhi); T. Hodgkinson (Tom); E.J. Gothard (Elizabeth J.); S. Boroumand (Soulmaz); R. Lamb (Rebecca); I. Cummins (Ian); P. Narang (Priyanka); A. Sawtell (Amy); J. Coles (Jenny); G. Leonov (German); A. Reboldi (Andrea); C.D. Buckley; T. Cupedo (Tom); C. Siebel (Christian); A. Bayat (Ardeshir); M. Coles (Mark); C.A. Ambler (Carrie A.)

    2016-01-01

    textabstractNotch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epide

  14. ICAM-1 is necessary for epithelial recruitment of gammadelta T cells and efficient corneal wound healing.

    Science.gov (United States)

    Wound healing and inflammation are both significantly reduced in mice that lack gammadelta T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in gammadelta T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epi...

  15. GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1

    NARCIS (Netherlands)

    Thambyrajah, Roshana; Mazan, Milena; Patel, Rahima; Moignard, Victoria; Stefanska, Monika; Marinopoulou, Elli; Li, Yaoyong; Lancrin, Christophe; Clapes, Thomas; Möröy, Tarik; Robin, Catherine; Miller, Crispin; Cowley, Shaun; Göttgens, Berthold; Kouskoff, Valerie; Lacaud, Georges

    2016-01-01

    In vertebrates, the first haematopoietic stem cells (HSCs) with multi-lineage and long-term repopulating potential arise in the AGM (aorta-gonad-mesonephros) region. These HSCs are generated from a rare and transient subset of endothelial cells, called haemogenic endothelium (HE), through an endothe

  16. Soluble fms-like tyrosine kinase-1 and endothelial adhesion molecules (intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) as predictive markers for blood pressure reduction after renal sympathetic denervation.

    Science.gov (United States)

    Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Rixe, Johannes; Hamm, Christian; Nef, Holger

    2014-05-01

    Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (P<0.001) as were ICAM-1 (P<0.001) and VCAM-1 levels (P<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718-0.921; P<0.001), 0.754 (0.654-0.854; P<0.001), and 0.684 (0.564-804; P=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation. PMID:24470464

  17. NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

    Science.gov (United States)

    Huang, Enyu; Liu, Ronghua; Lu, Zhou; Liu, Jiajing; Liu, Xiaoming; Zhang, Dan; Chu, Yiwei

    2016-05-27

    Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer. PMID:27063801

  18. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    Directory of Open Access Journals (Sweden)

    Ohannessian Arthur

    2004-05-01

    Full Text Available Abstract Background Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK. Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK. Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC lines. Methods Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. Results In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. Conclusions We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway.

  19. Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells

    OpenAIRE

    Conomos, Dimitri; Stutz, Michael D.; Hills, Mark; Neumann, Axel A.; Bryan, Tracy M.; Reddel, Roger R; Hilda A Pickett

    2012-01-01

    Telomeres in cells that use the recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length. We therefore investigated whether ALT telomeres contain structural abnormalities that contribute to ALT activity. Here we used next generation sequencing to analyze the DNA content of ALT telomeres. We discovered that variant repeats were interspersed throughout the telomeres of ALT cells. We found that the C-type...

  20. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Rubina, Kseniya A., E-mail: rkseniya@mail.ru; Surkova, Ekaterina I.; Semina, Ekaterina V.; Sysoeva, Veronika Y.; Kalinina, Natalia I. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation); Poliakov, Alexei A. [Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom); Treshalina, Helena M. [Federal State Budgetary Scietific Institution «N.N. Blokhin Russian Cancer Research Center» (FSBSI “N.N.Blokhin RCRC”), Kashirskoe Shosse 24, Moscow 115478 (Russian Federation); Tkachuk, Vsevolod A. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation)

    2015-07-21

    T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate that T-cadherin overexpression leads to the increase in the expression of anti-angiogenic molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells.

  1. IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune suppression.

    Science.gov (United States)

    Eller, Kathrin; Wolf, Dominik; Huber, Julia M; Metz, Martin; Mayer, Gert; McKenzie, Andrew N J; Maurer, Marcus; Rosenkranz, Alexander R; Wolf, Anna M

    2011-01-01

    Both mast cells (MCs) and regulatory T cells (Tregs) have gained attention as immunosuppressive cell populations. To investigate a possible interaction, we used the Th1- and Th17-dependent model of nephrotoxic serum nephritis (NTS), in which both MCs and Tregs have been shown to play a protective role. Transfer of wild-type (wt) Tregs into wt recipients almost completely prevents development of NTS and leads to a profound increase of MCs in the renal draining lymph nodes (LNs). By contrast, transfer of wt Tregs into animals deficient in MCs, which are characterized by an exaggerated susceptibility to NTS, no longer exhibited protective effects. Blocking the pleiotropic cytokine IL-9, known to be involved in MC recruitment and proliferation, by means of a mAb in mice receiving Tregs abrogated protection from NTS. Moreover, transfer of IL-9-deficient Tregs also failed to protect from NTS. In the absence of Treg-derived IL-9, MCs fail to accumulate in the LNs, despite the fact that IL-9 deficiency does not alter the general suppressive activity of Tregs. In summary, to our knowledge, we provide the first direct in vivo evidence that the nephroprotective, anti-inflammatory effects of Tregs critically depend on IL-9-mediated attraction of MCs into kidney-draining LNs. PMID:21115728

  2. Fundamental differences in dedifferentiation and stem cell recruitment during skeletal muscle regeneration in two salamander species.

    Science.gov (United States)

    Sandoval-Guzmán, Tatiana; Wang, Heng; Khattak, Shahryar; Schuez, Maritta; Roensch, Kathleen; Nacu, Eugeniu; Tazaki, Akira; Joven, Alberto; Tanaka, Elly M; Simon, András

    2014-02-01

    Salamanders regenerate appendages via a progenitor pool called the blastema. The cellular mechanisms underlying regeneration of muscle have been much debated but have remained unclear. Here we applied Cre-loxP genetic fate mapping to skeletal muscle during limb regeneration in two salamander species, Notophthalmus viridescens (newt) and Ambystoma mexicanum (axolotl). Remarkably, we found that myofiber dedifferentiation is an integral part of limb regeneration in the newt, but not in axolotl. In the newt, myofiber fragmentation results in proliferating, PAX7(-) mononuclear cells in the blastema that give rise to the skeletal muscle in the new limb. In contrast, myofibers in axolotl do not generate proliferating cells, and do not contribute to newly regenerated muscle; instead, resident PAX7(+) cells provide the regeneration activity. Our results therefore show significant diversity in limb muscle regeneration mechanisms among salamanders and suggest that multiple strategies may be feasible for inducing regeneration in other species, including mammals. PMID:24268695

  3. CD11b deficiency suppresses intestinal tumor growth by reducing myeloid cell recruitment

    OpenAIRE

    Qian-Qian Zhang; Xi-Wen Hu; Yi-Long Liu; Zhi-Jin Ye; Yi-He Gui; Da-Lei Zhou; Cui-Ling Qi; Xiao-Dong He; Honglin Wang; Li-Jing Wang

    2015-01-01

    Mac-1 (CD11b) is expressed on bone marrow-derived immune cells. CD11b binds to ligands to regulate leukocyte adhesion and migration across the endothelium or epithelium. Here, we employed CD11b knockout mice and an Apc Min/+ spontaneous intestinal adenoma mouse model to clarify the function of CD11b in intestinal tumorigenesis. We showed that CD11b deficiency may contribute to the inhibition of myeloid cell trafficking to the tumor microenvironment and inactivated Wnt/β-catenin pathway to sup...

  4. Targeted Intra-arterial Transplantation of Stem Cells to the Injured CNS is More Effective than Intravenous Administration - Engraftment is Dependent on Cell Type and Adhesion Molecule Expression

    DEFF Research Database (Denmark)

    Lundberg, Johan; Södersten, Erik; Sundström, Erik;

    2011-01-01

    with inflammation, such as traumatic brain injury, there is a transient up-regulation of ICAM-1 and VCAM-1 which might provide enviromental cues for migration of stem cells from blood to parenchyma. The aim of this study was to i) analyze the effect of intra-arterial administration on cellular engraftment, ii...

  5. Could both vitamin D and geomagnetic activity impact serum levels of soluble cell adhesion molecules in young men?

    Science.gov (United States)

    Bleizgys, Andrius; Šapoka, Virginijus

    2016-07-01

    Vitamin D might have a role in diminishing endothelial dysfunction (ED). The initial aim was to test the hypothesis of reciprocity between levels of 25-hydroxyvitamin D (25(OH)D) and levels of soluble endothelial cell adhesion molecules (CAMs) that could serve as biomarkers of ED. Randomly selected men of age 20-39 were examined at February or March (cold season) and reexamined at August or September (warm season). Some lifestyle and anthropometrical data were recorded. Laboratory measurements, including those for serum levels of soluble CAMs—sICAM-1, sVCAM-1, sE-selectin and sP-selectin—were also performed. As some of the results were rather unexpected, indices of geomagnetic activity (GMA), obtained from the online database, were included in further analysis as a confounder. In 2012-2013, 130 men were examined in cold season, and 125 of them were reexamined in warm season. 25(OH)D levels were found to be significantly negatively associated with sVCAM-1 levels ( β = -0.15, p = 0.043 in warm season; β = -0.19, p = 0.007 for changes). Levels of sVCAM-1 and sICAM-1 from the same seasons were notably different between years and have changed in an opposite manner. Soluble P-selectin levels were higher at warm season in both years. GMA was positively associated with sVCAM-1 ( β = 0.17, p = 0.039 in cold season; β = 0.22, p = 0.002 for changes) and negatively with sICAM-1 ( β = -0.30. p Vitamin D might play a role in diminishing sVCAM-1 levels. Levels of sVCAM-1 and sICAM-1 were associated with the GMA; this implies a need for further research.

  6. Could both vitamin D and geomagnetic activity impact serum levels of soluble cell adhesion molecules in young men?

    Science.gov (United States)

    Bleizgys, Andrius; Šapoka, Virginijus

    2015-11-01

    Vitamin D might have a role in diminishing endothelial dysfunction (ED). The initial aim was to test the hypothesis of reciprocity between levels of 25-hydroxyvitamin D (25(OH)D) and levels of soluble endothelial cell adhesion molecules (CAMs) that could serve as biomarkers of ED. Randomly selected men of age 20-39 were examined at February or March (cold season) and reexamined at August or September (warm season). Some lifestyle and anthropometrical data were recorded. Laboratory measurements, including those for serum levels of soluble CAMs—sICAM-1, sVCAM-1, sE-selectin and sP-selectin—were also performed. As some of the results were rather unexpected, indices of geomagnetic activity (GMA), obtained from the online database, were included in further analysis as a confounder. In 2012-2013, 130 men were examined in cold season, and 125 of them were reexamined in warm season. 25(OH)D levels were found to be significantly negatively associated with sVCAM-1 levels (β = -0.15, p = 0.043 in warm season; β = -0.19, p = 0.007 for changes). Levels of sVCAM-1 and sICAM-1 from the same seasons were notably different between years and have changed in an opposite manner. Soluble P-selectin levels were higher at warm season in both years. GMA was positively associated with sVCAM-1 (β = 0.17, p = 0.039 in cold season; β = 0.22, p = 0.002 for changes) and negatively with sICAM-1 (β = -0.30. p Vitamin D might play a role in diminishing sVCAM-1 levels. Levels of sVCAM-1 and sICAM-1 were associated with the GMA; this implies a need for further research.

  7. Could both vitamin D and geomagnetic activity impact serum levels of soluble cell adhesion molecules in young men?

    Science.gov (United States)

    Bleizgys, Andrius; Šapoka, Virginijus

    2016-07-01

    Vitamin D might have a role in diminishing endothelial dysfunction (ED). The initial aim was to test the hypothesis of reciprocity between levels of 25-hydroxyvitamin D (25(OH)D) and levels of soluble endothelial cell adhesion molecules (CAMs) that could serve as biomarkers of ED. Randomly selected men of age 20-39 were examined at February or March (cold season) and reexamined at August or September (warm season). Some lifestyle and anthropometrical data were recorded. Laboratory measurements, including those for serum levels of soluble CAMs—sICAM-1, sVCAM-1, sE-selectin and sP-selectin—were also performed. As some of the results were rather unexpected, indices of geomagnetic activity (GMA), obtained from the online database, were included in further analysis as a confounder. In 2012-2013, 130 men were examined in cold season, and 125 of them were reexamined in warm season. 25(OH)D levels were found to be significantly negatively associated with sVCAM-1 levels ( β = -0.15, p = 0.043 in warm season; β = -0.19, p = 0.007 for changes). Levels of sVCAM-1 and sICAM-1 from the same seasons were notably different between years and have changed in an opposite manner. Soluble P-selectin levels were higher at warm season in both years. GMA was positively associated with sVCAM-1 ( β = 0.17, p = 0.039 in cold season; β = 0.22, p = 0.002 for changes) and negatively with sICAM-1 ( β = -0.30. p < 0.001 in cold season) levels. Vitamin D might play a role in diminishing sVCAM-1 levels. Levels of sVCAM-1 and sICAM-1 were associated with the GMA; this implies a need for further research.

  8. Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca

    OpenAIRE

    Catarina F. P. Teixeira; Stella R. Zamuner

    2002-01-01

    It has been shown that Bothrops jararaca venom (BjV) induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-alpha, interleukin (I...

  9. IL-17A promotes immune cell recruitment in human esophageal cancers and the infiltrating dendritic cells represent a positive prognostic marker for patient survival.

    Science.gov (United States)

    Lu, Lin; Pan, Ke; Zheng, Hai-Xia; Li, Jian-Jun; Qiu, Hui-Juan; Zhao, Jing-Jing; Weng, De-Sheng; Pan, Qiu-Zhong; Wang, Dan-Dan; Jiang, Shan-Shan; Chang, Alfred E; Li, Qiao; Xia, Jian-Chuan

    2013-10-01

    We previously reported that tumor-infiltrating interleukin (IL)-17A-producing cells play a protective role in human esophageal squamous cell carcinoma (ESCC). However, the potential mechanisms involved remain unclear. In the present study, we investigated the effects of IL-17A on immune cell recruitment and function in ESCC. In vitro chemotaxis assays using the ESCC cell lines EC109 and KYSE30 demonstrated that although IL-17A showed no significant direct effects on the migration of T cells, natural killer (NK) cells as well as dendritic cells (DCs), it could induce ESCC tumor cells to produce inflammatory chemokines, for example, CXCL9, CXCL10 and CCL2, CCL20, which are associated with the migration of T cells, NK cells, and DCs, respectively. In addition, IL-17A enhanced the cytotoxic effects of NK cells against tumor cells by augmenting the expression of cytotoxic molecules, for example, tumor necrosis factor-α, interferon-γ, Perforin, and Granzyme B and activation receptors, for example, NKp46, NKp44, NTB-A, and NKG2D on NK cells. Furthermore, immunohistochemical analysis revealed that the density of IL-17A-producing cells was positively and significantly associated with the density of CD1a DCs in tumor tissues. With the analyses of 181 ESCC patients, we found a correlation of higher number of tumor-infiltrating CD1a DCs with significantly improved overall survival of patients with ESCC. This study provides further understanding of the roles of Th17 cells in ESCC, which may contribute to the development of novel cancer immunotherapy strategies.

  10. 抵挡汤早期干预对2型糖尿病大鼠肿瘤坏死因子-α与血管细胞黏附分子-1表达的影响%Effects of Early Intervention with Didang Decoction on Expression of VCAM-1 and TNF-α in Experimental Type 2 Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    常柏; 李巧芬; 常宝成; 潘从清; 孟东; 陈莉明; 李春深

    2012-01-01

    目的 观察抵挡汤早期干预对2型糖尿病大鼠血管病变中大血管的保护作用,探讨其机制.方法 采用高脂饲料喂养及链脲佐菌素诱导方法制成大鼠糖尿病模型,抵挡汤早期干预组、抵挡汤中期干预组和抵挡汤晚期干预组分别于实验成模前4周、成模和成模后4周给予抵挡汤灌胃,辛伐他汀组和罗格列酮组大鼠于成模时分别给予辛伐他汀和罗格列酮灌胃,至实验24周时结束.酶联免疫吸附法检测大鼠血清血管细胞黏附分子-1(VCAM-1)水平,实时荧光定量PCR法检测主动脉肿瘤坏死因子-α(TNF-α)mRNA表达.结果 与正常对照组比较,模型对照组大鼠血清VCAM-1水平明显升高(P<0.05),主动脉TNF-α mRNA表达明显升高(P<0.05);与模型对照组比较,抵挡汤早期干预组和辛伐他汀组大鼠血清VCAM-1水平明显降低(P<0.05),并且抵挡汤早期干预组、抵挡汤中期干预组和罗格列酮组大鼠主动脉TNF-α mRNA的表达明显降低(P<0.05).结论 抵挡汤早期干预能抑制大鼠主动脉TNF-α mRNA表达升高,抑制大血管病变的炎性损伤,延缓糖尿病大血管病变的发展,发挥其保护大血管的作用.%Objective To observe the protective effects of the early intervention with Didang decoction on the experimental type 2 diabetic rats with macrovascular lesions. Methods Experimental diabetic rats were induced by high fat diet and streptozotocin. The rats in Didang decoction late group, Didang decoction middle group and Didang decoction early group were given Didang decoction from 4 weeks before modeling, modeling completed and 4 weeks after modeling respectively to 24th week. The rats in simvastatin group and rosiglitazone group were given simvastatin and rosiglitazone respectively from modeling completed to 24th week. The level of VCAM-1 in serum was detected by ELASA and the mRNA expression of TNF-a in aorta using real-time PCR. Results Compared with normal control group

  11. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  12. TNF and CD28 Signaling Play Unique but Complementary Roles in the Systemic Recruitment of Innate Immune Cells after Staphylococcus aureus Enterotoxin A Inhalation.

    Science.gov (United States)

    Svedova, Julia; Tsurutani, Naomi; Liu, Wenhai; Khanna, Kamal M; Vella, Anthony T

    2016-06-01

    Staphylococcus aureus enterotoxins cause debilitating systemic inflammatory responses, but how they spread systemically and trigger inflammatory cascade is unclear. In this study, we showed in mice that after inhalation, Staphylococcus aureus enterotoxin A rapidly entered the bloodstream and induced T cells to orchestrate systemic recruitment of inflammatory monocytes and neutrophils. To study the mechanism used by specific T cells that mediate this process, a systems approach revealed inducible and noninducible pathways as potential targets. It was found that TNF caused neutrophil entry into the peripheral blood, whereas CD28 signaling, but not TNF, was needed for chemotaxis of inflammatory monocytes into blood and lymphoid tissue. However, both pathways triggered local recruitment of neutrophils into lymph nodes. Thus, our findings revealed a dual mechanism of monocyte and neutrophil recruitment by T cells relying on overlapping and nonoverlapping roles for the noninducible costimulatory receptor CD28 and the inflammatory cytokine TNF. During sepsis, there might be clinical value in inhibiting CD28 signaling to decrease T cell-mediated inflammation and recruitment of innate cells while retaining bioactive TNF to foster neutrophil circulation. PMID:27183621

  13. Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.

    Science.gov (United States)

    Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Lacchini, Silvia; Kallás, Esper Georges; Irigoyen, Maria Cláudia; Consolim-Colombo, Fernanda M

    2016-04-15

    We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats.

  14. Activation and increase of radio-sensitive CD11b+ recruited Kupffer cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice

    Science.gov (United States)

    Nakashima, Hiroyuki; Nakashima, Masahiro; Kinoshita, Manabu; Ikarashi, Masami; Miyazaki, Hiromi; Hanaka, Hiromi; Imaki, Junko; Seki, Shuhji

    2016-01-01

    We have recently reported that Kupffer cells consist of two subsets, radio-resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+ Kupffer cells/macrophages (Mφs). Non-alcoholic steatohepatitis (NASH) is characterized not only by hepatic steatosis but also chronic inflammation and fibrosis. In the present study, we investigated the immunological mechanism of diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice. After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed severe steatohepatitis and fibrosis resembling human NASH. F4/80+ Mφs which were both CD11b and CD68 positive accumulated in the liver. The production of TNF and FasL indicated that they are the pivotal effectors in this hepatitis. The weak phagocytic activity and lack of CRIg mRNA suggested that they were recruited Mφs. Intermittent exposure to 1 Gy irradiation markedly decreased these Mφs and dramatically inhibited liver inflammation without attenuating steatosis. However, depletion of the resident subset by clodronate liposome (c-lipo) treatment increased the Mφs and tended to exacerbate disease progression. Recruited CD11b+ CD68+ Kupffer cells/Mφs may play an essential role in steatohepatitis and fibrosis in FGF5 null mice fed with a HFD. Recruitment and activation of bone marrow derived Mφs is the key factor to develop steatohepatitis from simple steatosis. PMID:27708340

  15. A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan); Kameshima, Satoshi; Usui, Tatsuya; Okada, Muneyoshi; Hara, Yukio [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Chemerin is a novel adipocytokine with almost unknown function in vasculature. Black-Right-Pointing-Pointer Chemerin activates Akt/eNOS/NO pathways in endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-{alpha}-induced monocyte adhesion to endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-induced VCAM-1 via suppressing NF-{kappa}B and p38 signal. Black-Right-Pointing-Pointer Chemerin is anti-inflammatory through producing NO in vascular endothelium. -- Abstract: Chemerin is a recently identified adipocytokine which plays a role on inflammation and adipocytes metabolism. However, its function in vasculature is largely unknown. We examined the effects of chemerin on vascular endothelial inflammatory states. Treatment of human umbilical vein endothelial cells with chemerin (300 ng/ml, 20 min) induced phosphorylation of Akt (Ser473) and endothelial nitric oxide (NO) synthase (eNOS) (Ser1177). Consistently, chemerin increased intracellular cyclic GMP content. Pretreatment with chemerin (1-300 ng/ml, 24 h) significantly inhibited phosphorylation of nuclear factor (NF)-{kappa}B p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1 expression induced by tumor necrosis factor (TNF)-{alpha} (5 ng/ml, 20 min-6 h). Inhibitor of NF-{kappa}B or p38 significantly inhibited the TNF-{alpha}-induced VCAM-1 expression. Chemerin also inhibited TNF-{alpha}-induced VCAM-1 expression in rat isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to TNF-{alpha}-stimulated endothelial cells. The inhibitory effect of chemerin on TNF-{alpha}-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor, sodium nitroprusside significantly inhibited TNF-{alpha}-induced VCAM-1. The present results for the first time demonstrate that chemerin plays anti-inflammatory roles by preventing TNF-{alpha}-induced VCAM-1 expression and monocytes adhesion in vascular

  16. Recruitment of stem cells by hepatocyte growth factor via intracoronary gene transfection in the postinfarction heart failure

    Institute of Scientific and Technical Information of China (English)

    YANG; ZhiJian; WANG; Wei; MA; DongChao; ZHANG; YouRong; WANG; LianSheng; ZHANG; YuQing; XU; ShunLin; CHEN; Bo; MIAO; DengShun; CAO; KeJiang

    2007-01-01

    We aim to study the amelioration effect of adenovirus5-mediated human hepatocyte growth factor gene transfer on postinfarction heart failure in swine model. Twelve Suzhong young swine were randomly divided into 2 groups of 6 pigs each: Ad5-HGF group and mock-vector Ad5 group. Four weeks after ligation of the left anterior descending coronary artery, Ad5-HGF was intracoronarily transferred into the myocardium. Simultaneously, gate cardiac perfusion imaging was performed to evaluate the heart function. Three weeks later, gate cardiac perfusion imaging was performed again, then the hearts were removed and sectioned for immunohistochemical examination to illustrate the effects of Ad5-HGF on infarcted myocardium. The expression of HGF was examined by ELISA. The results were: (1) compared with the mock-vector Ad5 group, high expression of human HGF was observed in the myocardium of Ad5-HGF group; (2) in the Ad5-HGF group, the number of CD117+ cells co-expressing c-Met per mm2 was significantly larger; (3) the improvement in LVEF was greater in the Ad5-HGF group than in the mock-vector Ad5 group. We concluded that: (1) high expression of human HGF was observed in the myocardium through intracoronary gene transfection; (2) HGF can improve the mobilization of CD117+/c-Met+ stem cells into ischemic myocardium. The amelioration effect of HGF on postinfarction heart failure could not be limited to stimulating angiogenesis, anti-apoptosis, anti-fibrosis, but was also involved in the recruitment of stem cells into myocardium.

  17. Fibroblast Growth Factor-2 Enhanced The Recruitment of Progenitor Cells and Myelin Repair in Experimental Demyelination of Rat Hippocampal Formations

    Directory of Open Access Journals (Sweden)

    Mahdieh Azin

    2015-10-01

    Full Text Available Objective: Hippocampal insults have been observed in multiple sclerosis (MS patients. Fibroblast growth factor-2 (FGF2 induces neurogenesis in the hippocampus and enhances the proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs. In the current study, we have investigated the effect of FGF2 on the processes of gliotoxin induced demyelination and subsequent remyelination in the hippocampus. Materials and Methods: In this experimental study adult male Sprague-Dawley rats received either saline or lysolecithin (LPC injections to the right hippocampi. Animals received intraperitoneal (i.p. injections of FGF2 (5 ng/g on days 0, 5, 12 and 26 post-LPC. Expressions of myelin basic protein (Mbp as a marker of myelination, Olig2 as a marker of OPC proliferation, Nestin as a marker of neural progenitor cells, and glial fibrillary acidic protein (Gfap as a marker of reactive astrocytes were investigated in the right hippocampi by reverse transcriptase-polymerase chain reaction (RT-PCR. Results: There was reduced Mbp expression at seven days after LPC injection, increased expressions of Olig2 and Nestin, and the level of Gfap did not change. FGF2 treatment reversed the expression level of Mbp to the control, significantly enhanced the levels of Olig2 and Nestin, but did not change the level of Gfap. At day-28 post- LPC, the expression level of Mbp was higher than the control in LPC-treated animals that received FGF2. The levels of Olig2, Nestin and Gfap were at the control level in the non-treated LPC group but significantly higher in the FGF2-t reated LPC group. Conclusion: FGF2 enhanced hippocampal myelination and potentiated the recruitment of OPCs and neural stem cells (NSCs to the lesion area. Long-term application of FGF2 might also enhance astrogliosis in the lesion site.

  18. Leptin augments recruitment of IRF-1 and CREB to thrombospondin-1 gene promoter in vascular smooth muscle cells in vitro.

    Science.gov (United States)

    Sahu, Soumyadip; Ganguly, Rituparna; Raman, Priya

    2016-08-01

    We previously reported that high pathophysiological concentrations of leptin, the adipocyte-secreted peptide, upregulate the expression of a potent proatherogenic matricellular protein, thrombospondin-1 (TSP-1), in vascular smooth muscle cells. Moreover, this regulation was found to occur at the level of transcription; however, the underlying molecular mechanisms remain unknown. The goal of the present study was to investigate the specific transcriptional mechanisms that mediate upregulation of TSP-1 expression by leptin. Primary human aortic smooth muscle cell cultures were transiently transfected with different TSP-1 gene (THBS1) promoter-linked luciferase reporter constructs, and luciferase activity in response to leptin (100 ng/ml) was assessed. We identified a long THBS1 promoter (-1270/+750) fragment with specific leptin response elements that are required for increased TSP-1 transcription by leptin. Promoter analyses, protein/DNA array and gel shift assays demonstrated activation and association of transcription factors, interferon regulatory factor-1 (IRF-1) and cAMP response element-binding protein (CREB), to the distal fragment of the THBS1 promoter in response to leptin. Supershift, chromatin immunoprecipitation, and coimmunoprecipitation assays revealed formation of a single complex between IRF-1 and CREB in response to leptin; importantly, recruitment of this complex to the THBS1 promoter mediated leptin-induced TSP-1 transcription. Finally, binding sequence decoy oligomer and site-directed mutagenesis revealed that regulatory elements for both IRF-1 (-1019 to -1016) and CREB (-1198 to -1195), specific to the distal THBS1 promoter, were required for leptin-induced TSP-1 transcription. Taken together, these findings demonstrate that leptin promotes a cooperative association between IRF-1 and CREB on the THBS1 promoter driving TSP-1 transcription in vascular smooth muscle cells. PMID:27281481

  19. Dynamics of glucose-induced membrane recruitment of protein kinase C beta II in living pancreatic islet beta-cells.

    Science.gov (United States)

    Pinton, Paolo; Tsuboi, Takashi; Ainscow, Edward K; Pozzan, Tullio; Rizzuto, Rosario; Rutter, Guy A

    2002-10-01

    The mechanisms by which glucose may affect protein kinase C (PKC) activity in the pancreatic islet beta-cell are presently unclear. By developing adenovirally expressed chimeras encoding fusion proteins between green fluorescent protein and conventional (betaII), novel (delta), or atypical (zeta) PKCs, we show that glucose selectively alters the subcellular localization of these enzymes dynamically in primary islet and MIN6 beta-cells. Examined by laser scanning confocal or total internal reflection fluorescence microscopy, elevated glucose concentrations induced oscillatory translocations of PKCbetaII to spatially confined regions of the plasma membrane. Suggesting that increases in free cytosolic Ca(2+) concentrations ([Ca(2+)](c)) were primarily responsible, prevention of [Ca(2+)](c) increases with EGTA or diazoxide completely eliminated membrane recruitment, whereas elevation of cytosolic [Ca(2+)](c) with KCl or tolbutamide was highly effective in redistributing PKCbetaII both to the plasma membrane and to the surface of dense core secretory vesicles. By contrast, the distribution of PKCdelta.EGFP, which binds diacylglycerol but not Ca(2+), was unaffected by glucose. Measurement of [Ca(2+)](c) immediately beneath the plasma membrane with a ratiometric "pericam," fused to synaptic vesicle-associated protein-25, revealed that depolarization induced significantly larger increases in [Ca(2+)](c) in this domain. These data demonstrate that nutrient stimulation of beta-cells causes spatially and temporally complex changes in the subcellular localization of PKCbetaII, possibly resulting from the generation of Ca(2+) microdomains. Localized changes in PKCbetaII activity may thus have a role in the spatial control of insulin exocytosis.

  20. Heat shock factor 1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of bone marrow stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Masayuki Kubo

    Full Text Available Bone marrow (BM-derived stem/progenitor cells play an important role in ischemia-induced angiogenesis in cardiovascular diseases. Heat shock factor 1 (HSF1 is known to be induced in response to hypoxia and ischemia. We examined whether HSF1 contributes to ischemia-induced angiogenesis through the mobilization and recruitment of BM-derived stem/progenitor cells using HSF1-knockout (KO mice. After the induction of ischemia, blood flow and microvessel density in the ischemic hindlimb were significantly lower in the HSF1-KO mice than in the wild-type (WT mice. The mobilization of BM-derived Sca-1- and c-kit-positive cells in peripheral blood after ischemia was significantly lower in the HSF1-KO mice than in the WT mice. BM stem/progenitor cells from HSF1-KO mice showed a significant decrease in their recruitment to ischemic tissue and in migration, adhesion, and survival when compared with WT mice. Blood flow recovery in the ischemic hindlimb significantly decreased in WT mice receiving BM reconstitution with donor cells from HSF1-KO mice. Conversely, blood flow recovery in the ischemic hindlimb significantly increased in HSF1-KO mice receiving BM reconstitution with donor cells from WT mice. These findings suggest that HSF1 contributes to ischemia-induced angiogenesis by regulating the mobilization and recruitment of BM-derived stem/progenitor cells.

  1. The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury

    Science.gov (United States)

    Jones, Kathryn S; Connor, Bronwen J

    2016-01-01

    Despite the presence of on-going neurogenesis in the adult mammalian brain, neurons are generally not replaced after injury. Using a rodent model of excitotoxic cell loss and retroviral (RV) lineage tracing, we previously demonstrated transient recruitment of precursor cells from the subventricular zone (SVZ) into the lesioned striatum. In the current study we determined that these cells included migratory neuroblasts and oligodendrocyte precursor cells (OPC), with the predominant response from glial cells. We attempted to override this glial response by ectopic expression of the pro-neurogenic genes Pax6 or Dlx2 in the adult rat SVZ following quinolinic acid lesioning. RV-Dlx2 over-expression stimulated repair at a previously non-neurogenic time point by enhancing neuroblast recruitment and the percentage of cells that retained a neuronal fate within the lesioned area, compared to RV-GFP controls. RV-Pax6 expression was unsuccessful at inhibiting glial fate and intriguingly, increased OPC cell numbers with no change in neuronal recruitment. These findings suggest that gene choice is important when attempting to augment endogenous repair as the lesioned environment can overcome pro-neurogenic gene expression. Dlx2 over-expression however was able to partially overcome an anti-neuronal environment and therefore is a promising candidate for further study of striatal regeneration.

  2. Recruitment of HDAC4 by transcription factor YY1 represses HOXB13 to affect cell growth in AR-negative prostate cancers

    DEFF Research Database (Denmark)

    Ren, Guoling; Zhang, Guocui; Dong, Zhixiong;

    2008-01-01

    -immunoprecipitation assays revealed that HDAC4 and YY1 formed a complex. The chromatin immunoprecipitation (ChIP) assays verified that HDAC4 was recruited to HOXB13 promoter by YY1. Moreover, promoter truncation and point mutation studies determined that the two proximal YY1 binding sites on the HOXB13 promoter were...... essential for the recruitments of YY1 and HDAC4. Data presented in this report suggest that YY1 and HDAC4 affected cell growth by repressing transcriptional regulation of HOXB13 through an epigenetic modification of histones....

  3. 三伏灸对支气管哮喘患者血浆sICAM-1、sVCAM-1和sE-slectin水平的影响%Effect of Dog Day Moxibustion on Soluble Cellular Adhesion Molecules in Treating Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    杨君军; 唐纯志; 赖新生

    2005-01-01

    目的:观察三伏灸对支气管哮喘患者血浆可溶性细胞黏附分子的影响,探讨三伏灸治疗支气管哮喘作用机制.方法:对28例哮喘缓解期患者行三伏灸治疗,观察3个月后的近期疗效,于治疗前及治疗后10 d分别检测血浆可溶性细胞黏附分子(sCAM)及IgE水平,并与10例正常人作对照.结果:三伏灸治疗支气管哮喘的总有效率为92.86%.三伏灸能显著降低患者血浆可溶性细胞间黏附分子-1(sICAM-1)水平和血清IgE含量(P﹤0.01),降低血浆可溶性血管-细胞间黏附分子-1(sVCAM-1)和可溶性E选择素(sE-selectin)水平(P﹤0.05).患者血清IgE含量与sICAM-1含量呈显著相关性(r =0.641,P =0.000),sICAM-1与sVCAM-1之间亦呈正相关(r =0.449,P=0.017).结论:三伏灸可能通过抑制黏附分子的表达或直接抑制白细胞与内皮细胞的黏附,从而减少炎细胞的浸润,达到治疗效果.

  4. p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression

    Science.gov (United States)

    Tian, Linjie; Choi, Seung-Chul; Murakami, Yousuke; Allen, Joselyn; Morse, Herbert C., III; Qi, Chen-Feng; Krzewski, Konrad; Coligan, John E.

    2014-01-01

    Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as FcγRIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.

  5. Role of exosomes released by chronic myelogenous leukemia cells in angiogenesis

    OpenAIRE

    Taverna, S; Flugy Papè, AM; SAIEVA, L; Kohn, EC; A. Santoro; Meraviglia, S; De Leo, G; ALESSANDRO, R

    2011-01-01

    The present study is designed to assess if exosomes released from Chronic Myelogenous Leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of a...

  6. Polyphenolic extracts from cowpea (Vigna unguiculata) protect colonic myofibroblasts (CCD18Co cells) from lipopolysaccharide (LPS)-induced inflammation--modulation of microRNA 126.

    Science.gov (United States)

    Ojwang, Leonnard O; Banerjee, Nivedita; Noratto, Giuliana D; Angel-Morales, Gabriela; Hachibamba, Twambo; Awika, Joseph M; Mertens-Talcott, Susanne U

    2015-01-01

    Cowpea (Vigna unguiculata) is a drought tolerant crop with several agronomic advantages over other legumes. This study evaluated varieties from four major cowpea phenotypes (black, red, light brown and white) containing different phenolic profiles for their anti-inflammatory property on non-malignant colonic myofibroblasts (CCD18Co) cells challenged with an endotoxin (lipopolysaccharide, LPS). Intracellular reactive oxygen species (ROS) assay on the LPS-stimulated cells revealed antioxidative potential of black and red cowpea varieties. Real-time qRT-PCR analysis in LPS-stimulated cells revealed down-regulation of proinflammatory cytokines (IL-8, TNF-α, VCAM-1), transcription factor NF-κB and modulation of microRNA-126 (specific post-transcriptional regulator of VCAM-1) by cowpea polyphenolics. The ability of cowpea polyphenols to modulate miR-126 signaling and its target gene VCAM-1 were studied in LPS-stimulated endothelial cells transfected with a specific inhibitor of miR-126, and treated with 10 mg GAE/L black cowpea extract where the extract in part reversed the effect of the miR-126 inhibitor. This suggests that cowpea may exert their anti-inflammatory activities at least in part through induction of miR-126 that then down-regulate VCAM-1 mRNA and protein expressions. Overall, Cowpea therefore is promising as an anti-inflammatory dietary component. PMID:25300227

  7. Distinct Upstream Role of Type I IFN Signaling in Hematopoietic Stem Cell-Derived and Epithelial Resident Cells for Concerted Recruitment of Ly-6Chi Monocytes and NK Cells via CCL2-CCL3 Cascade.

    Directory of Open Access Journals (Sweden)

    Erdenebileg Uyangaa

    Full Text Available Type I interferon (IFN-I-dependent orchestrated mobilization of innate cells in inflamed tissues is believed to play a critical role in controlling replication and CNS-invasion of herpes simplex virus (HSV. However, the crucial regulators and cell populations that are affected by IFN-I to establish the early environment of innate cells in HSV-infected mucosal tissues are largely unknown. Here, we found that IFN-I signaling promoted the differentiation of CCL2-producing Ly-6Chi monocytes and IFN-γ/granzyme B-producing NK cells, whereas deficiency of IFN-I signaling induced Ly-6Clo monocytes producing CXCL1 and CXCL2. More interestingly, recruitment of Ly-6Chi monocytes preceded that of NK cells with the levels peaked at 24 h post-infection in IFN-I-dependent manner, which was kinetically associated with the CCL2-CCL3 cascade response. Early Ly-6Chi monocyte recruitment was governed by CCL2 produced from hematopoietic stem cell (HSC-derived leukocytes, whereas NK cell recruitment predominantly depended on CC chemokines produced by resident epithelial cells. Also, IFN-I signaling in HSC-derived leukocytes appeared to suppress Ly-6Ghi neutrophil recruitment to ameliorate immunopathology. Finally, tissue resident CD11bhiF4/80hi macrophages and CD11chiEpCAM+ dendritic cells appeared to produce initial CCL2 for migration-based self-amplification of early infiltrated Ly-6Chi monocytes upon stimulation by IFN-I produced from infected epithelial cells. Ultimately, these results decipher a detailed IFN-I-dependent pathway that establishes orchestrated mobilization of Ly-6Chi monocytes and NK cells through CCL2-CCL3 cascade response of HSC-derived leukocytes and epithelium-resident cells. Therefore, this cascade response of resident-to-hematopoietic-to-resident cells that drives cytokine-to-chemokine-to-cytokine production to recruit orchestrated innate cells is critical for attenuation of HSV replication in inflamed tissues.

  8. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xia, E-mail: zhongxia1977@126.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  9. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    Science.gov (United States)

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-07-16

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalignant lung adenomas through CC chemokine receptor 1 (CCR1)-dependent mechanisms. Stromal IMCs promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Furthermore, we have found that IMC recruitment to the microenvironment is restrained by the cholesterol-binding protein, Niemann-Pick type C2 (NPC2). Studies on isolated cells ex vivo confirm that NPC2 is secreted from tumour cells and is taken up by IMCs wherein it suppresses secretion of the CCR1 ligand CC chemokine 6 (CCL6), at least in part by facilitating its lysosomal degradation. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer.

  10. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    Science.gov (United States)

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-09-01

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalignant lung adenomas through CC chemokine receptor 1 (CCR1)-dependent mechanisms. Stromal IMCs promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Furthermore, we have found that IMC recruitment to the microenvironment is restrained by the cholesterol-binding protein, Niemann-Pick type C2 (NPC2). Studies on isolated cells ex vivo confirm that NPC2 is secreted from tumour cells and is taken up by IMCs wherein it suppresses secretion of the CCR1 ligand CC chemokine 6 (CCL6), at least in part by facilitating its lysosomal degradation. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer. PMID:26183450

  11. Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation

    OpenAIRE

    Ali, Shahina; Kaur, Jaswinder; Patel, Kamala D.

    2000-01-01

    Eosinophils are usually associated with parasitic and allergic diseases; however, eosinophilia is also observed in several types of human tumors, including breast carcinomas. In this study we examined several human breast carcinoma cell lines for adhesion molecule expression and the ability to bind and activate eosinophils. MDA-MB-435S and MDA-MB-468 cells constitutively expressed both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and this expressio...

  12. Recruitment of exogenous mesenchymal stem cells in mandibular distraction osteogenesis by the stromal cell-derived factor-1/chemokine receptor-4 pathway in rats.

    Science.gov (United States)

    Cao, Jian; Wang, Lei; Du, Zhao-jie; Liu, Peng; Zhang, Ya-bo; Sui, Jian-fu; Liu, Yan-pu; Lei, De-lin

    2013-12-01

    Distraction osteogenesis is widely used in orthopaedic and craniofacial surgery. However, its exact mechanism is still poorly understood. The purpose of this study was to find out whether there is systemic recruitment of mesenchymal stem cells (MSC) to the neocallus in the distraction gap by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis during osteogenesis. We examined the migration of MSC towards a gradient of SDF-1 in vitro. We also transplanted MSC labelled with green fluorescent protein (GFP) intravenously, with or without treatment with CXCR4-blocking antibody, into rats that had had unilateral mandibular distraction osteogenesis, and investigated the distribution of cells labelled with GFP in the soft callus after 24 h. We found that SDF-1 facilitated the migration potency of MSC both in vitro and in vivo, and this migration could be inhibited by AMD3100, an antagonist of CXCR4, and promoted by local infusion of exogenous SDF-1 into the distraction gap. This study provides a new insight into the molecular basis of how new bone is regenerated during distraction osteogenesis.

  13. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours

    OpenAIRE

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-01-01

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the V600 EBRAF-driven mouse lung model that develop premalignant lesions to understand stroma–tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalign...

  14. CXCL9 Is Important for Recruiting Immune T Cells into the Brain and Inducing an accumulation of the T Cells to the areas of tachyzoite proliferation to prevent reactivation of chronic cerebral infection with Toxoplasma gondii

    Science.gov (United States)

    T cells are required to maintain the latency of chronic infection with Toxoplasma gondii in the brain. In the present study, we examined the role of non-ELR (glutamic acid-leucine-arginine) CXC chemokine CXCL9 for T cell recruitment to prevent reactivation of infection with T. gondii. SCID mice were...

  15. Inhibition of MAP kinase promotes the recruitment of corepressor SMRT by tamoxifen-bound estrogen receptor alpha and potentiates tamoxifen action in MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Wei, E-mail: hongwei@tijmu.edu.cn [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China); Department of Laboratory Medicine, Tianjin Medical University, 300070 Tianjin (China); Chen, Linfeng [Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, 02115 MA (United States); Li, Juan [Department of Laboratory Medicine, Tianjin Medical University, 300070 Tianjin (China); Yao, Zhi [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China)

    2010-05-28

    Estrogen receptor alpha (ER{alpha}), a ligand controlled transcription factor, plays an important role in breast cancer growth and endocrine therapy. Tamoxifen (TAM) antagonizes ER{alpha} activity and has been applied in breast cancer treatment. TAM-bound ER{alpha} associates with nuclear receptor-corepressors. Mitogen-activated protein kinase (MAPK) has been elucidated to result in cross-talk between growth factor and ER{alpha} mediated signaling. We show that activated MAPK represses interaction of TAM-bound ER{alpha} with silencing mediator for retinoid and thyroid hormone receptors (SMRT) and inhibits the recruitment of SMRT by ER{alpha} to certain estrogen target genes. Blockade of MAPK signaling cascade with MEK inhibitor U0126 promotes the interaction and subsequently inhibits ER{alpha} activity via enhanced recruitment of SMRT, leading to reduced expression of ER{alpha} target genes. The growth rate of MCF-7 cells was decelerated when treated with both TAM and U0126. Moreover, the growth of MCF-7 cells stably expressing SMRT showed a robust repression in the presence of TAM and U0126. These results suggest that activated MAPK signaling cascade attenuates antagonist-induced recruitment of SMRT to ER{alpha}, suggesting corepressor mediates inhibition of ER{alpha} transactivation and breast cancer cell growth by antagonist. Taken together, our finding indicates combination of antagonist and MAPK inhibitor could be a helpful approach for breast cancer therapy.

  16. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.

    Science.gov (United States)

    Saxena, Neeraj K; Vertino, Paula M; Anania, Frank A; Sharma, Dipali

    2007-05-01

    Numerous epidemiological studies documented that obesity is a risk factor for breast cancer development in postmenopausal women. Leptin, the key player in the regulation of energy balance and body weight control also acts as a growth factor on certain organs in both normal and disease state. In this study, we analyzed the role of leptin and the molecular mechanism(s) underlying its action in breast cancer cells that express both short and long isoforms of leptin receptor. Leptin increased MCF7 cell population in the S-phase of the cell cycle along with a robust increase in CYCLIN D1 expression. Also, leptin induced Stat3-phosphorylation-dependent proliferation of MCF7 cells as blocking Stat3 phosphorylation with a specific inhibitor, AG490, abolished leptin-induced proliferation. Using deletion constructs of CYCLIN D1 promoter and chromatin immunoprecipitation assay, we show that leptin induced increase in CYCLIN D1 promoter activity is mediated through binding of activated Stat3 at the Stat binding sites and changes in histone acetylation and methylation. We also show specific involvement of coactivator molecules, histone acetyltransferase SRC1, and mediator complex in leptin-mediated regulation of CYCLIN D1 promoter. Importantly, silencing of SRC1 and Med1 abolished the leptin induced increase in CYCLIN D1 expression and MCF7 cell proliferation. Intriguingly, recruitment of both SRC1 and Med1 was dependent on phosphorylated Stat3 as AG490 treatment inhibited leptin-induced recruitment of these coactivators to CYCLIN D1 promoter. Our data suggest that CYCLIN D1 may be a target gene for leptin mediated growth stimulation of breast cancer cells and molecular mechanisms involve activated Stat3-mediated recruitment of distinct coactivator complexes.

  17. Tissue kinetics, ion transport, and recruitment of mitochondria-rich cells in the skin of the toad (Bufo bufo) in response to exposure to distilled water

    DEFF Research Database (Denmark)

    Budtz, Poul Egede; Christoffersen, Betina C.; Johansen, Jesper S.;

    1995-01-01

    Mitochondria-rich cells (MRC) of the amphibian epidermis are responsible for active chloride uptake at low external salinity, and new MRCs are recruited in response to exposure to distilled (deionized) water. The time-course of this recruitment, the tissue kinetics and ion transport have been...

  18. Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment

    Directory of Open Access Journals (Sweden)

    Sarah Cooper

    2014-06-01

    Full Text Available The mechanisms by which the major Polycomb group (PcG complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation and Polycomb activity, we demonstrate that, in methylation-deficient embryonic stem cells (ESCs, CpG density combined with antagonistic effects of H3K9me3 and H3K36me3 redirects PcG complexes to pericentric heterochromatin and gene-rich domains. Surprisingly, we find that PRC1-linked H2A monoubiquitylation is sufficient to recruit PRC2 to chromatin in vivo, suggesting a mechanism through which recognition of unmethylated CpG determines the localization of both PRC1 and PRC2 at canonical and atypical target sites. We discuss our data in light of emerging evidence suggesting that PcG recruitment is a default state at licensed chromatin sites, mediated by interplay between CpG hypomethylation and counteracting H3 tail modifications.

  19. Rho kinase's role in myosin recruitment to the equatorial cortex of mitotic Drosophila S2 cells is for myosin regulatory light chain phosphorylation.

    Directory of Open Access Journals (Sweden)

    Sara O Dean

    Full Text Available BACKGROUND: Myosin II recruitment to the equatorial cortex is one of the earliest events in establishment of the cytokinetic contractile ring. In Drosophila S2 cells, we previously showed that myosin II is recruited to the furrow independently of F-actin, and that Rho1 and Rok are essential for this recruitment [1]. Rok phosphorylates several cellular proteins, including the myosin regulatory light chain (RLC. METHODOLOGY/PRINCIPAL FINDINGS: Here we express phosphorylation state mimic constructs of the RLC in S2 cells to examine the role of RLC phosphorylation involving Rok in the localization of myosin. Phosphorylation of the RLC is required for myosin localization to the equatorial cortex during mitosis, and the essential role of Rok in this localization and for cytokinesis is to maintain phosphorylation of the RLC. The ability to regulate the RLC phosphorylation state spatio-temporally is not essential for the myosin localization. Furthermore, the essential role of Citron in cytokinesis is not phosphorylation of the RLC. CONCLUSIONS/SIGNIFICANCE: We conclude that the Rho1 pathway leading to myosin localization to the future cytokinetic furrow is relatively straightforward, where only Rok is needed, and it is only needed to maintain phosphorylation of the myosin RLC.

  20. The genomic context and co-recruitment of SP1 affect ERRα co-activation by PGC-1α in muscle cells

    Science.gov (United States)

    Baresic, Mario; van Nimwegen, Erik; Handschin, Christoph

    2016-01-01

    The peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, e.g. by co-activating the estrogen-related receptor α (ERRα) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these two proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERRα to DNA in a skeletal muscle cell line with elevated PGC-1α and linked the DNA recruitment to global PGC-1α target gene regulation. We found that, surprisingly, ERRα co-activation by PGC-1α is only observed in the minority of all PGC-1α recruitment sites. Nevertheless, a majority of PGC-1α target gene expression is dependent on ERRα. Intriguingly, the interaction between these two proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat binding site configuration for ERRα, and adjacent recruitment of the transcription factor SP1. These findings thus not only reveal a novel insight into the regulatory network underlying muscle cell plasticity, but also strongly link the genomic context of DNA response elements to control transcription factor – co-regulator interactions. PMID:27182621

  1. Mesenchymal stem cell recruitment by stromal derived factor-1-delivery systems based on chitosan/poly(γ-glutamic acid polyelectrolyte complexes

    Directory of Open Access Journals (Sweden)

    RM Gonçalves

    2012-04-01

    Full Text Available Human mesenchymal stem cells (hMSCs have an enormous potential for tissue engineering and cell-based therapies. With a potential of differentiation into multiple lineages and immune-suppression, these cells play a key role in tissue remodelling and regeneration.Here a method of hMSC recruitment is described, based on the incorporation of a chemokine in Chitosan (Ch/Poly(γ-glutamic acid (γ-PGA complexes. Ch is a non-toxic, cationic polysaccharide widely investigated. γ-PGA is a hydrophilic, non-toxic, biodegradable and negatively charged poly-amino acid. Ch and γ-PGA, being oppositely charged, can be combined through electrostatic interactions. These biocompatible structures can be used as carriers for active substances and can be easily modulated in order to control the delivery of drugs, proteins, DNA, etc.Using the layer-by-layer method, Ch and γ-PGA were assembled into polyelectrolyte multilayers films (PEMs with thickness of 120 nm. The chemokine stromal-derived factor-1 (SDF-1 was incorporated in these complexes and was continuously released during 120 h. The method of SDF-1 incorporation is of crucial importance for polymers assembly into PEMs and for the release kinetics of this chemokine. The Ch/γ-PGA PEMs with SDF-1 were able to recruit hMSCs, increasing the cell migration up to 6 fold to a maximum of 16.2 ± 4.9 cells/mm2. The controlled release of SDF-1 would be of great therapeutic value in the process of hMSC homing to injured tissues. This is the first study suggesting Ch/γ-PGA PEMs as SDF-1 reservoirs to recruit hMSCs, describing an efficient method of chemokine incorporation that allows a sustained released up to 5 days and that can be easily scaled-up.

  2. The Measure of DAMPs and a role for S100A8 in recruiting suppressor cells in breast cancer lung metastasis.

    Science.gov (United States)

    Vrakas, Christine N; O'Sullivan, Ryan M; Evans, Samantha E; Ingram, DaMarcus A; Jones, Carli B; Phuong, Tiffany; Kurt, Robert A

    2015-01-01

    To determine whether there was a relationship between damage associated molecular pattern molecule (DAMP) expression and recruitment of suppressor cells to sites of metastasis we measured relative expression of DAMPs, regulatory T cells (Tregs), and myeloid derived suppressor cells (MDSC) in mice at various stages of breast cancer progression using the 4T1 model. Although S100A8 was expressed at relatively low levels in the tumor cells, expression was 100-fold higher in the lung and liver which are common sites of metastasis for this tumor. Despite the relatively high level of S100A8 expression in the lungs of naïve mice, the level of expression increased further and was significantly elevated after only 7 days of tumor growth. The same pattern was observed for MDSC, and both S100A8 and MDSC expression peaked in the lungs of mice following 21 days of tumor growth. Characterization of MDSC from the lungs revealed expression of RAGE, and the cells were capable of migrating in a dose-dependent manner toward S100A8. In addition, the MDSC expressed low levels of MHC Class I, MHC Class II, CD80, and secreted TGF-β. Taken together, these data suggest that expression of S100A8 in the lungs may facilitate recruitment of MDSC, which may in turn aid in establishing a metastatic niche capable of suppressing a localized immune response. PMID:25255046

  3. Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis.

    Science.gov (United States)

    Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratì, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillà, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella

    2015-01-01

    Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis.

  4. Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis.

    Science.gov (United States)

    Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratì, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillà, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella

    2015-01-01

    Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis. PMID:25313007

  5. Human epicardium-derived cells fuse with high efficiency with skeletal myotubes and differentiate toward the skeletal muscle phenotype: a comparison study with stromal and endothelial cells.

    Science.gov (United States)

    Gentile, Antonietta; Toietta, Gabriele; Pazzano, Vincenzo; Tsiopoulos, Vasileios D; Giglio, Ada Francesca; Crea, Filippo; Pompilio, Giulio; Capogrossi, Maurizio C; Di Rocco, Giuliana

    2011-03-01

    Recent studies have underscored a role for the epicardium as a source of multipotent cells. Here, we investigate the myogenic potential of adult human epicardium-derived cells (EPDCs) and analyze their ability to undergo skeletal myogenesis when cultured with differentiating primary myoblasts. Results are compared to those obtained with mesenchymal stromal cells (MSCs) and with endothelial cells, another mesodermal derivative. We demonstrate that EPDCs spontaneously fuse with pre-existing myotubes with an efficiency that is significantly higher than that of other cells. Although at a low frequency, endothelial cells may also contribute to myotube formation. In all cases analyzed, after entering the myotube, nonmuscle nuclei are reprogrammed to express muscle-specific genes. The fusion competence of nonmyogenic cells in vitro parallels their ability to reconstitute dystrophin expression in mdx mice. We additionally show that vascular cell adhesion molecule 1 (VCAM1) expression levels of nonmuscle cells are modulated by soluble factors secreted by skeletal myoblasts and that VCAM1 function is required for fusion to occur. Finally, treatment with interleukin (IL)-4 or IL-13, two cytokines released by differentiating myotubes, increases VCAM1 expression and enhances the rate of fusion of EPDCs and MSCs, but not that of endothelial cells. PMID:21209317

  6. Cdk-dependent phosphorylation regulates TRF1 recruitment to PML bodies and promotes C-circle production in ALT cells.

    Science.gov (United States)

    Wilson, Florence R; Ho, Angus; Walker, John R; Zhu, Xu-Dong

    2016-07-01

    TRF1, a duplex telomeric DNA binding protein, is implicated in homologous-recombination-based alternative lengthening of telomeres, known as ALT. However, how TRF1 promotes ALT activity has yet to be fully characterized. Here we report that Cdk-dependent TRF1 phosphorylation on T371 acts as a switch to create a pool of TRF1, referred to as (pT371)TRF1, which is recruited to ALT-associated PML bodies (APBs) in S and G2 phases independently of its binding to telomeric DNA. We find that phosphorylation of T371 is essential for APB formation and C-circle production, both of which are hallmarks of ALT. We show that the interaction of (pT371)TRF1 with APBs is dependent upon ATM and homologous-recombination-promoting factors Mre11 and BRCA1. In addition, (pT371)TRF1 interaction with APBs is sensitive to transcription inhibition, which also reduces DNA damage at telomeres. Furthermore, overexpression of RNaseH1 impairs (pT371)TRF1 recruitment to APBs in the presence of campothecin, an inhibitor that prevents topoisomerase I from resolving RNA-DNA hybrids. These results suggest that transcription-associated DNA damage, perhaps arising from processing RNA-DNA hybrids at telomeres, triggers (pT371)TRF1 recruitment to APBs to facilitate ALT activity. PMID:27185864

  7. The occurrence of recruitment supported from the finding of an increase in radiosensitivity of quiescent cells in solid tumors after fractionated irradiation with X-rays

    International Nuclear Information System (INIS)

    We examined the behavior of quiescent cells in solid tumors irradiated twice at various intervals with X-rays, using our recently developed method for selectively detecting the response of quiescent cells in solid tumors. To determine the labeling indices of tumors at the second irradiation, each mouse group included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted before the first irradiation. Radiosensitivity of total tumor cells at the second irradiation decreased in proportion to the increase in interval time. However, radiosensitivity of quiescent cells was raised with increase in the interval time. In addition, the labeling index at the second irradiation was higher than that at the first irradiation. These findings supported the occurrence of recruitment from quiescent to proliferating state during fractionated irradiation. (author)

  8. CCR9 Is Not Required for the Homing of Pro-inflammatory Effector T cells, but Is Crucial for Recruitment and Expansion of FoxP3+ CD8+ Tregs in the Small Intestine

    DEFF Research Database (Denmark)

    Gomez-Casado, Cristina; Joeris, Thorsten; Holmkvist, Petra;

    Chemokine receptor 9 (CCR9) is required for the homeostatic recruitment of T cells to the mucosa of the small intestine. Accordingly, CCR9 has been suggested as a potential target to inhibit the recruitment of proinflammatory effector T cells (Teff) in inflammatory bowel disease (IBD). Since...... the contribution of CCR9 to the recruitment of Teff in inflammation is not entirely clear, we aimed to address this question using IFABPtOva mice. These mice express Ovalbumin (Ova) specifically in small intestinal epithelial cells, which allows triggering of acute inflammation following transfer of Ova......-specific CD8+ T cells (OT-I cells) and adjuvant treatment. Strikingly, intestinal inflammation in IFABP-tOva mice could also be triggered following transfer of CCR9-deficient OT-I cells, demonstrating that CCR9 is not required for homing of Teff cells. Interestingly, OTI cells transferred to IFABP-tOva mice...

  9. L-plastin is involved in NKG2D recruitment into lipid rafts and NKG2D-mediated NK cell migration.

    Science.gov (United States)

    Serrano-Pertierra, Esther; Cernuda-Morollón, Eva; Brdička, Tomáš; Hoøejši, Václav; López-Larrea, Carlos

    2014-09-01

    Membrane rafts are microdomains of the plasma membrane that have multiple biological functions. The involvement of these structures in the biology of T cells, namely in signal transduction by the TCR, has been widely studied. However, the role of membrane rafts in immunoreceptor signaling in NK cells is less well known. We studied the distribution of the activating NKG2D receptor in lipid rafts by isolating DRMs in a sucrose density gradient or by raft fractionation by β-OG-selective solubility in the NKL cell line. We found that the NKG2D-DAP10 complex and pVav are recruited into rafts upon receptor stimulation. Qualitative proteomic analysis of these fractions showed that the actin cytoskeleton is involved in this process. In particular, we found that the actin-bundling protein L-plastin plays an important role in the clustering of NKG2D into lipid rafts. Moreover, coengagement of the inhibitory receptor NKG2A partially disrupted NKG2D recruitment into rafts. Furthermore, we demonstrated that L-plastin participates in NKG2D-mediated inhibition of NK cell chemotaxis.

  10. E-recruitment

    DEFF Research Database (Denmark)

    Holm, Anna B.

    2012-01-01

    large organisations in Denmark in 2008-2010. The findings indicate that e-recruitment transforms the traditional recruitment process into a time- and space-independent, collaborative hiring process. The most significant changes are recorded in the sequence and increased divisibility of main recruitment......Up to now, there has been little research on the impact of e-recruitment on the recruitment process as a whole. The present study fills part of this gap by investigating the effect of e-recruitment on the design of the recruitment process. Three explorative case studies were carried out in three...

  11. Telomerase activation after recruitment in fission yeast.

    OpenAIRE

    Armstrong, C. A.; Pearson, S R; Amelina, H.; Moiseeva, V.; Tomita, K.

    2014-01-01

    Summary Current models depict that telomerase recruitment equates to activation. Telomeric DNA-binding proteins and the telomerase accessory proteins coordinate the recruitment of telomerase to the ends of chromosomes in a telomere length- and cell-cycle-dependent manner [1–4]. Recent studies have demonstrated that the telomeric protein TPP1 and its binding protein TIN2 are key proteins for both telomerase recruitment and processivity in mammalian cells [5–7]. Although the precise molecular m...

  12. A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Tong; Sun, Fumou; Xie, Wei; Tang, Mingying; He, Hua; Jia, Xuelian; Tian, Xuemei; Wang, Min; Zhang, Juan

    2016-03-28

    MHC class I-related chain A (MICA) is a principal immunoligand of the natural killer (NK) cell receptor NK group 2, member D (NKG2D) and plays a key role in NK cell-mediated immune recognition. Shedding of MICA from tumor cells leads to immunosuppression. To reconstitute the immunosurveilance function of NK cells, we constructed a fusion protein rG7S-MICA and explored its potential anti-tumor activity against hepatocellular carcinoma (HCC). rG7S-MICA consists of human MICA and a single-chain antibody fragment (scFv) targeting the tumor-associated antigen cluster of differentiation 24 (CD24). In vitro, rG7S-MICA engaged both NK cells and CD24(+) human HCC cells, and triggered NK cell-mediated cytolysis. Furthermore, in CD24(+) HCC-bearing nude mice, rG7S-MICA specifically targeted to the tumor tissue, where it effectively recruited NK cells and induced the release of cytokines, and showed superior anti-tumor activity. In conclusion, rG7S-MICA provides a new approach for HCC-targeting immunotherapy and has attracting potentials for clinical applications.

  13. Genistein inhibits human TNF-α-induced porcine endothelial cell adhesiveness for human monocytes and natural killer cells

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Cellular immune response is a major barrier to xenotransplantation. Human tumor necrosis factor-α (hTNF-α) possesses cross-species activity and directly amplifies the immune rejection via the upregulation of adhesion molecules on porcine endothelium. We investigated the role of protein tyrosine phosphorylation in the induction of expression of E-sclectin and vascular cell adhesion molecule-1 (VCAM-1), and the augmentation of adhesion of human peripheral blood monocytes (PBMo) and natural killer cells (PBNK), after rhTNF-α-stimulation of porcine aortic endothelial cells (PAEC) in vitro, rhTNF-α-increased adhesiveness of PAEC for both PBMo and PBNK was dose-dependently reduced by pretreatment of PAEC with the selective protein tyrosine kinase (PTK) inhibitor genistein. The inhibitory effect occurred at the early time of PAEC activation triggered by rhTNF-α, and was completely reversible. PTK activity assay indicated that genistein also suppressed rhTNF-α stimulated activation of protein tyrosine kinases (PTKs) in PAEC in a dose-dependent manner. Flow cytometric analysis showed that genistein inhibited the upregulation of E-selectin and VCAM-1 by rhTNF-α. These results suggest that PTKs may regulate the expression of E-selectin and VCAM-1 on PAEC and the adherence of PBMo and PBNK induced by rhTNF-α. Moreover, dietary genistein, used as an adhesion antagonist, may contribute to managing the cell-mediated rejection in the clinical application.

  14. IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune-suppression

    OpenAIRE

    Eller, Kathrin; Wolf, Dominik; Huber, Julia M; Metz, Martin; Mayer, Gert; McKenzie, Andrew N.J.; Maurer, Marcus; Rosenkranz, Alexander R.; Wolf, Anna M

    2010-01-01

    Both, mast cells (MC) and regulatory T cells (Treg) have gained attention as immunosuppressive cell populations. To investigate a possible interaction, we used the Th1- and Th17-dependent model of nephrotoxic serum nephritis (NTS), in which both MC and Treg have been shown to play a protective role.

  15. Study of Serum Soluble Vascular Cell Adhesion Molecule-1 Level in Type 2 Diabetic Patients with Diabetic Retinopathy%可溶性血管细胞黏附分子-1与2型糖尿病视网膜病变的相关性研究

    Institute of Scientific and Technical Information of China (English)

    张秀坤; 石雪松; 杨宝林; 徐明艳; 侯英; 张羽

    2011-01-01

    Objective To study the change and the correlation of serum soluble vascular cell adhesion molecuh-1(sVCAM-1)level with diabetic retinopathy in type 2 diabetic patients.Methods 60 type 2 diabetic patients were selected for the study through the examination of ophthalmoscope and/or fundus fluorescence angiography by ophthalmologist.Diabetic patients were divided into three main groups:No signs of diabetic retinopathy(NDR)(n=20);Background DR(BDR)(n=20)Proliferative DR(PDR)(n=20).Healthy individuals matching sex and age of the patients were used as controls(n=20);Serum sVCAM-1 level was measured by ELISA,compared in diabetes without DR,with BDR,with PDR.These levels were compared with those of 20 controls.Results The serum level of sVCAM-1 in the DM patients with PDR or BDR and those without DR were significantly higher than those in healthy controls(all P<0.001);Serum level of sVCAM-1 in PDR groups were higherthan those in DM patients with BDR or patients without DR(all P<0.001);There was no difference between the patients with BDR and those without DR (P>0.05).(4)In the DM patients,there was a positive correlation between serum sVCAM-1 and the course of diseases(r=0.338,P<0.05),but no relationship with HbA1C,FBG,CHO,TG,LDL and INS.Conclusion Increased serum level of sVCAM-1 in different stage of DR patients suggested that they hagbe play an important role in the development of DR,and may assess the severity of diabetic retinopathy.The measuremem of serum sVCAM-1 levels in type 2 diabetic patients could be clinically useful for early diagnosis or treatment of diabetic retinopathy.%目的 研究2型糖尿病视网膜病变患者血清可溶性血管细胞黏附分子-1(sVCAM-1)水平的变化与糖尿病病程、视网膜病变程度、糖化血红蛋白、胰岛素、血糖及血脂之间的相关性.方法 选取2型糖尿病不伴视网膜病变患者[无视网膜病变组(NDR)]20例、2型糖尿病伴背景型视网膜病变患者[

  16. The Salmonella effector SopB prevents ROS-induced apoptosis of epithelial cells by retarding TRAF6 recruitment to mitochondria.

    Science.gov (United States)

    Ruan, Haihua; Zhang, Zhen; Tian, Li; Wang, Suying; Hu, Shuangyan; Qiao, Jian-Jun

    2016-09-16

    Microbial pathogens enter host cells by injecting effector proteins of the Type III secretion system (T3SS), which facilitate pathogen translocation across the host cell membrane. These effector proteins exert their effects by modulating a variety of host innate immune responses, thereby facilitating bacterial replication and systemic infection. Salmonella enterica serovar typhimurium (S.typhimurium) is a clinically important pathogen that causes food poisoning and gastroenteritis. The SopB effector protein of S. typhimurium, encoded by Salmonella pathogenicity islands (SPI)-1 T3SS, protects host epithelial cells from infection-induced apoptosis. However, how SopB influences apoptosis induction remains unclear. Here, we investigated the mechanism of SopB action in host cells. We found that SopB inhibits infection-induced apoptosis by attenuating the production of reactive oxygen species (ROS) in mitochondria, the crucial organelles for apoptosis initiation. Further investigation revealed that SopB binds to cytosolic tumor necrosis factor receptor associated factor 6 (TRAF6) and forms a trap preventing the mitochondrial recruitment of TRAF6, an essential event for ROS generation within mitochondria. By studying the response of Traf6(+/+) and Traf6(-/-)mouse embryonic fibroblasts to S. typhimurium infection, we found that TRAF6 promoted apoptosis by increasing ROS accumulation, which led to increased Bax/Bcl-2 ratio, Bax recruitment to mitochondrial membrane, and release of Cyt c into the cytoplasm. These findings show that SopB suppresses host cell apoptosis by binding to TRAF6 and preventing mitochondrial ROS generation. PMID:27473656

  17. TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression.

    Science.gov (United States)

    Martianov, Igor; Velt, Amandine; Davidson, Guillaume; Choukrallah, Mohamed-Amin; Davidson, Irwin

    2016-01-01

    Mammalian genomes encode two genes related to the TATA-box binding protein (TBP), TBP-related factors 2 and 3 (TRF2 and TRF3). Male Trf2(-/-) mice are sterile and characterized by arrested spermatogenesis at the transition from late haploid spermatids to early elongating spermatids. Despite this characterization, the molecular function of murine Trf2 remains poorly characterized and no direct evidence exists to show that it acts as a bona fide chromatin-bound transcription factor. We show here that Trf2 forms a stable complex with TFIIA or the testis expressed paralogue ALF chaperoned in the cytoplasm by heat shock proteins. We demonstrate for the first time that Trf2 is recruited to active haploid cell promoters together with Tbp, Taf7l and RNA polymerase II. RNA-seq analysis identifies a set of genes activated in haploid spermatids during the first wave of spermatogenesis whose expression is down-regulated by Trf2 inactivation. We therefore propose that Trf2 is recruited to the preinitiation complex as a testis-specific subunit of TFIIA/ALF that cooperates with Tbp and Taf7l to promote haploid cell gene expression. PMID:27576952

  18. Recruitment of HIV-1 target cells at topical mucosal sites: a sensitive and early marker for determining the safety of microbicide candidates.

    Science.gov (United States)

    Li, Liangzhu; Ben, Yinyin; Yuan, Songhua; Liu, Aiping; Wu, Huanmei; Xu, Jianqing; Zhang, Xiaoyan

    2013-07-01

    To explore early biomarkers for establishing more sensitive safety evaluation assays in preclinical settings that determine the potential risks during the application of microbicide candidates, three representative microbicide candidates (cellulose sulphate, nonoxynol-9 and tenofovir), whose safety profiles have been well established in clinical trials, were included to gauge the sensitivities of different assays. Both mouse models and cell lines were employed to determine the sensitivities. The recruitment of immune cells at topical mucosal sites and the upregulation of HIV receptor/coreceptors in vitro were identified as highly sensitive biomarkers of the impact of microbicide candidates. Our data suggest that different evaluations/assays have their inherent sensitivities, and at least one assay from each sensitivity level should be included in the safety evaluation algorithm. PMID:26038476

  19. Dynamic regulation of genes involved in mitochondrial DNA replication and transcription during mouse brown fat cell differentiation and recruitment

    DEFF Research Database (Denmark)

    Murholm, Maria; Dixen, Karen; Qvortrup, Klaus;

    2009-01-01

    ) and a remarkably higher mitochondrial abundance in brown adipocytes. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a comprehensive characterisation of gene expression linked to mitochondrial DNA replication, transcription and function during white and brown fat cell differentiation in vitro as well as in white...... precursor cells promotes mitochondrial DNA replication, and that silencing of PRDM16 expression during brown fat cell differentiation blunts mitochondrial biogenesis and expression of brown fat cell markers. CONCLUSIONS/SIGNIFICANCE: Using both in vitro and in vivo model systems of white and brown fat cell...

  20. Clinical research of Effects of Astragali on sICAM-1 and sVCAM-1 Levels in Patients with Acute Leucemia%黄芪对急性白血病患者血清黏附分子水平影响的临床研究

    Institute of Scientific and Technical Information of China (English)

    朱飞跃; 张卓; 曹朝晖; 姜志平

    2007-01-01

    目的:探讨黄芪对急性白血病病人可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平的影响.方法:64例初治急性白血病患者随机分为化疗组32例和化疗加黄芪组32例,采用酶联免疫吸附测定方法(ELISA法),对治疗前后的血清可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平进行检测.结果:①与正常组比较,急性白血病病人治疗前后可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平升高(P<0 05).②治疗后,化疗加黄芪组与化疗组血清可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平均下降(P<0 05),化疗加黄芪组下降尤为明显(P<0 05).结论黄芪可通过降低白血病血清sICAM-1和sVCAM-1水平的而发挥抗肿瘤作用.

  1. In situ vascular regeneration using substance P-immobilised poly(L-lactide-co-ε-caprolactone) scaffolds: stem cell recruitment, angiogenesis, and tissue regeneration.

    Science.gov (United States)

    Shafiq, M; Jung, Y; Kim, S H

    2015-01-01

    In situ tissue regeneration holds great promise for regenerative medicine and tissue engineering applications. However, to achieve control over long-term and localised presence of biomolecules, certain barriers must be overcome. The aim of this study was to develop electrospun scaffolds for the fabrication of artificial vascular grafts that can be remodelled within a host by endogenous cell recruitment. We fabricated scaffolds by mixing appropriate proportions of linear poly (l-lactide-co-ε-caprolactone) (PLCL) and substance P (SP)-immobilised PLCL, using electrospinning to develop vascular grafts. Substance P was released in a sustained fashion from electrospun membranes for up to 30 d, as revealed by enzyme-linked immunosorbent assay. Immobilised SP remained bioactive and recruited human bone marrow-derived mesenchymal stem cells (hMSCs) in an in vitro Trans-well migration assay. The biocompatibility and biological performance of the scaffolds were evaluated by in vivo experiments involving subcutaneous scaffold implantations in Sprague-Dawley rats for up to 28 d followed by histological and immunohistochemical studies. Histological analysis revealed a greater extent of accumulative host cell infiltration and collagen deposition in scaffolds containing higher contents of SP than observed in the control group at both time points. We also observed the presence of a large number of laminin-positive blood vessels and Von Willebrand factor (vWF+) cells in the explants containing SP. Additionally, scaffolds containing SP showed the existence of CD90+ and CD105+ MSCs. Collectively, these findings suggest that the methodology presented here may have broad applications in regenerative medicine, and the novel scaffolding materials can be used for in situ tissue regeneration of soft tissues. PMID:26614483

  2. In situ vascular regeneration using substance P-immobilised poly(L-lactide-co-ε-caprolactone) scaffolds: stem cell recruitment, angiogenesis, and tissue regeneration.

    Science.gov (United States)

    Shafiq, M; Jung, Y; Kim, S H

    2015-11-27

    In situ tissue regeneration holds great promise for regenerative medicine and tissue engineering applications. However, to achieve control over long-term and localised presence of biomolecules, certain barriers must be overcome. The aim of this study was to develop electrospun scaffolds for the fabrication of artificial vascular grafts that can be remodelled within a host by endogenous cell recruitment. We fabricated scaffolds by mixing appropriate proportions of linear poly (l-lactide-co-ε-caprolactone) (PLCL) and substance P (SP)-immobilised PLCL, using electrospinning to develop vascular grafts. Substance P was released in a sustained fashion from electrospun membranes for up to 30 d, as revealed by enzyme-linked immunosorbent assay. Immobilised SP remained bioactive and recruited human bone marrow-derived mesenchymal stem cells (hMSCs) in an in vitro Trans-well migration assay. The biocompatibility and biological performance of the scaffolds were evaluated by in vivo experiments involving subcutaneous scaffold implantations in Sprague-Dawley rats for up to 28 d followed by histological and immunohistochemical studies. Histological analysis revealed a greater extent of accumulative host cell infiltration and collagen deposition in scaffolds containing higher contents of SP than observed in the control group at both time points. We also observed the presence of a large number of laminin-positive blood vessels and Von Willebrand factor (vWF+) cells in the explants containing SP. Additionally, scaffolds containing SP showed the existence of CD90+ and CD105+ MSCs. Collectively, these findings suggest that the methodology presented here may have broad applications in regenerative medicine, and the novel scaffolding materials can be used for in situ tissue regeneration of soft tissues.

  3. Recruitment and Training. Symposium.

    Science.gov (United States)

    2002

    This document contains three papers from a symposium on recruitment and training. "College Choice: The State of Marketing and Effective Student Recruitment Strategies" (Fredrick Muyia Nafukho, Michael F. Burnett) reports on a study of the recruitment strategies used by Louisiana State University's admissions office and College of Agriculture that…

  4. Involvement of SRSF11 in cell cycle-specific recruitment of telomerase to telomeres at nuclear speckles

    OpenAIRE

    Lee, Ji Hoon; Jeong, Sun Ah; Khadka, Prabhat; Hong, Juyeong; Chung, In Kwon

    2015-01-01

    Telomerase, a unique ribonucleoprotein complex that contains the telomerase reverse transcriptase (TERT), the telomerase RNA component (TERC) and the TERC-binding protein dyskerin, is required for continued cell proliferation in stem cells and cancer cells. Here we identify SRSF11 as a novel TERC-binding protein that localizes to nuclear speckles, subnuclear structures that are enriched in pre-messenger RNA splicing factors. SRSF11 associates with active telomerase enzyme through an interacti...

  5. Increase of circulating CD11b(+)Gr1(+) cells and recruitment into the synovium in osteoarthritic mice with hyperlipidemia.

    Science.gov (United States)

    Uchida, Kentaro; Naruse, Kouji; Satoh, Masashi; Onuma, Kenji; Ueno, Masaki; Takano, Shotaro; Urabe, Ken; Takaso, Masashi

    2013-01-01

    Although recent studies suggest that hyperlipidemia is a risk factor for osteoarthritis (OA), the link between OA and hyperlipidemia is not fully understood. As the number of activated, circulating myeloid cells is increased during hyperlipidemia, we speculate that myeloid cells contribute to the pathology of OA. Here, we characterized myeloid cells in STR/Ort mice, a murine osteoarthritis model, under hyperlipidemic conditions. Ratios of myeloid cells in bone marrow, the spleen, and peripheral blood were determined by flow cytometry. To examine the influence of the hematopoietic environment, including abnormal stem cells, on the hematopoietic profile of STR/Ort mice, bone marrow transplantations were performed. The relationship between hyperlipidemia and abnormal hematopoiesis was examined by evaluating biochemical parameters and spleen weight of F2 animals (STR/Ort x C57BL/6J). In STR/Ort mice, the ratio of CD11b(+)Gr1(+) cells in spleens and peripheral blood was increased, and CD11b(+)Gr1(+) cells were also present in synovial tissue. Splenomegaly was observed and correlated with the ratio of CD11b(+)Gr1(+) cells. When bone marrow from GFP-expressing mice was transplanted into STR/Ort mice, no difference in the percentage of CD11b(+)Gr1(+) cells was observed between transplanted and age-matched STR/Ort mice. Analysis of biochemical parameters in F2 mice showed that spleen weight correlated with serum total cholesterol. These results suggest that the increase in circulating and splenic CD11b(+)Gr1(+) cells in STR/Ort mice originates from hypercholesterolemia. Further investigation of the function of CD11b(+)Gr1(+) cells in synovial tissue may reveal the pathology of OA in STR/Ort mice.

  6. IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response.

    Science.gov (United States)

    Lombard, Robin; Doz, Emilie; Carreras, Florence; Epardaud, Mathieu; Le Vern, Yves; Buzoni-Gatel, Dominique; Winter, Nathalie

    2016-01-01

    During chronic infection with Mycobacterium tuberculosis (Mtb), bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible. Signals that regulate neutrophil recruitment to the lung during mycobacterial infection need to be better understood. We demonstrated here, in the mouse model, that neutrophils were recruited to the lung in two waves after intranasal infection with virulent Mtb or the live attenuated vaccine strain Bacillus Calmette Guérin (BCG). A first wave of neutrophils was swiftly recruited, followed by a subsequent adaptive wave that reached the lung together with IFN-γ- and IL-17A-producing T cells. Interestingly, the second neutrophil wave did not participate to mycobacteria control in the lung and established contacts with T cells. The adaptive wave was critically dependent on the expression of IL-17RA, the receptor for IL-17A, expressed in non-hematopoietic cells. In absence of this receptor, curtailed CXCL-1 and 5 production in the lung restrained neutrophil recruitment. CXCL-1 and 5 instillation reconstituted lung neutrophil recruitment in BCG-infected IL17RA-/- mice. PMID:26871571

  7. IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response.

    Directory of Open Access Journals (Sweden)

    Robin Lombard

    Full Text Available During chronic infection with Mycobacterium tuberculosis (Mtb, bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible. Signals that regulate neutrophil recruitment to the lung during mycobacterial infection need to be better understood. We demonstrated here, in the mouse model, that neutrophils were recruited to the lung in two waves after intranasal infection with virulent Mtb or the live attenuated vaccine strain Bacillus Calmette Guérin (BCG. A first wave of neutrophils was swiftly recruited, followed by a subsequent adaptive wave that reached the lung together with IFN-γ- and IL-17A-producing T cells. Interestingly, the second neutrophil wave did not participate to mycobacteria control in the lung and established contacts with T cells. The adaptive wave was critically dependent on the expression of IL-17RA, the receptor for IL-17A, expressed in non-hematopoietic cells. In absence of this receptor, curtailed CXCL-1 and 5 production in the lung restrained neutrophil recruitment. CXCL-1 and 5 instillation reconstituted lung neutrophil recruitment in BCG-infected IL17RA-/- mice.

  8. The Recruitment Process:

    DEFF Research Database (Denmark)

    Holm, Anna

    The aim of this research was to determine whether the introduction of e-recruitment has an impact on the process and underlying tasks, subtasks and activities of recruitment. Three large organizations with well-established e-recruitment practices were included in the study. The three case studies......, which were carried out in Denmark in 2008-2009 using qualitative research methods, revealed changes in the sequence, divisibility and repetitiveness of a number of recruitment tasks and subtasks. The new recruitment process design was identified and presented in the paper. The study concluded...... that the main task of the process shifted from processing applications to communicating with candidates....

  9. Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine

    Science.gov (United States)

    Iwasaki, Akiko; Kelsall, Brian L.

    2000-01-01

    We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment. By two-color in situ immunofluorescence, CD11b+ myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8α+ lymphoid DCs are present in the T cell–rich interfollicular region (IFR). DCs that lack expression of CD8α or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3α mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED. In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3α. These data support a distinct role for MIP-3α/CCR6 in recruitment of CD11b+ DCs toward the mucosal surfaces and for MIP-3β/CCR7 in attraction of CD8α+ DCs to the T cell regions. Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections. PMID:10770804

  10. Crosstalk between medulloblastoma cells and endothelium triggers a strong chemotactic signal recruiting T lymphocytes to the tumor microenvironment.

    Directory of Open Access Journals (Sweden)

    Vita S Salsman

    Full Text Available Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF" is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant "Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES." This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications.

  11. Adhesion molecule expression stimulated by Bacteroides thetaiotaomicron cell-surface antigens.

    Science.gov (United States)

    Rokosz, A; Meisel-Mikołajczyk, F; Malchar, C; Nowaczyk, M; Górski, A

    1999-01-01

    Bacteroides thetaiotaomicron, a Gram-negative anaerobic rod belonging to the Bacteroides fragilis group (BFG), is involved in many systemic and local, most frequently suppurative infections in man. The cell envelope of these rods is composed of two carbohydrate-containing antigens: lipopolysaccharide (LPS) and capsular polysaccharide (CPS). Adhesion molecules ICAM-1, VCAM-1 and E-selectin (ELAM-1) are induced on the endothelial cells by mediators of inflammation. The aim of this study was to assay the ability of B. thetaiotaomicron surface antigens to induce adhesion molecule expression on the endothelial cells. The influence of LPS and CPS on the expression of adhesion molecules on HMEC-1 cell line was examined in an ELISA test. ELISA was performed with monoclonal mouse anti-human: ICAM-1, VCAM-1 and E-selectin antibodies of the IgG class. B. thetaiotaomicron lipopolysaccharides revealed the ability to induce ICAM-1, VCAM-1 and E-selectin expression on the endothelial cells. Their activities were similar, but lower than the activity of Eschericha coli LPS. ICAM-1 was the most stimulated adhesion molecule. The strongest activation by LPS was achieved at the concentrations of 10.0 and 1.0 micrograms/ml. The ability of capsular polysaccharide to induce the expression of adhesion molecules was considerably weaker.

  12. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity.

    OpenAIRE

    Turner, G D; Ly, V. C.; Nguyen, T.H.; Nguyen, H.P.; Bethell, D.; Wyllie, S.; Louwrier, K.; Fox, S B; Gatter, K C; Day, N P; Tran, T. H.; White, N J; Berendt, A R

    1998-01-01

    Fatal Plasmodium falciparum malaria is accompanied by systemic endothelial activation. To study endothelial activation directly during malaria and sepsis in vivo, the expression of cell adhesion molecules on dermal microvascular endothelium was examined in skin biopsies and correlated with plasma levels of soluble (circulating) ICAM-1, E-selectin, and VCAM-1 and the cytokine tumor necrosis factor (TNF)-alpha. Skin biopsies were obtained from 61 cases of severe malaria, 42 cases of uncomplicat...

  13. Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    Qun Li; Yves Laumonnier; Tatiana Syrovets; Thomas Simmet

    2013-01-01

    In the present study,monocyte-derived human macrophages were differentiated from buffy coats.Na(i)ve CD4+ T-cells enriched from peripheral blood mononuclear cells using anti-CD4 magnetic beads and the autoMACS separation system were polarized under T-helper 17 (Th17)-promoting conditions for 6 days to get Th17 cells.The frequency of Th17 cell differentiation and the expression of C-C chemokine receptor type 6 (CCR6) on Th17 cells were investigated by flow cytometry.Plasmin-triggered induction of macrophage inflammatory protein-3alpha/C-C chemokine ligand 20 (CCL20) genes in macrophages was assessed by reverse transcription-polymerase chain reaction,and secreted protein levels were measured by enzymelinked immunosorbent assay.Th17 cell migration induced by CCL20 secreted from plasmin-stimulated macrophages was tested in vitro by chemotaxis using a transwell system.These results demonstrate that plasmin triggers the expression of chemokine CCL20 messenger RNA and the release of CCL20 protein in human monocyte-derived macrophages,which critically depend on the proteolytic activity of plasmin and activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways.Expression of CCR6 was detected on 87.23 ± 8.6% of Th17 cells in vitro.Similar to chemotaxis triggered by recombinant human CCL20,supernatants collected from plasmin-stimulated macrophage-induced chemotactic migration of Th17 cells,which could be inhibited by an anti-CCL20 neutralizing antibody.These results suggest that plasmin generated in inflamed tissues might elicit production of chemokine CCL20 by human macrophages leading to the recruitmentof CCR6 positive Th17 cells to the inflammatory sites.

  14. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M.; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  15. Helicobacter pylori Activates HMGB1 Expression and Recruits RAGE into Lipid Rafts to Promote Inflammation in Gastric Epithelial Cells.

    Science.gov (United States)

    Lin, Hwai-Jeng; Hsu, Fang-Yu; Chen, Wei-Wei; Lee, Che-Hsin; Lin, Ying-Ju; Chen, Yi-Ywan M; Chen, Chih-Jung; Huang, Mei-Zi; Kao, Min-Chuan; Chen, Yu-An; Lai, Hsin-Chih; Lai, Chih-Ho

    2016-01-01

    Helicobacter pylori infection is associated with several gastrointestinal disorders in the human population worldwide. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. The interaction between HMGB1 and receptor for advanced glycation end-products (RAGE) triggers nuclear factor (NF)-κB expression, which in turn stimulates the release of proinflammatory cytokines, such as interleukin (IL)-8, and enhances the inflammatory response. However, how H. pylori activates HMGB1 expression and mobilizes RAGE into cholesterol-rich microdomains in gastric epithelial cells to promote inflammation has not been explored. In this study, we found that HMGB1 and RAGE expression increased significantly in H. pylori-infected cells compared with -uninfected cells. Blocking HMGB1 by neutralizing antibody abrogated H. pylori-elicited RAGE, suggesting that RAGE expression follows HMGB1 production, and silenced RAGE-attenuated H. pylori-mediated NF-κB activation and IL-8 production. Furthermore, significantly more RAGE was present in detergent-resistant membranes extracted from H. pylori-infected cells than in those from -uninfected cells, indicating that H. pylori exploited cholesterol to induce the HMGB1 signaling pathway. These results indicate that HMGB1 plays a crucial role in H. pylori-induced inflammation in gastric epithelial cells, which may be valuable in developing treatments for H. pylori-associated diseases. PMID:27667993

  16. Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells

    International Nuclear Information System (INIS)

    The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs in current immunosuppressive regimes for solid organ transplantation. However, they are nephrotoxic and promote death and profibrotic responses in tubular cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the mechanisms are poorly understood. We have now studied molecular pathways leading to inflammation elicited by the CNIs in cultured and kidney tubular cells. Both CsA and tacrolimus elicited a proinflammatory response in tubular cells as evidenced by a transcriptomics approach. Transcriptomics also suggested several potential pathways leading to expression of proinflammatory genes. Validation and functional studies disclosed that in tubular cells, CNIs activated protein kinases such as the JAK2/STAT3 and TAK1/JNK/AP-1 pathways, TLR4/Myd88/IRAK signaling and the Unfolded Protein Response (UPR) to promote NF-κB activation and proinflammatory gene expression. CNIs also activated an Nrf2/HO-1-dependent compensatory response and the Nrf2 activator sulforaphane inhibited JAK2 and JNK activation and inflammation. A murine model of CsA nephrotoxicity corroborated activation of the proinflammatory pathways identified in cell cultures. Human CNIs nephrotoxicity was also associated with NF-κB, STAT3 and IRE1α activation. In conclusion, CNIs recruit several intracellular pathways leading to previously non-described proinflammatory actions in renal tubular cells. Identification of these pathways provides novel clues for therapeutic intervention to limit CNIs nephrotoxicity. - Highlights: • Molecular mechanisms modulating CNI renal inflammation were investigated. • Kinases, immune receptors and ER stress mediate the inflammatory response to CNIs. • Several intracellular pathways activate NF-κB in CNIs-treated tubular cells. • A NF-κB-dependent cytokine profile characterizes CNIs-induced inflammation. • CNI nephrotoxicity was associated to inflammatory

  17. ICAM-1 expression and organization in human endothelial cells is sensitive to gravity

    Science.gov (United States)

    Zhang, Yu; Sang, Chen; Paulsen, Katrin; Arenz, Andrea; Zhao, Ziyan; Jia, Xiaoling; Ullrich, Oliver; Zhuang, Fengyuan

    2010-11-01

    Transendothelial migration (TEM) of immune cells is a crucial process during a multitude of physiological and pathological conditions such as development, defense against infections and wound healing. Migration within the body tissues and through endothelial barriers is strongly dependent and regulated both by cytoskeletal processes and by expression of surface adhesion molecules such as ICAM-1 and VCAM-1. Space flight experiments have confirmed that TEM will be inhibited and may cause astronauts' immune function decreased and make them easy for infection. We used NASA RCCS to provide a simulated microgravity environment; endothelial cells were cultured on microcarrier beads and activated by TNF-α. Results demonstrate after clinorotation ICAM-1 expression increased, consistent with the notion in parabolic flights. However, VCAM-1 showed no significant change between activated or inactivated cells. Depolymerization of F-actin and clustering of ICAM-1 on cell membrane were also observed in short-term simulated microgravity, and after 24 h clinorotation, actin fiber rearrangement was initiated and clustering of ICAM-1 became stable. ICAM-1 mRNA and VCAM-1 mRNA were up-regulated after 30 min clinorotation, and returned to the same level with controls after 24 h clinorotation.

  18. Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

    Directory of Open Access Journals (Sweden)

    D. Carlos

    2011-04-01

    Full Text Available It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B4 (LTB4 production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group with 1000 embryonated eggs containing third-stage (L3 T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB4 levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB4-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

  19. Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.

    Directory of Open Access Journals (Sweden)

    Zahra Hassani

    Full Text Available MAIN OBJECTIVES: Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised. This study investigated the cellular events occurring after CTX0E03 transplantation in the brains of rats that underwent ischemic stroke. METHODS: We focused on the endogenous proliferative activity of the host brain in response to cell transplantation and determined the identity of the proliferating cells using markers for young neurons (doublecortin, Dcx and microglia (CD11b. So as to determine the chronology of events occurring post-transplantation, we analysed the engrafted brains one week and four weeks post-transplantation. RESULTS: We observed a significantly greater endogenous proliferation in the striatum of ischemic brains receiving a CTX0E03 graft compared to vehicle-treated ischemic brains. A significant proportion of these proliferative cells were found to be Dcx+ striatal neuroblasts. Further, we describe an enhanced immune response after CTX0E03 engraftment, as shown by a significant increase of proliferating CD11b+ microglial cells. CONCLUSIONS: Our study demonstrates that few Dcx+ neuroblasts are proliferative in normal conditions, and that this population of proliferative neuroblasts is increased in response to stroke. We further show that CTX0E03 transplantation after stroke leads to the maintenance of this proliferative activity. Interestingly, the preservation of neuronal proliferative activity upon CTX0E03 transplantation is preceded and accompanied by a high rate of proliferating microglia. Our study suggests that microglia might mediate in part the effect of CTX0E03 transplantation on neuronal proliferation in ischemic stroke conditions.

  20. E-recruitment

    DEFF Research Database (Denmark)

    Holm, Anna

    2012-01-01

    E-recruitment, also known as online or web-based recruitment, is little discussed in research from an organizational perspective. The purpose of this chapter is therefore to analyze and discuss the process of e-recruitment, its key constituents and organizing principles. In doing so I draw on the...... results of a qualitative study conducted in 2008-2009, and on data stemming from industrial reports, articles from practitioner magazines, and in-depth interviews. The chapter provides a summary of e-recruitment properties and a composite matrix of the overall elements of e-recruitment organizing. E-recruitment...... is viewed as a case of virtual organizing- the organization of processes and activities which, via technology and human agents, facilitate time- and space-independent interaction and collaboration. In closure I offer a brief discussion of implications of the findings for HR managers and professionals...

  1. DNA vaccination in fish promotes an early chemokine-related recruitment of B cells to the muscle

    DEFF Research Database (Denmark)

    Castro, R.; Martínez-Alonso, S.; Fischer, U.;

    2013-01-01

    In fish, intramuscular injection of plasmid DNA encoding viral proteins has proved as the most effective vaccination strategy against many viral pathogens. The efficacy of DNA vaccination in teleost fish is based on a high level of viral antigen expression in muscle cells inducing a strong and lo...

  2. Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Jiayao [Institute of Nephrology, State Key Laboratory of Kidney Disease (2011DAV00088), The Chinese PLA General Hospital, Beijing 100853 (China); Medical College of NanKai University, Tianjin (China); Li, Qinggang; Xie, Yuansheng; Zhang, Xueguang; Cui, Shaoyuan; Shi, Suozhu [Institute of Nephrology, State Key Laboratory of Kidney Disease (2011DAV00088), The Chinese PLA General Hospital, Beijing 100853 (China); Chen, Xiangmei, E-mail: xmchen301@126.com [Institute of Nephrology, State Key Laboratory of Kidney Disease (2011DAV00088), The Chinese PLA General Hospital, Beijing 100853 (China); Medical College of NanKai University, Tianjin (China)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Overexpression of Robo2 caused reduced UB branching and glomerular number. Black-Right-Pointing-Pointer Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. Black-Right-Pointing-Pointer No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. Black-Right-Pointing-Pointer Overexpression of Robo2 affected MM cells migration and caused UB deficit. Black-Right-Pointing-Pointer The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2-Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2-Robo2 signaling is also important for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that

  3. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    Directory of Open Access Journals (Sweden)

    David Gallego-Ortega

    2015-12-01

    Full Text Available During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer.

  4. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    Science.gov (United States)

    Gallego-Ortega, David; Ledger, Anita; Roden, Daniel L; Law, Andrew M K; Magenau, Astrid; Kikhtyak, Zoya; Cho, Christina; Allerdice, Stephanie L; Lee, Heather J; Valdes-Mora, Fatima; Herrmann, David; Salomon, Robert; Young, Adelaide I J; Lee, Brian Y; Sergio, C Marcelo; Kaplan, Warren; Piggin, Catherine; Conway, James R W; Rabinovich, Brian; Millar, Ewan K A; Oakes, Samantha R; Chtanova, Tatyana; Swarbrick, Alexander; Naylor, Matthew J; O'Toole, Sandra; Green, Andrew R; Timpson, Paul; Gee, Julia M W; Ellis, Ian O; Clark, Susan J; Ormandy, Christopher J

    2015-12-01

    During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angiogenesis, and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. Myeloid-derived suppressor cells, a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis, were recruited to the tumor in response to ELF5. Depletion of these cells using specific Ly6G antibodies prevented ELF5 from driving vasculogenesis and metastasis. Expression signatures in luminal A breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with ELF5 expression, and increased ELF5 immunohistochemical staining predicted much shorter metastasis-free and overall survival of luminal A patients, defining a group who experienced unexpectedly early disease progression. Thus, in the MMTV-PyMT mouse mammary model, increased ELF5 levels drive metastasis by co-opting the innate immune system. As ELF5 has been previously implicated in the development of antiestrogen resistance, this finding implicates ELF5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal A breast cancer. PMID:26717410

  5. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs and Eosinophils (Eos with Host Mast Cells (MCs and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Directory of Open Access Journals (Sweden)

    Mahin Khatami

    2014-01-01

    Full Text Available Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates is heavy investment on numerous genetic mutations (molecular false-flags in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance. Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs demonstrated at least three stages of interactions between resident (host and recruited immune cells: (a, acute phase; activation of mast cells (MCs, IgE Abs, histamine and prostaglandin synthesis; (b, intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos infiltrations into epithelia and goblet cells (GCs, tissue hypertrophy and neovascularization; and (c, chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mfs, increased (irregular size B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth and/or thinning (necrosis and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  6. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    International Nuclear Information System (INIS)

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  7. Chronic Inflammation: Synergistic Interactions of Recruiting Macrophages (TAMs) and Eosinophils (Eos) with Host Mast Cells (MCs) and Tumorigenesis in CALTs. M-CSF, Suitable Biomarker for Cancer Diagnosis!

    Energy Technology Data Exchange (ETDEWEB)

    Khatami, Mahin [Inflammation and Cancer Biology, National Cancer Institute (Ret), the National Institutes of Health, Bethesda, MD 20817 (United States)

    2014-01-27

    Ongoing debates, misunderstandings and controversies on the role of inflammation in cancer have been extremely costly for taxpayers and cancer patients for over four decades. A reason for repeated failed clinical trials (90% ± 5 failure rates) is heavy investment on numerous genetic mutations (molecular false-flags) in the chaotic molecular landscape of site-specific cancers which are used for “targeted” therapies or “personalized” medicine. Recently, unresolved/chronic inflammation was defined as loss of balance between two tightly regulated and biologically opposing arms of acute inflammation (“Yin”–“Yang” or immune surveillance). Chronic inflammation could differentially erode architectural integrities in host immune-privileged or immune-responsive tissues as a common denominator in initiation and progression of nearly all age-associated neurodegenerative and autoimmune diseases and/or cancer. Analyses of data on our “accidental” discoveries in 1980s on models of acute and chronic inflammatory diseases in conjunctival-associated lymphoid tissues (CALTs) demonstrated at least three stages of interactions between resident (host) and recruited immune cells: (a), acute phase; activation of mast cells (MCs), IgE Abs, histamine and prostaglandin synthesis; (b), intermediate phase; down-regulation phenomenon, exhausted/degranulated MCs, heavy eosinophils (Eos) infiltrations into epithelia and goblet cells (GCs), tissue hypertrophy and neovascularization; and (c), chronic phase; induction of lymphoid hyperplasia, activated macrophages (Mϕs), increased (irregular size) B and plasma cells, loss of integrity of lymphoid tissue capsular membrane, presence of histiocytes, follicular and germinal center formation, increased ratios of local IgG1/IgG2, epithelial thickening (growth) and/or thinning (necrosis) and angiogenesis. Results are suggestive of first evidence for direct association between inflammation and identifiable phases of immune

  8. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Ana M. Santander

    2015-01-01

    Full Text Available The relationship between obesity and breast cancer (BC has focused on serum factors. However, the mammary gland contains adipose tissue (AT which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations. In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.

  9. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

    International Nuclear Information System (INIS)

    The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity

  10. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Santander, Ana M.; Lopez-Ocejo, Omar; Casas, Olivia; Agostini, Thais; Sanchez, Lidia; Lamas-Basulto, Eduardo; Carrio, Roberto [Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136 (United States); Cleary, Margot P. [Hormel Institute, University of Minnesota, Austin, MN 55912 (United States); Gonzalez-Perez, Ruben R. [Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30314 (United States); Torroella-Kouri, Marta, E-mail: mtorroella@med.miami.edu [Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136 (United States); Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1475 NW 12th Ave, Miami, FL 33136 (United States)

    2015-01-15

    The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.

  11. Recruitment and Consolidation of Cell Assemblies for Words by Way of Hebbian Learning and Competition in a Multi-Layer Neural Network.

    Science.gov (United States)

    Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

    2009-06-01

    Current cognitive theories postulate either localist representations of knowledge or fully overlapping, distributed ones. We use a connectionist model that closely replicates known anatomical properties of the cerebral cortex and neurophysiological principles to show that Hebbian learning in a multi-layer neural network leads to memory traces (cell assemblies) that are both distributed and anatomically distinct. Taking the example of word learning based on action-perception correlation, we document mechanisms underlying the emergence of these assemblies, especially (i) the recruitment of neurons and consolidation of connections defining the kernel of the assembly along with (ii) the pruning of the cell assembly's halo (consisting of very weakly connected cells). We found that, whereas a learning rule mapping covariance led to significant overlap and merging of assemblies, a neurobiologically grounded synaptic plasticity rule with fixed LTP/LTD thresholds produced minimal overlap and prevented merging, exhibiting competitive learning behaviour. Our results are discussed in light of current theories of language and memory. As simulations with neurobiologically realistic neural networks demonstrate here spontaneous emergence of lexical representations that are both cortically dispersed and anatomically distinct, both localist and distributed cognitive accounts receive partial support.

  12. The Effect of Incorporation of SDF-1α into PLGA Scaffolds on Stem Cell Recruitment and the Inflammatory Response

    OpenAIRE

    Thevenot, Paul; Nair, Ashwin; Shen, Jinhui; Lotfi, Parisa; Ko, Cheng Yu; Tang, Liping

    2010-01-01

    Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design. ...

  13. Inhibition of the activation and recruitment of microglia-like cells protects against neomycin-induced ototoxicity.

    Science.gov (United States)

    Sun, Shan; Yu, Huiqian; Yu, Hui; Honglin, Mei; Ni, Wenli; Zhang, Yanping; Guo, Luo; He, Yingzi; Xue, Zhen; Ni, Yusu; Li, Jin; Feng, Yi; Chen, Yan; Shao, Ruijin; Chai, Renjie; Li, Huawei

    2015-02-01

    One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 μg/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.

  14. Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3

    Science.gov (United States)

    Tao, Ting; Shi, Hui; Lo, Li Jan; Wang, Yingchun; Chen, Jun; Peng, Jinrong

    2016-01-01

    Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis. PMID:27657329

  15. Angiotensin II modulates interleukin-1{beta}-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-{kappa}B crosstalk

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Shanqin [Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA (United States); Zhi, Hui [Cardiovascular Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Hou, Xiuyun [Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA (United States); Jiang, Bingbing, E-mail: bjiang1@rics.bwh.harvard.edu [Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA (United States); Cardiovascular Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States)

    2011-07-08

    Highlights: {yields} We examine how angiotensin II modulates ERK-NF-{kappa}B crosstalk and gene expression. {yields} Angiotensin II suppresses IL-1{beta}-induced prolonged ERK and NF-{kappa}B activation. {yields} ERK-RSK1 signaling is required for IL-1{beta}-induced prolonged NF-{kappa}B activation. {yields} Angiotensin II modulates NF-{kappa}B responsive genes via regulating ERK-NF-{kappa}B crosstalk. {yields} ERK-NF-{kappa}B crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. In cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1{beta}-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-{kappa}B, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1{beta}-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1{beta}, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE{sup -/-}) mice. VCAM-1 and iNOS expression were higher in ApoE{sup -/-} than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE{sup -/-} mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that angiotensin

  16. The Stem Cell-Expressed Receptor Lgr5 Possesses Canonical and Functionally Active Molecular Determinants Critical to β-arrestin-2 Recruitment

    Science.gov (United States)

    Snyder, Joshua C.; Rochelle, Lauren K.; Barak, Larry S.; Caron, Marc G.

    2013-01-01

    Lgr5 is a membrane protein related to G protein-coupled receptors (GPCR)s whose expression identifies stem cells in multiple tissues and is strongly correlated with cancer. Despite the recent identification of endogenous ligands for Lgr5, its mode of signaling remains enigmatic. The ability to couple to G proteins and βarrestins are classical molecular behaviors of GPCRs that have yet to be observed for Lgr5. Therefore, the goal of this study was to determine if Lgr5 can engage a classical GPCR behavior and elucidate the molecular determinants of this process. Structural analysis of Lgr5 revealed several motifs consistent with its ability to recruit βarr2. Among them, a “SSS” serine cluster located at amino acid position 873-875 within the C-terminal tail (C-tail), is in a region consistent with other GPCRs that bind βarr2 with high-affinity. To test its functionality, a ligand-independent βarr2 translocation assay was implemented. We show that Lgr5 recruits βarr2 and that the “SSS” amino acids (873-875) are absolutely critical to this process. We also demonstrate that for full efficacy, this cluster requires other Lgr5 C-tail serines that were previously shown to be important for constitutive and βarr2 independent internalization of Lgr5. These data are proof of principle that a classical GPCR behavior can be manifested by Lgr5. The existence of alternative ligands or missing effectors of Lgr5 that scaffold this classical GPCR behavior and the downstream signaling pathways engaged should be considered. Characterizing Lgr5 signaling will be invaluable for assessing its role in tissue maintenance, repair, and disease. PMID:24386388

  17. The stem cell-expressed receptor Lgr5 possesses canonical and functionally active molecular determinants critical to β-arrestin-2 recruitment.

    Directory of Open Access Journals (Sweden)

    Joshua C Snyder

    Full Text Available Lgr5 is a membrane protein related to G protein-coupled receptors (GPCRs whose expression identifies stem cells in multiple tissues and is strongly correlated with cancer. Despite the recent identification of endogenous ligands for Lgr5, its mode of signaling remains enigmatic. The ability to couple to G proteins and βarrestins are classical molecular behaviors of GPCRs that have yet to be observed for Lgr5. Therefore, the goal of this study was to determine if Lgr5 can engage a classical GPCR behavior and elucidate the molecular determinants of this process. Structural analysis of Lgr5 revealed several motifs consistent with its ability to recruit βarr2. Among them, a "SSS" serine cluster located at amino acid position 873-875 within the C-terminal tail (C-tail, is in a region consistent with other GPCRs that bind βarr2 with high-affinity. To test its functionality, a ligand-independent βarr2 translocation assay was implemented. We show that Lgr5 recruits βarr2 and that the "SSS" amino acids (873-875 are absolutely critical to this process. We also demonstrate that for full efficacy, this cluster requires other Lgr5 C-tail serines that were previously shown to be important for constitutive and βarr2 independent internalization of Lgr5. These data are proof of principle that a classical GPCR behavior can be manifested by Lgr5. The existence of alternative ligands or missing effectors of Lgr5 that scaffold this classical GPCR behavior and the downstream signaling pathways engaged should be considered. Characterizing Lgr5 signaling will be invaluable for assessing its role in tissue maintenance, repair, and disease.

  18. Recruitment and activation of pancreatic stellate cells from the bone marrow in pancreatic cancer: a model of tumor-host interaction.

    Directory of Open Access Journals (Sweden)

    Christopher J Scarlett

    Full Text Available BACKGROUND AND AIMS: Chronic pancreatitis and pancreatic cancer are characterised by extensive stellate cell mediated fibrosis, and current therapeutic development includes targeting pancreatic cancer stroma and tumor-host interactions. Recent evidence has suggested that circulating bone marrow derived stem cells (BMDC contribute to solid organs. We aimed to define the role of circulating haematopoietic cells in the normal and diseased pancreas. METHODS: Whole bone marrow was harvested from male β-actin-EGFP donor mice and transplanted into irradiated female recipient C57/BL6 mice. Chronic pancreatitis was induced with repeat injections of caerulein, while carcinogenesis was induced with an intrapancreatic injection of dimethylbenzanthracene (DMBA. Phenotype of engrafted donor-derived cells within the pancreas was assessed by immunohistochemistry, immunofluorescence and in situ hybridisation. RESULTS: GFP positive cells were visible in the exocrine pancreatic epithelia from 3 months post transplantation. These exhibited acinar morphology and were positive for amylase and peanut agglutinin. Mice administered caerulein developed chronic pancreatitis while DMBA mice exhibited precursor lesions and pancreatic cancer. No acinar cells were identified to be donor-derived upon cessation of cerulein treatment, however rare occurrences of bone marrow-derived acinar cells were observed during pancreatic regeneration. Increased recruitment of BMDC was observed within the desmoplastic stroma, contributing to the activated pancreatic stellate cell (PaSC population in both diseases. Expression of stellate cell markers CELSR3, PBX1 and GFAP was observed in BMD cancer-associated PaSCs, however cancer-associated, but not pancreatitis-associated BMD PaSCs, expressed the cancer PaSC specific marker CELSR3. CONCLUSIONS: This study demonstrates that BMDC can incorporate into the pancreas and adopt the differentiated state of the exocrine compartment. BMDC that

  19. Recruitment of general practices

    DEFF Research Database (Denmark)

    Riis, Allan; Jensen, Cathrine E; Maindal, Helle T;

    2016-01-01

    -factors as determinants for successfully recruiting healthcare professionals: relationships, reputation, requirements, rewards, reciprocity, resolution, and respect. METHOD: This is a process evaluation of the seven R-factors. We applied these factors to guide the design of our recruitment strategy as well as to make...... underestimated. CONCLUSION: The framework of the seven R-factors was a feasible tool in our recruitment process. However, we suggest further investigation in developing systematic approaches to support the recruitment of healthcare professionals to research.......INTRODUCTION: Health service research often involves the active participation of healthcare professionals. However, their ability and commitment to research varies. This can cause recruitment difficulties and thereby prolong the study period and inflate budgets. Solberg has identified seven R...

  20. Dopamine D3 receptors modulate the rate of neuronal recovery, cell recruitment in Area X, and song tempo after neurotoxic damage in songbirds.

    Science.gov (United States)

    Lukacova, Kristina; Pavukova, Eva; Kostal, Lubor; Bilcik, Boris; Kubikova, Lubica

    2016-09-01

    Songbirds, like humans, learn vocalizations and their striatum recruits new neurons in adulthood. Injury in striatal vocal nucleus Area X, involved in song learning and production in songbirds, is followed by massive regeneration. The newborn neurons arise from the subventricular zone (SVZ) rich in dopamine D3 receptors (D3Rs). The aim of this study was to investigate whether the D3Rs affect the rate of neuronal recovery in Area X. Male zebra finches (Taeniopygia guttata) received bilateral neurotoxic lesion of Area X and were implanted with osmotic minipumps containing D3R agonist 7-OH-DPAT, antagonist U99194, or saline. Treatment with 7-OH-DPAT but not U99194 led to significant reduction of lesion size and increased numbers of migrating neuroblasts and newborn cells in the Area X. These cells were detected in the lesion border as well as the lesion center. Lesion also led to increased mRNA expression of the D3Rs in the neurogenic SVZ and in the nucleus robustus arcopallialis (RA) involved in song production. Moreover, lesion alone prolonged the song duration and this may be facilitated by D3Rs in RA. Parallel lesion and stimulation of D3Rs prolonged it even more, while blocking of D3Rs abolished the lesion-induced effect. These data suggest that D3R stimulation after striatal injury accelerates the striatal recovery and can cause behavioral alterations. PMID:27339729

  1. Cell Recruitment and Cytokines in Skin Mice Sensitized with the Vaccine Adjuvants: Saponin, Incomplete Freund’s Adjuvant, and Monophosphoryl Lipid A

    Science.gov (United States)

    Vitoriano-Souza, Juliana; Moreira, Nádia das Dores; Teixeira-Carvalho, Andréa; Carneiro, Cláudia Martins; Siqueira, Fernando Augusto Mathias; Vieira, Paula Melo de Abreu; Giunchetti, Rodolfo Cordeiro; Moura, Sandra Aparecida de Lima; Fujiwara, Ricardo Toshio; Melo, Maria Norma; Reis, Alexandre Barbosa

    2012-01-01

    Vaccine adjuvants are substances associated with antigens that are fundamental to the formation of an intense, durable, and fast immune response. In this context, the use of vaccine adjuvants to generate an effective cellular immune response is crucial for the design and development of vaccines against visceral leishmaniasis. The objective of this study was to evaluate innate inflammatory response induced by the vaccine adjuvants saponin (SAP), incomplete Freund’s adjuvant (IFA), and monophosphoryl lipid A (MPL). After a single dose of adjuvant was injected into the skin of mice, we analyzed inflammatory reaction, selective cell migration, and cytokine production at the injection site, and inflammatory cell influx in the peripheral blood. We found that all vaccine adjuvants were able to promote cell recruitment to the site without tissue damage. In addition, they induced selective migration of neutrophils, macrophages, and lymphocytes. The influx of neutrophils was notable at 12 h in all groups, but at other time points it was most evident after inoculation with SAP. With regard to cytokines, the SAP led to production of interleukin (IL)-2, IL-6, and IL-4. IFA promoted production of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, IL-17, IL-4, and IL-10. We also observed that MPL induced high production of IL-2, TNF-α, and IFN-γ, in addition to IL-6, IL-17, and IL-10. In peripheral blood, values of certain cell populations in the local response changed after stimulation. Our data demonstrate that the three vaccine adjuvants stimulate the early events of innate immune response at the injection site, suggesting their ability to increase the immunogenicity of co-administered antigens. Moreover, this work provides relevant information about elements of innate and acquired immune response induced by vaccine adjuvants administered alone. PMID:22829882

  2. Small interfering RNA-mediated suppression of Ccl2 in Müller cells attenuates microglial recruitment and photoreceptor death following retinal degeneration

    Directory of Open Access Journals (Sweden)

    Rutar Matt

    2012-09-01

    Full Text Available Abstract Background The recruitment and activation of inflammatory cells is thought to exacerbate photoreceptor death in retinal degenerative conditions such as age-related macular degeneration (AMD. We investigated the role of Müller cell-derived chemokine (C-C motif ligand (Ccl2 expression on monocyte/microglia infiltration and photoreceptor death in light-mediated retinal degeneration, using targeted small interfering (siRNA. Methods Adult Sprague–Dawley rats were injected intravitreally with 1 μg of either Ccl2 siRNA or scrambled siRNA, and were then exposed to 1000 lux of light for a period of 24 hours. The mice were given an overdose of barbiturate, and the retinas harvested and evaluated for the effects of bright-light exposure. Ccl2 expression was assessed by quantitative PCR, immunohistochemistry, and in situ hybridization. Monocytes/microglia were counted on retinal cryostat sections immunolabeled with the markers ED1 and ionized calcium binding adaptor (IBA1, and photoreceptor apoptosis was assessed using terminal dUTP nick end labeling. Results Intravitreal injection of Ccl2 siRNA significantly reduced the expression of Ccl2 following light damage to 29% compared with controls. In retinas injected with Ccl2 siRNA, in situ hybridization and immunohistochemistry on retinal cryostat sections showed a substantial decrease in Ccl2 within Müller cells. Cell counts showed significantly fewer ED1-positive and IBA1-positive cells in the retinal vasculature and outer nuclear layer of Ccl2 siRNA-injected retinas, compared with controls. Moreover, there was significantly less photoreceptor apoptosis in Ccl2 siRNA-injected retinas compared with controls. Conclusions Our data indicate that Ccl2 expression by Müller cells promotes the infiltration of monocytes/microglia, thereby contributing to the neuroinflammatory response and photoreceptor death following retinal injury. Modulation of exaggerated chemokine responses using siRNA may have

  3. Astrocyte-Derived CCL2 is Associated with M1 Activation and Recruitment of Cultured Microglial Cells

    Directory of Open Access Journals (Sweden)

    Mingfeng He

    2016-02-01

    Full Text Available Background/Aims: Microglia are an essential player in central nervous system inflammation. Recent studies have demonstrated that the astrocytic chemokine, CCL2, is associated with microglial activation in vivo. However, CCL2-induced microglial activation has not yet been studied in vitro. The purpose of the current study was to understand the role of astrocyte-derived CCL2 in microglial activation and to elucidate the underlying mechanism(s. Methods: Primary astrocytes were pre-treated with CCL2 siRNA and stimulated with TNF-α. The culture medium (CM was collected and added to cultures of microglia, which were incubated with and without CCR2 inhibitor. Microglial cells were analyzed by quantitative RT-PCR to determine whether they polarized to the M1 or M2 state. Microglial migratory ability was assessed by transwell migration assay. Results: TNF-α stimulated the release of CCL2 from astrocytes, even if the culture media containing TNF-α was replaced with fresh media after 3 h. CM from TNF-α-stimulated astrocytes successfully induced microglial activation, which was ascertained by increased activation of M1 and enhanced migration ability. In contrast, CM from astrocytes pretreated with CCL2 siRNA showed no effect on microglial activation, compared to controls. Additionally, microglia pre-treated with RS102895, a CCR2 inhibitor, were resistant to activation by CM from TNF-α-stimulated astrocytes. Conclusion: This study demonstrates that the CCL2/CCR2 pathway of astrocyte-induced microglial activation is associated with M1 polarization and enhanced migration ability, indicating that this pathway could be a useful target to ameliorate inflammation in the central nervous system.

  4. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  5. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Science.gov (United States)

    Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

    2013-01-01

    Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  6. Correlation of Serum Concentrations of Soluble Thrombomodulin, Soluble Vascular Cell Adhesion Molecule-1,Intracellular Adhesion Molecule -1 And E-Selectin In Patients WithSystemic Lupus Erythematosus

    OpenAIRE

    Malak., A. Mohsen*, Magda.A.Gamil*,Maha. I.Shehata

    2003-01-01

    To date no specific serological parameters are available to assess disease activity in systemic lupus erythematosus (SLE). The objective of this study was to correlate serum levels of thrombomodulin (TM), intracellular adhesion molecule-1 sICAM-1, vascular cell adhesion molecule-1 sVCAM-1, and E-selectin with standard laboratory tests and clinical indices of disease activity in 40 patients with SLE and 20 apparently healthy persons as controls. According to British Isles Lupus Assessment Grou...

  7. Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes.

    Directory of Open Access Journals (Sweden)

    Margaret Veselits

    Full Text Available Casitas B-lineage lymphoma-b (Cbl-b is a ubiquitin ligase (E3 that modulates signaling by tagging molecules for degradation. It is a complex protein with multiple domains and binding partners that are not involved in ubiquitinating substrates. Herein, we demonstrate that Cbl-b, but not c-Cbl, is recruited to the clustered B cell antigen receptor (BCR and that Cbl-b is required for entry of endocytosed BCRs into late endosomes. The E3 activity of Cbl-b is not necessary for BCR endocytic trafficking. Rather, the ubiquitin associated (UBA domain is required. Furthermore, the Cbl-b UBA domain is sufficient to confer the receptor trafficking functions of Cbl-b on c-Cbl. Cbl-b is also required for entry of the Toll-like receptor 9 (TLR9 into late endosomes and for the in vitro activation of TLR9 by BCR-captured ligands. These data indicate that Cbl-b acts as a scaffolding molecule to coordinate the delivery of the BCR and TLR9 into subcellular compartments required for productively delivering BCR-captured ligands to TLR9.

  8. Association of serum soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1 and hypersensitivity-CRP levels with peripheral vascular disease of lower limbs in patients with type 2 diabetes mellitus%2型糖尿病患者血清可溶性细胞间和血管细胞黏附分子1及CRP与下肢血管病变的关系

    Institute of Scientific and Technical Information of China (English)

    谭擎缨; 王静; 阮芸; 阮勇; 王秀景; 姚佳琦; 姚乐燕

    2013-01-01

    Objective To investigate the association of serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1),soluble vascular cell adhesion molecule-1 (sVCAM-1) and high sensitivity C-reactive protein (hs-CRP) with peripheral vascular disease of lower limbs in patients with type 2 diabetes mellitus (T2DM).Methods One hundred and thirty T2DM patients admitted from October 2011 to October 2012,and 30 age/sex-matched healthy subjects were enrolled in the study.The serum levels of sICAM-1,sVCAM-1,hs-CRP and other clinical parameters were measured; the peripheral blood vessels of lower limbs were examined with color Doppler ultrasonography.Based on the extent of angiopathy of lower limbs T2DM patients were classified as normal vascular group (n =26),mild angiopathy group (n =45),moderate/severe angiopathy group (n =59).Results The serum levels of sICAM-1 and sVCAM-1 in moderate/ severe angiopathy group of T2DM patients were higher than those in mild angiopathy group,normal vascular group and healthy controls (t:4.15-8.93,all P <0.05) ; the serum levels of hs-CRP in moderate/severe angiopathy group were higher than those in mild angiopathy group,normal vascular group and healthy controls (t:2.18-4.27,all P < 0.05).The serum sICAM-1 level was positively correlated with total cholesterol (TC),low density lipoprotein cholesterol (LDL-C) and sVCAM-1.The serum sVCAM-1 level was positively correlated with course of disease,systolic blood pressure and CRP.Conclusions Serum levels of sICAM-1,sVCAM-1 and hs-CRP are correlated with the extent of angiopathy of lower limbs in T2DM patients,and the elevated sICAM-1 ; sVCAM-1 and hs-CRP levels are also associated with hyper blood pressure,dislipidemia and chronic inflammation.%目的 探讨2型糖尿病患者血清可溶性细胞间黏附分子1(sICAM-1)、血管细胞黏附分子1(sVCAM-1)及高敏CRP(hsCRP)水平与下肢大血管病变程度的关系.方法 对130例2型糖尿病患者(糖尿病组)与30例年龄匹配

  9. Electronic Recruitment at CERN

    CERN Multimedia

    2004-01-01

    The Human Resources Department switches to electronic recruitment. From now on whenever you are involved in a recruitment action you will receive an e-mail giving you access to a Web folder. Inside you will find a shortlist of applications drawn up by the Human Resources Department. This will allow you to consult the folder, at the same time as everyone else involved in the recruitment process, for the vacancy you are interested in. This new electronic recruitment system, known as e-RT, will be introduced in a presentation given at 10 a.m. on 11 February in the Main Auditorium. Implemented by AIS (Administrative Information Services) and the Human Resources Department, e-RT will cover vacancies open in all of CERN's recruitment programmes. The electronic application system was initially made available to technical students in July 2003. By December it was extended to summer students, fellows, associates and Local Staff. Geraldine Ballet from the Recruitment Service prefers e-RT to mountains of paper! The Hu...

  10. Effects of Estrogen Level on the Function of Vascular Endothelial Cells and Expression of Vascular Cell Adhesion Molecule - 1φ

    Institute of Scientific and Technical Information of China (English)

    WU Saizhu(吴赛珠); LIU Jiangguo(刘建国); TAN Jiayu(谭家余); ZHoU Kexiang(周可祥); Gorge D Webb; WEI Heming(隗和明); GUO Zhiguang(郭志刚)

    2002-01-01

    Objectives To ob- serve the effect of different estrogen levels on the se- cretory function of vascular endothelial cells of female rats, and study the effect of modulation of estrogen level on the expression of vascular cell adhesion molecule - 1 and the concentration of estrogen receptorin vascular endothelial cells. Methods Radioim-munology was used to measure the serum concentrationof endothelin and PGI2, and copper-cadmium re-duction was employed to measure the serum content ofnitrogen monoxide. Radioligand binding and flowcy-tometry were used to measure the expression of estrogenreceptor and vascular cell adhesion molecule (VCAM-1 ) of vascular endothelial cells respectively. Re-sults 1. The serum concentration of nitric oxide andPGI2 decreased when the ovaries of female rats wereremoved. In ovariectomized rats, given estrogen, theconcentration rose ( P < 0.05), but the plasma con-centration of endothelin was adverse to it. 2. Theconcentration of estrogen receptor of vascular endothe-lial cells decreased remarkably when the ovaries of fe-male rats were removed. When given estrogen, it in-creased. 3. The percent of expressed VCAM - 1 in-creased siguificantly after interleukin- lβoperated onthe cells, but 17 - βestradiol at 3 × 10-8 ~ 10-6 mol/lall decreased the percent. Conclusions Estrogenlevel can influence the secretion of nitrogen monoxide,PGI2 and endothlin of vascular endothelial cells, andalso influence the concentration of estrogen receptor ofvascular endothelial cells. 17 -β Estradiol at 3 × 10-8~ 10-6 M can decrease the elevation of VCAM - 1 ofvascular endothelial cells induced by interleukin - 1 β.

  11. Glatiramer acetate (GA) prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Guoqian; Zhang, Xueyan; Su, Zhendong; Li, Xueqi, E-mail: xueqili075@yeah.net

    2015-01-30

    Highlights: • GA inhibited TNF-α-induced binding of monocytes to endothelial cells. • GA inhibited the induction of adhesion molecules MCP-1, VCAM-1 and E-selectin. • GA inhibits NF-κB p65 nuclear translocation and transcriptional activity. • GA inhibits TNF-α-induced IκBα degradation. - Abstract: Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) is considered to be the major one contributing to the process of development of endothelial dysfunction. Exposure to TNF-α induces the expression of a number of proinflammatory chemokines, such as monocyte chemotactic protein-1 (MCP-1), and adhesion molecules, including vascular adhesion molecule-1 (VCAM-1) and E-selectin, which mediate the interaction of invading monocytes with vascular endothelial cells. Glatiramer acetate (GA) is a licensed clinical drug for treating patients suffering from multiple sclerosis (MS). The effects of GA in vascular disease have not shown before. In this study, we found that GA significantly inhibited TNF-α-induced binding of monocytes to endothelial cells. Mechanistically, we found that GA ameliorated the upregulation of MCP-1, VCAM-1, and E-selectin induced by TNF-α. Notably, this process is mediated by inhibiting the nuclear translocation and activation of NF-κB. Our results also indicate that GA pretreatment attenuates the up-regulation of COX-2 and iNOS. These data suggest that GA might have a potential benefit in therapeutic endothelial dysfunction related diseases.

  12. Cytoplasmic localization and redox cysteine residue of APE1/Ref-1 are associated with its anti-inflammatory activity in cultured endothelial cells.

    Science.gov (United States)

    Park, Myoung Soo; Kim, Cuk-Seong; Joo, Hee Kyoung; Lee, Yu Ran; Kang, Gun; Kim, Soo Jin; Choi, Sunga; Lee, Sang Do; Park, Jin Bong; Jeon, Byeong Hwa

    2013-11-01

    Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and transcriptional regulation of gene expression. APE1/Ref-1 is mainly localized in the nucleus, but cytoplasmic localization has also been reported. However, the functional role of cytoplasmic APE1/Ref-1 and its redox cysteine residue are still unknown. We investigated the role of cytoplasmic APE1/Ref-1 on tumor necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. Endogenous APE1/Ref-1 was mainly observed in the nucleus, however, cytoplasmic APE1/Ref-1 was increased by TNF-α. Cytoplasmic APE1/Ref-1 expression was not blunted by cycloheximide, a protein synthesis inhibitor, suggesting cytoplasmic translocation of APE1/Ref-1. Transfection of an N-terminus deletion mutant APE1/Ref-1(29-318) inhibited TNF-α-induced VCAM-1 expression, indicating an anti-inflammatory role for APE1/Ref-1 in the cytoplasm. In contrast, redox mutant of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-α-induced VCAM-1 expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues of APE1/Ref-1 are associated with its anti-inflammatory activity in endothelial cells.

  13. 蛋白激酶Cβ_2通过调控PPARα介导高糖诱导的人内皮细胞损伤%Protein kinase Cβ_2 mediated high glucose-induced human umbilical vein endothelial cells injury via regulation of peroxisome proliferator-activated receptor α

    Institute of Scientific and Technical Information of China (English)

    林雪波; 周波; 孙芳; 陈芳芳; 李启富; 邓华聪

    2010-01-01

    Objective To investigate the roles of protein kinase C(PKC)β_2 and PPARα in the mRNA expression of vascular endothelial growth factor(VEGF)and vascular cell adhesion molecule-1(VCAM-1)in human umbilical vein endothelial cells(HUVECs)exposed to high glucose,and to explore their relationship.Methods The HUVECs were divided into eight groups:normal glucose(NG,5 mmoL/L D-glucose)group,high glucose(HG,25 mmol/L D-ucose)group,osmotic control(L,NG+20 mmol/L L-glucose)group,normal glucose transfected with empty vector(NN,NG+AdS-null)group,high glucose transfected with PKCβ_2(HB,HG+Ad5-PKCβ_2)group,high glucose plus fenofibrate(HF,HG+40 μmol/L fenofibrate)group,and HB plus fenofibrate (HBF,HB+40μmol/L fenofibrate)group.HUVECs were incubated with fenofibrate for 20 minutes as HF20 group.All cells in various groups were cultured for 6 days.The expressions of VEGF and VCAM-1 mRNA were detected by RT-PCR.PPARα protein expression was tested by Western blot.The expression and traaslocation of PKCβ_2 protein were observed by confocal laser scanning microscopo.Results (1)HG increased VEGF and VCAM-1 mRNA expressions,with 1.91 and 1.56 folds of NG group,respectively(both P<0.05).VEGF and VCAM-1 mRNA expressions in HB group further increased,with 2.59 and 2.07 folds of NG group,respectively(both P<0.05).Fenofibrate significantly decreased VEGF and VCAM-1 mRNA expressions,with 68%and 74%of HG group,respectively(both P<0.05).There were no significant difierences in the expressiong of VEGF,VCAM-1 mRNA between HF20 and HG groups.(2)The protein expression of PPARα decreased by 20%in HG group compared with NG group,and further decreased in HB group,being 78%of HG group.Compared with HG group,PPARαexpression increased by 13%in HF group(P<0.05).(3)HG induced PKCβ_2 translocation from cytosol to nucleus and quantitative analysis showed the ratio of plasma/nuclear fluorescence intensity in HG group decreased by 37% compared with NG group(P<0.05).The PKCβ_2 translocation was more

  14. Seminal Fluid Regulates Accumulation of FOXP3(+) Regulatory T Cells in the Preimplantation Mouse Uterus Through Expanding the FOXP3(+) Cell Pool and CCL19-Mediated Recruitment

    NARCIS (Netherlands)

    Guerin, Leigh R.; Moldenhauer, Lachlan M.; Prins, Jelmer R.; Bromfield, John J.; Hayball, John D.; Robertson, Sarah A.

    2011-01-01

    Regulatory T (Treg) cells facilitate maternal immune tolerance of the semiallogeneic conceptus in early pregnancy, but the origin and regulation of these cells at embryo implantation is unclear. During the preimplantation period, factors in the seminal fluid delivered at coitus cause expansion of a

  15. 升温对湖泊底泥藻细胞复苏及其生理特性的影响%EFFECTS OF ENHANCED TEMPERATURE ON ALGAE CELLS RECRUITMENT FROM SEDIMENT AND THEIR PHYSIOLOGICAL CHARACTERISTICS

    Institute of Scientific and Technical Information of China (English)

    李国文; 董静; 李根保; 刘永定

    2012-01-01

    Many reports have suggested that the recruitment of some overwintered phytoplankton in the sediment may be important for the pelagic populations and may even be responsible for bloom formation. However, so far no single overwhelming environmental factor has been reported to trigger the recruitment of algal cells. And no study focused on the variation of Na+K+-ATPase and Ca2+Mg2+-ATPase activities, which may be of crucial importance for the process of algal recruitment. Besides, the sediment in lakes suffered from algal blooms could be considered as "seed bank" as many studies reported, could provide "seed" for the pelagic populations in the lake and is also significance for bloom formation. Therefore, the growth and the photosynthetic activity of the "seed" triggered by the favorable outside conditions, the variation of Na+K+-ATPase and Ca2+Mg2+-ATPase activities during the period of algal recruitment, all have critical significance for further research on the process of recruitment. The article mainly focused on the environmental factors and the characteristics of the recruited algal cells, and wanted to study their effects in the process of algal recruitment. Sediment in the experiment was collected from Meili-ang Bay (31°26'14" N, 120°H'O4" E) in Lake Taihu suffered from cyanobacaterial blooms. Three media with different N:P ratio (45:1, 29:1, 7:1) based on the BG11 medium were prepared. In the condition of enhancing temperature, the abundance of recruited algal cells and the variation of algal community in the three different media with laying the sediment were detected. What is more, algal cells photosynthetic activity measured with PHYTO-PAM-2000 in the three different media was compared. The variation of Na+K+-ATPase and Ca2+Mg2+-ATPase activities in the algal cells were also detected using the ATPase kit. The results showed that there were 62 species of algae in the study, belonging to 7 phyla. Therefore, the sediment in Lake Taihu should be considered as

  16. Pre-diagnostic levels of adiponectin and soluble vascular cell adhesion molecule-1 are associated with colorectal cancer risk

    Institute of Scientific and Technical Information of China (English)

    Mathilde Touvier; Pilar Galan; Sébastien Czernichow; Léopold Fezeu; Namanjeet Ahluwalia; Chantal Julia; Nathalie Charnaux; Angela Sutton; Caroline Méjean; Paule Latino-Martel; Serge Hercberg

    2012-01-01

    AIM:To examine the relationships between pre-diag-nostic biomarkers and colorectal cancer risk and assess their relevance in predictive models.METHODS:A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the SUpplementation en VItamines et Minéraux AntioXydants cohort in 1994 and the end of follow-up in 2007.Cases (n =50) were matched with two randomly selected controis (n =100).Conditional logistic regression models were used to investigate the associations between prediagnostic levels of hs-CRP,adiponectin,leptin,soluble vascular cell adhesion molecule-1 (sVCAM-1),soluble intercellular adhesion molecule-1,E-selectin,monocyte chemoattractant protein-1 and colorectal cancer risk.Area under the receiver operating curves (AUC) and relative integrated discrimination improvement (RIDI) statistics were used to assess the discriminatory poten tial of the models.RESULTS:Plasma adiponectin level was associated with decreased colorectal cancer risk (P for linear trend =0.03).Quartiles of sVCAM-1 were associated with increased colorectal cancer risk (P for linear trend =0.02).No association was observed with any of the other biomarkers.Compared to standard models with known risk factors,those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction (P for AUC improvement =0.01,RIDI =26.5%).CONCLUSION:These results suggest that pre-diagnostic plasma adiponectin and sVCAM-1 levels are associated with decreased and increased colorectal cancer risk,respectively.These relationships must be confirmed in large validation studies.

  17. Anti-TNF-α therapy reduces endothelial cell activation in non-diabetic ankylosing spondylitis patients.

    Science.gov (United States)

    Genre, Fernanda; López-Mejías, Raquel; Miranda-Filloy, José A; Ubilla, Begoña; Mijares, Verónica; Carnero-López, Beatriz; Gómez-Acebo, Inés; Dierssen-Sotos, Trinidad; Remuzgo-Martínez, Sara; Blanco, Ricardo; Pina, Trinitario; González-Juanatey, Carlos; Llorca, Javier; González-Gay, Miguel A

    2015-12-01

    Endothelial dysfunction can be detected by the presence of elevated levels of biomarkers of endothelial cell activation. In this study, we aimed to establish whether correlations of these biomarkers with characteristics of patients with ankylosing spondylitis (AS) exist. We also studied the effect of anti-TNF-α therapy on these biomarkers. Serum sE-selectin, MCP-1 and sVCAM-1 levels were measured by ELISA in 30 non-diabetic AS patients undergoing anti-TNF-α therapy, immediately before and after an infusion of infliximab. Correlations of these biomarkers with clinical features, systemic inflammation, metabolic syndrome and other serum and plasma biomarkers of cardiovascular risk were studied. Potential changes in the concentration of these biomarkers following an infliximab infusion were also assessed. sE-selectin showed a positive correlation with CRP (p = 0.02) and with other endothelial cell activation biomarkers such as sVCAM-1 (p = 0.019) and apelin (p = 0.008). sVCAM-1 negatively correlated with BMI (p = 0.018), diastolic blood pressure (p = 0.008) and serum glucose (p = 0.04). sVCAM-1 also showed a positive correlation with VAS spinal pain (p = 0.014) and apelin (p < 0.001). MCP-1 had a negative correlation with LDL cholesterol (p = 0.026) and ESR (p = 0.017). Patients with hip involvement and synovitis and/or enthesitis in other peripheral joints showed higher levels of MCP-1 (p = 0.004 and 0.02, respectively). A single infliximab infusion led to a significant reduction in sE-selectin (p = 0.0015) and sVCAM-1 (p = 0.04). Endothelial dysfunction correlates with inflammation and metabolic syndrome features in patients with AS. A beneficial effect of the anti-TNF-α blockade on endothelial dysfunction, manifested by a reduction in levels of biomarkers of endothelial cell activation, was observed.

  18. HIF-α/MIF and NF-κB/IL-6 Axes Contribute to the Recruitment of CD11b+Gr-1+ Myeloid Cells in Hypoxic Microenvironment of HNSCC

    OpenAIRE

    Guiquan Zhu; Yaling Tang; Ning Geng; Min Zheng; Jian Jiang; Ling Li; Kaide Li; Zhengge Lei; Wei Chen; Yunlong Fan; Xiangrui Ma; Longjiang Li; Xiaoyi Wang; Xinhua Liang

    2014-01-01

    CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF) and interleukin-6 (IL-6) by head an...

  19. Recruitment. Hello, goodbye.

    Science.gov (United States)

    Moore, Alison

    2008-07-10

    The UK is "moving to a policy of self-sufficiency" according to the Department of Health. The numbers of new overseas entrants into healthcare, including doctors, nurses and midwives has slumped. Several other countries, including Canada, the US and Australia, are aggressively recruiting from overseas, including from the UK. There is an increasing perception the UK does not want overseas staff.

  20. Sales Force Recruitment

    OpenAIRE

    Flaviu MEGHISAN

    2008-01-01

    The sales plan is put into practice through the tasks associated with sales plan implementation. Whereas sales plan formulation focuses on "doing the right things," implementation emphasizes "doing things right." The three major tasks involved in implementing a sales plan are (1) salesforce recruitment and selection, (2) salesforce training, and (3) salesforce motivation and compensation.

  1. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels;

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is...... lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on...

  2. GAPDH--a recruits a plant virus movement protein to cortical virus replication complexes to facilitate viral cell-to-cell movement.

    Directory of Open Access Journals (Sweden)

    Masanori Kaido

    2014-11-01

    Full Text Available The formation of virus movement protein (MP-containing punctate structures on the cortical endoplasmic reticulum is required for efficient intercellular movement of Red clover necrotic mosaic virus (RCNMV, a bipartite positive-strand RNA plant virus. We found that these cortical punctate structures constitute a viral replication complex (VRC in addition to the previously reported aggregate structures that formed adjacent to the nucleus. We identified host proteins that interacted with RCNMV MP in virus-infected Nicotiana benthamiana leaves using a tandem affinity purification method followed by mass spectrometry. One of these host proteins was glyceraldehyde 3-phosphate dehydrogenase-A (NbGAPDH-A, which is a component of the Calvin-Benson cycle in chloroplasts. Virus-induced gene silencing of NbGAPDH-A reduced RCNMV multiplication in the inoculated leaves, but not in the single cells, thereby suggesting that GAPDH-A plays a positive role in cell-to-cell movement of RCNMV. The fusion protein of NbGAPDH-A and green fluorescent protein localized exclusively to the chloroplasts. In the presence of RCNMV RNA1, however, the protein localized to the cortical VRC as well as the chloroplasts. Bimolecular fluorescence complementation assay and GST pulldown assay confirmed in vivo and in vitro interactions, respectively, between the MP and NbGAPDH-A. Furthermore, gene silencing of NbGAPDH-A inhibited MP localization to the cortical VRC. We discuss the possible roles of NbGAPDH-A in the RCNMV movement process.

  3. 白藜芦醇对高糖诱导内皮细胞损伤代谢记忆效应的研究%Effects of resveratrol on high glucose memory-induced injury to endothelial cell

    Institute of Scientific and Technical Information of China (English)

    丁慧; 王鹏; 王颜刚

    2014-01-01

    Cultured human umbilical vein endothelial cells (HUVECs) were divided and assigned to 6 groups:normal control group,mannitol control group,high glucose group,low dose resveratrol group,medium dose resveratrol group,and high dose resveratrol group.HUVECs were pretreated with or without 30 mmol/L glucose plus various concentrations of resveratrol (0.1,1,10 μmol/L) for 16 hours and then incubated with 5.5 mmol/L glucose for 6 days.The levels of vascular cell adhesion molecule 1 (VCAM-1),monocyte chemotactic protein 1 (MCP-1),and plasminogen activator inhibitor 1 (PAI-1) in the culture supernatant were measured by ELISA.NF-κB expression was detected by Western blot.Compared with normal glucose group,high glucose up-regulated the expression of NF-κB,along with the increased levels of VCAM-1,MCP-1,and PAI-1 (all P<0.05),which were still maintained at high levels even after withdrawal of high glucose.Resveratrol treatment down-regulated the expression of NF-κB and lowered the levels of VCAM-1,MCP-1,and PAI-1 (all P<0.05).These results suggest that resveratrol may decrease the secretion of VCAM-1,MCP-1,and PAI-1 and prevent high glucose memory-induced injury to endothelial cell via NF-κB pathway.%人脐静脉内皮细胞分为正常对照组、甘露醇对照组、高糖组和白藜芦醇低、中、高剂量组,细胞于30 mmol/L葡萄糖和0.1、1和10 μmol/L白藜芦醇培养16h后,再以5.5 mmol/L葡萄糖培养6d,应用ELISA法检测细胞培养上清中血管细胞黏附分子1(VCAM-1)、单核细胞趋化蛋白1(MCP-1)和纤溶酶原激活物抑制剂1(PAI-1)水平,以Western印迹法检测细胞内NF-κB蛋白表达.与正常对照组相比,高糖可诱导内皮细胞NF-κB表达上调(P<0.05),同时VCAM-1、MCP-1和PAI-1水平升高(均P<0.05),且在糖浓度恢复正常后仍持续上升.与高糖组相比,白藜芦醇预处理可以明显减少NF-κB表达,降低VCAM-1、MCP-1和PAI-1水平(均P<0.05).结果提示白藜芦醇可能通过NF-κB通路降低VCAM

  4. Increased concentrations of soluble vascular cell adhesion molecule-1 and soluble CD40L in subjects with metabolic syndrome.

    Science.gov (United States)

    Palomo, Iván G; Jaramillo, Julio C; Alarcón, Marcelo L; Gutiérrez, César L; Moore-Carrasco, Rodrigo; Segovia, Fabián M; Leiva, Elba M; Mujica, Verónica E; Icaza, Gloria; Dí, Nora S

    2009-01-01

    Metabolic syndrome (MS) is associated with a high incidence rate of cardiovascular disease. It is characterized by abdominal obesity, elevated blood pressure, atherogenic dyslipidemia [high LDL-c (low density lipoprotein cholesterol) and low HDL-c (high density lipoprotein cholesterol)] and insulin resistance or glucose intolerance. In the context of MS, alterations in the plasmatic levels of some soluble forms of cell adhesion molecules can appear, e.g., soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L). The objective of this study was to compare the serum levels of sVCAM-1, sE-selectin and sCD40L in MS and non-MS groups and to associate these molecules with the diagnostic criteria of MS. A total of 185 non-smokers between 45 and 64 years of age were included. Of these, 93 corresponded to the MS group and the remaining 92 to a non-MS group (according to modified ATP III criteria). The serum concentration of sVCAM-1, sE-selectin and sCD40L was determined by commercial solid phase ELISA. The results were expressed as a median and interquartile range. The MS group showed high levels of sVCAM-1 (558.9 ng/ml; 481.3-667.6 ng/ml) compared with the non-MS group (405.2 ng/ml; 361.0-470.5 ng/ml) (p<0.0001). As well, the median level of sCD40L (3.0 ng/ml; 2.1l-11.7 ng/ml) was significantly higher in the MS group than that in the non-MS group (2.6 ng/ml; 2.3-3.4 ng/ml) (p=0.0061). sE-selectin levels did not differ significantly between the groups: 73.9 ng/ml (58.3-87.0 ng/ml) and 68.5 ng/ml (51.6-97.5 ng/ml) in the MS and non-MS group, respectively. In conclusion, the serum levels of sVCAM-1 and sCD40L, but not sE-selectin, were significantly higher in patients with MS than in subjects that did not present MS. MS may therefore increase the expression of cell adhesion molecules, probably through endothelial activation. PMID:21475854

  5. Marek's Disease Viral Interleukin-8 Promotes Lymphoma Formation through Targeted Recruitment of B Cells and CD4+ CD25+ T Cells

    OpenAIRE

    Engel, Annemarie T.; Selvaraj, Ramesh K.; Kamil, Jeremy P.; Osterrieder, Nikolaus; Kaufer, Benedikt B

    2012-01-01

    Marek's disease virus (MDV) is a cell-associated and highly oncogenic alphaherpesvirus that infects chickens. During lytic and latent MDV infection, a CXC chemokine termed viral interleukin-8 (vIL-8) is expressed. Deletion of the entire vIL-8 open reading frame (ORF) was shown to severely impair disease progression and tumor development; however, it was unclear whether this phenotype was due to loss of secreted vIL-8 or of splice variants that fuse exons II and III of vIL-8 to certain upstrea...

  6. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus.

    Science.gov (United States)

    Shechter, Ravid; Miller, Omer; Yovel, Gili; Rosenzweig, Neta; London, Anat; Ruckh, Julia; Kim, Ki-Wook; Klein, Eugenia; Kalchenko, Vyacheslav; Bendel, Peter; Lira, Sergio A; Jung, Steffen; Schwartz, Michal

    2013-03-21

    Monocyte-derived macrophages are essential for recovery after spinal cord injury, but their homing mechanism is poorly understood. Here, we show that although of common origin, the homing of proinflammatory (M1) and the "alternatively activated" anti-inflammatory (M2) macrophages to traumatized spinal cord (SC) was distinctly regulated, neither being through breached blood-brain barrier. The M1 macrophages (Ly6c(hi)CX3CR1(lo)) derived from monocytes homed in a CCL2 chemokine-dependent manner through the adjacent SC leptomeninges. The resolving M2 macrophages (Ly6c(lo)CX3CR1(hi)) derived from monocytes trafficked through a remote blood-cerebrospinal-fluid (CSF) barrier, the brain-ventricular choroid plexus (CP), via VCAM-1-VLA-4 adhesion molecules and epithelial CD73 enzyme for extravasation and epithelial transmigration. Blockage of these determinants, or mechanical CSF flow obstruction, inhibited M2 macrophage recruitment and impaired motor-function recovery. The CP, along with the CSF and the central canal, provided an anti-inflammatory supporting milieu, potentially priming the trafficking monocytes. Overall, our finding demonstrates that the route of monocyte entry to central nervous system provides an instructional environment to shape their function.

  7. 二苯乙烯苷对H2O2诱导血管内皮细胞黏附分子表达的影响%Effect of TSG on expression of adhesion molecule induced by H2O2 on vascular endothelial cell

    Institute of Scientific and Technical Information of China (English)

    张彩平; 杨滢; 田英; 乔新惠; 龙石银; 陈志军; 田汝芳

    2012-01-01

    Aim To study the effect of 2,3,5,4' -tetra-hydroxystilbene-2-O-β-D-glucoside on expression of adhesion molecules P-selectin, E-selectin, ICAM-1, VCAM-1 and MCP-1 induced by H2O2 on human umbilical vein endothelial cells ( HUVECs). Methods HUVECs were cultured in vitro. The experiment was divided into four groups: control group, H2 O2 group, positive group, and TSG group. The expression of P-selectin, E-selectin, ICAM-1, VCAM-1 and MCP-1 mRNA and protein were respectively detected by re-verse transcriptase polymerase chain reaction ( RT-PCR ) and enzyme-linked immunosorbent assay ( ELISA). Results After endothelial cells treated with 200 μmol · L-1 H2O2 for 24 h, the expression of P-se-lectin, E-selectin, ICAM-1, VCAM-1 and MCP-1 mR-NA and protein level was significant higher. After TSG pretreatment endothelial cells for 4h before treated with 200 μmol · L-1 H2O2, results showed that TSG could inhibit the expression of P-selectin, E-selectin, ICAM-1, VCAM-1 and MCP-1 mRNA and protein level induced by H2O2 on endothelial cells. Conclusion TSG can inhibit the expression of adhesion molecules induced by H2O2 on human umbilical vein endothelial cells and accordingly slow down atherosclerosis.%目的 研究二苯乙烯苷(TSG)对过氧化氢(H2O2)诱导损伤的人脐静脉内皮细胞P-selectin、E-selectin、ICAM-1、VCAM-1和MCP-1表达的影响.方法 体外培养人脐静脉内皮细胞,实验分为空白对照组、H2O2组、辛伐他汀组、TSG组,运用逆转录聚合酶链式反应和酶联免疫吸附试验分别检测P-selectin、E-selectin、ICAM-1、VCAM-1和MCP-1 mRNA与蛋白的表达.结果 200 μmol·L-1的H2O2作用内皮细胞24 h后,P-selectin、E-selectin、ICAM-1、VCAM-1和MCP-1的mRNA和蛋白表达水平均明显上调;经TSG预处理内皮细胞4 h后,再加200 μmol·L-1的H2O2作用内皮细胞24 h,结果显示:TSG能抑制H2O2诱导的内皮细胞P-selnecti、E-selectin、ICAM-1、VCAM-1和MCP-1的 mRNA和蛋白的表达.结论 TSG

  8. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    International Nuclear Information System (INIS)

    Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects. Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs. These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis

  9. HIF-α/MIF and NF-κB/IL-6 axes contribute to the recruitment of CD11b+Gr-1+ myeloid cells in hypoxic microenvironment of HNSCC.

    Science.gov (United States)

    Zhu, Guiquan; Tang, Yaling; Geng, Ning; Zheng, Min; Jiang, Jian; Li, Ling; Li, Kaide; Lei, Zhengge; Chen, Wei; Fan, Yunlong; Ma, Xiangrui; Li, Longjiang; Wang, Xiaoyi; Liang, Xinhua

    2014-02-01

    CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF) and interleukin-6 (IL-6) by head and neck squamous cell carcinoma (HNSCC) cells. Hypoxia-inducible factor-1α (HIF-1α)- and HIF-2α-dependent MIF regulated chemotaxis, differentiation, and pro-angiogenic function of CD11b+Gr-1+ myeloid cells through binding to CD74/CXCR2, and CD74/CXCR4 complexes, and then activating p38/mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinases (PI3K)/AKT signaling pathways. Knockdown (KD) of HIF-1α and HIF-2α in HNSCC cells decreased MIF level but failed to inhibit the CD11b+Gr-1+ myeloid cell migration, because HIF-1α/2α KD enhanced nuclear factor κB (NF-κB) activity that increased IL-6 secretion. Simultaneously blocking NF-κB and HIF-1α/HIF-2α had better inhibitory effect on CD11b+Gr-1+ myeloid cell recruitment in the hypoxic zone than individually silencing HIF-1α/2α or NF-κB. In conclusion, the interaction between HIF-α/MIF and NF-κB/IL-6 axes plays an important role in the hypoxia-induced accumulation of CD11b+Gr-1+ myeloid cells and tumor growth in HNSCC. PMID:24709424

  10. HIF-α/MIF and NF-κB/IL-6 Axes Contribute to the Recruitment of CD11b+Gr-1+ Myeloid Cells in Hypoxic Microenvironment of HNSCC

    Directory of Open Access Journals (Sweden)

    Guiquan Zhu

    2014-02-01

    Full Text Available CD11b+Gr-1+ myeloid cells have gained much attention due to their roles in tumor immunity suppression as well as promotion of angiogenesis, invasion, and metastases. However, the mechanisms by which CD11b+Gr-1+ myeloid cells recruit to the tumor site have not been well clarified. In the present study, we showed that hypoxia could stimulate the migration of CD11b+Gr-1+ myeloid cells through increased production of macrophage migration inhibitory factor (MIF and interleukin-6 (IL-6 by head and neck squamous cell carcinoma (HNSCC cells. Hypoxia-inducible factor-1α (HIF-1α- and HIF-2α-dependent MIF regulated chemotaxis, differentiation, and pro-angiogenic function of CD11b+Gr-1+ myeloid cells through binding to CD74/CXCR2, and CD74/CXCR4 complexes, and then activating p38/mitogen-activated protein kinase (MAPK and phosphatidylinositide 3-kinases (PI3K/AKT signaling pathways. Knockdown (KD of HIF-1α and HIF-2α in HNSCC cells decreased MIF level but failed to inhibit the CD11b+Gr-1+ myeloid cell migration, because HIF-1α/2α KD enhanced nuclear factor κB (NF-κB activity that increased IL-6 secretion. Simultaneously blocking NF-κB and HIF-1α/HIF-2α had better inhibitory effect on CD11b+Gr-1+ myeloid cell recruitment in the hypoxic zone than individually silencing HIF-1α/2α or NF-κB. In conclusion, the interaction between HIF-α/MIF and NF-κB/IL-6 axes plays an important role in the hypoxia-induced accumulation of CD11b+Gr-1+ myeloid cells and tumor growth in HNSCC.

  11. Recruitment Practices And Institutional Change

    DEFF Research Database (Denmark)

    Holm, Anna; Ulhøi, John Parm

    Up to now, there has been little research on recruitment practices from an organizational perspective, and in part it lags behind practice. This paper attempts to rectify this by studying recent changes in the recruitment practices of Danish organizations. We employ new institutional theory...... as a theoretical lens in order to understand how shared rules, norms and beliefs guide recruitment professionals in their choice of recruitment tactics and ways of performing recruitment tasks. Our findings suggest that recruitment practices have been strongly influenced by changes in the labour market, technology......, and individuals’ social cognition. Among other things, this is reflected in the use of online recruitment and employer branding. The study concludes that the recruitment field has transformed and reviewed its practices due to institutional changes in how individuals search for employment and expect to be hired....

  12. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    OpenAIRE

    Yang, Chen-Chieh; Chang, Shun-Fu; Chao, Jian-Kang; Lai, Yi-Liang; Chang, Wei-En; Hsu, Wen-Hsiu; Kuo, Wu-Hsien

    2014-01-01

    Background Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Methods Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to hu...

  13. Profile of the successful recruiter.

    OpenAIRE

    Gandolfo, Robin Ragsdale.

    1987-01-01

    This thesis develops and analyzes a model to identify attributes of a successful recruiter. Expert Systems software is used to elicit from twenty U.S. Army recruiters and instructors, who are experts in the field, characteristics associated with recruiter success. An interactive computer program based on Quasi-Artificial Intelligence (QAI) captured the expert's intuition, knowledge, experience, and judgements to create expert systems that can be used to select U.S. Army recruiters before they...

  14. Recruiting in remote locations

    Energy Technology Data Exchange (ETDEWEB)

    Ionel, C. [Enerflex Systems Ltd., Calgary, AB (Canada)

    2006-07-01

    This presentation provided details of Enerflex, a leading supplier of products and services to the oil and gas industry, and outlined their personnel hiring policies. Enerflex's core values include community involvement and divisional logo branding. The extensive training that is provided places an emphasis on employee empowerment. The company also places an emphasis on employee safety, diversity, and team building. Competitive salaries are offered along with generous equipment allowances and a flexible benefits program. Benefits include travel and overtime rates; health benefits; retirement savings; scholarship programs; career opportunities; and apprenticeship programs. External technical training is provided. An employee referral program has been developed, and the company's recruitment program also advertises in remote newspapers to develop career streams within remote communities. tabs., figs.

  15. Differential Recruitment of Distinct Amygdalar Nuclei across Appetitive Associative Learning

    Science.gov (United States)

    Cole, Sindy; Powell, Daniel J.; Petrovich, Gorica D.

    2013-01-01

    The amygdala is important for reward-associated learning, but how distinct cell groups within this heterogeneous structure are recruited during appetitive learning is unclear. Here we used Fos induction to map the functional amygdalar circuitry recruited during early and late training sessions of Pavlovian appetitive conditioning. We found that a…

  16. A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment.

    Science.gov (United States)

    Lauridsen, Holly M; Pober, Jordan S; Gonzalez, Anjelica L

    2014-03-01

    Neutrophil extravasation occurs across postcapillary venules, structures composed of endothelial cells (ECs), pericytes (PCs), and basement membrane (BM). We constructed composite models of the human postcapillary venule, combining ECs with PCs or PC-deposited BM, to better study this process. Quiescent and tumor necrosis factor α (TNF-α)-activated composites demonstrated in situ-like expression of cadherins, E-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), platelet-endothelial cell adhesion molecule 1 (PECAM-1), CD99, and interleukin 8 (IL-8). After TNF-α activation, the ECs supported greater neutrophil adhesion (66.1 vs. 23.7% of input cells) and transmigration (35.1 vs. 7.20% of input cells) than did the PCs, but the composites behaved comparably (no significant difference) to ECs in both assays. TNF-α-activated EC-conditioned medium (CM) increased transmigration across the PCs, whereas TNF-α-activated PC-CM decreased transmigration across the ECs, and culturing on PC-derived BM decreased both adhesion to and transmigration across the ECs. Anti-very late antigen 4 (VLA-4; on neutrophils) inhibited adhesion to TNF-α-activated composites, but not to ECs alone. Anti-CD99 (expressed on all 3 cell types) inhibited transmigration across the composites (14.5% of control) more than across the ECs (39.0% of control), and venular shear stress reduced transmigration across the ECs (17.3% of static) more than across the composites (36.7% of static). These results provide proof of concept that our composite human EC/PC/BM venular construct can reveal new interactions in the inflammatory cascade. PMID:24297702

  17. From Traditional Recruiting To E-Recruiting in Public Organizations

    Directory of Open Access Journals (Sweden)

    ARTENE Adela Suzana

    2013-05-01

    Full Text Available Recruiting is the activity that determines, in quantitative and qualitative terms, the structure of the sample of people from which the selection will be made for a specific position and / or public office, for a position that is already created in the organizational structure. The recruitment process is triggered when in the organizational structure of public institutions appear new functions or positions, or when the existing ones become vacant through retirement, death, transfer or dismissal. E-Recruiting represents the process through which the personnel is recruited using electronic resources.

  18. Expression profile of vascular cell adhesion molecule-1 (CD106) in inflammatory foci using rhenium-188 labelled monoclonal antibody in mice.

    Science.gov (United States)

    Kairemo, K J; Strömberg, S; Nikula, T K; Karonen, S L

    1998-06-01

    Rhenium (Re)-188 is a generator (W-188/Re-188) produced high energy beta-emitter suitable for radionuclide therapy (T1/2 is 16.9 hrs and Emax 2.1 MeV (range 11 mm)). We have labelled monoclonal antibody (MAb) raised against vascular cell adhesion molecule-1 (VCAM-1) with Re-188 using glucoheptonate chelation technique and SnCl2 as reducing agent. The labelling efficiency, free perrhenate and reduced Re were controlled with thin layer chromatography and the purification of Re-188-MoAbs was performed using gel filtration. Our results indicate that Re-188-labelled antibodies remain in vitro stable and the labelling purity is > 90%. We also have applied these Re-188-MoAbs for detection of inflammatory disease in a mouse. The effective half-lives of organs of interest after an injection of Re-188-anti-VCAM1 were as follows: blood 5.2 hr, kidney 4.7 hr, and liver 9.6 hr. Re-188-anti-VCAM-1 was found to accumulate mainly in kidney and liver. One hour after the injection, the kidney contained in average as high as 12.5% and the liver 2.8 ID/g tissue. After 6 hr, the kidney contained 5.5% ID/g and the liver 2.6% ID/g. At 24 hr, the kidney uptake was 0.5% ID/g and the liver uptake 0.8% ID/g, respectively. The inflamed foci, subcutaneous lesions in the footpad skin, were visualized using gamma camera. From the distribution data the uptakes in the inflamed foci as follows: at 1 hr 2.18 (inflammation) and 1.72% ID/g (control), at 6 hr 1.42 (inflammation) and 0.85% ID/g (control), and at 24 hr 0.17 (inflammation) and 0.084% ID/g (control), respectively. Anti-VCAM-1 MAb showed better targeting as compared to control MoAbs in inflammation (caused by E.coli lipoplysaccaride). In conclusion, Re-188 is suitable for MAb labelling, and MAb against VCAM-1 may be used for detection of local inflammatory disease. PMID:9762472

  19. Preconditioning Serum Levels of Endothelial Cell-Derived Molecules and the Risk of Posttransplant Complications in Patients Treated with Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Roald Lindås

    2014-01-01

    Full Text Available Endothelial cells are involved in the pathogenesis of acute graft-versus-host disease (GVHD after allogeneic stem cell transplantation. These cells express several molecules that can be detected as biologically active soluble forms; serum levels of these molecules may thereby reflect the functional status of endothelial cells. Furthermore, acute GVHD is an inflammatory reaction and endothelial cells function as local regulators of inflammation. We therefore investigated whether differences in preconditioning/pretransplant serum levels of endothelium-expressed molecules (i.e., endocan, vascular cell adhesion molecule 1 (VCAM-1, and E-selectin were associated with a risk of posttransplant GVHD. Our study should be regarded as a population-based study of consecutive and thereby unselected patients (n=56. Analysis of this pretreatment endothelium biomarker profile by unsupervised hierarchical clustering identified a subset of patients with increased early nonrelapse mortality. Furthermore, low endocan levels were significantly associated with acute GVHD in the liver and gastrointestinal tract, whereas high VCAM-1 levels were associated with acute GVHD in the skin only. Our study suggests that the preconditioning/pretransplant status of endothelial cells (possibly through altered trafficking of immunocompetent cells is important for the risk and the organ involvement of later acute GVHD.

  20. All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Marumi; Ikenaka, Yoshinori [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan); Ishizuka, Mayumi, E-mail: ishizum@vetmed.hokudai.ac.jp [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer AHR and ARNT transcriptionally regulate genes related to metabolisms such as CYP1A1. Black-Right-Pointing-Pointer We investigated the effect of retinoic acid (RA) on the function of AHR/ARNT. Black-Right-Pointing-Pointer RA inhibited the recruitment of ARNT, not AHR, to the regulatory region of CYP1A1. Black-Right-Pointing-Pointer It resulted in a reduction of constitutive expression of CYP1A1 to less than half. -- Abstract: Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) are well-conserved transcription factors among species. However, there are a very limited number of reports on the physiological function of AHR, particularly on the regulation of AHR by endogenous compounds. We hence investigated the effects of all-trans retinoic acid (atRA) on cytochrome P450 (CYP) 1A1 gene transcription as a model of AHR-regulated transcription mechanisms in HepG2 cells, a human hepatoma cell line. Treatment with atRA significantly reduced transactivation and expression of CYP1A1 mRNA to less than half of its control value, and this inhibitory effect was mediated by RAR{alpha}. The result of chromatin immunoprecipitation assay indicated that treatment with atRA at 1-100 nM drastically inhibited the recruitment of ARNT to DNA regions containing xenobiotic responsive elements. In conclusion, atRA at physiological concentrations could reduce AHR-mediated gene transcription via the inhibition of recruitment of ARNT to relevant DNA regions.

  1. Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

    Directory of Open Access Journals (Sweden)

    Ying An

    2011-01-01

    Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression 

  2. Recruitment in small japanese company

    OpenAIRE

    Jarošová, Ilona

    2007-01-01

    The thesis focuses on employee recruitment in japanese environment. Among others, the discussed topics include interview process, experiences of recruitment agences with japanese companies on the Czech market and recommendations of specific steps for the analysed company. The hypothesis of the thesis is that japanese compnanies are unsuccessful regarding employee recruitment in the Czech Republic, suffer from insufficient interest of potencial candidates . All these factors combined with gene...

  3. 6 CFR 17.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Recruitment. 17.310 Section 17.310 Domestic... in Admission and Recruitment Prohibited § 17.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  4. 14 CFR 1253.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Recruitment. 1253.310 Section 1253.310... in Admission and Recruitment Prohibited § 1253.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  5. 28 CFR 54.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Recruitment. 54.310 Section 54.310... in Admission and Recruitment Prohibited § 54.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  6. 40 CFR 5.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Recruitment. 5.310 Section 5.310... in Admission and Recruitment Prohibited § 5.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  7. 43 CFR 41.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.310 Section 41.310 Public... in Admission and Recruitment Prohibited § 41.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  8. 15 CFR 8a.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Recruitment. 8a.310 Section 8a.310... in Admission and Recruitment Prohibited § 8a.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  9. 41 CFR 101-4.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Recruitment. 101-4.310... Admission and Recruitment Prohibited § 101-4.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient... recruitment and admission of students. A recipient may be required to undertake additional recruitment...

  10. NADPH oxidase and lipid raft-associated redox signaling are required for PCB153-induced upregulation of cell adhesion molecules in human brain endothelial cells

    International Nuclear Information System (INIS)

    Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), can lead to chronic inflammation and the development of vascular diseases. Because cell adhesion molecules (CAMs) of the cerebrovascular endothelium regulate infiltration of inflammatory cells into the brain, we have explored the molecular mechanisms by which ortho-substituted polychlorinated biphenyls (PCBs), such as PCB153, can upregulate CAMs in brain endothelial cells. Exposure to PCB153 increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as elevated adhesion of leukocytes to brain endothelial cells. These effects were impeded by inhibitors of EGFR, JAKs, or Src activity. In addition, pharmacological inhibition of NADPH oxidase or disruption of lipid rafts by cholesterol depleting agents blocked PCB153-induced phosphorylation of JAK and Src kinases and upregulation of CAMs. In contrast, silencing of caveolin-1 by siRNA interference did not affect upregulation of ICAM-1 and VCAM-1 in brain endothelial cells stimulated by PCB153. Results of the present study indicate that lipid raft-dependent NADPH oxidase/JAK/EGFR signaling mechanisms regulate the expression of CAMs in brain endothelial cells and adhesion of leukocytes to endothelial monolayers. Due to its role in leukocyte infiltration, induction of CAMs may contribute to PCB-induced cerebrovascular disorders and neurotoxic effects in the CNS.

  11. Nuclear IL-33 is a transcriptional regulator of NF-{kappa}B p65 and induces endothelial cell activation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yeon-Sook; Park, Jeong Ae; Kim, Jihye; Rho, Seung-Sik; Park, Hyojin [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Young-Myeong [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon (Korea, Republic of); Kwon, Young-Guen, E-mail: ygkwon@yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer IL-33 as nuclear factor regulated expression of ICAM-1 and VCAM-1. Black-Right-Pointing-Pointer Nuclear IL-33 increased the transcription of NF-{kappa}B p65 by binding to the p65 promoter. Black-Right-Pointing-Pointer Nuclear IL-33 controls NF-{kappa}B-dependent inflammatory responses. -- Abstract: Interleukin (IL)-33, an IL-1 family member, acts as an extracellular cytokine by binding its cognate receptor, ST2. IL-33 is also a chromatin-binding transcriptional regulator highly expressed in the nuclei of endothelial cells. However, the function of IL-33 as a nuclear factor is poorly defined. Here, we show that IL-33 is a novel transcriptional regulator of the p65 subunit of the NF-{kappa}B complex and is involved in endothelial cell activation. Quantitative reverse transcriptase PCR and Western blot analyses indicated that IL-33 mediates the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in endothelial cells basally and in response to tumor necrosis factor-{alpha}-treatment. IL-33-induced ICAM-1/VCAM-1 expression was dependent on the regulatory effect of IL-33 on the nuclear factor (NF)-{kappa}B pathway; NF-{kappa}B p65 expression was enhanced by IL-33 overexpression and, conversely, reduced by IL-33 knockdown. Moreover, NF-{kappa}B p65 promoter activity and chromatin immunoprecipitation analysis revealed that IL-33 binds to the p65 promoter region in the nucleus. Our data provide the first evidence that IL-33 in the nucleus of endothelial cells participates in inflammatory reactions as a transcriptional regulator of NF-{kappa}B p65.

  12. Fast-Track Teacher Recruitment.

    Science.gov (United States)

    Grant, Franklin Dean

    2001-01-01

    Schools need a Renaissance human-resources director to implement strategic staffing and fast-track teacher-recruitment plans. The HR director must attend to customer satisfaction, candidate supply, web-based recruitment possibilities, stabilization of newly hired staff, retention of veteran staff, utilization of retired employees, and latest…

  13. Diversity employment and recruitment sources

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    Effective human resources management has been identified as one of four critical success factors in the Department of Energy Strategic Plan. The Plan states relative to this factor: ``The Department seeks greater alignment of resources with agency priorities and increased diversification of the workforce, including gender, ethnicity, age, and skills. This diversification will bring new thinking and perspectives that heretofore have not had a voice in departmental decision-making.`` This Guide has been developed as a key tool to assist Department of Energy management and administrative staff in achieving Goal 2 of this critical success factor, which is to ``Ensure a diverse and talented workforce.`` There are numerous sources from which to recruit minorities, women and persons with disabilities. Applying creativity and proactive effort, using traditional and non-traditional approaches, and reaching out to various professional, academic and social communities will increase the reservoir of qualified candidates from which to make selections. In addition, outreach initiatives will undoubtedly yield further benefits such as a richer cultural understanding and diversity awareness. The resource listings presented in this Guide are offered to encourage active participation in the diversity recruitment process. This Guide contains resource listings by state for organizations in the following categories: (1) African American Recruitment Sources; (2) Asian American/Pacific Islander Recruitment Sources; (3) Hispanic Recruitment Sources; (4) Native American/Alaskan Native Recruitment Sources; (5) Persons with Disabilities Recruitment Sources; and (6) Women Recruitment Sources.

  14. Three Keys to Better Recruiting

    Science.gov (United States)

    Brazington, Alicia

    2012-01-01

    Recruitment is an expensive business: In 2010-2011, the median cost to recruit an undergraduate was $2,185 among private colleges and universities, according to Noel-Levitz, an enrollment management consultancy. In these tough fiscal times, admissions departments are under pressure to keep those costs down even as they pursue higher enrollment and…

  15. Recruit and ADVANCE

    Science.gov (United States)

    Rosser, Sue V.

    2007-04-01

    Beginning in 2001, the National Science Foundation launched the ADVANCE Initiative, which has now awarded more than 70 million to some thirty institutions for transformations to advance women. Results of studies on how to attract and retain women students and faculty underpinned our ADVANCE Institutional Transformation grant funded by the NSF for 3.7 million for five years, beginning in 2001. As co-principal investigator on this grant, I insured that this research informed the five major threads of the grant: 1) Four termed ADVANCE professors to mentor junior women faculty in each college; 2) Collection of MIT-Report-like data indicators to assess whether advancement of women really occurs during and after the institutional transformation undertaken through ADVANCE; 3) Family-friendly policies and practices to stop the tenure clock and provide active service, modified duties, lactation stations and day care; 4) Mini-retreats to facilitate access for tenure-track women faculty to male decision-makers and administrators for informal conversations and discussion on topics important to women faculty; 5) Removal of subtle gender, racial, and other biases in promotion and tenure. The dynamic changes resulting from the grant in quality of mentoring, new understanding of promotion and tenure, numbers of women retained and given endowed chairs, and emergence of new family friendly policies gave me hope for genuine diversification of leadership in science and technology. As the grant funding ends, the absence of NSF prestige and monitoring, coupled with a change in academic leadership at the top, provide new challenges for institutionalization, recruitment, and advancement of women into leadership positions in science and engineering.

  16. A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity

    OpenAIRE

    Smith, Aileen M.; Sánchez, María José; Follows, George A.; Kinston, Sarah; Donaldson, Ian J.; Green, Anthony R.; Göttgens, Berthold

    2008-01-01

    Altered cis-regulation is thought to underpin much of metazoan evolution, yet the underlying mechanisms remain largely obscure. The stem cell leukemia TAL1 (also known as SCL) transcription factor is essential for the normal development of blood stem cells and we have previously shown that the Tal1 +19 enhancer directs expression to hematopoietic stem cells, hematopoietic progenitors, and to endothelium. Here we demonstrate that an adjacent region 1 kb upstream (+18 element) is in an open chr...

  17. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells

    OpenAIRE

    Gallego-Ortega, David; Ledger, Anita; Roden, Daniel L.; Law, Andrew M. K.; Magenau, Astrid; Kikhtyak, Zoya; Cho, Christina; Allerdice, Stephanie L.; Lee, Heather J.; Valdes-Mora, Fatima; Herrmann, David; Salomon, Robert; Young, Adelaide I. J.; Lee, Brian Y.; Sergio, C Marcelo

    2015-01-01

    During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angi...

  18. ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.

    OpenAIRE

    David Gallego-Ortega; Anita Ledger; Roden, Daniel L.; Law, Andrew M. K.; Astrid Magenau; Zoya Kikhtyak; Christina Cho; Allerdice, Stephanie L.; Lee, Heather J.; Fatima Valdes-Mora; David Herrmann; Robert Salomon; Young, Adelaide I. J.; Lee, Brian Y.; C Marcelo Sergio

    2015-01-01

    During pregnancy, the ETS transcription factor ELF5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. In breast cancer, ELF5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. In the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT) model of luminal breast cancer, induction of ELF5 levels increased leukocyte infiltration, angi...

  19. Identification of the key genes connected with plasma cells of multiple myeloma using expression profiles

    Directory of Open Access Journals (Sweden)

    Zhang K

    2015-07-01

    Full Text Available Kefeng Zhang,1 Zhongyang Xu,1 Zhaoyun Sun2 1Spinal Surgery, Jining No 1 People’s Hospital, Jining, 2Department of Orthopedics, The People’s Hospital of Laiwu City, Laiwu, Shandong Province, People’s Republic of China Objective: To uncover the potential regulatory mechanisms of the relevant genes that contribute to the prognosis and prevention of multiple myeloma (MM. Methods: Microarray data (GSE13591 were downloaded, including five plasma cell samples from normal donors and 133 plasma cell samples from MM patients. Differentially expressed genes (DEGs were identified by Student’s t-test. Functional enrichment analysis was performed for DEGs using the Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG databases. Transcription factors and tumor-associated genes were also explored by mapping genes in the TRANSFAC, the tumor suppressor gene (TSGene, and tumor-associated gene (TAG databases. A protein–protein interaction (PPI network and PPI subnetworks were constructed by Cytoscape software using the Search Tool for the Retrieval of Interacting Genes (STRING database. Results: A total of 63 DEGs (42 downregulated, 21 upregulated were identified. Functional enrichment analysis showed that HLA-DRB1 and VCAM1 might be involved in the positive regulation of immune system processes, and HLA-DRB1 might be related to the intestinal immune network for IgA production pathway. The genes CEBPD, JUND, and ATF3 were identified as transcription factors. The top ten nodal genes in the PPI network were revealed including HLA-DRB1, VCAM1, and TFRC. In addition, genes in the PPI subnetwork, such as HLA-DRB1 and VCAM1, were enriched in the cell adhesion molecules pathway, whereas CD4 and TFRC were both enriched in the hematopoietic cell pathway. Conclusion: Several crucial genes correlated to MM were identified, including CD4, HLA-DRB1, TFRC, and VCAM1, which might exert their roles in MM progression via immune-mediated pathways. There

  20. Opiates Upregulate Adhesion Molecule Expression in Brain MicroVascular Endothelial Cells (BMVEC: Implications for Altered Blood Brain Barrier (BBB Permeability

    Directory of Open Access Journals (Sweden)

    Madhavan P.N. Nair

    2006-01-01

    Full Text Available The blood-brain barrier (BBB is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of immunocompetent cells into the central nervous system (CNS. Expression of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 on brain microvascular endothelial cells (BMVEC and their interaction with human immunodeficiency virus (HIV-1 viral proteins may help enhance viral adhesion and virus-cell fusion resulting in increased infectivity. Additionally, transmigration through the BBB is facilitated by both endothelial and monocyte/macrophage-derived nitric oxide (NO. Dysregulated production of NO by BMVEC due to opiates and HIV-1 viral protein interactions play a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB. Opioids act as co-factors in the neuropathogenesis of HIV-1 by facilitating BBB dysfunction however, no studies have been done to investigate the role of opiates alone or in combination with HIV-1 viral proteins on adhesion molecule expression in BMVEC. We hypothesize that opiates such as heroin and morphine in conjunction with the HIV-1 viral protein gp120 increase the expression of adhesion molecules ICAM-1 and VCAM-1 and these effects are mediated via the modulation of NO. Results show that opiates alone and in synergy with gp120 increase both the genotypic and phenotypic expression of ICAM-1 and VCAM-1 by BMVEC, additionally, these opiate induced effects may be the result of increased NO production. These studies will provide a better understanding of how opiate abuse in conjunction with HIV-1 infection facilitates the breakdown of the BBB and exacerbates the neuropathogenesis of HIV-1. Elucidation of the mechanisms of BBB modulation will provide new therapeutic approaches to maintain BBB integrity

  1. Amplitude recruitment of cochlear potential

    Institute of Scientific and Technical Information of China (English)

    LI Xingqi; SUN Wei; SUN Jianhe; YU Ning; JIANG Sichang

    2001-01-01

    Intracellular recordings were made from outer hair cells (OHC) and the cochlear microphonics (CM) were recorded from scala media (SM) in three turn of guinea pig cochlea,the compound action potential (CAP) were recorded at the round window (RW) before and after the animal were exposed to white noise. The results suggest that the nonlinear properties with “saduration” of Input/output (I/O) function of OHC AC recepter potential and CM were founded; the nonlinear properties with “Low”, “Platean” and “high” of CAP also were investigated. After explosion, the threshold shift of CAP has about 10 dB. The I/O of OHC responses and CM were changed in a linearizing (i.e., nonlinearity loss), the “platean” of I/O CAP disappeared and the growth rate of CAP amplitude were larger than before explosion. The response amplitude recruitment of OHC appears to result from reduction in gain (i.e., hearing loss); It was due to the nonlinear growth function of OHC receptor potentials was changed in linearzing that the basilar membrance motion was changed in linearizing. Since intensity coding in the inner ear depends on an interactions of nonlinear basilar membrance and nerve fibers. So that it must lead to a linearizing of CAP as input responses.

  2. Recruitment dynamics in adaptive social networks

    OpenAIRE

    Shkarayev, Maxim S.; Schwartz, Ira B.; Shaw, Leah B.

    2011-01-01

    We model recruitment in adaptive social networks in the presence of birth and death processes. Recruitment is characterized by nodes changing their status to that of the recruiting class as a result of contact with recruiting nodes. Only a susceptible subset of nodes can be recruited. The recruiting individuals may adapt their connections in order to improve recruitment capabilities, thus changing the network structure adaptively. We derive a mean field theory to predict the dependence of the...

  3. HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1/CDK2 signaling.

    Science.gov (United States)

    Hu, Jiao-Jiao; Song, Wei; Zhang, Shao-Dan; Shen, Xiao-Hui; Qiu, Xue-Mei; Wu, Hua-Zhang; Gong, Pi-Hai; Lu, Sen; Zhao, Zhu-Jiang; He, Ming-Liang; Fan, Hong

    2016-01-01

    It is well accepted that HBx plays the major role in hepatocarcinogenesis associated with hepatitis B virus (HBV) infections. However, little was known about its role in regulating long noncoding RNAs (lncRNAs), a large group of transcripts regulating a variety of biological processes including carcinogenesis in mammalian cells. Here we report that HBx upregulates UCA1 genes and downregulates p27 genes in hepatic LO2 cells. Further studies show that the upregulated UCA1 promotes cell growth by facilitating G1/S transition through CDK2 in both hepatic and hepatoma cells. Knock down of UCA1 in HBx-expressing hepatic and hepatoma cells resulted in markedly increased apoptotic cells by elevating the cleaved caspase-3 and caspase-8. More importantly, UCA1 is found to be physically associated with enhancer of zeste homolog 2 (EZH2), which suppresses p27Kip1 through histone methylation (H3K27me3) on p27Kip1 promoter. We also show that knockdown of UCA1 in hepatoma cells inhibits tumorigenesis in nude mice. In a clinic study, UCA1 is found to be frequently up-regulated in HBx positive group tissues in comparison with the HBx negative group, and exhibits an inverse correlation between UCA1 and p27Kip1 levels. Our findings demonstrate an important mechanism of hepatocarcinogenesis through the signaling of HBx-UCA1/EZH2-p27Kip1 axis, and a potential target of HCC. PMID:27009634

  4. Temporal pattern of ICAM-I mediated regulatory T cell recruitment to sites of inflammation in adoptive transfer model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sebastian Doerck

    Full Text Available Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS. However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3 only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development.

  5. Recruitment Maneuvers and PEEP Titration.

    Science.gov (United States)

    Hess, Dean R

    2015-11-01

    The injurious effects of alveolar overdistention are well accepted, and there is little debate regarding the importance of pressure and volume limitation during mechanical ventilation. The role of recruitment maneuvers is more controversial. Alveolar recruitment is desirable if it can be achieved, but the potential for recruitment is variable among patients with ARDS. A stepwise recruitment maneuver, similar to an incremental PEEP titration, is favored over sustained inflation recruitment maneuvers. Many approaches to PEEP titration have been proposed, and the best method to choose the most appropriate level for an individual patient is unclear. A PEEP level should be selected that balances alveolar recruitment against overdistention. The easiest approach to select PEEP might be according to the severity of the disease: 5-10 cm H2O PEEP in mild ARDS, 10-15 cm H2O PEEP in moderate ARDS, and 15-20 cm H2O PEEP in severe ARDS. Recruitment maneuvers and PEEP should be used within the context of lung protection and not just as a means of improving oxygenation. PMID:26493593

  6. Human Resources Marketing and Recruiting: Essentials of Digital Recruiting

    CERN Document Server

    Purvis, James

    2016-01-01

    This chapter will cover digital recruitment from its definition thru to its history in recruitment and trends. The subject itself could cover an entire book or an entire module at university, so this chapter will broadly touch upon the key elements and considerations. Under cultural perspective, the recruitment life cycle will be broken down into its individual parts, and digital solutions will be examined for each individual part of the process together with the impact this has on the knowledge and challenges for the manager and team. The economic perspective will assist in prioritizing initiatives and building a business case for the introduction of digital recruiting solutions. The risk perspective will raise awareness of the potential pitfalls and the operational perspective on the key considerations for a successful implementation. Finally, the key messages of this chapter are summarized in the Do’s and Don’ts.

  7. Bench-to-bedside review: Recruitment and recruiting maneuvers.

    Science.gov (United States)

    Lapinsky, Stephen E; Mehta, Sangeeta

    2005-02-01

    In patients with acute respiratory distress syndrome (ARDS), the lung comprises areas of aeration and areas of alveolar collapse, the latter producing intrapulmonary shunt and hypoxemia. The currently suggested strategy of ventilation with low lung volumes can aggravate lung collapse and potentially produce lung injury through shear stress at the interface between aerated and collapsed lung, and as a result of repetitive opening and closing of alveoli. An 'open lung strategy' focused on alveolar patency has therefore been recommended. While positive end-expiratory pressure prevents alveolar collapse, recruitment maneuvers can be used to achieve alveolar recruitment. Various recruitment maneuvers exist, including sustained inflation to high pressures, intermittent sighs, and stepwise increases in positive end-expiratory pressure or peak inspiratory pressure. In animal studies, recruitment maneuvers clearly reverse the derecruitment associated with low tidal volume ventilation, improve gas exchange, and reduce lung injury. Data regarding the use of recruitment maneuvers in patients with ARDS show mixed results, with increased efficacy in those with short duration of ARDS, good compliance of the chest wall, and in extrapulmonary ARDS. In this review we discuss the pathophysiologic basis for the use of recruitment maneuvers and recent evidence, as well as the practical application of the technique. PMID:15693985

  8. 10 CFR 1042.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Recruitment. 1042.310 Section 1042.310 Energy DEPARTMENT... Recruitment Prohibited § 1042.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 1042.300 through 1042.310 apply shall not discriminate on the basis of sex in the recruitment and...

  9. 45 CFR 86.23 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 86.23 Section 86.23 Public Welfare... in Admission and Recruitment Prohibited § 86.23 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which this subpart applies shall not discriminate on the basis of sex in the recruitment...

  10. 22 CFR 146.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 146.310 Section 146.310 Foreign... Recruitment Prohibited § 146.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 146.300 through 146.310 apply shall not discriminate on the basis of sex in the recruitment and...

  11. 22 CFR 229.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 229.310 Section 229.310 Foreign... and Recruitment Prohibited § 229.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 229.300 through 229.310 apply shall not discriminate on the basis of sex in the recruitment...

  12. 49 CFR 25.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Recruitment. 25.310 Section 25.310 Transportation... Recruitment Prohibited § 25.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 25.300 through 25.310 apply shall not discriminate on the basis of sex in the recruitment and admission...

  13. Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels.

    Directory of Open Access Journals (Sweden)

    Marc B Bigler

    Full Text Available Acute stress drives a 'high-alert' response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans.3,4-methylenedioxymethamphetamine (MDMA, methylphenidate (MPH, or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells.MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment.The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats.

  14. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10

    Science.gov (United States)

    Park, Soojin; Seok, Jin Kyung; Kwak, Jun Yup; Suh, Hwa-Jin; Kim, Young Mi; Boo, Yong Chool

    2016-01-01

    Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of pomegranate peel extract (PPE) on THP-1 monocytic cells exposed to PM10. PM10 induced cytotoxicity and the production of ROS. It also increased the expression and secretion of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), and cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). PPE at 10–100 μg mL−1 attenuated the production of ROS and the expression of TNF-α, IL-1β, MCP-1, and ICAM-1, but not VCAM-1, in THP-1 cells stimulated by PM10 (100 μg mL−1). PPE also attenuated the adhesion of PM10-stimulated THP-1 cells to EA.hy926 endothelial cells. PPE constituents, punicalagin and ellagic acid, attenuated PM10-induced monocyte adhesion to endothelial cells, and punicalagin was less cytotoxic compared to ellagic acid. The present study suggests that PPE and punicalagin may be useful in alleviating inflammatory reactions due to particulate matter. PMID:27247608

  15. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10

    Directory of Open Access Journals (Sweden)

    Soojin Park

    2016-01-01

    Full Text Available Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of <10 μM (PM10. PM10 stimulates the production of reactive oxygen species (ROS and inflammatory mediators. Thus, we assumed that natural antioxidants might provide health benefits attenuating hazardous effects of PM10. In the present study, we examined the effects of pomegranate peel extract (PPE on THP-1 monocytic cells exposed to PM10. PM10 induced cytotoxicity and the production of ROS. It also increased the expression and secretion of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and monocyte chemoattractant protein-1 (MCP-1, and cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1. PPE at 10–100 μg mL−1 attenuated the production of ROS and the expression of TNF-α, IL-1β, MCP-1, and ICAM-1, but not VCAM-1, in THP-1 cells stimulated by PM10 (100 μg mL−1. PPE also attenuated the adhesion of PM10-stimulated THP-1 cells to EA.hy926 endothelial cells. PPE constituents, punicalagin and ellagic acid, attenuated PM10-induced monocyte adhesion to endothelial cells, and punicalagin was less cytotoxic compared to ellagic acid. The present study suggests that PPE and punicalagin may be useful in alleviating inflammatory reactions due to particulate matter.

  16. Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages.

    Directory of Open Access Journals (Sweden)

    Kees Meijer

    Full Text Available BACKGROUND: Obesity promotes inflammation in adipose tissue (AT and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA in obese state activate AT macrophages (ATM that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT. METHODS AND RESULTS: Using mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-α and TNF-β highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%. CONCLUSION: Human adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by

  17. Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity

    DEFF Research Database (Denmark)

    Wood, Stephanie M; Meeths, Marie; Chiang, Samuel C C;

    2009-01-01

    -4 do not colocalize extensively with perforin. However, phorbol 12-myristate 13-acetate and ionomycin stimulation or conjugation to susceptible target cells induced myosin-dependent colocalization of Rab27a and Munc13-4 with perforin. Unexpectedly, individual engagement of receptors leukocyte...

  18. Axonal elongation through long acellular nerve segments depends on recruitment of phagocytic cells from the near-nerve environment. Electrophysiological and morphological studies in the cat

    DEFF Research Database (Denmark)

    Sørensen, J; Fugleholm, K; Moldovan, M;

    2001-01-01

    or tissue ingrowth, respectively. In a second set of experiments, tibial nerves were crushed and either frozen for 20+20 mm, leaving a 10 mm segment with viable cells in the center (stepping-stone segment) or frozen for 50 mm. These nerves were enclosed in cuffs with 2.0 mm holes corresponding to the viable...

  19. 3-Methylcholanthrene, an AhR agonist, caused cell-cycle arrest by histone deacetylation through a RhoA-dependent recruitment of HDAC1 and pRb2 to E2F1 complex.

    Directory of Open Access Journals (Sweden)

    Chih-Cheng Chang

    Full Text Available We previously showed that treating vascular endothelial cells with 3-methylcholanthrene (3MC caused cell-cycle arrest in the Go/G1 phase; this resulted from the induction of p21 and p27 and a decreased level and activity of the cyclin-dependent kinase, Cdk2. We further investigated the molecular mechanisms that modulate cell-cycle regulatory proteins through the aryl-hydrocarbon receptor (AhR/Ras homolog gene family, member A (RhoA dependent epigenetic modification of histone. AhR/RhoA activation mediated by 3MC was essential for the upregulation of retinoblastoma 2 (pRb2 and histone deacetylase 1 (HDAC1, whereas their nuclear translocation was primarily modulated by RhoA activation. The combination of increased phosphatase and tensin homolog (PTEN activity and decreased phosphatidylinositide 3-kinase (PI3K activation by 3MC led to the inactivation of the Ras-cRaf pathway, which contributed to pRb2 hypophosphorylation. Increased HDAC1/pRb2 recruitment to the E2F1 complex decreased E2F1-transactivational activity and H3/H4 deacetylation, resulting in the downregulation of cell-cycle regulatory proteins (Cdk2/4 and Cyclin D3/E. Co-immunoprecipitation and electrophoretic mobility shift assay (EMSA results showed that simvastatin prevented the 3MC-increased binding activities of E2F1 proteins in their promoter regions. Additionally, RhoA inhibitors (statins reversed the effect of 3MC in inhibiting DNA synthesis by decreasing the nuclear translocation of pRb2/HDAC1, leading to a recovery of the levels of cell-cycle regulatory proteins. In summary, 3MC decreased cell proliferation by the epigenetic modification of histone through an AhR/RhoA-dependent mechanism that can be rescued by statins.

  20. Effect of tetramethylpyrazine on expression of vascular cell adhension molecule-1 in mice with ulcerative colitis%川芎嗪对结肠炎模型小鼠血管细胞黏附分子-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈文敏; 江琼

    2012-01-01

    Objective To investigate the effect of tetramethylpyrazine(TMP) on expression of vascular cell adhension molecule-1 (VCAM-l) in mice with ulcerative colitis (UC) as well as role of TMP in treatment of UC. Methods Mice were randomly divided into normal control, model and TMP groups. Mouse model of UC was established by induction with dextran sulfate sodium (DSS), then observed for inflammation evaluation indexes, such as disease activity index (DAI) as well as morphology and lesion of colon tissue,and determined for expression of VCAM-l in colon mucosa by immunohistochemical assay. Results The inflammation evaluation indexes of mice in model group were significantly higher than those in normal control group (P < 0. 01). Though little expression of VCAM-l was observed in colon mucosa of mice in normal control group, the expression level increased significantly in model group (P < 0. 01) and decreased significantly in TMP group (P < 0. 01). Conclusion The expression of VCAM-l increased in mouse model of UC induced by DSS, which was inhibited by TMP.%目的 研究川芎嗪对结肠炎模型小鼠血管细胞黏附分子-1(Vascular cell adhension molecule-1,VCAM-1)表达的影响,探讨川芎嗪在治疗溃疡性结肠炎(Ulcerative colitis,UC)中的作用.方法 将小鼠随机分为正常对照组、模型组和川芎嗪组,采用葡聚糖硫酸钠(Dextran sulfate sodium,DSS)诱导小鼠UC模型,观察UC炎症评价指标[疾病活动指数(Disease activity index,DAI)、结肠组织形态学及组织学损伤],采用免疫组化法检测VCAM-1在结肠黏膜中的表达.结果 与正常对照组比较,模型组的炎症评价指标均明显增高(P<0.01);正常对照组结肠黏膜中几乎不表达VCAM-1,模型组VCAM-1的表达明显升高(P<0.01),而川芎嗪组VCAM-1的表达较模型组明显降低(P<0.01).结论 DSS诱导的结肠炎模型小鼠中VCAM-1表达增强,川芎嗪具有抑制VCAM-1表达的作用.

  1. Red wine polyphenolics reduce the expression of inflammation markers in human colon-derived CCD-18Co myofibroblast cells: potential role of microRNA-126.

    Science.gov (United States)

    Angel-Morales, Gabriela; Noratto, Giuliana; Mertens-Talcott, Susanne

    2012-07-01

    Chronic intestinal inflammation is an established risk factor for colon cancer. Polyphenolic compounds from fruit and vegetables have been shown to have anti-inflammatory properties in several cell lines and tissues. However, their anti-inflammatory mechanisms, involving microRNAs in the regulation of inflammation, have not been extensively investigated. The goal of this research was to assess the chemopreventive potential of polyphenolics extracted from red wine made with Lenoir grapes (Vitis aestivalis hybrid) in human colon-derived CCD-18Co myofibroblasts cells, and to assess the potential involvement of microRNA-126 (miR-126) in the underlying mechanisms. The results show that the polyphenolic red wine extract (WE) decreased mRNA expression of lipopolysaccharide (LPS)-induced inflammatory mediators NF-kB, ICAM-1, VCAM-1, and PECAM-1 by 1.95-, 1.98-, 1.52-, and 1.84-fold respectively, in a dose dependent manner (0-100 μg of gallic acid equivalent (GAE) mL(-1)) down to 0.80-, 0.79-, 0.66-, and 0.68-fold in DMSO-treated control cells not challenged with LPS, respectively. Correspondingly, miR-126, which has a target region within the 3'-UTR of VCAM-1 mRNA, was increased 2.79-fold by the WE at 100 μg GAE mL(-1). The potential role of miR-126 was confirmed by transfecting cells with a specific miR-126-antagomir, as-miR-126. Transfection with as-miR-126 down-regulated miR-126 to 0.71-fold in the control cells and up-regulated mRNA levels of NF-kB, ICAM-1, VCAM-1, and PECAM-1 to 1.80-, 1.49-, 2.30-, and 1.95-fold of controls, respectively. WE at 100 μg GAE mL(-1) partially reversed the effects of the as-miR-126 to 1.02-, 1.01-, 1.04-, and 1.05-fold, for mRNA levels of NF-kB, ICAM-1, VCAM-1, and PECAM-1 respectively. This indicates the potential role of miR-126 in the anti-inflammatory properties of polyphenolics from red wine in CCD-18Co myofibroblasts cells. PMID:22572890

  2. Characterization of a Distinct Population of Circulating Human Non-Adherent Endothelial Forming Cells and Their Recruitment via Intercellular Adhesion Molecule-3

    OpenAIRE

    Appleby, Sarah L.; Cockshell, Michaelia P.; Pippal, Jyotsna B.; Thompson, Emma J.; Barrett, Jeffrey M.; Katie Tooley; Shaundeep Sen; Wai Yan Sun; Randall Grose; Ian Nicholson; Vitalina Levina; Ira Cooke; Gert Talbo; Lopez, Angel F.; Bonder, Claudine S.

    2012-01-01

    Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenotypic and functional heterogeneity. Herein we have isolated, enriched for and then characterized a human umbilical cord blood derived CD133(+) popul...

  3. Repression of Runx2 by Androgen Receptor (AR) in Osteoblasts and Prostate Cancer Cells: AR Binds Runx2 and Abrogates Its Recruitment to DNA

    OpenAIRE

    Baniwal, Sanjeev K.; Khalid, Omar; Sir, Donna; Buchanan, Grant; Coetzee, Gerhard A.; Frenkel, Baruch

    2009-01-01

    Runx2 and androgen receptor (AR) are master transcription factors with pivotal roles in bone metabolism and prostate cancer (PCa). We dissected AR-mediated repression of Runx2 in dihydrotestosterone (DHT)-treated osteoblastic and PCa cells using reporter assays and endogenous Runx2 target genes. Repression required DHT, but not AR’s transactivation function, and was associated with nuclear colocalization of the two proteins. Runx2 and AR coimmunoprecipitated and interacted directly in glutath...

  4. Recruitment of HIV-1 target cells at topical mucosal sites: a sensitive and early marker for determining the safety of microbicide candidates

    OpenAIRE

    Li, Liangzhu; Ben, Yinyin; Yuan, Songhua; Liu, Aiping; Wu, Huanmei; Xu, Jianqing; Zhang, Xiaoyan

    2013-01-01

    To explore early biomarkers for establishing more sensitive safety evaluation assays in preclinical settings that determine the potential risks during the application of microbicide candidates, three representative microbicide candidates (cellulose sulphate, nonoxynol-9 and tenofovir), whose safety profiles have been well established in clinical trials, were included to gauge the sensitivities of different assays. Both mouse models and cell lines were employed to determine the sensitivities. ...

  5. Potential of mZD7349-conjugated PLGA nanoparticles for selective targeting of vascular cell-adhesion molecule-1 in inflamed endothelium.

    Science.gov (United States)

    Imanparast, Fatemeh; Paknejad, Maliheh; Faramarzi, Mohammad Ali; Kobarfard, Farzad; Amani, Amir; Doosti, Mahmood

    2016-07-01

    Early diagnosis and restoring normal function of dysfunctional endothelium is an attractive strategy for prevention of inflammatory diseases such as atherosclerosis. Inhibition of cell adhesion in the process of atherosclerosis plaque formation, mediated by peptide antagonists of very late antigen-4 (VLA-4) has already been developed and evaluated both in vitro and in vivo. In this study, for the first time, modified ZD7349 (mZD7349) peptide, as an antagonist for VLA-4, was used for targeting fluorescein isothiocyanate-loaded poly (DL-lactic-co-glycolic acid) nanoparticles (FITC-PLGA NPs). Rate of binding and internalization of mZD7349-NPs to activated human umbilical vein endothelial cells (HUVECs) were compared with that of untargeted. Effects of temperature reduction and clathrin-mediated endocytosis inhibitor (0.45M sucrose) were also studied on the binding and internalization of mZD7349-NPs and NPs. Results showed that binding of the conjugated NPs could be significantly blocked by pre-incubating cells with the free peptide, suggesting that the binding of NPs is mediated by attaching the surface peptide to VCAM-1 on HUVECs. Also, conjugated FITC-loaded NPs were shown to be rapidly endocytosized to a greater extent than the unconjugated ones. The binding and internalization of mZD7349-NPs and NPs were slowed down at low temperature and in the presence of sucrose with greater reductions for mZD7349-NPs. To conclude, the peptide-NPs targeting the VCAM-1 is suggested as a theranostic carrier for lesions upregulating VCAM-1. PMID:27105996

  6. Informed consent--suggested procedures for informed consent for unrelated haematopoietic stem cell donors at various stages of recruitment, donor evaluation, and donor workup.

    Science.gov (United States)

    Rosenmayr, A; Hartwell, L; Egeland, T

    2003-04-01

    The Ethics Working Group of the World Marrow Donor Association (WMDA) was established to address the increasing and complex number of ethical issues surrounding unrelated haematopoietic stem cell donation where the selected donor and recipient reside in different countries. This paper considers the topic of informed donor consent, but recognises that the recommendations contained within the paper may be subject to cultural variances in interpretation, and to adjustment to meet the legal requirements of individual countries. Nevertheless, the extent of international cooperation establishes sufficient common denominators for the recommendations to be widely adhered to in the interests of best practice. PMID:12692618

  7. A novel pathway down-modulating T cell activation involves HPK-1–dependent recruitment of 14-3-3 proteins on SLP-76

    OpenAIRE

    Bartolo, Vincenzo Di; Montagne, Benjamin; Salek, Mogjiborahman; Jungwirth, Britta; Carrette, Florent; Fourtane, Julien; Sol-Foulon, Nathalie; Michel, Frédérique; Schwartz, Olivier; Lehmann, Wolf D.; Acuto, Oreste

    2007-01-01

    The SH2 domain–containing leukocyte protein of 76 kD (SLP-76) is a pivotal element of the signaling machinery controlling T cell receptor (TCR)-mediated activation. Here, we identify 14-3-3ɛ and ζ proteins as SLP-76 binding partners. This interaction was induced by TCR ligation and required phosphorylation of SLP-76 at serine 376. Ribonucleic acid interference and in vitro phosphorylation experiments showed that serine 376 is the target of the hematopoietic progenitor kinase 1 (HPK-1). Intere...

  8. Spatial synchrony in cisco recruitment

    Science.gov (United States)

    Myers, Jared T.; Yule, Daniel L.; Jones, Michael L.; Ahrenstorff, Tyler D.; Hrabik, Thomas R.; Claramunt, Randall M.; Ebener, Mark P.; Berglund, Eric K.

    2015-01-01

    We examined the spatial scale of recruitment variability for disparate cisco (Coregonus artedi) populations in the Great Lakes (n = 8) and Minnesota inland lakes (n = 4). We found that the scale of synchrony was approximately 400 km when all available data were utilized; much greater than the 50-km scale suggested for freshwater fish populations in an earlier global analysis. The presence of recruitment synchrony between Great Lakes and inland lake cisco populations supports the hypothesis that synchronicity is driven by climate and not dispersal. We also found synchrony in larval densities among three Lake Superior populations separated by 25–275 km, which further supports the hypothesis that broad-scale climatic factors are the cause of spatial synchrony. Among several candidate climate variables measured during the period of larval cisco emergence, maximum wind speeds exhibited the most similar spatial scale of synchrony to that observed for cisco. Other factors, such as average water temperatures, exhibited synchrony on broader spatial scales, which suggests they could also be contributing to recruitment synchrony. Our results provide evidence that abiotic factors can induce synchronous patterns of recruitment for populations of cisco inhabiting waters across a broad geographic range, and show that broad-scale synchrony of recruitment can occur in freshwater fish populations as well as those from marine systems.

  9. Uncover the recruiter in you!

    CERN Multimedia

    2013-01-01

    2013 saw the launch of the one-day training course "Selecting the best person for CERN". So far, 10 courses have taken place and over 100 participants have taken part in this interactive, hands on experience.   The course has been met with much enthusiasm and positive feedback, with participants not only feeling better prepared and organised for the recruitment boards, but also equipped with concrete tools on how to prepare and conduct an effective selection interview. Following on from this success, further sessions are planned in 2014: we look forward to welcoming recruiting supervisors and board members who are likely to take part in a recruitment process, whether for LD or LD2IC, and who are interested in finding out more about how to get the most out of this important process! To enrol to this course, please follow this link: "Selecting the best person for CERN".

  10. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

  11. 7 CFR 15a.53 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Recruitment. 15a.53 Section 15a.53 Agriculture Office... Activities Prohibited § 15a.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient...

  12. 45 CFR 2555.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recruitment. 2555.310 Section 2555.310 Public... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 2555.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 2555.300 through 2555.310 apply shall not discriminate on...

  13. 22 CFR 229.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 229.510 Section 229.510 Foreign... in Education Programs or Activities Prohibited § 229.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and...

  14. 34 CFR 106.53 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Recruitment. 106.53 Section 106.53 Education... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  15. 20 CFR 655.156 - Recruitment report.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Recruitment report. 655.156 Section 655.156... the United States (H-2A Workers) Post-Acceptance Requirements § 655.156 Recruitment report. (a) Requirements of a recruitment report. The employer must prepare, sign, and date a written recruitment...

  16. 36 CFR 1211.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Recruitment. 1211.510 Section... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  17. 13 CFR 113.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Recruitment. 113.510 Section 113... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  18. 32 CFR 196.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Recruitment. 196.510 Section 196.510 National... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  19. 18 CFR 1317.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Recruitment. 1317.310... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 1317.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 1317.300 through 1317.310 apply shall not discriminate on...

  20. 49 CFR 25.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Recruitment. 25.510 Section 25.510 Transportation... Education Programs or Activities Prohibited § 25.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of...

  1. 44 CFR 19.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.310 Section... RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 19.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 19.300 through...

  2. 18 CFR 1317.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Recruitment. 1317.510... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  3. 38 CFR 23.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Recruitment. 23.510... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  4. 44 CFR 19.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.510 Section... Programs or Activities Prohibited § 19.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where...

  5. 10 CFR 1042.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Recruitment. 1042.510 Section 1042.510 Energy DEPARTMENT... Education Programs or Activities Prohibited § 1042.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of...

  6. 10 CFR 5.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Recruitment. 5.510 Section 5.510 Energy NUCLEAR REGULATORY... Prohibited § 5.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been...

  7. 45 CFR 83.12 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 83.12 Section 83.12 Public Welfare... § 83.12 Recruitment. (a) Comparable recruitment. A federally supported entity shall, with respect to... demonstrate that such action is part of a recruitment program which does not have the effect of...

  8. 41 CFR 101-4.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Recruitment. 101-4.510... Employment in Education Programs or Activities Prohibited § 101-4.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and...

  9. 24 CFR 3.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Recruitment. 3.510 Section 3.510... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  10. 45 CFR 2555.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recruitment. 2555.510 Section 2555.510 Public... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  11. 45 CFR 618.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Recruitment. 618.510 Section 618.510 Public... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be...

  12. 32 CFR 196.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Recruitment. 196.310 Section 196.310 National... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 196.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 196.300 through 196.310 apply shall not discriminate on...

  13. 38 CFR 23.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Recruitment. 23.310... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 23.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 23.300 through 23.310 apply shall not discriminate on...

  14. 13 CFR 113.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Recruitment. 113.310 Section 113... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 113.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 113.300 through 113.310 apply shall not discriminate on...

  15. 24 CFR 3.310 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Recruitment. 3.310 Section 3.310... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 3.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 3.300 through 3.310 apply shall not discriminate on the...

  16. 10 CFR 5.310 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Recruitment. 5.310 Section 5.310 Energy NUCLEAR REGULATORY... FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 5.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 5.300 through 5.310 apply shall...

  17. 31 CFR 28.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Recruitment. 28.310 Section 28.310... Basis of Sex in Admission and Recruitment Prohibited § 28.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 28.300 through 28.310 apply shall not discriminate on the basis of sex...

  18. 36 CFR 1211.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Recruitment. 1211.310 Section... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 1211.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 1211.300 through 1211.310 apply shall not discriminate on...

  19. 45 CFR 618.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Recruitment. 618.310 Section 618.310 Public... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 618.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 618.300 through 618.310 apply shall not discriminate on...

  20. 7 CFR 15a.23 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Recruitment. 15a.23 Section 15a.23 Agriculture Office... FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 15a.23 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which this subpart applies...

  1. 22 CFR 146.510 - Recruitment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Recruitment. 146.510 Section 146.510 Foreign... Education Programs or Activities Prohibited § 146.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of...

  2. Screening scFv Specific to Vcam-1 by Phage Display Library and Its Activity Evaluation%噬菌体展示库筛选构建血管细胞黏附分子-1单链抗体及其效价检测

    Institute of Scientific and Technical Information of China (English)

    刘纯宝; 宋夷龄; 张永学

    2015-01-01

    目的:从噬菌体重组抗体库中筛选获得靶向血管细胞黏附分子‐1(Vcam‐1)的单链抗体,纯化浓缩后进行亲和性鉴定,并与单克隆抗体效价进行比较。方法扩增Vcam‐1基因克隆质粒并转入真核细胞中表达获得Vcam‐1抗原蛋白,纯化后包被免疫管,通过4轮压力逐渐增大的“吸附‐洗脱‐扩增”过程筛选获得阳性克隆。对阳性克隆进行ELISA检测,选取效价高的克隆送予测序并转入大肠埃希菌进行表达,认定高表达的样品为最终的阳性克隆。将该阳性克隆转染入感受态细胞表达单链抗体,纯化后经ELISA检测并评价其抗原亲和性。结果真核细胞表达的Vcam‐1抗原蛋白的分子量为85~90 kD。以Vcam‐1抗原蛋白为免疫原筛选4轮所得的阳性克隆进行单噬菌体ELISA检测,从检测结果中选取9个效价高的克隆经基因测序共获得3个序列,其中1个序列对应的克隆高表达。表达的单链抗体分子量约30 kD ,ELISA检测其对Vcam‐1抗原蛋白有较高亲和性,效价较单克隆抗体低。结论利用噬菌体展示技术获得了靶向Vcam‐1的单链抗体,为随后的诊断和治疗应用奠定了基础。%Objective To screen out single chain variable fragment antibody (scFv)specific to vascular cell adhesion mole‐cule 1(Vcam‐1)from phage recombinant antibody library ,and to evaluate its activity and compare its activity with full‐length monoclonal antibody.Methods Amplification of Vcam‐1 was performed by PCR and Vcam‐1 gene plasmid was transferred into eukaryotic cells to express Vcam‐1 antigen protein.Immune cuvette was coated with purified Vcam‐1 antigen ,and the positive clones were screened out by 4 rounds of “adhesion‐elution‐proliferation” process with gradually increasing pressure.The posi‐tive clones were tested by ELISA method and high titer clones were chosen for gene sequencing.Then the high‐titer clones

  3. Novel process of intrathymic tumor-immune tolerance through CCR2-mediated recruitment of Sirpα+ dendritic cells: a murine model.

    Directory of Open Access Journals (Sweden)

    Tomohisa Baba

    Full Text Available Immune surveillance system can detect more efficiently secretory tumor-specific antigens, which are superior as a target for cancer immunotherapy. On the contrary, immune tolerance can be induced in the thymus when a tumor antigen is massively secreted into circulation. Thus, the secretion of tumor-specific antigen may have contradictory roles in tumor immunity in a context-dependent manner. However, it remains elusive on the precise cellular mechanism of intrathymic immune tolerance against tumor antigens. We previously demonstrated that a minor thymic conventional dendritic cell (cDC subset, CD8α(-Sirpα(+ cDCs, but not the major subset, CD8α(+Sirpα(- cDCs can selectively capture blood-borne antigens and crucially contribute to the self-tolerance. In the present study, we further demonstrated that Sirpα(+ cDCs can capture a blood-borne antigen leaking inside the interlobular vascular-rich regions (IVRs. Blood-borne antigen selectively captured by Sirpα(+ cDCs can induce antigen-specific Treg generation or negative selection, depending on the immunogenicity of the presented antigen. Furthermore, CCR2 expression by thymic Sirpα(+ cDCs and abundant expression of its ligands, particularly, CCL2 by tumor-bearing mice prompted us to examine the function of thymic Sirpα(+ cDCs in tumor-bearing mice. Interestingly, tumor-bearing mice deposited CCL2 inside IVRs in the thymus. Moreover, tumor formation induced the accumulation of Sirpα(+ cDCs in IVRs under the control of CCR2-CCL2 axis and enhanced their capacity to take up antigens, resulting in the shift from Treg differentiation to negative selection. Finally, intrathymic negative selection similarly ensued in CCR2-competent mice once the tumor-specific antigen was secreted into bloodstream. Thus, we demonstrated that thymic Sirpα(+ cDCs crucially contribute to this novel process of intrathymic tumor immune tolerance.

  4. Do recruitment ties affect wages?

    DEFF Research Database (Denmark)

    Larsen, Anna Folke; Rand, John; Torm, Nina Elisabeth

    This paper examines the extent to which recruitment ties affect individual wage outcomes in small and medium scale manufacturing firms. Based on a unique matched employer-employee dataset from Vietnam we find that there is a significant positive wage premium associated with obtaining a job through...

  5. Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Elham Khanicheh

    Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

  6. Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model

    Science.gov (United States)

    Lopez-Vilchez, I; Diaz-Ricart, M; Navarro, V; Torramade, S; Zamorano-Leon, J; Lopez-Farre, A; Galan, A M; Gasto, C; Escolar, G

    2016-01-01

    There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (Pcultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (Pcultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks. PMID:27598970

  7. Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model.

    Science.gov (United States)

    Lopez-Vilchez, I; Diaz-Ricart, M; Navarro, V; Torramade, S; Zamorano-Leon, J; Lopez-Farre, A; Galan, A M; Gasto, C; Escolar, G

    2016-01-01

    There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (Ptreatment. Conversely, EPC levels were lower in MD-0, tending to increase throughout treatment. In vitro studies were performed in human endothelial cells cultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (Ptreatment for 24 weeks. PMID:27598970

  8. Recruitment & Social networking : The Future for International Recruitment Agency A

    OpenAIRE

    Juusola, Toni

    2010-01-01

    The online world is changing rapidly and making waves across many aspects of life, notably business. The author was able to observe some of these changes firsthand during his time at International Recruitment Agency A (IRAA). The combination of a developing online environment and the economic climate in 2009 forced IRAA to re-assess its strategic position. This study was therefore carried out to explore the current employment market situation and online environment to predict future trends in...

  9. Arabidopsis poly(A) polymerase PAPS1 limits founder-cell recruitment to organ primordia and suppresses the salicylic acid-independent immune response downstream of EDS1/PAD4.

    Science.gov (United States)

    Trost, Gerda; Vi, Son Lang; Czesnick, Hjördis; Lange, Peggy; Holton, Nick; Giavalisco, Patrick; Zipfel, Cyril; Kappel, Christian; Lenhard, Michael

    2014-03-01

    Polyadenylation of pre-mRNAs by poly(A) polymerase (PAPS) is a critical process in eukaryotic gene expression. As found in vertebrates, plant genomes encode several isoforms of canonical nuclear PAPS enzymes. In Arabidopsis thaliana these isoforms are functionally specialized, with PAPS1 affecting both organ growth and immune response, at least in part by the preferential polyadenylation of subsets of pre-mRNAs. Here, we demonstrate that the opposite effects of PAPS1 on leaf and flower growth reflect the different identities of these organs, and identify a role for PAPS1 in the elusive connection between organ identity and growth patterns. The overgrowth of paps1 mutant petals is due to increased recruitment of founder cells into early organ primordia, and suggests that PAPS1 activity plays unique roles in influencing organ growth. By contrast, the leaf phenotype of paps1 mutants is dominated by a constitutive immune response that leads to increased resistance to the biotrophic oomycete Hyaloperonospora arabidopsidis and reflects activation of the salicylic acid-independent signalling pathway downstream of ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1)/PHYTOALEXIN DEFICIENT4 (PAD4). These findings provide an insight into the developmental and physiological basis of the functional specialization amongst plant PAPS isoforms.

  10. Insulin and hypertonicity recruit GLUT4 to the plasma membrane of muscle cells by using N-ethylmaleimide-sensitive factor-dependent SNARE mechanisms but different v-SNAREs: role of TI-VAMP.

    Science.gov (United States)

    Randhawa, Varinder K; Thong, Farah S L; Lim, Dawn Y; Li, Dailin; Garg, Rami R; Rudge, Rachel; Galli, Thierry; Rudich, Assaf; Klip, Amira

    2004-12-01

    Insulin and hypertonicity each increase the content of GLUT4 glucose transporters at the surface of muscle cells. Insulin enhances GLUT4 exocytosis without diminishing its endocytosis. The insulin but not the hypertonicity response is reduced by tetanus neurotoxin, which cleaves vesicle-associated membrane protein (VAMP)2 and VAMP3, and is rescued upon introducing tetanus neurotoxin-resistant VAMP2. Here, we show that hypertonicity enhances GLUT4 recycling, compounding its previously shown ability to reduce GLUT4 endocytosis. To examine whether the canonical soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) mechanism is required for the plasma membrane fusion of the tetanus neurotoxin-insensitive GLUT4 vesicles, L6 myoblasts stably expressing myc-tagged GLUT4 (GLUT4myc) were transiently transfected with dominant negative N-ethylmaleimide-sensitive factor (NSF) (DN-NSF) or small-interfering RNA to tetanus neurotoxin-insensitive VAMP (TI-VAMP siRNA). Both strategies markedly reduced the basal level of surface GLUT4myc and the surface gain of GLUT4myc in response to hypertonicity. The insulin effect was abolished by DN-NSF, but only partly reduced by TI-VAMP siRNA. We propose that insulin and hypertonicity recruit GLUT4myc from partly overlapping, but distinct sources defined by VAMP2 and TI-VAMP, respectively.

  11. Effects of nitric oxide-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) on melanoma cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Huiwen [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States); Mollica, Molly Y.; Lee, Shin Hee [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Wang, Lei [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States); Velázquez-Martínez, Carlos A., E-mail: velazque@ualberta.ca [Chemistry Section, Laboratory of Comparative Carcinogenesis and Basic Research Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton Alberta, Canada T6G 2N8 (Canada); Wu, Shiyong, E-mail: wus1@ohio.edu [Edison Biotechnology Institute, Ohio University, Athens, OH 45701 (United States); Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701 (United States)

    2012-10-15

    A new class of nitric oxide (NO•)-releasing nonsteroidal anti-inflammatory drugs (NONO-NSAIDs) were developed in recent years and have shown promising potential as NSAID substitutes due to their gentle nature on cardiovascular and gastrointestinal systems. Since nitric oxide plays a role in regulation of cell adhesion, we assessed the potential use of NONO-NSAIDs as anti-metastasis drugs. In this regard, we compared the effects of NONO-aspirin and a novel NONO-naproxen to those exerted by their respective parent NSAIDs on avidities of human melanoma M624 cells. Both NONO-NSAIDs, but not the corresponding parent NSAIDs, reduced M624 adhesion on vascular cellular adhesion molecule-1 (VCAM-1) by 20–30% and fibronectin by 25–44% under fluid flow conditions and static conditions, respectively. Only NONO-naproxen reduced (∼ 56%) the activity of β1 integrin, which binds to α4 integrin to form very late antigen-4 (VLA-4), the ligand of VCAM-1. These results indicate that the diazeniumdiolate (NO•)-donor moiety is critical for reducing the adhesion between VLA-4 and its ligands, while the NSAID moiety can impact the regulation mechanism of melanoma cell adhesion. -- Highlights: ► NONO-naproxen, a novel nitric oxide-releasing NSAID, was synthesized. ► NONO-NSAIDs, but not their parent NSAIDs, reduced melanoma adhesion. ► NONO-naproxen, but not NONO-aspirin and NSAIDs, reduced activity of β1 integrin.

  12. Pentosan polysulfate treatment ameliorates motor function with increased serum soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic disease.

    Science.gov (United States)

    Nakamura, Tatsufumi; Satoh, Katsuya; Fukuda, Taku; Kinoshita, Ikuo; Nishiura, Yoshihiro; Nagasato, Kunihiko; Yamauchi, Atsushi; Kataoka, Yasufumi; Nakamura, Tadahiro; Sasaki, Hitoshi; Kumagai, Kenji; Niwa, Masami; Noguchi, Mitsuru; Nakamura, Hideki; Nishida, Noriyuki; Kawakami, Atsushi

    2014-06-01

    The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis. We conducted a clinical trial to test the effect of subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled design. There was a marked improvement in lower extremity motor function, based on reduced spasticity, such as a reduced time required for walking 10 m and descending a flight of stairs. There were no significant changes in HTLV-I proviral copy numbers in peripheral blood contrary to the inhibitory effect of PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular cell adhesion molecule (sVCAM)-1 was significantly increased without significant changes of serum level of chemokines (CXCL10 and CCL2). There was a positive correlation between increased sVCAM-1and reduced time required for walking 10 m. PPS might induce neurological improvement by inhibition of chronic inflammation in the spinal cord, through blocking the adhesion cascade by increasing serum sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has the potential to be a new therapeutic tool for HAM/TSP.

  13. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    Science.gov (United States)

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release. PMID:27454856

  14. Recruitment dynamics in adaptive social networks.

    Science.gov (United States)

    Shkarayev, Maxim S; Schwartz, Ira B; Shaw, Leah B

    2013-01-01

    We model recruitment in adaptive social networks in the presence of birth and death processes. Recruitment is characterized by nodes changing their status to that of the recruiting class as a result of contact with recruiting nodes. Only a susceptible subset of nodes can be recruited. The recruiting individuals may adapt their connections in order to improve recruitment capabilities, thus changing the network structure adaptively. We derive a mean field theory to predict the dependence of the growth threshold of the recruiting class on the adaptation parameter. Furthermore, we investigate the effect of adaptation on the recruitment level, as well as on network topology. The theoretical predictions are compared with direct simulations of the full system. We identify two parameter regimes with qualitatively different bifurcation diagrams depending on whether nodes become susceptible frequently (multiple times in their lifetime) or rarely (much less than once per lifetime). PMID:25395989

  15. Recruitment dynamics in adaptive social networks

    International Nuclear Information System (INIS)

    We model recruitment in adaptive social networks in the presence of birth and death processes. Recruitment is characterized by nodes changing their status to that of the recruiting class as a result of contact with recruiting nodes. Only a susceptible subset of nodes can be recruited. The recruiting individuals may adapt their connections in order to improve recruitment capabilities, thus changing the network structure adaptively. We derive a mean-field theory to predict the dependence of the growth threshold of the recruiting class on the adaptation parameter. Furthermore, we investigate the effect of adaptation on the recruitment level, as well as on network topology. The theoretical predictions are compared with direct simulations of the full system. We identify two parameter regimes with qualitatively different bifurcation diagrams depending on whether nodes become susceptible frequently (multiple times in their lifetime) or rarely (much less than once per lifetime). (paper)

  16. Manganese-induced integrin affinity maturation promotes recruitment of alpha V beta 3 integrin to focal adhesions in endothelial cells: evidence for a role of phosphatidylinositol 3-kinase and Src.

    Science.gov (United States)

    Dormond, Olivier; Ponsonnet, Lionel; Hasmim, Meriem; Foletti, Alessandro; Rüegg, Curzio

    2004-07-01

    Integrin activity is controlled by changes in affinity (i.e. ligand binding) and avidity (i.e. receptor clustering). Little is known, however, about the effect of affinity maturation on integrin avidity and on the associated signaling pathways. To study the effect of affinity maturation on integrin avidity, we stimulated human umbilical vein endothelial cells (HUVEC) with MnCl(2) to increase integrin affinity and monitored clustering of beta 1 and beta 3 integrins. In unstimulated HUVEC, beta 1 integrins were present in fibrillar adhesions, while alpha V beta 3 was detected in peripheral focal adhesions. Clustered beta 1 and beta 3 integrins expressed high affinity/ligand-induced binding site (LIBS) epitopes. MnCl(2)-stimulation promoted focal adhesion and actin stress fiber formation at the basal surface of the cells, and strongly enhanced mAb LM609 staining and expression of beta 3 high affinity/LIBS epitopes at focal adhesions. MnCl(2)-induced alpha V beta 3 clustering was blocked by a soluble RGD peptide, by wortmannin and LY294002, two pharmacological inhibitors of phosphatidylinositol 3-kinase (PI 3-K), and by over-expressing a dominant negative PI 3-K mutant protein. Conversely, over-expression of active PI 3-K and pharmacological inhibiton of Src with PP2 and CGP77675, enhanced basal and manganese-induced alpha V beta 3 clustering. Transient increased phosphorylation of protein kinase B/Akt, a direct target of PI 3K, occurred upon manganese stimulation. MnCl(2) did not alter beta 1 integrin distribution or beta1 high-affinity/LIBS epitope expression. Based on these results, we conclude that MnCl(2)-induced alpha V beta 3 integrin affinity maturation stimulates focal adhesion and actin stress fiber formation, and promotes recruitment of high affinity alpha V beta 3 to focal adhesions. Affinity-modulated alpha V beta 3 clustering requires PI3-K signaling and is negatively regulate by Src.

  17. Bee Venom Accelerates Wound Healing in Diabetic Mice by Suppressing Activating Transcription Factor-3 (ATF-3) and Inducible Nitric Oxide Synthase (iNOS)-Mediated Oxidative Stress and Recruiting Bone Marrow-Derived Endothelial Progenitor Cells.

    Science.gov (United States)

    Badr, Gamal; Hozzein, Wael N; Badr, Badr M; Al Ghamdi, Ahmad; Saad Eldien, Heba M; Garraud, Olivier

    2016-10-01

    Multiple mechanisms contribute to impaired diabetic wound healing including impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the effect of BV on the healing of diabetic wounds has not been studied. Therefore, in this study, we investigated the impact of BV on diabetic wound closure in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated with BV. We found that the diabetic mice exhibited delayed wound closure characterized by a significant decrease in collagen production and prolonged elevation of inflammatory cytokines levels in wounded tissue compared to control non-diabetic mice. Additionally, wounded tissue in diabetic mice revealed aberrantly up-regulated expression of ATF-3 and iNOS followed by a marked elevation in free radical levels. Impaired diabetic wound healing was also characterized by a significant elevation in caspase-3, -8, and -9 activity and a marked reduction in the expression of TGF-β and VEGF, which led to decreased neovascularization and angiogenesis of the injured tissue by impairing EPC mobilization. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen production and restoring the levels of inflammatory cytokines, free radical, TGF-β, and VEGF. Most importantly, BV-treated diabetic mice exhibited mobilized long-lived EPCs by inhibiting caspase activity in the wounded tissue. Our findings reveal the molecular mechanisms underlying improved diabetic wound healing and closure following BV treatment. J. Cell. Physiol. 231: 2159-2171, 2016. © 2016 Wiley Periodicals, Inc. PMID:26825453

  18. The Effects of Arterial Blood Pressure Reduction on Endocan and Soluble Endothelial Cell Adhesion Molecules (CAMs and CAMs Ligands Expression in Hypertensive Patients on Ca-Channel Blocker Therapy

    Directory of Open Access Journals (Sweden)

    Refmir Tadzic

    2013-04-01

    Full Text Available Background/Aims: To determine the effect of arterial blood pressure (BP reduction on endocan and soluble cell adhesion molecules' (sCAM plasma concentration and expression of their ligands on circulatory leukocyte subpopulations. Methods: 24 hypertensive subjects of both sexes (age: 53±8 yrs were treated with Ca-channel blocker, amlodipin (5-10 mg/day for 8 weeks; to reach BP≤139/89mmHg. The serum sCAMs and endocan concentrations were determined by ELISA kits. Level of ICAM/VCAM ligands on leukocytes was assessed by flow cytometry. Paired t-test, or t-test were used as appropriate, with Pearson's correlation calculated; pResults: sICAM-1 and sVCAM-1 were decreased (p≤0.001 and p=0.002, respectively, while E-selectin concentration was increased after amlodipin treatment (P=0.014. CD11a/LFA-1 (ICAM-1 and endocan ligand was significantly increased in all three cell types with BP decrease. CD15 and CD49d/VLA-4 (VCAM-1 ligand did not change after the treatment. There was significant positive correlation of systolic and diastolic BP with ICAM-1 and VCAM-1, and significant negative correlation of systolic BP with CD11a/LFA-1. Endocan significantly positively correlated with ICAM-1. Conclusions: The increased expression of ICAM/VACM ligands, together with decrease of sCAMs and endocan suggests the de-activation of endothelium with reduction in BP, decreasing the adherence of circulatory leukocytes to endothelium; subsequently decreasing the risk for development of atherosclerosis.

  19. Effects of external radiation in a co-culture model of endothelial cells and adipose-derived stem cells

    International Nuclear Information System (INIS)

    The inflammatory response clinically observed after radiation has been described to correlate with elevated expression of cytokines and adhesion molecules by endothelial cells. Therapeutic compensation for this microvascular compromise could be an important approach in the treatment of irradiated wounds. Clinical reports describe the potential of adipose-derived stem cells to enhance wound healing, but the underlying cellular mechanisms remain largely unclear. Human dermal microvascular endothelial cells (HDMEC) and human adipose-derived stem cells (ASC) were cultured in a co-culture setting and irradiated with sequential doses of 2 to 12 Gy. Cell count was determined 48 h after radiation using a semi-automated cell counting system. Levels of interleukin-6 (IL-6), basic fibroblast growth factor (FGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined in the supernatants using enzyme-linked immunosorbent assay (ELISA). Irradiated HDMEC and ASC as well as non-irradiated co-cultures, HDMEC or ASC respectively were used as controls. Cell count was significantly reduced in irradiated co-cultures of HDMEC and ASC compared to non-irradiated controls. Levels of IL-6, FGF, ICAM-1 and VCAM-1 in the supernatants of the co-cultures were significantly less affected by external radiation in comparison to HDMEC. The increased expression of cytokines and adhesion molecules by HDMEC after external radiation is mitigated in the co-culture setting with ASC. These in vitro changes seem to support the clinical observation that ASC may have a stabilizing effect when injected into irradiated wounds

  20. Patterns of Saccharina latissima recruitment.

    Directory of Open Access Journals (Sweden)

    Guri Sogn Andersen

    Full Text Available The lack of recovery in Norwegian populations of the kelp Saccharina latissima (Linnaeus C. E. Lane, C. Mayes, Druehl & G. W. Saunders after a large-scale disturbance that occurred sometime between the late 1990s and early 2000s has raised considerable concerns. Kelp forests are areas of high production that serve as habitats for numerous species, and their continued absence may represent the loss of an entire ecosystem. Some S. latissima populations remain as scattered patches within the affected areas, but today, most of the areas are completely devoid of kelp. The question is if natural recolonization by kelp and the reestablishment of the associated ecosystem is possible. Previous studies indicate that a high degree of reproductive synchrony in macrophytes has a positive effect on their potential for dispersal and on the connectivity between populations, but little is known about the patterns of recruitment in Norwegian S. latissima. More is, however, known about the development of fertile tissue (sori on adult individuals, which is easily observed. The present study investigated the degree of coupling between the appearance of sori and the recruitment on clean artificial substrate beneath adult specimens. The pattern of recruitment was linked to the retreat of visible sori (i.e. spore release and a seasonal component unrelated to the fertility of the adults. The formation and the retreat of visible sori are processes that seem synchronized along the south coast of Norway, and the link between sori development and recruitment may therefore suggest that the potential for S. latissima dispersal is relatively large. These results support the notion that the production and dispersal of viable spores is unlikely to be the bottleneck preventing recolonization in the south of Norway, but studies over larger temporal and spatial scales are still needed to confirm this hypothesis.

  1. Sida rhomboidea.Roxb aqueous extract down-regulates in vivo expression of vascular cell adhesion molecules in atherogenic rats and inhibits in vitro macrophage differentiation and foam cell formation.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Salunke, Sunita P; Devkar, Ranjitsinh V; Ramachandran, A V

    2012-10-01

    The present study evaluates efficacy of Sida rhomboidea.Roxb (SR) leaves extract in ameliorating experimental atherosclerosis using in vitro and in vivo experimental models. Atherogenic (ATH) diet fed rats recorded significant increment in the serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very LDL (VLDL), autoantibody against oxidized LDL (Ox-LDL), markers of LDL oxidation and decrement in high-density lipoprotein (HDL) along with increment in aortic TC and TG. The ex vivo LDL oxidation assay revealed an increased susceptibility of LDL isolated from ATH rats to undergo copper mediated oxidation. These set of changes were minimized by simultaneous co-supplementation of SR extract to ATH diet fed rats. Histopathology of aorta and immunolocalization studies recorded pronounced atheromatous plaque formation, vascular calcification, significant elastin derangements and higher expression of macrophage surface marker (F4/80), vascular cell adhesion molecule-1 (VCAM-1) and p-selectin in ATH rats. Whereas, ATH+SR rats depicted minimal evidence of atheromatous plaque formation, calcium deposition, distortion/defragmentation of elastin and accumulation of macrophages along with lowered expression of VCAM-1 and P-selectin compared to ATH rats. Further, monocyte to macrophage differentiation and in vitro foam cell formation were significantly attenuated in presence of SR extract. In conclusion, SR extract has the potency of controlling experimental atherosclerosis and can be used as promising herbal supplement in combating atherosclerosis.

  2. Gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells during sepsis

    Institute of Scientific and Technical Information of China (English)

    吴荣谦; 徐迎新; 宋旭华; 孟宪钧

    2002-01-01

    To study the gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells during sepsis in mice. Methods: Male mice were subjected to cecal ligation and puncture (CLP) and microvascular endothelial cells in pulmonary and hepatic tissues were harvested at 3 hours (early sepsis) and 12 hours (late sepsis) after CLP, respectively. Gene expression of the adhesion molecules was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the alterations of myeloperoxidase (MPO) activity in pulmonary and hepatic tissues were also examined. Results: E-selectin mRNA levels markedly increased at 3 hours after CLP in both pulmonary and hepatic microvascular endothelial cells, then they returned to the normal level at 12 hours after CLP. Increases in intercellular adhesion molecule-1 (ICAM-1) mRNA levels were found at 3 hours after CLP in both pulmonary and hepatic microvascular endothelial cells, and these levels became higher at 12 hours after CLP. Adhesion molecule-1 (VCAM-1) mRNA expression of vascular cells also increased significantly at 3 hours and 12 hours after CLP in both pulmonary and hepatic microvascular endothelial cells. The level of VCAM-1 mRNA in hepatic microvascular endothelial cells was higher at 3 hours than that at 12 hours after CLP, while the level of VCAM-1 mRNA in pulmonary microvascular endothelial cells was higher at 12 hours than that at 3 hours after CLP. The MPO activity in pulmonary and hepatic tissues increased at 3 hours after CLP, compared with that of the sham group. They both declined significantly at 12 hours after CLP, but they were still higher than that of the sham group. Conclusions: The up-regulation of the gene expression of adhesion molecules in pulmonary and hepatic microvascular endothelial cells is an important step for the migration and accumulation of leukocytes at the site of inflammation, which plays a critical role in organ damage during sepsis. And the contribution

  3. Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-α Stimulated Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Chaur-Jong Hu

    2009-01-01

    Full Text Available Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1 is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1 in human umbilical vein endothelial cells (HUVECs. Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.

  4. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.

    Science.gov (United States)

    Pérez de Diego, Rebeca; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Ferreira Cerdán, Antonio; Casanova, Jean-Laurent; Puel, Anne

    2015-11-01

    Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. PMID:26277595

  5. Changes in the vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and c-reactive protein following administration of aqueous extract of piper sarmentosum on experimental rabbits fed with cholesterol diet

    Directory of Open Access Journals (Sweden)

    Al-Mekhlafi Hesham M

    2011-01-01

    Full Text Available Abstract Background Inflammation process plays an important role in the development of atherosclerosis. Hypercholesterolemia is one of the major risk factors for atherosclerosis. The present study aimed to evaluate the effect of aqueous extract of Piper sarmentosum (P.s on inflammatory markers like vascular cell adhesion molecule-1 (VCAM-1, intercellular adhesion molecule-1 (ICAM-1, and C-reactive protein (CRP. Methods Forty two male New Zealand white rabbits were divided equally into seven groups; (i C- control group fed normal rabbit chow (ii CH- cholesterol diet (1%cholesterol (iii X1- 1% cholesterol with water extract of P.s (62.5 mg/kg (iv X2- 1% cholesterol with water extract of P.s (125 mg/kg (v X3- 1% cholesterol with water extract of P.s (250 mg/kg (vi X4- 1% cholesterol with water extract of P.s (500 mg/kg and (vii SMV group fed with 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg. All animals were treated for 10 weeks. Blood serum was taken for observing the inflammatory markers at the beginning and end of the experiment. Results Rabbits fed with 1% cholesterol diet (CH showed significant increase in the level of VCAM-1, ICAM-1 and CRP compared to the C group. The levels of VCAM-1, ICAM-1 and CRP in the 1% cholesterol group and supplemented with P.s (500 mg/kg were significantly reduced compared to the cholesterol group. Similar results were also reported with simvistatin group. Conclusion These results suggest that the supplementation of Piper sarmentosum extract could inhibit inflammatory markers which in turn could prevent atherosclerosis.

  6. Screening Job Applicants: Recruiter Decision Strategies.

    Science.gov (United States)

    Hultz, Brian M.; And Others

    A project explored the process by which recruiters used information to make decisions on whom to interview. Data were collected from recruiters seeking candidates in electrical engineering, computer science, business, accounting, and social sciences/liberal arts, including communications. Recruiters relied heavily on major grade point average…

  7. 14 CFR 1253.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Recruitment. 1253.510 Section 1253.510... in Employment in Education Programs or Activities Prohibited § 1253.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  8. 40 CFR 5.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Recruitment. 5.510 Section 5.510... in Employment in Education Programs or Activities Prohibited § 5.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  9. 20 CFR 655.205 - Recruitment period.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Recruitment period. 655.205 Section 655.205... Agricultural Employment § 655.205 Recruitment period. (a) If the OFLC Administrator determines that the... carry out the assurances contained in § 655.203 with respect to the recruitment of U.S. workers....

  10. Faculty Recruitment in an Era of Change

    Science.gov (United States)

    Levine, Marilyn; Schimpf, Martin

    2010-01-01

    Faculty recruitment is a challenge for administration and departments, especially in an era of change in the academy. This article builds on information from an interactive conference panel session that focused on faculty recruitment best practices. The article addresses faculty recruitment strategies that focus on the optimization of search…

  11. 45 CFR 86.53 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Recruitment. 86.53 Section 86.53 Public Welfare... in Employment in Education Programs or Activities Prohibited § 86.53 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  12. 6 CFR 17.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Recruitment. 17.510 Section 17.510 Domestic... in Employment in Education Programs or Activities Prohibited § 17.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  13. 31 CFR 28.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Recruitment. 28.510 Section 28.510... Basis of Sex in Employment in Education Programs or Activities Prohibited § 28.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  14. 28 CFR 345.31 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Recruitment. 345.31 Section 345.31 Judicial Administration FEDERAL PRISON INDUSTRIES, INC., DEPARTMENT OF JUSTICE FEDERAL PRISON INDUSTRIES (FPI) INMATE WORK PROGRAMS Recruitment and Hiring Practices § 345.31 Recruitment. Inmate workers...

  15. 28 CFR 54.510 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Recruitment. 54.510 Section 54.510... in Employment in Education Programs or Activities Prohibited § 54.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  16. 43 CFR 41.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.510 Section 41.510 Public... in Employment in Education Programs or Activities Prohibited § 41.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  17. 15 CFR 8a.510 - Recruitment.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Recruitment. 8a.510 Section 8a.510... in Employment in Education Programs or Activities Prohibited § 8a.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the...

  18. 29 CFR 36.310 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Recruitment. 36.310 Section 36.310 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 36.310 Recruitment. (a)...

  19. Gender bias in academic recruitment

    DEFF Research Database (Denmark)

    Abramo, Giovanni; D’Angelo, Ciriaco Andrea; Rosati, Francesco

    2016-01-01

    It is well known that women are underrepresented in the academic systems of many countries. Gender discrimination is one of the factors that could contribute to this phenomenon. This study considers a recent national academic recruitment campaign in Italy, examining whether women are subject...... to more or less bias than men. The findings show that no gender-related differences occur among the candidates who benefit from positive bias, while among those candidates affected by negative bias, the incidence of women is lower than that of men. Among the factors that determine success in a competition...

  20. Oxidative stress, genotoxicity, and vascular cell adhesion molecule expression in cells exposed to particulate matter from combustion of conventional diesel and methyl ester biodiesel blends

    DEFF Research Database (Denmark)

    Hemmingsen, Jette Gjerke; Møller, Peter; Nøjgaard, Jakob Klenø;

    2011-01-01

    Our aim was to compare hazards of particles from combustion of biodiesel blends and conventional diesel (D(100)) in old and improved engines. We determined DNA damage in A549 cells, mRNA levels of CCL2 and IL8 in THP-1 cells, and expression of ICAM-1 and VCAM-1 in human umbilical cord endothelial...... cells (HUVECs). Viability and production of reactive oxygen species (ROS) were investigated in all cell types. We collected particles from combustion of D(100) and 20% (w/w) blends of animal fat or rapeseed oil methyl esters in light-duty vehicle engines complying with Euro2 or Euro4 standards....... Particles emitted from the Euro4 engine were smaller in size and more potent than particles emitted from the Euro2 engine with respect to ROS production and DNA damage, but similarly potent concerning cytokine mRNA expression. Particles emitted from combustion of biodiesel blends were larger in size...

  1. Optimal counterterrorism and the recruitment effect of large terrorist attacks

    DEFF Research Database (Denmark)

    Jensen, Thomas

    2011-01-01

    We analyze a simple dynamic model of the interaction between terrorists and authorities. Our primary aim is to study optimal counterterrorism and its consequences when large terrorist attacks lead to a temporary increase in terrorist recruitment. First, we show that an increase in counterterrorism...... makes it more likely that terrorist cells plan small rather than large attacks and therefore may increase the probability of a successful attack. Analyzing optimal counterterrorism we see that the recruitment effect makes authorities increase the level of counterterrorism after large attacks. Therefore...

  2. Selective suppression of leukocyte recruitment in allergic inflammation

    Directory of Open Access Journals (Sweden)

    CL Weller

    2005-03-01

    Full Text Available Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.

  3. Anti-Inflammatory Effects of Concentrated Ethanol Extracts of Edelweiss (Leontopodium alpinum Cass. Callus Cultures towards Human Keratinocytes and Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Lulli Daniela

    2012-01-01

    Full Text Available Edelweiss (Leontopodium alpinum Cass. is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with leontopodic acid representing 55±2% of the total phenolic fraction (ECC55, was characterized for anti-inflammatory properties in primary human keratinocytes (PHKs and endotheliocytes (HUVECs. Inflammatory responses were induced by UVA+UVB, lipopolysaccharide (LPS, oxidized low-density lipoprotein (oxLDL, and a mixture of proinflammatory cytokines. Trichostatin A, a sirtuin inhibitor, was used to induce keratinocyte inflammatory senescence. ECC55 (10–50 μg/mL protected PHK from solar UV-driven damage, by enhancing early intracellular levels of nitric oxide, although not affecting UV-induced expression of inflammatory genes. Comparison of the dose-dependent inhibition of chemokine (IL-8, IP-10, MCP-1 and growth factor (GM-CSF release from PHK activated by TNFα + IFNγ showed that leontopodic acid was mainly responsible for the inhibitory effects of ECC55. Sirtuin-inhibited cell cycle, proliferation, and apoptosis markers were restored by ECC55. The extract inhibited LPS-induced IL-6 and VCAM1 genes in HUVEC, as well as oxLDL-induced selective VCAM1 overexpression. Conclusion. Edelweiss cell cultures could be a valuable source of anti-inflammatory substances potentially applicable for chronic inflammatory skin diseases and bacterial and atherogenic inflammation.

  4. Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies.

    Science.gov (United States)

    Schipper-Krom, Sabine; Juenemann, Katrin; Jansen, Anne H; Wiemhoefer, Anne; van den Nieuwendijk, Rianne; Smith, Donna L; Hink, Mark A; Bates, Gillian P; Overkleeft, Hermen; Ovaa, Huib; Reits, Eric

    2014-01-01

    Neurodegenerative disorders such as Huntington's disease are hallmarked by neuronal intracellular inclusion body formation. Whether proteasomes are irreversibly recruited into inclusion bodies in these protein misfolding disorders is a controversial subject. In addition, it has been proposed that the proteasomes may become clogged by the aggregated protein fragments, leading to impairment of the ubiquitin-proteasome system. Here, we show by fluorescence pulse-chase experiments in living cells that proteasomes are dynamically and reversibly recruited into inclusion bodies. As these recruited proteasomes remain catalytically active and accessible to substrates, our results challenge the concept of proteasome sequestration and impairment in Huntington's disease, and support the reported absence of proteasome impairment in mouse models of Huntington's disease.

  5. Recruitment to the Norwegian fishing fleet: storylines, paradoxes, and pragmatism in Norwegian fisheries and recruitment policy

    OpenAIRE

    Sønvisen, Signe Annie

    2013-01-01

    The majority of actors in the Norwegian fisheries consider recruitment of fishers to be the main future challenge for the Norwegian fishing fleet. As fleet recruitment is a highly politicized field, the problem of how to mitigate the recruitment problem is a subject of heavy debate. Some argue that recruitment problems are caused by low fleet profitability, while others argue that recruitment problems are caused by fleet restructuring polices. This article aims to explore th...

  6. Activation of small ruminant aortic endothelial cells after in vitro infection by caprine arthritis encephalitis virus.

    Science.gov (United States)

    Jan, C L; Greenland, T; Gounel, F; Balleydier, S; Mornex, J F

    2000-12-01

    Small ruminants infected by the lentiviruses caprine arthritis-encephalitis virus (CAEV), originally isolated from a goat, or maedi-visna virus, originally from sheep, typically develop an organising lymphoid infiltration of affected tissues. This could reflect modulation of the migration pattern of lymphocytes in infected animals. Possible active contribution by vascular endothelial cells was investigated using an in vitro model. Low-passage cultured ovine aortic endothelium proved susceptible to productive infection by CAEV without significant cytotoxicity. Infected endothelial cells maintained expression of endothelial markers, increased MHC class I antigen expression and initiated expression of the adhesion molecule VCAM -1 and, at a late stage, MHC class II antigens. Infected endothelial cells showed a two-fold increase in binding capacity for sheep peripheral blood leucocytes over uninfected controls. Such events could contribute to the tissue distribution of lymphoid cells and local immune responses in lentiviral infections of small ruminants. PMID:11124093

  7. Tissue formation and tissue engineering through host cell recruitment or a potential injectable cell-based biocomposite with replicative potential: Molecular mechanisms controlling cellular senescence and the involvement of controlled transient telomerase activation therapies.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2015-12-01

    Accumulated data indicate that wound-care products should have a composition equivalent to that of the skin: a combination of particular growth factors and extracellular matrix (ECM) proteins endogenous to the skin, together with viable epithelial cells, fibroblasts, and mesenchymal stem cells (MSCs). Strategies consisting of bioengineered dressings and cell-based products have emerged for widespread clinical use; however, their performance is not optimal because chronic wounds persist as a serious unmet medical need. Telomerase, the ribonucleoprotein complex that adds telomeric repeats to the ends of chromosomes, is responsible for telomere maintenance, and its expression is associated with cell immortalization and, in certain cases, cancerogenesis. Telomerase contains a catalytic subunit, the telomerase reverse transcriptase (hTERT). Introduction of TERT into human cells extends both their lifespan and their telomeres to lengths typical of young cells. The regulation of TERT involves transcriptional and posttranscriptional molecular biology mechanisms. The manipulation, regulation of telomerase is multifactorial in mammalian cells, involving overall telomerase gene expression, post-translational protein-protein interactions, and protein phosphorylation. Reactive oxygen species (ROS) have been implicated in aging, apoptosis, and necrosis of cells in numerous diseases. Upon production of high levels of ROS from exogenous or endogenous generators, the redox balance is perturbed and cells are shifted into a state of oxidative stress, which subsequently leads to modifications of intracellular proteins and membrane lipid peroxidation and to direct DNA damage. When the oxidative stress is severe, survival of the cell is dependent on the repair or replacement of damaged molecules, which can result in induction of apoptosis in the injured with ROS cells. ROS-mediated oxidative stress induces the depletion of hTERT from the nucleus via export through the nuclear pores

  8. Tissue formation and tissue engineering through host cell recruitment or a potential injectable cell-based biocomposite with replicative potential: Molecular mechanisms controlling cellular senescence and the involvement of controlled transient telomerase activation therapies.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2015-12-01

    Accumulated data indicate that wound-care products should have a composition equivalent to that of the skin: a combination of particular growth factors and extracellular matrix (ECM) proteins endogenous to the skin, together with viable epithelial cells, fibroblasts, and mesenchymal stem cells (MSCs). Strategies consisting of bioengineered dressings and cell-based products have emerged for widespread clinical use; however, their performance is not optimal because chronic wounds persist as a serious unmet medical need. Telomerase, the ribonucleoprotein complex that adds telomeric repeats to the ends of chromosomes, is responsible for telomere maintenance, and its expression is associated with cell immortalization and, in certain cases, cancerogenesis. Telomerase contains a catalytic subunit, the telomerase reverse transcriptase (hTERT). Introduction of TERT into human cells extends both their lifespan and their telomeres to lengths typical of young cells. The regulation of TERT involves transcriptional and posttranscriptional molecular biology mechanisms. The manipulation, regulation of telomerase is multifactorial in mammalian cells, involving overall telomerase gene expression, post-translational protein-protein interactions, and protein phosphorylation. Reactive oxygen species (ROS) have been implicated in aging, apoptosis, and necrosis of cells in numerous diseases. Upon production of high levels of ROS from exogenous or endogenous generators, the redox balance is perturbed and cells are shifted into a state of oxidative stress, which subsequently leads to modifications of intracellular proteins and membrane lipid peroxidation and to direct DNA damage. When the oxidative stress is severe, survival of the cell is dependent on the repair or replacement of damaged molecules, which can result in induction of apoptosis in the injured with ROS cells. ROS-mediated oxidative stress induces the depletion of hTERT from the nucleus via export through the nuclear pores

  9. Recruitment strategies and colony size in ants.

    Directory of Open Access Journals (Sweden)

    Robert Planqué

    Full Text Available Ants use a great variety of recruitment methods to forage for food or find new nests, including tandem running, group recruitment and scent trails. It has been known for some time that there is a loose correlation across many taxa between species-specific mature colony size and recruitment method. Very small colonies tend to use solitary foraging; small to medium sized colonies use tandem running or group recruitment whereas larger colonies use pheromone recruitment trails. Until now, explanations for this correlation have focused on the ants' ecology, such as food resource distribution. However, many species have colonies with a single queen and workforces that grow over several orders of magnitude, and little is known about how a colony's organization, including recruitment methods, may change during its growth. After all, recruitment involves interactions between ants, and hence the size of the colony itself may influence which recruitment method is used--even if the ants' behavioural repertoire remains unchanged. Here we show using mathematical models that the observed correlation can also be explained by recognizing that failure rates in recruitment depend differently on colony size in various recruitment strategies. Our models focus on the build up of recruiter numbers inside colonies and are not based on optimality arguments, such as maximizing food yield. We predict that ant colonies of a certain size should use only one recruitment method (and always the same one rather than a mix of two or more. These results highlight the importance of the organization of recruitment and how it is affected by colony size. Hence these results should also expand our understanding of ant ecology.

  10. Nanostructures to modulate vascular inflammation: Multifunctional nanoparticles for quantifiable siRNA delivery and molecular imaging

    Science.gov (United States)

    Kaneda, Megan Marie

    Early steps in the progression of inflammatory diseases such as atherosclerosis involve the recruitment of leukocytes to the vascular endothelium through the expression or up-regulation of adhesion molecules. These adhesion molecules are critical mediators of leukocyte attachment and subsequent extravasation through transendothelial migration. One of these adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) is particularly attractive as a marker of early atherosclerotic activity due to its low expression level on normal endothelium and up-regulation prior to and during the development of early lesions. With this in mind, the purpose of this thesis was to develop nanostructures for the detection and down-regulation of adhesion molecules by the vascular endothelium. To detect early inflammation we designed a perfluorocarbon nanoparticle (PFC-NP) probe, which was used for in vivo targeting of VCAM-1. Nanoparticles were detected ex vivo by the magnetic resonance (MR) signature from the fluorine core of the particle. Nanoparticles accumulated in tissues characterized by early inflammatory processes. To down-regulate VCAM-1 expression by vascular endothelial cells, cationic PFC-NP were produced through the addition of the cationic lipid 1,2-Dioleoyl-3-Trimethylammonium-Propane. Cationic PFC-NP were able to deliver anti-VCAM-1 siRNA to endothelial cells through a non-standard lipid raft mediated endocytic pathway. VCAM-1 levels were significantly reduced in treated cells indicating that this delivery mechanism may be advantageous for delivery of cargo into the cytoplasm. Using the fluorine signature from the core of the cationic PFC-NP, we were able to quantify and localize this siRNA delivery agent both in vitro and in vivo. The ability to quantify the local concentrations of these particles could be of great benefit for estimating local drug concentrations and developing new pharmacokinetic and pharmacodynamic paradigms to describe this new class of

  11. Effects of macrolides on proinflammatory epitopes on endothelial cells in vitro.

    Science.gov (United States)

    Millrose, Michael; Kruse, Matthias; Flick, Burkhard; Stahlmann, Ralf

    2009-05-01

    An inflammatory reaction at the site of infusion is a common clinical problem that is observed after the intravenous application of antibiotics and other drugs. The pathomechanism of this infusion-related phlebitis is not fully understood. We analyzed the effects of the three macrolide antibiotics erythromycin, clarithromycin and azithromycin on human endothelial cells in vitro. As a positive control quinupristin/dalfopristin was studied. The cytotoxicity of all substances was analyzed by a modified MTT cytotoxicity assay with 3T3-fibroblasts and EA.hy 926 endothelial cells. Cells were incubated for 10 days with the antibiotics. After adding MTT the optical density was measured which correlates with cell death. Clarithromycin exhibited the strongest cytotoxic effect on EA.hy 926 cells (EC(50) 30 mg/L), followed by azithromycin (EC(50) 40 mg/L), a cytotoxic effect of erythromycin could only be observed at much higher concentrations (EC(50) 310 mg/L). The reaction of the endothelial cells was further analyzed in detail by means of flow cytometry. For these experiments the endothelial cell line EA.hy 926 as well as primary cells (HUVEC) were used. The antigens were stained with fluoresceinisothiocyanat- or phycoerythrin-conjugated monoclonal antibodies for the following surface antigens: CD34, E-selectin (CD62E), ICAM-1 (CD54) and VCAM-1 (CD106). Cells were incubated with the antibiotics at concentrations ranging from 100 to 800 mg/L (clarithromycin and azithromycin) and from 200 to 1,200 mg/L (erythromycin). These concentrations occur under therapeutic conditions at the site of infusion. Cells were incubated for 2 h and analysis was carried out after an additional culture period of 22 h without test compounds. A significantly enhanced expression of all four antigens was observed which was most pronounced at 800 mg/L (erythromycin), 600 mg/L (azithromycin) and 400 mg/L (clarithromycin). A concentration of 800 mg/L erythromycin medium caused an increase of the

  12. Longitudinal study of magnesium status of Israeli military recruits.

    Science.gov (United States)

    Dolev, E; Burstein, R; Wishnitzer, R; Lubin, F; Chetriet, A; Shefi, M; Deuster, P A

    The following study was conducted to assess the biochemical and nutritional status of new military recruits during 12 weeks of strenuous physical activity. Calorie and magnesium (Mg) intake, energy expenditure, and serum, red blood cell (RBC) and mononuclear cell (MNC) Mg were assessed at the start, after 6 weeks and after 12 weeks of training. The results provide evidence that MNC Mg content decreases, whereas serum Mg increases, under prolonged, strenuous training conditions in previously unconditioned military recruits. Mg dietary intake alone could not account for these changes. It is postulated that this decrease in MNC Mg (from 64.76 +/- 34.99 to 23.81 +/- 15.55 fg/cell), unparalleled by similar changes in serum Mg or RBC Mg, reflects a reduction in exchangeable Mg body stores, and the onset of a Mg deficiency state.

  13. Adenovirus viral interleukin-10 inhibits adhesion molecule expressions induced by hypoxia/reoxygenation in cerebrovascular endothelial cells1

    Institute of Scientific and Technical Information of China (English)

    Hui KANG; Peng-yuan YANG; Yao-cheng RUI

    2008-01-01

    Aim: To investigate the effects of recombinant adenovirus encoding viral interleukin-10 (vIL-10), a potent anti-inflammatory cytokine, on adhesion mol-ecule expressions and the adhesion rates of leukocytes to endothelial cells in cerebrovascular endothelial cells injured by hypoxia/reoxygenation (H/R). Methods: A recombinant adenovirus expressing vIL-10 (Ad/vIL-10 (or the green fluorescent protein (Ad/GFP) gene was constructed. A cerebrovascular endothe-lial cell line bend.3 was pretreated with a different multiplicity of infection (MOI) of Ad/vIL-10 or Ad/GFP and then exposed to hypoxia for 9 h followed by reoxygenation for 12 h. The culture supernatants were tested for the expression of vIL-10 and endogenous murine IL-10 (mIL-10) by ELISA. The effects of Ad/vIL-10 on monocyte-endothelial cell adhesion were represented as the adhesion rate. Subsequently, the expressions of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1(VCAM-1) in the endothelial cells after treat-ment with Ad/vIL-10 and H/R were analyzed by Western blotting and real-time PCR. Results: vIL-10 was expressed in cultured bEnd.3 after Ad/vIL-10 transfec-tion and was significantly increased by H/R. Ad/vIL-10 or Ad/GFP did not affect the mlL-10 level. H/R increased the mIL-10 expression, but insignificantly. Mono-cyte-endothelial cell adhesion induced by H/R was significantly inhibited by pretreatment with Ad/vIL-10 (MOI: 80). ICAM-I, and VCAM-1 in bEnd.3 and were significantly increased after H/R, while pretreatment with Ad/vIL-10 (MOI: 80) significantly inhibited their expressions. Ad/GFP did not markedly affect mono-cyte-endothelial adhesion and the expressions of ICAM-1 and VCAM-1 induced by H/R. Conclusion: Ad/vIL-10 significantly inhibits the upregulation of endot-helial adhesion molecule expressions and the increase of adhesion of monocytes-endothelial cells induced by H/R, indicating that vIL-10 gene transfer is of far-reaching significance in the therapy of

  14. Recruiting African American smokers into intervention research: Relationships between recruitment strategies and participant characteristics.

    Science.gov (United States)

    Webb, Monica S; Seigers, Danielle; Wood, Elizabeth A

    2009-02-01

    The purposes of this study were to (a) to describe an 8-month recruitment campaign to enroll African American smokers (N = 249) into a randomized controlled trial and (b) examine characteristics of participants recruited through proactive (face-to-face), reactive (television, radio, or newspaper ads inviting participants), and combination (both reactive and proactive) approaches. Reactive recruitment was most successful (43%), followed by proactive (31%), and combination (26%) recruitment. Compared to proactive recruitment, reactive recruitment was associated with lower nicotine dependence, and greater readiness to quit, processes of change engagement, and acculturation. Combination recruitment was associated with lower nicotine dependence and greater readiness to quit. The differences according to recruitment strategy could be used to tailor recruitment strategies for African American smokers. PMID:18767129

  15. Improving Human Resources Recruitment in Maritime Domain

    OpenAIRE

    Surugiu Felicia; Dragomir Cristina

    2011-01-01

    In order to improve maritime human resources recruitment, most crewing and shipping companies implement an internal procedure of recruitment and management of ship’s crew. Based on observations at several crewing companies, this paper presents an example of such procedure meant to ensure that qualified and competent personnel is recruited and all ships in the fleet have crew members understanding their roles, duties and responsibilities and capable of working effectively in teams

  16. Research on Online Recruitment in Chinese Enterprises

    OpenAIRE

    Hao, Chen

    2009-01-01

    Abstract With the development of new information technology, HRM also changes in many aspects, in which recruitment method has the greatest change, because online recruitment emerges and develops in many countries. While in China, there are fewer researches on online recruitment, not to mention the study on its development and problems, so this study aims to fill up with the gap between theoretical and practical. In this dissertation, there are totally five chapters. The main contents are...

  17. Recruitment and retention of lung volume

    OpenAIRE

    Lapinsky, Stephen E

    2002-01-01

    Both a reduction in tidal volume and alveolar recruitment may be necessary to prevent ventilator-induced lung injury in the management of patients with acute respiratory distress syndrome. The lung collapse associated with endotracheal suctioning produces hypoxaemia, but it also causes de-recruitment, potentially aggravating lung injury. A study conducted by Dyhr and colleagues demonstrates the benefit of lung recruitment manoeuvres after suctioning, which help to improve oxygenation and rest...