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Sample records for ccl daresbury laboratory

  1. Beam tomography research at Daresbury Laboratory

    International Nuclear Information System (INIS)

    Hock, K.M.; Ibison, M.G.; Holder, D.J.; Muratori, B.D.; Wolski, A.; Kourkafas, G.; Shepherd, B.J.A.

    2014-01-01

    Beam tomography research at Daresbury Laboratory has focussed on the development of normalised phase space techniques—starting with the idea of sampling tomographic projections at equal phase advances. This idea has influenced the design and operation of the tomography sections at the Photo Injector Test Facility at Zeuthen (PITZ) and at the Accelerator and Lasers in Combined Experiments (ALICE) at Daresbury. We have studied the feasibility of using normalised phase space to measure the effect of space charge. Quadrupole scan measurements are carried out at two different parts of a beamline. Reconstructions at the same location give results that are clearly rotated with respect to each other in normalised phase space. We are able to show that a significant part of this rotation can be attributed to the effect of space charge. We show how the normalised phase space technique can be used to increase the reliability of the Maximum Entropy Technique (MENT). While MENT is known for its ability to work with just a few projections, the accuracy of its reconstructions has seldom been questioned. We show that for typical phase space distributions, MENT could produce results that look quite different from the original. We demonstrate that a normalised phase space technique could give results that are closer to the actual distribution. We also present simpler ways of deriving the phase space tomography formalism and the Maximum Entropy Technique

  2. The Daresbury Laboratory 1993/1994

    International Nuclear Information System (INIS)

    Buckley, A.G.

    1993-01-01

    The scientific programme based on the Synchrotron Radiation Source (SRS) has continued in 1993/94 to be at the centre of the Daresbury Laboratory's work. The wide range of research in materials and surface science, atomic and molecular physics, chemistry and structural and molecular biology using SRS includes: the interaction between the proteins actin and gelsolin which has relevance to genetic disease; the crystallinity of polythene; the epitaxial growth of lattice-mismatched semi-conducting material systems; cell uptake of molecules by receptor-mediated endocytosis; the crystal structure of copper-palladium alloys; the kinetics of intercalation and its application to molecular electronics; the crystal structure of the minerals antigorite and chrysotile; the development of experimental facilities to allow surface studies of catalytic processes. Major upgrades and improvements in the SRS are also reported. Highlights of the continuing successful use of parallel supercomputers and distributed computing in the collaborative research undertaken by the Theory, Computational Science and Computing group are presented. These range over applications to pharmaceuticals, plasma and ionization on processes, crystal structures of organic molecules and magnetic storage media. (UK)

  3. The nuclear structure facility tandem at Daresbury laboratory

    International Nuclear Information System (INIS)

    Voss, R.G.P.

    1976-01-01

    A 30MV tandem electrostatic accelerator for ions of all types, including heavy ions, is being built at Daresbury Laboratory. Construction is well advanced, and considerable effort is continuing to be devoted to R and D programme into the technology of electrostatic accelerators

  4. Daresbury 1980

    International Nuclear Information System (INIS)

    1981-01-01

    This annual report of the Daresbury Laboratory describes work carried out during 1980 on: (1) Synchrotron radiation (synchrotron radiation source, synchrotron radiation experiments, theoretical studies, new projects). (2) Nuclear structure (nuclear structure facility, experimental physics, nuclear physics). (3) Computer services and computational science. (4) Laboratory services. Publications are listed in an appendix. (U.K.)

  5. Daresbury 1977

    International Nuclear Information System (INIS)

    1978-01-01

    The programme of the Daresbury Laboratory is described. Sections on nuclear structure (the building of the Nuclear Structure Facility (NSF), tandem construction, experimental physics, nuclear theory), synchrotron radiation (the synchrotron Radiation Sourse (SRS) and its use in atomic, molecular and solid state physics and X-ray Studies) high energy physics (the NINA and CERN programmes and the closure of the electron synchrotron) and computer systems are included. (U.K.)

  6. Daresbury 1975

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    This annual report falls under the following headings: high energy physics (including the NINA programme, CERN programme, technical support and theoretical studies); synchrotron radiation (including studies for the new Synchrotron Radiation Source); nuclear structure (including details of the new Nuclear Structure Facility); computer systems; and appendices covering finance and administration, health and safety, and a list of publications by Daresbury Laboratory staff. (U.K.)

  7. Daresbury 1984/5

    International Nuclear Information System (INIS)

    1985-01-01

    The 1984/85 annual report of the Daresbury Laboratory, United Kingdom, is presented. Attention is centred on the Synchrotron Radiation Source and its scientific programme, and the Nuclear Structure Facility and its experimental work. Theoretical work at Daresbury including computational science is described, as well as computing and electronics. (U.K.)

  8. 4GLS and the Energy Recovery Linac Prototype Project at Daresbury Laboratory

    CERN Document Server

    Seddon, Elaine

    2005-01-01

    4GLS is a novel next generation proposal for a UK national light source to be sited at Daresbury Laboratory. It is based on a superconducting energy recovery linac (ERL) with capabilities for both high average current spontaneous photon sources (undulators and bending magnets) and high peak current free electron lasers. Key features of the proposal are a high gain, seeded FEL amplifier to generate XUV radiation and the prospect of advanced dynamics work arising from its unique combinations of sources and its femtosecond pulse structure. To meet the challenging accelerator technology involved, a significant R&D programme has commenced and a major part of this is a 35 MeV demonstrator, the ERL Prototype (ERLP), currently under construction. This paper summarises the 4GLS design activities, describes the ERLP in detail and explains the 4GLS project status and plans.

  9. Daresbury 1981/82

    International Nuclear Information System (INIS)

    1982-01-01

    This annual report covers the work of the Daresbury Laboratory during the period January 1981 - March 1982 under the headings; nuclear structure (nuclear structure facility, experimental physics), synchrotron radiation (synchrotron radiation source, experimental physics), theory and computational science, computing and electronics, other activities and services. Figures concerning staffing and expenditure are given and laboratory publications covering the period are listed. (U.K.)

  10. Daresbury 1990/91

    International Nuclear Information System (INIS)

    1991-01-01

    This report highlights some of the diverse range of work engaged in at the Daresbury Laboratory of the United Kingdom Science and Engineering Research Council in 1990/91. It contains brief descriptions of the Laboratory's facilities and research programmes. These fall into three main areas; theory, computational science and computing; lower temperature nuclear physics using the Nuclear Structure Facility; and the development and application of the synchrotron radiation source. Separate appendices to the report cover these areas in greater detail. (UK)

  11. Daresbury 1985/6

    International Nuclear Information System (INIS)

    1986-01-01

    The paper is the annual report of the Daresbury Laboratory, United Kingdom, 1985/6. The research programme using the Nuclear Structure Facility (NSF) and the Synchrotron Radiation Source (SRS) is described, along with some of the scientific highlights. The performance, operation and other activities associated with the SRS and NSF are summarized. Computational science studies concerned with atoms, molecules, condensed matter, chemical databank service and the FPS-164 computer system, are also outlined. (U.K.)

  12. Daresbury 1989/90

    International Nuclear Information System (INIS)

    1990-01-01

    This annual report on Daresbury Laboratory for 1989/90 focuses on existing and prospective research efforts. The Synchrotron Radiation Source has been operating effectively and successfully. The Theory and Computational Science group has used many increasingly powerful computing tools. The Nuclear Structure Facility is now fully operational and exciting discoveries, some not predicted by theory, have been observed. Collaboration with the external scientific community has continued successfully as well. (UK)

  13. Daresbury 1987/8

    International Nuclear Information System (INIS)

    1988-01-01

    1987 was the twenty fifth anniversary of the Daresbury Laboratory and special events were held to celebrate this. Over the twenty five years the projects have changed but the role of the laboratory, which is to provide and operate facilities too large for a single University to operate on its own and to collaborate with the Universities using them, has not changed. The report covers the main facilities at Daresbury. The main events and progress throughout the year are highlighted. For the Nuclear Structure facility highlights included collaboration on the largest array of high resolution germanium gamma-ray detectors ever assembled, work on super deformed nuclei at high angular momentum and the use of the polarised heavy ion source. At the Synchrotron Radiation Source a High Brightness Lattice has been installed and this has resulted in improved imaging and diffraction. Protein molecules, semiconductor materials, very small crystals and muscle structure have been studied using the high brightness lattice facility. A review of the computational science support for projects is included. Facts and figures about Daresbury are presented and a list of publications resulting from work done at the Laboratory during the year is given. (U.K.)

  14. Daresbury 1991/92

    International Nuclear Information System (INIS)

    1992-01-01

    The report gives an overview of the activities over the year 1991/92. There are more than 4000 registered uses of the facilities at Daresbury so only the highlights can be included. The largest programme is that centred on the Synchrotron Radiation source. During the year this was shut down so that a second superconducting wiggler magnet could be installed. The smallest programme is that associated with Theory, Computational Science and Computing. Collaboration between the Medical and the Science and Engineering Research Councils reflects the interest of both in structural biology. A feasibility study for an Advanced Proton Source has been undertaken as part of the long-term planning for the laboratory. The work on EUROGAM, a Joint UK/France Gamma-Ray Detector is reported. A list of publications of scientists using the facilities at the laboratory is included. Separate appendices are available on the SRS, NSF (Nuclear Structure) and the Theory, Computational Science and Computing facilities. (UK)

  15. Daresbury 1978

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    The report falls under the following headings: introduction; synchrotron radiation (synchrotron radiation source, synchrotron radiation experiments, theoretical studies); nuclear structure (nuclear structure facility, NSF experimental physics, nuclear theory); computational science; high energy physics; computer systems; laboratory services; appendix (publications). (U.K.)

  16. Daresbury 1988/89

    International Nuclear Information System (INIS)

    1989-01-01

    The main areas of research reported from the Daresbury Laboratory are in synchrotron radiation, nuclear physics and theory and computational science. The Synchrotron Radiation source research programme has employed the experimental techniques of small angle scattering, protein crystallography, surface diffraction, powder diffraction and x-ray absorption spectroscopy. These have been applied to such problems as corrosion in steels, kinetics in cell biology, the structure of viruses (notably the foot-and-mouth virus), sulphur disruption of metal surfaces, metal-semiconductor interfaces, and the electronic and vibrational structure of molecules. Research with the Nuclear Structure Facility has included experiments to study nuclear collective motion, nuclei far from stability and nuclear reaction mechanisms. Much development effort has been directed towards the production of beams of polarized nuclei. Other highlights have been work with the Recoil Separator on exotic nuclei, the Giant Dipole Resonance and isomers. A problem of particular theoretical interest is the effect of breakup on the nucleus-nucleus potential. In computational science, the Laboratory is in the forefront of software development for the collection and theoretical analysis of experimental data and university research is supported through a series of Collaborative Computational Projects. Industrial collaboration in computational science is extending the contribution of the Laboratory to the solution of significant technological problems. (UK)

  17. Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

    CERN Multimedia

    1969-01-01

    Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

  18. Daresbury 1992/93

    International Nuclear Information System (INIS)

    1993-01-01

    An overview of the activities at Daresbury over the year 1992/3 is given. The Nuclear Structure Facility (NSF) was closed at the end of March 1993. The EUROGAM gamma-ray spectrometer was brought into operation in October 1992 and the scheduled experiments were completed before the NSF closure. The results are still being analysed by the participating groups. A detailed explanation of EUROGAM and some of the experimental results obtained are given. The Synchrotron Radiation Source has continued to provide powerful light beams for academic and and industrial users to study the physical properties of matter. A new wiggler magnet has improved its operation and research into solid catalysts sleeping sickness, the measurement of spin and orbital angular momentum, surface structure and the photodissociation and photoionization of hydrogen has been carried out. The computational science activities are described. Two new areas of research are medium energy ion scattering and the Research Unit for Surfaces, Transforms and Interfaces. (UK)

  19. A 2D MWPC area detector for use with synchrotron X-radiation at the Daresbury Laboratory for small angle diffraction and scattering

    International Nuclear Information System (INIS)

    Helliwell, J.R.; Hughes, G.; Przybylski, M.M.; Ridley, P.A.; Sumner, I.; Bateman, J.E.; Connolly, J.F.; Stephenson, R.

    1982-01-01

    A 2D multiwire proportional chamber area detector is being developed to provide a real time data acquisition system for small angle scattering and diffraction experiments with synchrotron X-radiation at the Daresbury synchrotron radiation source (SRS). The chamber has a circular aperture, 200 mm diameter with an anode and cathode wire pitch of 1 mm; a front cathode-anode spacing of 6 mm and a 6 mm spacing between anode and rear cathode. A 1 mm thick front beryllium window and a rear aluminium cover plate with indium seals provide a gas-tight system. Previous experiments with a similar chamber design allowed continual use of the chamber for up to 2 years without refill. A digitising time of 2 μs is expected based on a 260 mm delay line and Lecroy TDC linked to a mass semiconductor memory of 512 x 256 elements. The experiment will be controlled by a PDP 11/04 computer with 28 K memory interfaced to a CAMAC create with 64 K fast access CAMAC memory. The system should be relatively easy to use with good order to order resolution and reasonable rate for small angle diffraction and scattering experiments on biological systems. Evaluation of the set-up for protein crystallography is planned though a TV based image intensifier (Enraf-Nonius) is preferred for this application at the SRS. (orig.)

  20. The Daresbury personnel safety system

    International Nuclear Information System (INIS)

    Poole, D.E.; Ring, T.

    1989-01-01

    The personnel safety system designed for the SRS at Daresbury is a unified system covering the three accelerators of the source itself, the beamlines and the experimental stations. The system has also been applied to the experimental areas of the Nuclear Structure Facility, and is therefore established as a site standard. A dual guardline interlock module forms a building block for a relay based interlock system completely independent of the machine control system, although comprehensive monitoring of the system status via the control system computer is a feature. An outline of the design criteria adopted for the system is presented together with a more detailed description of the philosophy of the guardline logic and the way this is implemented in a standard modular form. The emphasis is on the design features of a modern microprocessor based variant of the original SRS system. Experience with the original system during build-up and operation of the SRS facility is described. 2 refs., 4 figs

  1. Electron beam measurements on the Daresbury SRS

    International Nuclear Information System (INIS)

    Laundy, D.; Cummings, S.

    1992-01-01

    Two experiments which use hard x-ray synchrotron radiation have been carried out to allow us to monitor the electron beam on the Daresbury SRS. The beam spatial and angular vertical position and size was determined over a period of time when the SRS was operating normally. From these measurements, the position and angular stability of the electron beam during the measurement period was assessed and correlation of the beam emittance to the electron current was determined

  2. Daresbury senses victory in battle for UK synchrotron

    CERN Multimedia

    Loder, N

    1999-01-01

    Scientists campaigning for the future synchrotron source, Diamond, to be sited at Daresbury rather than RAL, believe they have won their case following a meeting between the Office of Science & Technology and the director of the Welcome Trust (1 pg).

  3. Intershield to tank sparks at the Daresbury tandem

    International Nuclear Information System (INIS)

    James, A.N.

    1983-04-01

    The causes of serious metallic melting and denting due to discharges in the insulating gas of the Daresbury tandem are examined. In order to explain the melting, high oscillating currents have to flow in the spark channels, and those can only be expected when return strokes excite local electromagnetic modes at the site of the origin of breakdown. In the case of intershield to tank sparks, evidence that magnetic confinement of the spark channel produces denting is presented. A model which accounts for the differences between sparks at Oak Ridge and sparks at Daresbury is also presented. (author)

  4. VME applications to the Daresbury SRS control system

    International Nuclear Information System (INIS)

    Martlew, B.G.; McCarthy, M.; Rawlinson, W.R.

    1992-01-01

    The control system for the Daresbury SRS has recently been extended with a VME based alarm system which is operational. A further development is a steering system to provide servo control of the electron beam orbit position in the storage ring. (author)

  5. Synchrotron radiation. Appendix to the Daresbury annual report 1993/1994

    International Nuclear Information System (INIS)

    Cernik, R.J.

    1993-01-01

    This appendix to the main report of the Daresbury Laboratory contains 387 contributions on research carried out using the Synchrotron Radiation Source. The research areas covered include: biological solution scattering; protein crystallography; biological radiation damage; biological spectroscopy; fibre diffraction of biological systems; membranes and liquid systems; machine physics; polymer studies; quantum wells; carbon fibre diffraction; organometallics; phase studies at high pressure; semiconductors; metal oxides; magnetic materials; non-linear optics; alloys; metallic glass; amorphous materials/aqueous solutions; porous silicon and mesoporous materials; silica sols and emulsions; thin films; geology and mineralogy; liquid crystals; catalysis; ceramics and glass; superconductors; detectors for structural biology; metal oxide gas sensors; X-ray scattering techniques; new developments in X-ray techniques; structural studies of powders; single crystal and small molecule crystallography; molecular spectroscopy; lime resolved spectroscopy; surface spectroscopy; topography and diffuse scattering; X-ray microscopy; X-ray studies of surfaces. (UK)

  6. Synchrotron radiation: appendix to the Daresbury annual report 1990/91

    International Nuclear Information System (INIS)

    1991-01-01

    This Appendix to the Annual Report of the Daresbury Laboratory of the United Kingdom Science and Engineering Research Council contains the 1990 Annual Report of the Synchrotron Radiation Facilities Committee, specifications for the beamlines and stations, the index for the synchrotron radiation user reports, the reports themselves and the list of publications detailing work performed on the Synchrotron Radiation Source. By far the largest part of the Appendix is taken up with the user reports for the period 1990 to 1991. They include reports on structural determination of sodium methyl, an investigation of DNA-Binding Proteins, monitoring of vital processes in live cells, the structure of semiconductor interfaces, the structure and properties of glasses and soft x-ray absorption spectroscopy of liquid samples. (author)

  7. Nuclear physics: appendix to the Daresbury annual report 1990/91

    International Nuclear Information System (INIS)

    1991-01-01

    This nuclear physics chapter of the Annual Report of the Daresbury Laboratory of the United Kingdom Science and Engineering Research Council describes the work of the Nuclear Structure Facility. In the limited space available it necessarily provides only a broad outline of the facility, its development and a flavour of the research in a selection of a few highlighted topics. This appendix complements the first volume of the Report reproducing users' short camera ready scientific reports. These describe the progress and results of each experimental proposal. Reports are grouped in five sections: research into nuclear structure with contributions ordered in increasing Z number of the nuclei studies; investigations of nuclear reaction mechanisms; nuclear theory; atomic physics; and accelerator operations, developments and instrumentation. The appendix forms a compact record of the work of the Nuclear Structure Facility for the year 1990/91. (author)

  8. CCL22-specific T Cells

    DEFF Research Database (Denmark)

    Martinenaite, Evelina; Munir Ahmad, Shamaila; Hansen, Morten

    2016-01-01

    Tumor cells and tumor-infiltrating macrophages produce the chemokine CCL22, which attracts regulatory T cells (Tregs) into the tumor microenvironment, decreasing anticancer immunity. Here, we investigated the possibility of targeting CCL22-expressing cells by activating specific T cells. We...... analyzed the CCL22 protein signal sequence, identifying a human leukocyte antigen A2- (HLA-A2-) restricted peptide epitope, which we then used to stimulate peripheral blood mononuclear cells (PMBCs) to expand populations of CCL22-specific T cells in vitro. T cells recognizing an epitope derived from...... the signal-peptide of CCL22 will recognize CCL22-expressing cells even though CCL22 is secreted out of the cell. CCL22-specific T cells recognized and killed CCL22-expressing cancer cells. Furthermore, CCL22-specific T cells lysed acute monocytic leukemia cells in a CCL22 expression-dependent manner. Using...

  9. The Correlation of Serums CCL11, CCL17, CCL26, and CCL27 and Disease Severity in Patients with Urticaria.

    Science.gov (United States)

    Lu, Tao; Jiao, Xiaoyang; Si, Mengya; He, Ping; Zou, Jinbo; Zhang, Shuping; Zeng, Kang

    2016-01-01

    Chemokines may be involved in the pathogenesis of urticaria, but their correlation with disease severity as well as eruption type is unclear. The aim of this study was to explore the expression of chemokines in patients with urticaria. The association between disease severity and levels of chemokines was analysed. Serums CCL11, CCL17, CCL26, and CCL27, D-dimer, C-reactive protein, and total IgE were measured in 51 patients with urticaria and in 25 healthy control subjects. Serums CCL11, CCL17, CCL26, and CCL27 were significantly higher in patients with urticaria than in the healthy controls (P urticaria. Further study in larger cohort is needed to testify whether they could be the biomarkers for predicting the severity of urticaria.

  10. Age dating ground water by use of chlorofluorocarbons (CCl3F and CCl2F2), and distribution of chlorofluorocarbons in the unsaturated zone, Snake River Plain aquifer, Idaho National Engineering Laboratory, Idaho

    International Nuclear Information System (INIS)

    Busenberg, E.; Weeks, E.P.; Plummer, L.N.; Bartholomay, R.C.

    1993-04-01

    Detectable concentrations of chlorofluorocarbons (CFC's) were observed in ground water and unsaturated-zone air at the Idaho National Engineering Laboratory (INEL) and vicinity. The recharge ages of waters were determined to be from 4 to more than 50 years on the basis of CFC concentrations and other environmental data; most ground waters have ages of 14 to 30 years. These results indicate that young ground water was added at various locations to the older regional ground water (greater than 50 years) within and outside the INEL boundaries. The wells drilled into the Snake River Plain aquifer at INEL sampled mainly this local recharge. The Big Lost River, Birch Creek, the Little Lost River, and the Mud Lake-Terreton area appear to be major sources of recharge of the Snake River Plain aquifer at INEL. An average recharge temperature of 9.7±1.3 degrees C (degrees Celsius) was calculated from dissolved nitrogen and argon concentrations in the ground waters, a temperature that is similar to the mean annual soil temperature of 9 degrees C measured at INEL. This similarity indicates that the aquifer was recharged at INEL and not at higher elevations that would have cooler soil temperatures than INEL. Soil-gas concentrations at Test Area North (TAN) are explained by diffusion theory

  11. The chemokines CCL11, CCL20, CCL21, and CCL24 are preferentially expressed in polarized human secondary lymphoid follicles.

    Science.gov (United States)

    Buri, Caroline; Gutersohn, Andreas; Hauser, Chantal; Kappeler, Andreas; Mueller, Christoph

    2004-10-01

    Chemokines regulate cellular trafficking to and from lymphoid follicles. Here, the distribution pattern of four CCL chemokines is defined by in situ hybridization in human lymphoid follicles from tonsils and lymph nodes (LNs) of newborns and adults. Cells expressing CCL11 (eotaxin) and CCL20 (Exodus) were preferentially located within follicles, while cells expressing CCL21 (secondary lymphoid-tissue chemokine) and CCL24 (eotaxin-2) mRNA were almost exclusively found in the perifollicular areas. Hence, the two CCR3-binding chemokines, CCL11 and CCL24, showed a mutually exclusive expression pattern in the intra- and extra-follicular areas, respectively. Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA-positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non-polarized. No intrafollicular chemokine expression was detectable in the primary follicles from newborns. Extrafollicular cells expressing CCL21 and CCL24 were again more frequent in tonsils than in LNs from adults. The observed preferential presence of cells expressing CC chemokines in polarized human lymphoid follicles indicates that chemokines are not only instrumental in the induction of follicle formation, but may also be involved in their further differentiation.

  12. SRP meeting: social and political implications of communicating radiation risk, Daresbury, Warrington, 20 June 2001

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Karen

    2001-12-01

    The SRP held a very interesting meeting in June at the Daresbury Laboratory in Warrington on the social and political implications of communicating radiation risk. In today's risk-aware society, effective communication is just as important as the control measures introduced to prevent or restrict exposure. In relation to radiation protection, risk communicators had a hard job because of: Public dread Likelihood of risk intensification Perceived inequitable distribution of risks. The higher the uncertainty, the more wary people were likely to be. Julie cited the International Nuclear Events Scale (INES) as a possible tool for promoting a consistent message across all publics. This was because it aimed to put events into proper perspective and provide a common understanding amongst the nuclear community, the media and the public. Julie summed up by saying that the risk communication was not just any form of communication and the issue of communicating radiation risks involved special consideration. Further research established that the more information given to the local population, the more likely that they would deny that there was a problem. Denial could moderate beliefs or emotional reactions to a situation. This then affected their dose as they were more likely to adopt risky behaviour by eating contaminated food and entering contaminated areas. Avoiding the need to undertake safe behaviour reduced stress levels. Furthermore, people adopted beliefs to suit their situation. For example, some inhabitants of the affected areas became adapted to the radiation and actually felt worse outside the contaminated area. There was strong pressure for the maintenance of a situation which actually prevented appropriate precautions being taken. Peter concluded that there was often confusion over the details of technical information that sometimes might not help to prevent a course of action being taken. However on a positive note the research did find credence and

  13. CCL21 Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Yuan Lin

    2014-05-01

    Full Text Available Cancer, a major health problem, affects 12 million people worldwide every year. With surgery and chemo-radiation the long term survival rate for the majority of cancer patients is dismal. Thus novel treatments are urgently needed. Immunotherapy, the harnessing of the immune system to destroy cancer cells is an attractive option with potential for long term anti-tumor benefit. Cytokines are biological response modifiers that stimulate anti-tumor immune responses. In this review, we discuss the anti-tumor efficacy of the chemotactic cytokine CCL21 and its pre-clinical and clinical application in cancer.

  14. CCL21 Cancer Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yuan, E-mail: yuanlin@mednet.ucla.edu [Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); UCLA Head and Neck Cancer Program, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Sharma, Sherven [Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Veterans’ Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073 (United States); John, Maie St. [Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); UCLA Head and Neck Cancer Program, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)

    2014-05-07

    Cancer, a major health problem, affects 12 million people worldwide every year. With surgery and chemo-radiation the long term survival rate for the majority of cancer patients is dismal. Thus novel treatments are urgently needed. Immunotherapy, the harnessing of the immune system to destroy cancer cells is an attractive option with potential for long term anti-tumor benefit. Cytokines are biological response modifiers that stimulate anti-tumor immune responses. In this review, we discuss the anti-tumor efficacy of the chemotactic cytokine CCL21 and its pre-clinical and clinical application in cancer.

  15. The role of nuclear shapes in nuclear structure (from the perspective of the Daresbury Tandem)

    International Nuclear Information System (INIS)

    Nazarewicz, W.

    1993-01-01

    In specific regions of the nuclear periodic chart, large multipole moments are observed and the low-lying excitations have a rotational character. These features are understood if the nuclei in question are assumed to have a stable deformation, i.e., a non-spherical distribution of the nuclear matter. In other (transitional) regions the quasi-rotational bands are present; they are strongly coupled to low-lying vibrational modes. Those nuclei are best understood in terms of small static deformations but large dynamic fluctuations around local equilibria. As a matter of fact, the vast majority of nuclei are deformed; even in those which are spherical or almost spherical, the dynamical couplings to shape vibrations are crucial. The issue of nuclear deformation is many-faceted. If the nuclear shape (nuclear mean field) is deformed, characteristic excitation modes are present, such as rotations and vibrations built upon the non-spherical equilibrium. Through the particle-core coupling, nuclear deformations can dramatically influence the single-particle properties of nucleons moving in the average nuclear potential. Many experimental investigations using the Daresbury Tandem were related in one way or another to the physics of nuclear shapes. Fundamental discoveries from Daresbury include the observation of superdeformed structures in rapidly rotating nuclei, the observation of identical (open-quotes twinnedclose quotes) rotational bands, various studies of structural changes induced by very fast rotation (band-crossings, band-terminations), the observation of the oblate-deformed open-quotes dipoleclose quotes bands, studies of reflection-asymmetric shapes, studies of (quasimolecular) cluster configurations in light nuclei, and many, many others. The author reviews the forefront research at Daresbury from the global perspective; the common denominator being the nuclear shape deformation

  16. Studies of (p, γ) reactions with the Daresbury Recoil Separator at ORNL'S HRIBF

    International Nuclear Information System (INIS)

    Fitzgerald, R.; Abbotoy, E.; Bardayan, D.W.; Blackmon, J.C.; Champagne, A.E.; Chen, A.A.; Greife, U.; Hill, D.W.; James, A.N.; Kozub, R.L.; Lewis, T.A.; Livesay, R.; Ma, Z.; Mahan, S.L.; McConnell, J.W.; Milner, W.T.; Moazen, B.H.; Parker, P.D.; Pierce, D.E.; Roettger, M.E.; Sahin, L.; Shapira, D.; Smith, M.S.; Strieder, F.; Swartz, K.B.; Thomas, J.S.; Visser, D.W.

    2005-01-01

    The fusion of protons with radioactive nuclei is important in stellar explosions such as novae and X-ray bursts and for the production of neutrinos in the sun. The Daresbury Recoil Separator and a windowless gas target system have been installed at ORNL's Holifield Radioactive Ion Beam Facility (HRIBF) for measurements of proton capture reactions in inverse kinematics with radioactive ion beams. The performance of the system has been characterized with a number of experiments using stable ion beams. We report on results from these commissioning measurements and plans for measurements of the 1 H( 17 F, 18 Ne) and 1 H( 7 Be, 8 B) reactions

  17. Photoionization of ions and the general program in atomic and molecular physics at Daresbury

    International Nuclear Information System (INIS)

    West, J.B.

    1990-01-01

    The current program in Atomic and Molecular Science is focused on photoionization of atoms and small molecules. On the atomic side, experiments on the double ionization of helium were completed recently, verifying the Wannier threshold law for double photoionization. Also, the angular distribution of the electrons has just been measured, and these results show a marked divergence form theoretical expectations. Other experiments include fluorescence polarization measurements for the atomic ions calcium and strontium, which, when combined with photoelectron angular distribution measurements, form the complete photoionization experiment. A sizeable part of the program is devoted to studying molecular fragmentation. The triple coincidence technique, in which the two fragment ions are detected in coincidence with the photoelectron after the parent molecule has been doubly ionized, was developed at Daresbury, and experiments in this area continue with the addition of fluorescence measurements. Looking to the future, the atomic and molecular science program at Daresbury will move closer to applied science areas, with metal clusters and transient species becoming more prominent. Much of this work will require a source with two to three orders of magnitude advantage in photon intensity over the SRS, and a design study is presently under way for a VUV/Soft X-ray source to meet these requirements

  18. CAS - CERN Accelerator School and CLRC Daresbury Laboratory : Specialised CAS Course on Power Converters

    CERN Document Server

    CAS - CERN Accelerator School : Intermediate Accelerator Physics

    2006-01-01

    These proceedings contain the lectures given at the eighteenth specialized course organized by the CERN Accelerator School (CAS), the topic being ‘Power Converters for Particle Accelerators’. The course was held in Warrington, UK, from 12 to 18 May 2004. A similar course took place in Montreux, Switzerland in 1990, with proceedings published as CERN 90-07. After an interval of fourteen years, the aim of this course was to present a review of the actual state of the art and highlight the latest developments in the field. The course started with a basic recapitulation on accelerators, the required performance for the power converters, and the classification of converter topologies. Following this introductory section, more detailed aspects of active and passive components, converter topology analysis and simulations were presented. Based on these building blocks, the main power converter topologies were covered such as thyristor rectifiers, 1-quadrant and 4-quadrant switched-mode power converters. The impor...

  19. Diagnostic System Commissioning of the EMMA NS-FFAG Facility at Daresbury Laboratory

    CERN Document Server

    Kalinin, A

    2010-01-01

    We pre­sent pre­lim­i­nary re­sults of beam di­ag­nos­tics for the world's first Non-Scal­ing FFAG Ac­cel­er­a­tor 'EMMA'. Amongst other means, a sin­gle-shot/turn-by-turn BPM sys­tem is used, that was first test­ed on the ALICE in­jec­tor. The BPM sys­tem uti­lizes a front-end con­ver­sion of but­ton pick­up sig­nals into flat-top-en­ve­lope 700 MHz bursts, time-do­main mul­ti­plex­ing (in each plane, sig­nals are made spaced by 13.8 ns), and the man­u­fac­ture of both syn­chronous de­tec­tor and ADC clocks di­rect­ly from the beam sig­nal. The sys­tem per­for­mance is dis­cussed; re­sults of beam-based res­o­lu­tion mea­sure­ment are given. First turn beam tra­jec­to­ries fur­thest from the Sep­tum and Kick­er are pre­sent­ed.

  20. CCL8 BASED IMMUNOLOGICAL MONITORING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of CCL8.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...

  1. CCl4 cirrhosis in rats

    DEFF Research Database (Denmark)

    Fischer-Nielsen, A; Poulsen, H E; Hansen, B A

    1991-01-01

    measurements were reduced in a differentiated manner. Ranked according to the most pronounced changes they are: capacity of urea-N synthesis (CUNS), galactose elimination capacity (GEC) and antipyrine clearance (APC). Hepatic glutathione concentrations were only slightly decreased after the CCl4 treatment...

  2. Increased CCL19 and CCL21 levels promote fibroblast ossification in ankylosing spondylitis hip ligament tissue.

    Science.gov (United States)

    Qin, Yang; He, Li Da; Sheng, Zhou Jian; Yong, Miao Ming; Sheng, Yang Sheng; Wei Dong, Xu; Wen Wen, Tong; Ming, Zou Yu

    2014-09-26

    It is well-documented that both chemokine (C-C motif) ligand 19 (CCL19) and 21 (CCL21) mediate cell migration and angiogenesis in many diseases. However, these ligands' precise pathological role in ankylosing spondylitis (AS) has not been elucidated. The objective of this study was to examine the expression of CCL19 and CCL21 (CCL19/CCL21) in AS hip ligament tissue (LT) and determine their pathological functions. The expression levels of CCL19, CCL21 and their receptor CCR7 in AS (n = 31) and osteoarthritis (OA, n = 21) LT were analyzed via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). The expression of CCL19, CCL21 and CCR7 in AS ligament fibroblasts was also detected. The proliferation of ligament fibroblasts was measured via a cell counting kit-8 (CCK8) assay after exogenous CCL19/CCL21 treatment. Additionally, the role of CCL19/CCL21 in osteogenesis was evaluated via RT-PCR and enzyme-linked immunosorbent assay (ELISA) in individual AS fibroblast cultures. Furthermore, the expression of the bone markers alkaline phosphatase (ALP), osteocalcin (OCN), collagenase I (COL1), integrin-binding sialoprotein (IBSP) and the key regulators runt-related transcription factor-2 (Runx-2) and osterix were investigated. Moreover, the CCL19/CCL21 levels in serum and LT were measured via ELISA. The mRNA levels of CCL19/CCL21 in AS hip LT were significantly higher than that in OA LT, and IHC analysis revealed a similar result. Exogenous CCL19/CCL21 treatment did not affect the proliferation of ligament fibroblasts but significantly up-regulated the expression of bone markers, including ALP and OCN, and the key regulators Runx-2 and osterix. In addition, the serum levels of CCL19/CCL21 were apparently elevated in AS patients compared to healthy controls (HC), and the expression of the two chemokines correlated significantly in AS patients. CCL19 and CCL21, two chemokines displaying significantly associated expression in serum, indicating a

  3. Beneficial impact of CCL2 and CCL12 neutralization on experimental malignant pleural effusion.

    Directory of Open Access Journals (Sweden)

    Antonia Marazioti

    Full Text Available Using genetic interventions, we previously determined that C-C motif chemokine ligand 2 (CCL2 promotes malignant pleural effusion (MPE formation in mice. Here we conducted preclinical studies aimed at assessing the specific therapeutic potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous delivery of lung (LLC or colon (MC38 adenocarcinoma cells. Human lung adenocarcinoma cells (A549 were used to induce MPEs in severe combined immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three days. We found that high doses of CCL2/12 neutralizing antibody treatment (50 mg/kg were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and CCL12 neutralization was also effective against MC38-induced MPE and prolonged the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was associated with inhibition of immune and vascular MPE-related phenomena, such as inflammation, new blood vessel assembly and plasma extravasation into the pleural space. We conclude that CCL2 and CCL12 blockade are effective against experimental MPE induced by murine and human adenocarcinoma in mice. These results suggest that CCL2-targeted therapies may hold promise for future use against human MPE.

  4. Equine herpesvirus type-1 modulates CCL2, CCL3, CCL5, CXCL9, and CXCL10 chemokine expression.

    Science.gov (United States)

    Wimer, Christine L; Damiani, Armando; Osterrieder, Nikolaus; Wagner, Bettina

    2011-04-15

    Equine herpesvirus type 1 (EHV-1) is highly prevalent in horses and causes rhinopneumonitis, abortion, and encephalopathy. Studies on the related human herpes simplex virus and of murine models of EHV-1 suggest that chemokines play important roles in coordinating of innate and adaptive immune responses, and thus effective control of herpesvirus infection and prevention of severe clinical disease. Here, equine peripheral blood mononuclear cells (PBMC) were infected with one of three EHV-1 strains, which differ in pathogenicity (RacL11, NY03=abortogenic, Ab4=neurogenic). Changes in CCL2, CCL3, CCL5, CXCL9 and CXCL10 chemokine gene expression relative to non-infected PBMC were measured by real-time PCR. CXCL9 and CXCL10 gene expression was up-regulated 10h post infection and decreased to the level of non-infected cells after 24h. CCL2 and CCL3 were significantly down-regulated 24h post infection with NY03 and Ab4. CCL5 was up-regulated 24h after infection with RacL11. Ab4 infected PBMC had significantly lower expression of all chemokines except CCL2 24h post infection then RacL11 infected cells. While there was not a significant difference between NY03 and the other strains, there was a trend with each chemokine toward NY03 inducing less expression then RacL11 but more then Ab4. The data suggested that EHV-1 infection of PBMC induced up-regulation of inflammatory chemokines CCL5, CXCL9 and CXCL10, and down-regulation of chemotactic CCL2 and CCL3. The data also implies that different EHV-1 strains have varying effects on all five chemokines, with the nuropathogenic strain, Ab4, having the greatest suppressive potential. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Chemokines CXCL10 and CCL2

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Sellebjerg, F; Jensen, C V

    2001-01-01

    leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9...... patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials....... Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls...

  6. Immune response CC Chemokines, CCL2 and CCL5 are associated with Pulmonary Sarcoidosis

    LENUS (Irish Health Repository)

    Palchevskiy, Vyacheslav

    2011-04-04

    Abstract Background Pulmonary sarcoidosis involves an intense leukocyte infiltration of the lung with the formation of non-necrotizing granulomas. CC chemokines (chemokine (C-C motif) ligand 2 (CCL2)-CCL5) are chemoattractants of mononuclear cells and act through seven transmembrane G-coupled receptors. Previous studies have demonstrated conflicting results with regard to the associations of these chemokines with sarcoidosis. In an effort to clarify previous discrepancies, we performed the largest observational study to date of CC chemokines in bronchoalveolar lavage fluid (BALF) from patients with pulmonary sarcoidosis. Results BALF chemokine levels from 72 patients affected by pulmonary sarcoidosis were analyzed by enzyme-linked immunosorbent assay (ELISA) and compared to 8 healthy volunteers. BALF CCL3 and CCL4 levels from pulmonary sarcoidosis patients were not increased compared to controls. However, CCL2 and CCL5 levels were elevated, and subgroup analysis showed higher levels of both chemokines in all stages of pulmonary sarcoidosis. CCL2, CCL5, CC chemokine receptor type 1 (CCR1), CCR2 and CCR3 were expressed from mononuclear cells forming the lung granulomas, while CCR5 was only found on mast cells. Conclusions These data suggest that CCL2 and CCL5 are important mediators in recruiting CCR1, CCR2, and CCR3 expressing mononuclear cells as well as CCR5-expressing mast cells during all stages of pulmonary sarcoidosis.

  7. Preliminary report on electron energy-loss measurements for CCl3, CCl2F2, CCl3F

    International Nuclear Information System (INIS)

    Bushnell, D.L. Jr.; Huebner, R.H.; Celotta, R.J.; Mielczarek, S.R.

    1975-01-01

    Currently, nation-wide research efforts are devoted to studying the possible ozone (O 3 ) depletion in the stratosphere by the chemical action of chlorine atoms released from CCl 2 F 2 or CCl 3 F upon absorption of ultraviolet radiation. Since electron-impact data taken in the forward scattering direction can be used to derive oscillator strengths and thus to yield apparent photoabsorption cross sections, such an analysis for CCl 2 F 2 , CCLl 3 F, and CClF 3 was carried out. Oscillator-strength distributions were obtained between 5 and 20 eV and are compared to available photoabsorption data. Certain photoabsorption values agree very well with these electron-impact data, but other optical studies deviate in some spectral regions by as much as a factor of 5. Also, the electron energy-loss spectrum reveals electronic transitions previously undetected by photoabsorption

  8. CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer.

    Science.gov (United States)

    Svensson, Susanne; Abrahamsson, Annelie; Rodriguez, Gabriela Vazquez; Olsson, Anna-Karin; Jensen, Lasse; Cao, Yihai; Dabrosin, Charlotta

    2015-08-15

    Novel therapeutic targets of estrogen receptor (ER)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish. ER(+) cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment. Our findings shed new light on the mechanisms underlying the progression of ER(+) breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways. ©2015 American Association for Cancer Research.

  9. Fine structure of the CCl3 UV absorption spectrum and CCl3 kinetics

    DEFF Research Database (Denmark)

    Ellermann, T.

    1992-01-01

    The UV gas-phase spectrum of CCl3 was recorded in the range 220-300 nm using pulse radiolysis of CHCl3/SF6 or CCl4/Ar gas mixtures. The UV spectrum exhibits a pronounced vibrational fine structure which is assigned to transition into the (C2A1'(3s)) Rydberg state. The vibronic progression has...

  10. Diode laser spectra of CCl2F2 near 10.8 muon M: Air-broadening effects

    Science.gov (United States)

    Jennings, D. E.

    1977-01-01

    Laboratory spectra of CCL2F2 in the 10.8 micron region was recorded, using a tuneable diode laser spectrometer. Effects of air-broadening at pressures up to 48 Torr show that spectral structure should be exhibited under high resolution at altitudes as low as 19 Km. The single line, pressure-broadening coefficient for CCL2F2 was estimated to be 8 MHz/Torr FWHM.

  11. The Formation and Motion of CCl4- in CCl4 - Ar Mixture

    International Nuclear Information System (INIS)

    Martinez, H.; Yousif, F. B.

    2006-01-01

    This article deals with the measurement of the mobility of negative ions in the mixtures of CCl4 with Ar with the CCl4 ratio up to 33.3%. The Pulsed Townsend Technique was employed to produce an integrated ionic avalanches over a range of the density-reduced electric field E/N for which ionization is either negligible or absent, and attachment processes are dominant, leading to the formation of mostly CCl 4 - . The E/N range of measurement was 1 to 50 Td (1Td = 10-17 Vcm2). Our measurements strongly suggest that attachment is the dominant process and only negative ions are formed

  12. Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Yavar Mahmoodzadeh

    Full Text Available The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4.54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups, 4 of them were exposure groups which were respectively administered with 40, 80, and 120 mg/kg of TPE and silymarin for 14 days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120 mg/kg of TPE and silymarin 2, 6, 24, and 48 h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed.Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group.The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4. Keywords: Tanacetum parthenium, Carbon tetrachloride, Oxidative stress, Antioxidant enzymes, Liver damage

  13. Relevance of CCL3/CCR5 axis in oral carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Moreira Dos Santos, Tálita Pollyanna; Sobral, Lays Martin; Queiroz-Junior, Celso Martins; Rachid, Milene Alvarenga; Proudfoot, Amanda E I; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; Teixeira, Mauro Martins; Leopoldino, Andréia Machado; Russo, Remo Castro; Silva, Tarcília Aparecida

    2017-08-01

    The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro . The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3 -/- and CCR5 -/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1 -/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3 -/- and CCR5 -/- mice. OSCC from CCL3 -/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro , CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.

  14. Hepatoprotective effect of basil ( Ocimum basilicum L.) on CCl 4 ...

    African Journals Online (AJOL)

    The hepatoprotective effect of basil (Ocimum basilicum) extract against liver fibrosis-induced by carbon tetrachloride (CCl4) was studied in rats. Rats were allocated into five groups: Group I (control group); Group II [CCl4 group; rats were injected subcutaneously with CCl4 (1 ml/kg b.w.) twice weekly for 4 weeks ...

  15. CCR4 agonists CCL22 and CCL17 are elevated in pediatric OMS sera: rapid and selective down-regulation of CCL22 by ACTH or corticosteroids.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Colliver, Jerry A; Ransohoff, Richard M

    2013-05-01

    To study the role of Th2-attracting chemokines in opsoclonus-myoclonus syndrome (OMS), a serious neurological paraneoplastic disorder in need of better immunological understanding and therapy. The CCR4 agonists CCL22 and CCL17 were measured in serum by ELISA in children with OMS (238 and 260, respectively), pediatric controls (115 and 143), and other inflammatory neurological disorders (33 and 24). Both CCL22 (+55 %) and CCL17 (+121 %) were significantly elevated in untreated OMS compared to controls and inter-correlated (p OMS also were higher than in OIND (21 %, 41 %). The concentration of CCL22 in ACTH and steroids groups (not IVIg) was 51 % lower than in controls, but only a smaller effect of ACTH on CCL17 was found. Prospective longitudinal studies revealed a precipitous 81 % drop in CCL22 even by the first week of high-dose ACTH therapy, staying below control mean for at least 12 weeks, and a 34 % reduction after 8 months of combined treatment. Response to ACTH was dose-related (r = -0.50, p OMS. Marked and rapid reduction in CCL22, not CCL17, with either ACTH or steroid therapy suggests differential regulation and cellular sources of CCR4 ligands, and CCL22 as a potential candidate biomarker for ACTH or corticosteroid effect.

  16. IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells

    Directory of Open Access Journals (Sweden)

    Yoshitaka Hosokawa

    2016-01-01

    Full Text Available Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs. Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt and signal transducer and activator of transcription (STAT6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions.

  17. The in vitro NADPH-dependent inhibition by CCl4 of the ATP-dependent calcium uptake of hepatic microsomes from male rats. Studies on the mechanism of the inactivation of the hepatic microsomal calcium pump by the CCl3 radical

    International Nuclear Information System (INIS)

    Srivastava, S.P.; Chen, N.Q.; Holtzman, J.L.

    1990-01-01

    The hepatotoxicity of CCl4 is mediated through its initial reduction by cytochrome P-450 to the CCl3 radical. This radical then damages important metabolic systems such as the ATP-dependent microsomal Ca2+ pump. Previous studies from our laboratory on isolated microsomes have shown that NADPH in the absence of toxic agents inhibits this pump. We have now found in in vitro incubations that CCl4 (0.5-2.5 mM) enhanced the NADPH-dependent inhibition of Ca2+ uptake from 28% without CCl4 to a maximum of 68%. These concentrations are in the range found in the livers and blood of lethally intoxicated animals and are toxic to cultured hepatocytes. The inhibition of Ca2+ uptake was due both to a decrease in the Ca2(+)-dependent ATPase and to an enhanced release of Ca2+ from the microsomes. The NADPH-dependent CCl4 inhibition was greater under N2 and was totally prevented by CO. GSH (1-10 mM) added during the incubation with CCl4 prevented the inhibition. This protection was also seen when the incubations were performed under nitrogen. When samples were preincubated with CCl4, the CCl4 metabolism was stopped, and then the Ca2+ uptake was determined; GSH reversed the CCl4 inhibition of Ca2+ uptake. This reversal showed saturation kinetics for GSH with two Km values of 0.315 and 93 microM when both the preincubation and the Ca2+ uptake were performed under air, and 0.512 and 31 microM when both were performed under nitrogen. Cysteine did not prevent the NADPH-dependent CCl4 inhibition of Ca2+ uptake. CCl4 increased lipid peroxidation in air, but no lipid peroxidation was seen under nitrogen. Lipid peroxidation was only modestly reversed by GSH. GSH did not remove 14C bound to samples preincubated with the 14CCl4

  18. Plasma concentrations of CCL3 and CCL4 in the cardiac and digestive clinical forms of chronic Chagas disease.

    Science.gov (United States)

    de Oliveira, Amanda Priscila; Ayo, Christiane Maria; Mimura, Kallyne Kioko Oliveira; Oliani, Sonia Maria; Bernardo, Cássia Rubia; Camargo, Ana Vitória Silveira; Ronchi, Luís Sérgio; Borim, Aldenis Albaneze; de Campos Júnior, Eumildo; Brandão de Mattos, Cinara Cássia; Castiglioni, Lilian; Bestetti, Reinaldo Bulgarelli; Cavasini, Carlos Eugênio; de Mattos, Luiz Carlos

    2017-03-01

    The aim of this study was to investigate the plasma levels of the CCL3 and CCL4 chemokines in patients with the cardiac and digestive clinical forms of chronic Chagas disease and in cardiac patients with and without left ventricular systolic dysfunction (LVSD). Plasma samples from 75 patients were evaluated by enzyme-linked immunosorbent assay (ELISA) to confirm infection by T. cruzi. Plasma levels of the CCL3 and CCL4 chemokines were measured using Milliplex® MAP assay (Millipore). There were no significant differences in the levels of CCL3 and CCL4 between patients with the digestive and cardiac clinical forms of Chagas disease. Moreover, no significant differences were found between patients without LVSD and those with LVSD. Higher CCL3 and CCL4 plasma levels were found in patients with LVSD compared to those with the digestive form of the disease. The CCL3 and CCL4 chemokines might not be involved in differential susceptibility to the digestive and cardiac clinical forms of chronic Chagas disease, and it seems they do not influence the development of LVSD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The Carbon Tetrachloride (CCl4) Budget: Mystery or Not

    Science.gov (United States)

    Liang, Qing; Newman, Paul A.; Daniel, John S.; Reimann, Stefan; Hall, Bradley; Dutton, Geoff; Kuijpers, Lambert J. M.

    2014-01-01

    Carbon tetrachloride (CCl4) is a major anthropogenic ozone-depleting substance and greenhouse gas and has been regulated under the Montreal Protocol. However, atmospheric observations show a very slow decline in CCl4 concentrations, inconsistent with the nearly zero emissions estimate based on the UNEP reported production and feedstock usage in recent years. It is now apparent that there are either unidentified industrial leakages, an unknown production source of CCl4, or large legacy emissions from CCl4 contaminated sites. In this paper we use a global chemistry climate model to assess the budget mystery of atmospheric CCl4. We explore various factors that affect the global trend and the gradient between the Northern and Southern hemispheres or interhemispheric gradient (IHG): emissions, emission hemispheric partitioning, and lifetime variations. We find a present-day emission of 30-50 Gg per yr and a total lifetime 25 - 36 years are necessary to reconcile both the observed CCl4 global trend and IHG.

  20. Development of AWWA Recommendations for CCL4 Prioritization and Process

    OpenAIRE

    Bench, Ryan Worth

    2015-01-01

    Every 5 years the USEPA is responsible to publish a list of unregulated contaminants that are known or expected to occur in public water systems in the United States that may pose a risk on public health. This list is known as a contaminant candidate list (CCL). This year it is expected that the USEPA is to publish the 4th such list of the CCL or CCL4. Candidacy to be on the CCL4 is based on a compound’s occurrence in the environment, public health toxicity and recommendation from expert opin...

  1. BUPRENORPHINE DECREASES THE CCL2-MEDIATED CHEMOTACTIC RESPONSE OF MONOCYTES

    Science.gov (United States)

    Carvallo, Loreto; Lopez, Lillie; Che, Fa-Yun; Lim, Jihyeon; Eugenin, Eliseo; Williams, Dionna W.; Nieves, Edward; Calderon, Tina M.; Madrid-Aliste, Carlos; Fiser, Andras; Weiss, Louis; Angeletti, Ruth Hogue; Berman, Joan W.

    2015-01-01

    Despite successful cART, approximately 60% of HIV infected people exhibit HIV associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9, were identified and had not been shown previously be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction. PMID:25716997

  2. Vibrational Spectroscopy of the CCl[subscript 4] v[subscript 1] Mode: Theoretical Prediction of Isotopic Effects

    Science.gov (United States)

    Gaynor, James D.; Wetterer, Anna M.; Cochran, Rea M.; Valente, Edward J.; Mayer, Steven G.

    2015-01-01

    Raman spectroscopy is a powerful experimental technique, yet it is often missing from the undergraduate physical chemistry laboratory curriculum. Tetrachloromethane (CCl[subscript 4]) is the ideal molecule for an introductory vibrational spectroscopy experiment and the symmetric stretch vibration contains fine structure due to isotopic variations…

  3. Electron-impact dissociative ionization of CClF3 and CCl3F

    International Nuclear Information System (INIS)

    Martinez, Roberto; Sierra, Borja; Basterretxea, Francisco J.; Sanchez Rayo, Maria N.; Castano, Fernando

    2006-01-01

    A crossed-beam experiment of well characterized kinetic energy (KE) electrons and supersonic halomethanes CCl 3 F and CClF 3 in Ar carrier has been carried out in order to quantify the kinetic energy distributions (KEDs), the appearance energies (AEs) and the channels involved in the production of nascent ions. The ion KEDs were derived from the band profiles of the time-of-flight mass spectrum and the total KEDs computed using conservation laws. Heavier ions are created with KED peaked at thermal energies in contrast with low mass atoms or other fragments, where the distribution is broader and the maximum is at much higher energies. A discussion of the dissociative ionization pathways derived from the appearance energies, total average KEDs, thermodynamic enthalpies and computed electron dissociation energies is reported. The role of the vibrational and rotational energies into the dissociative processes is also discussed

  4. X-ray study of a test quadrant of the SODART telescopes using the expanded beam x-ray optics facility at the Daresbury synchrotron

    DEFF Research Database (Denmark)

    Christensen, Finn Erland; Hornstrup, Allan; Frederiksen, P.

    1994-01-01

    The imaging properties of a test model of the SODART telescopes have been studied using an expanded beam X-ray facility at the Daresbury synchrotron. The encircled power and the point spread function at three energies 6.627 keV, 8.837 keV and 11.046 keV have been measured using 1D and 2D position......V the HPD is 2.5 - 3.0 arcmin for all detectors whereas it is somewhat larger at 11.046 keV for HEPC and LEPC but essentially unchanged for SIXA. Finally, the data are used to point to improvements that can be introduced during the manufacture of the flight telescopes....

  5. X-ray study of a SODART flight telescope using the expanded beam x-ray optics beamline at the Daresbury synchrotron

    DEFF Research Database (Denmark)

    Christensen, Finn Erland; Hornstrup, Allan; Frederiksen, P. K.

    1995-01-01

    The on- and off-axis imaging properties of the first of two SODART flight telescopes have been studied using the expanded beam x-ray facility at the Daresbury synchrotron. From on- axis measurements the encircled power distribution and the point spread function at three energies 6.627 keV, 8.837 ke...... element solid state array detector (SIXA). We found that the HPD decreases with increasing energy due to poorer figure error of the outermost mirrors. The HPD falls in the range from 2.3 to 3 arcmin for all detectors. Residual misalignment of the individual quadrants of the telescope was found...... to contribute to the HPD by approximately 10%. If 33% of the geometric telescope area near the edges of the quadrants are covered a reduction of 10% of the HPD can be obtained. On- and off-axis images generated from the one dimensional intensity distribution are presented. Finally the data have been used...

  6. Protective effect of Euphorbia neriifolia saponin fraction on CCl 4 ...

    African Journals Online (AJOL)

    Saponin pretreatment improves bromsulphalein clearance and also increases the cellular viability. These effects substantiate protection of cellular phospholipid from peroxidative damage induced by highly reactive toxic intermediate radicals formed during biotransformation of CCl4. Key words: Euphorbia neriifolia, ...

  7. CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.

    Directory of Open Access Journals (Sweden)

    Hemant Kulkarni

    Full Text Available BACKGROUND: Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. METHODS AND FINDINGS: In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation. CONCLUSIONS: The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters

  8. Vapor pressure isotope effect in 13CClF3/12CClF3 by cryogenic distillation kinetics

    International Nuclear Information System (INIS)

    Wieck, H.J.; Ishida, T.

    1975-08-01

    The vapor pressure of 13 CClF 3 relative to the vapor pressure of 12 CClF 3 was measured as a function of temperature between 169 0 and 206 0 K by using a modified Bigeleisen distillation column. The transient build-up of the isotopic concentration gradient along the length of the packed column during the start-up period was monitored by taking samples from the condenser section as a function of time. The gaseous samples were completely oxidized to carbon dioxide in the presence of a platinum catalyst and a large excess of oxygen at temperatures between 1050 and 1100 0 C. The combustion products were purified by means of gas chromatography, and the purified carbon dioxide samples were analyzed in a Nier-type isotope-ratio mass spectrometer. The data of each distillation run were reduced in the light of Cohen's theory of the kinetics of square cascade of close-separation stages. The vapor pressure isotope effect for the carbon substitution in CClF 3 at temperatures between 169 0 and 206 0 K was found to be an inverse effect and to be rather insensitive to changes in temperature. The relative vapor pressure may be expressed 1n(P'/P) = [(1.5 +- 14.1)/T 2 ] - [(0.159 +- 0.076)/T], or 1n(P'/P) = [(0.173 +- 0.098)/T] - [(0.11 +- 0.53) x 10 -3 ], where P' and P are the vapor pressures of 12 CClF 3 and 13 CClF 3 , respectively. To the first-order, the presence of chlorine isotopes would not affect the fractionation of carbon isotopes by the distillation of CClF 3

  9. Elevated plasma chemokine CCL18/PARC in beta-thalassemia

    NARCIS (Netherlands)

    Dimitriou, E.; Verhoek, M.; Altun, S.; Karabatsos, F.; Moraitou, M.; Youssef, J.; Boot, R.; Sarafidou, J.; Karagiorga, M.; Aerts, H.; Michelakakis, H.

    2005-01-01

    Plasma CCL18/PARC, a member of the CC chemokine family, has been found to be several ten-fold increased in symptomatic Gaucher type I patients. Elevated plasma chitotriosidase levels are a well-known abnormality in Gaucher patients, however, its diagnostic use is limited by the frequent genetic

  10. 15 CFR 738.2 - Commerce Control List (CCL) structure.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Commerce Control List (CCL) structure. 738.2 Section 738.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS...

  11. Effect of Calitropis Procera Aqueous Root Extract Against CCL4 ...

    African Journals Online (AJOL)

    ABUBAKAR

    ABSTRACT. The hepatocurative effect of aqueous root extract of Calitropis Procera on CCl4 induced hepatotoxicity in rabbits was studied in groups of rabbit and the levels of liver enzymes; aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP). Serum concentrations of total ...

  12. The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity

    Directory of Open Access Journals (Sweden)

    Stefanie Scheu

    2017-11-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system (CNS. It affects more than two million people worldwide, mainly young adults, and may lead to progressive neurological disability. Chemokines and their receptors have been shown to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE, a murine disease model induced by active immunization with myelin proteins or transfer of encephalitogenic CD4+ T cells that recapitulates clinical and neuropathological features of MS. Chemokine ligand-receptor interactions orchestrate leukocyte trafficking and influence multiple pathophysiological cellular processes, including antigen presentation and cytokine production by dendritic cells (DCs. The C-C class chemokines 17 (CCL17 and 22 (CCL22 and their C-C chemokine receptor 4 (CCR4 have been shown to play an important role in homeostasis and inflammatory responses. Here, we provide an overview of the involvement of CCR4 and its ligands in CNS autoimmunity. We review key clinical studies of MS together with experimental studies in animals that have demonstrated functional roles of CCR4, CCL17, and CCL22 in EAE pathogenesis. Finally, we discuss the therapeutic potential of newly developed CCR4 antagonists and a humanized anti-CCR4 antibody for treatment of MS.

  13. Role of suppressed hepatocellular regeneration and Ca2+ in chlordecone-potentiated CCl4 hepatotoxicity

    International Nuclear Information System (INIS)

    Bell, A.N.

    1987-01-01

    The mechanism by which the chlorinated pesticide chlordecone (CD; Kepone) potentiates CCl 4 -induced hepatotoxicity and lethality was investigated. It was hypothesized that perturbations in Ca 2+ homeostasis, greater than those observed with a low dose of CCl 4 alone, in concert with a suppression of hepatocellular regeneration induced by CD alone or by CD + CCl 4 are responsible, at least in part, for CD-potentiated CCl 4 hepatotoxicity. Ca 2+ homeostasis was evaluated by measuring total cell Ca 2+ and 45 Ca 2+ uptake in viable isolated hepatocyte suspension obtained from normal and CD-pretreated rats receiving CCl 4 in vivo. In the normal rats in vivo CCL challenge did not affect 45 Ca 2+ uptake by viable isolated hepatocytes. In contrast, 45 Ca 2+ uptake was inhibited in viable isolated hepatocytes obtained from rats exposed to CD + CCl 4

  14. Current sources of carbon tetrachloride (CCl4) in our atmosphere

    Science.gov (United States)

    Sherry, David; McCulloch, Archie; Liang, Qing; Reimann, Stefan; Newman, Paul A.

    2018-02-01

    Carbon tetrachloride (CCl4 or CTC) is an ozone-depleting substance whose emissive uses are controlled and practically banned by the Montreal Protocol (MP). Nevertheless, previous work estimated ongoing emissions of 35 Gg year-1 of CCl4 into the atmosphere from observation-based methods, in stark contrast to emissions estimates of 3 (0-8) Gg year-1 from reported numbers to UNEP under the MP. Here we combine information on sources from industrial production processes and legacy emissions from contaminated sites to provide an updated bottom-up estimate on current CTC global emissions of 15-25 Gg year-1. We now propose 13 Gg year-1 of global emissions from unreported non-feedstock emissions from chloromethane and perchloroethylene plants as the most significant CCl4 source. Additionally, 2 Gg year-1 are estimated as fugitive emissions from the usage of CTC as feedstock and possibly up to 10 Gg year-1 from legacy emissions and chlor-alkali plants.

  15. Spin trapping of free radical products of CCl4 activation using pulse radiolysis and high energy radiation procedures

    International Nuclear Information System (INIS)

    Tomasi, A.; Albano, E.; Lott, K.A.K.; Slater, T.F.

    1980-01-01

    The authors have studied the interaction of CCl 3 with the spin-trap phenylbutylnitrone in a simplified model system where the CCl 3 radicals are produced by a pulse of high energy electrons. They have previously obtained kinetic data on the reactivity of CCl 3 and its peroxy-derivative CCl 3 O 2 in this model system. These data, together with ESR analysis with 13 CCl 4 , allow them to unequivocally identify the spin-trap adducts of CCl 3 and CCl 3 O 2 ; identical spectra are also reported for microsomal systems, intact hepatocytes and under conditions in vivo. (Auth.)

  16. Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch–Schönlein purpura susceptibility and severity

    Directory of Open Access Journals (Sweden)

    Hsin-Hui Yu

    2015-04-01

    Conclusion: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.

  17. Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte-derived Langerhans cells in patients with atopic dermatitis.

    Science.gov (United States)

    Miyano, Kyohei; Matsushita, Sho; Tsuchida, Tetsuya; Nakamura, Koichiro

    2016-09-01

    We examined the inhibitory effect of a histamine 4 receptor (H4R) antagonist (JNJ7777120) on CCL17 and CCL22 chemokine production by human monocyte-derived Langerhans cells (MoLC) in patients with atopic dermatitis (AD) and healthy controls (HC). We confirmed the significantly higher production of both CCL17 and CCL22 in the MoLC of AD patients compared with HC. The H4R antagonist significantly inhibited the production of both CCL17 and CCL22 in the MoLC of AD patients. With regard to TLR2-signaled enhancement, peptidoglycan (PGN)-enhanced production of CCL17 and CCL22 by MoLC was inhibited by the H4R. Immunoblotting analysis demonstrated that phosphorylated p38 mitogen-activated protein kinase was induced by PGN and that this enhancement was attenuated by the application of the H4R antagonist. These data indicate that H4 signaling modulates the production of T-helper 2 chemokine in MoLC and contributes to chronic inflammation in AD patients. Our data suggest a possible novel therapeutic approach using a H4R antagonist in the treatment of patients with AD. © 2016 Japanese Dermatological Association.

  18. Electron-impact dissociative ionization of CClF{sub 3} and CCl{sub 3}F

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Roberto [Facultad de Farmacia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Paseo de la Universidad 7. 01006 Vitoria (Spain); Sierra, Borja [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain); Basterretxea, Francisco J. [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain); Sanchez Rayo, Maria N. [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain); Castano, Fernando [Facultad de Ciencia y Tecnologia, Departamento de Quimica Fisica, Universidad del Pais Vasco, Apdo. 644. 48080 Bilbao (Spain)], E-mail: f.castano@ehu.es

    2006-11-08

    A crossed-beam experiment of well characterized kinetic energy (KE) electrons and supersonic halomethanes CCl{sub 3}F and CClF{sub 3} in Ar carrier has been carried out in order to quantify the kinetic energy distributions (KEDs), the appearance energies (AEs) and the channels involved in the production of nascent ions. The ion KEDs were derived from the band profiles of the time-of-flight mass spectrum and the total KEDs computed using conservation laws. Heavier ions are created with KED peaked at thermal energies in contrast with low mass atoms or other fragments, where the distribution is broader and the maximum is at much higher energies. A discussion of the dissociative ionization pathways derived from the appearance energies, total average KEDs, thermodynamic enthalpies and computed electron dissociation energies is reported. The role of the vibrational and rotational energies into the dissociative processes is also discussed.

  19. TPL-2 restricts Ccl24-dependent immunity to Heligmosomoides polygyrus

    Science.gov (United States)

    Kannan, Yashaswini; Entwistle, Lewis J.; Pelly, Victoria S.; Perez-Lloret, Jimena; Ley, Steven C.

    2017-01-01

    TPL-2 (COT, MAP3K8) kinase activates the MEK1/2-ERK1/2 MAPK signaling pathway in innate immune responses following TLR, TNFR1 and IL-1R stimulation. TPL-2 contributes to type-1/Th17-mediated autoimmunity and control of intracellular pathogens. We recently demonstrated TPL-2 reduces severe airway allergy to house dust mite by negatively regulating type-2 responses. In the present study, we found that TPL-2 deficiency resulted in resistance to Heligmosomoides polygyrus infection, with accelerated worm expulsion, reduced fecal egg burden and reduced worm fitness. Using co-housing experiments, we found resistance to infection in TPL-2 deficient mice (Map3k8–/–) was independent of microbiota alterations in H. polygyrus infected WT and Map3k8–/–mice. Additionally, our data demonstrated immunity to H. polygyrus infection in TPL-2 deficient mice was not due to dysregulated type-2 immune responses. Genome-wide analysis of intestinal tissue from infected TPL-2-deficient mice identified elevated expression of genes involved in chemotaxis and homing of leukocytes and cells, including Ccl24 and alternatively activated genes. Indeed, Map3k8–/–mice had a significant influx of eosinophils, neutrophils, monocytes and Il4GFP+ T cells. Conditional knockout experiments demonstrated that specific deletion of TPL-2 in CD11c+ cells, but not Villin+ epithelial cells, LysM+ myeloid cells or CD4+ T cells, led to accelerated resistance to H. polygyrus. In line with a central role of CD11c+ cells, CD11c+ CD11b+ cells isolated from TPL-2-deficient mice had elevated Ccl24. Finally, Ccl24 neutralization in TPL-2 deficient mice significantly decreased the expression of Arg1, Retnla, Chil3 and Ear11 correlating with a loss of resistance to H. polygyrus. These observations suggest that TPL-2-regulated Ccl24 in CD11c+CD11b+ cells prevents accelerated type-2 mediated immunity to H. polygyrus. Collectively, this study identifies a previously unappreciated role for TPL-2 controlling immune

  20. Interaction between CXCR4 and CCL20 pathways regulates tumor growth.

    Directory of Open Access Journals (Sweden)

    Katia Beider

    Full Text Available The chemokine receptor CXCR4 and its ligand CXCL12 is overexpressed in the majority of tumors and is critically involved in the development and metastasis of these tumors. CXCR4 is expressed in malignant tumor cells whereas its ligand SDF-1 (CXCL12 is expressed mainly by cancer associated fibroblasts (CAF. Similarly to CXCR4, the chemokine CCL20 is overexpressed in variety of tumors; however its role and regulation in tumors is not fully clear. Here, we show that the chemokine receptor CXCR4 stimulates the production of the chemokine CCL20 and that CCL20 stimulates the proliferation and adhesion to collagen of various tumor cells. Furthermore, overexpression of CCL20 in tumor cells promotes growth and adhesion in vitro and increased tumor growth and invasiveness in vivo. Moreover, neutralizing antibodies to CCL20 inhibit the in vivo growth of tumors that either overexpress CXCR4 or CCL20 or naturally express CCL20. These results reveal a role for CCL20 in CXCR4-dependent and -independent tumor growth and suggest a therapeutic potential for CCL20 and CCR6 antagonists in the treatment of CXCR4- and CCL20-dependent malignancies.

  1. CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Shih-Wei Wang

    Full Text Available BACKGROUND: Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells. CONCLUSIONS/SIGNIFICANCE: CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.

  2. CCL-1 in the spinal cord contributes to neuropathic pain induced by nerve injury.

    Science.gov (United States)

    Akimoto, N; Honda, K; Uta, D; Beppu, K; Ushijima, Y; Matsuzaki, Y; Nakashima, S; Kido, M A; Imoto, K; Takano, Y; Noda, M

    2013-06-20

    Cytokines such as interleukins are known to be involved in the development of neuropathic pain through activation of neuroglia. However, the role of chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, in the nociceptive transmission remains unclear. We found that CCL-1 was upregulated in the spinal dorsal horn after partial sciatic nerve ligation. Therefore, we examined actions of recombinant CCL-1 on behavioural pain score, synaptic transmission, glial cell function and cytokine production in the spinal dorsal horn. Here we show that CCL-1 is one of the key mediators involved in the development of neuropathic pain. Expression of CCL-1 mRNA was mainly detected in the ipsilateral dorsal root ganglion, and the expression of specific CCL-1 receptor CCR-8 was upregulated in the superficial dorsal horn. Increased expression of CCR-8 was observed not only in neurons but also in microglia and astrocytes in the ipsilateral side. Recombinant CCL-1 injected intrathecally (i.t.) to naive mice induced allodynia, which was prevented by the supplemental addition of N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. Patch-clamp recordings from spinal cord slices revealed that application of CCL-1 transiently enhanced excitatory synaptic transmission in the substantia gelatinosa (lamina II). In the long term, i.t. injection of CCL-1 induced phosphorylation of NMDA receptor subunit, NR1 and NR2B, in the spinal cord. Injection of CCL-1 also upregulated mRNA level of glial cell markers and proinflammatory cytokines (IL-1β, TNF-α and IL-6). The tactile allodynia induced by nerve ligation was attenuated by prophylactic and chronic administration of neutralizing antibody against CCL-1 and by knocking down of CCR-8. Our results indicate that CCL-1 is one of the key molecules in pathogenesis, and CCL-1/CCR-8 signaling system can be a potential target for drug development in the treatment for neuropathic pain.

  3. Carbon Characterization Laboratory Report

    Energy Technology Data Exchange (ETDEWEB)

    David Swank; William Windes; D.C. Haggard; David Rohrbaugh; Karen Moore

    2009-03-01

    The newly completed Idaho National Laboratory (INL) Carbon Characterization Laboratory (CCL) is located in Lab-C20 of the Idaho National Laboratory Research Center. This laboratory was established under the Next Generation Nuclear Plant (NGNP) Project to support graphite research and development activities. The CCL is designed to characterize and test carbon-based materials such as graphite, carbon-carbon composites, and silicon-carbide composite materials. The laboratory is fully prepared to measure material properties for nonirradiated carbon-based materials. Plans to establish the laboratory as a radiological facility within the next year are definitive. This laboratory will be modified to accommodate irradiated materials, after which it can be used to perform material property measurements on both irradiated and nonirradiated carbon-based material. Instruments, fixtures, and methods are in place for preirradiation measurements of bulk density, thermal diffusivity, coefficient of thermal expansion, elastic modulus, Young’s modulus, Shear modulus, Poisson ratio, and electrical resistivity. The measurement protocol consists of functional validation, calibration, and automated data acquisition.

  4. CCL23: a new CC chemokine involved in human brain damage.

    Science.gov (United States)

    Simats, A; García-Berrocoso, T; Penalba, A; Giralt, D; Llovera, G; Jiang, Y; Ramiro, L; Bustamante, A; Martinez-Saez, E; Canals, F; Wang, X; Liesz, A; Rosell, A; Montaner, J

    2018-02-07

    CCL23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL23 blood levels associate with acquired cerebral lesions and determined CCL23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL23 homologous chemokines in rodents, CCL9 and CCL6. Baseline CCL23 blood levels were determined on 245 individuals, including ischaemic strokes (IS), stroke mimics and controls. Temporal profile of circulating CCL23 was explored from baseline to 24 h in 20 of the IS. In an independent cohort of 120 IS with a 3-month follow-up, CCL23 blood levels were included in logistic regression models to predict IS outcome. CCL9/CCL6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia. Baseline CCL23 blood levels did not discriminate IS, but permitted an accurate discrimination of patients presenting acute brain lesions (P = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL23 (P < 0.001). Baseline CCL23 blood levels resulted an independent predictor of IS outcome at hospital discharge (OR adj : 19.702 [1.815-213.918], P = 0.014) and mortality after 3 months (OR adj : 21.47 [3.434-134.221], P = 0.001). In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL9 circulating levels decreased early after ischaemia (P < 0.001), whereas CCL6 did not alter within the first 24 h after ischaemia. Although preclinical models do not seem suitable to characterize CCL23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome. © 2018 The Association for the Publication of the Journal of Internal Medicine.

  5. Ciliary neurotrophic factor analogue aggravates CCl4-induced acute hepatic injury in rats.

    Science.gov (United States)

    Cui, Ming-Xia; Jiang, Jun-Feng; Min, Guang-Ning; Han, Wei; Wu, Yong-Jie

    2017-05-01

    Ciliary neurotrophic factor (CNTF) and CNTF analogs were reported to have hepatoprotective effect and ameliorate hepatic steatosis in db/db or high-fat-diet-fed mice. Because hepatic steatosis and injury are also commonly induced by hepatotoxin, the aim of the present study is to clarify whether CNTF could alleviate hepatic steatosis and injury induced by carbon tetrachloride (CCl 4 ). Unexpectedly, when combined with CCl 4 , CNTF aggravated hepatic steatosis and liver injury. The mechanism is associated with effects of CNTF that inhibited lipoprotein secretion and drastically impaired the ability of lipoproteins to act as transport vehicles for lipids from the liver to the circulation. While injected after CCl 4 cessation, CNTF could improve liver function. These data suggest that CNTF could be a potential hepatoprotective agent against CCl 4 -induced hepatic injury after the cessation of CCl 4 exposure. However, it is forbidden to combine recombinant mutant of human CNTF treatment with CCl 4 .

  6. CCL2 recruits T cells into the brain in a CCR2-independent manner

    DEFF Research Database (Denmark)

    Cédile, Oriane; Wlodarczyk, Agnieszka; Owens, Trevor

    2017-01-01

    CCR2, a receptor for CCL2. Expression of another receptor for CCL2, CCR4, and CXCR3, a receptor for CXCL10, which was also induced, were both increased in CCL2-treated CNS. CCR4 was expressed by neurons and astrocytes as well as CD4 T cells, and CXCR3 was expressed by CD4 and CD8 T cells. Chemokine...

  7. Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis

    Directory of Open Access Journals (Sweden)

    Jones Rebecca L

    2007-05-01

    Full Text Available Abstract Background Understanding the pathophysiology of chemokine secretion in endometriosis may offer a novel area of therapeutic intervention. This study aimed to identify chemokines differentially expressed in epithelial glands in eutopic endometrium from normal women and those with endometriosis, and to establish the expression profiles of key chemokines in endometriotic lesions. Methods Laser capture microdissection isolated epithelial glands from endometrial eutopic tissue from women with and without endometriosis in the mid-secretory phase of their menstrual cycles. Gene profiling of the excised glands used a human chemokine and receptor cDNA array. Selected chemokines were further examined using real-time PCR and immunohistochemistry. Results 22 chemokine/receptor genes were upregulated and two downregulated in pooled endometrial epithelium of women with endometriosis compared with controls. CCL16 and CCL21 mRNA was confirmed as elevated in some women with endometriosis compared to controls on individual samples. Immunoreactive CCL16 and CCL21 were predominantly confined to glands in eutopic and ectopic endometrium: leukocytes also stained. Immunoreactive CCL16 was overall higher in glands in ectopic vs. eutopic endometrium from the same woman (P Conclusion This study provides novel candidate molecules and suggests a potential local role for CCL16 and CCL21 as mediators contributing to the inflammatory events associated with endometriosis.

  8. TRPV1 receptor inhibition decreases CCL2-induced hyperalgesia

    Czech Academy of Sciences Publication Activity Database

    Špicarová, Diana; Adámek, Pavel; Kalynovska, Nataliia; Mrózková, Petra; Paleček, Jiří

    2014-01-01

    Roč. 81, JUN (2014), s. 75-84 ISSN 0028-3908 R&D Projects: GA ČR(CZ) GA305/09/1228; GA ČR(CZ) GPP303/12/P510; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LH12058 Grant - others:Univerzita Karlova(CZ) 253154 Institutional support: RVO:67985823 Keywords : pain * spinal cord * synaptic transmission * CCL2 * TRPV1 * EPSC Subject RIV: FH - Neurology Impact factor: 5.106, year: 2014

  9. Effect of budesonide and cetirizine hydrochloride on neurotrophic factor, airway function and chemokines CCL17 and CCL22 in patients with allergic rhinitis

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    Xiang Xu

    2017-11-01

    Full Text Available Objective: To investigate the effect of budesonide combined with cetirizine hydrochloride on neurotrophic factor, airway function and chemokines CCL17 and CCL12 in patients with allergic rhinitis. Methods: A total of 123 patients with Allergic Rhinitis were randomly divided into three groups, A group treated with budesonide nasal spray, B group treated with cetirizine hydrochloride, C group treated with budesonide combined with cetirizine hydrochloride, then the Neurotrophic factors, airway function indexes and chemokines CCL17 and CCL12 levels in three groups were compared. Results: Before the treatments, the three groups of patients in neurotrophic factor, airway function index and chemokines CCL17, CCL22 have no differences, Compared with before the treatments, after receiving different treatments, the three groups of patients in all indicators were Showed significant differences. In the indexes of neurotrophic factor (NGF, BDNF, NT-3mRNA expression, there was no significant difference between group A and group B, and group C was lower than group A and B. In airway function indexes (FVC, FEV1 and PEF, A group was significantly higher than B group, C group was significantly higher than A group; In the chemokines CCL17 and CCL22 indicators, C group was lower than A group, A group was lower than B group, the difference was significant. Conclusions: Budesonide combined with cetirizine hydrochloride in the treatment of Allergic Rhinitis, can effectively control the patients' neurotrophic factor, pulmonary ventilation and chemokine CC17, CCL22 indicators, the effect is better than Budesonide alone or Cetirizine hydrochloride.

  10. Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

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    Sligh, James [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Janda, Jaroslav [University of Arizona Cancer Center, Tucson, AZ 85724 (United States); Jandova, Jana, E-mail: jjandova@email.arizona.edu [Department of Medicine—Dermatology Division, University of Arizona, Tucson, AZ 857 24 (United States); University of Arizona Cancer Center, Tucson, AZ 85724 (United States)

    2014-11-15

    Highlights: • Alterations in mitochondrial DNA are commonly found in various human cancers. • Mutations in BALB mitochondrial DNA induce up-regulation of chemokine CCL20. • Increased growth and motility of mtBALB cells is associated with CCL20 levels. • mtDNA changes in BALB induce in vivo tumor growth through CCL20 up-regulation. • Mutations in mitochondrial DNA play important roles in keratinocyte neoplasia. - Abstract: mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF

  11. Impact of CCL4 gene polymorphisms and environmental factors on oral cancer development and clinical characteristics.

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    Lien, Ming-Yu; Lin, Chiao-Wen; Tsai, Hsiao-Chi; Chen, Yng-Tay; Tsai, Ming-Hsui; Hua, Chun-Hung; Yang, Shun-Fa; Tang, Chih-Hsin

    2017-05-09

    In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476-20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients.

  12. Parboiled Germinated Brown Rice Protects Against CCl4-Induced Oxidative Stress and Liver Injury in Rats.

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    Wunjuntuk, Kansuda; Kettawan, Aikkarach; Charoenkiatkul, Somsri; Rungruang, Thanaporn

    2016-01-01

    Parboiled germinated brown rice (PGBR) of Khao Dawk Mali 105 variety was produced by steaming germinated paddy rice, which is well-known for its nutrients and bioactive compounds. In this study we determined the in vivo antioxidant and hepatoprotective effects of PGBR in carbon tetrachloride (CCl(4))-induced oxidative stress in rats. Male Sprague-Dawley rats, (weight 200-250 g) were randomly divided into (1) control, (2) CCl(4), (3) white rice (WR)+CCl(4), (4) brown rice (BR)+CCl(4), and (5) PGBR+CCl(4) groups. PGBR, BR, and WR diets were produced by replacing corn starch in the AIN76A diet with cooked PGBR, BR, and WR powders, respectively. All rats except the control group were gavaged with 50% CCl4 in olive oil (v/v, 1 mL/kg) twice a week for 8 weeks. CCl(4)-treated rats exhibited significant liver injury, lipid peroxidation, protein oxidation, and DNA damage, as well as obvious changes to liver histopathology compared to control. In addition, CCl(4) treatment decreased the activities of CYP2E1 and antioxidant enzymes: glutathione S-transferase, glutathione peroxidase, superoxide dismutase and catalase, and glutathione (GSH) content. However, the PGBR+CCl(4) group exhibited less liver injury, lipid peroxidation, protein oxidation, and DNA damage, as well as better antioxidant enzyme activities and GSH content. Furthermore, PGBR inhibited degradation of CYP2E1 in CCl(4)-induced decrease of CYP2E1 activity. These data suggest that PGBR may prevent CCl(4)-induced liver oxidative stress and injury through enhancement of the antioxidant capacities, which may be due to complex actions of various bioactive compounds, including phenolic acids, γ-oryzanol, tocotrienol, and GABA.

  13. Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India.

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    Chowdhury, Purvita; Khan, Siraj Ahmed

    2017-10-20

    Japanese encephalitis (JE) is a major contributor for viral encephalitis in Asia. Vaccination programme has limited success for largely populated JE endemic countries like India and disease exposure is unavoidable. Involvement of chemokines and its co-receptors for adverse prognosis of JE have been documented both in vitro and in vivo. Identification of the genetic predisposing factor for JE infection in humans is crucial but not yet established. Therefore, we investigated the association of single nucleotide polymorphisms (SNPs) in chemokines (CCL2 and CCL5) and its co-receptors (CCR2 and CCR5) with their protein level for JE. The study enrolled 87 symptomatic JE cases (mild: severe = 24:63) and 94 asymptomatic controls. Our study demonstrated that CCL2 (rs1024611G), CCL5 (rs2280788G) and CCR2 (rs1799864A) significantly associated with JE (Odds ratio = 1.63, 2.95 and 2.62, respectively and P = 0.045, P = 0.05 and P = 0.0006, respectively). The study revealed that rs1024611G allele was associated with elevated level of CCL2. CCL5 elevation associated with JE mortality having a Cox proportional hazard of 1.004 (P = 0.033). In conclusion, SNPs of chemokine viz. CCL2 (rs1024611G) and its receptor CCR2 (rs1799864A) significantly associated with JE which may serve as possible genetic predisposing factor and CCL5 protein level may act as marker for disease survival.

  14. Propofol Attenuates Toxic Oxidative Stress by CCl4 in Liver Mitochondria and Blood in Rat.

    Science.gov (United States)

    Ranjbar, Akram; Sharifzadeh, Mohammad; Karimi, Jamshid; Tavilani, Heidar; Baeeri, Maryam; Heidary Shayesteh, Tavakol; Abdollahi, Mohammad

    2014-01-01

    Anti-oxidant effects of propofol (2, 6-diisopropylphenol) were evaluated agains carbon tetrachloridet CCl4 -induced oxidative stress in rat liver. 30 male rats were equally divided in to 6 groups (5 rats each). Group I (control), while Group II was given CCl4 (3 mL /Kg/day, IP). Animals of Groups III received only propofol (10 mg/Kg/day, IP). Group IV was given propofol+ CCl4. Group V was administered vitamin E (alpha-tocopherol acetate 15 mg/Kg/day, SC) .Animals of Group VII received alpha-tocopherol acetate + CCl4 once daily for two weeks. After treatment, blood and liver mitochondria were isolated. Anti-oxidant enzymes activity such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and oxidative stress marker such as reduced glutathione (GSH) and lipid peroxidation (LPO) concentration were measured. Oxidative stress induced with CCl4 in liver mitochondria was evident by a significant increase in enzymatic activities of GPx, SOD, and LPO and decreased of GSH and vailability of mitochondria. Propofol and vitamin E restored CCl4-induced changes in GSH, GPx, SOD and LPO in blood and liver mitochondria. CCl4 decreased viability of mitochondria that was recovered by propofol and vitamin E. It is concluded that oxidative damage is the mechanism of toxicity of CCl4 in the mitochondria that can be recovered by propofol comparable to vitamin E.

  15. The mucosae-associated epithelial chemokine (MEC/CCL28 modulates immunity in HIV infection.

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    Eleonora Castelletti

    2007-10-01

    Full Text Available CCL28 (MEC binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASC in the mucosal lamina propria (MLP. Mucosal HIV-specific IgA are detected in HIV-infection and exposure. The CCL28 circuit was analyzed in HIV-infected and-exposed individuals and in HIV-unexposed controls; the effect of CCL28 administration on gastrointestinal MLP IgA-ASC was verified in a mouse model.CCL28 was augmented in breast milk (BM plasma and saliva of HIV-infected and -exposed individuals; CCR3+ and CCR10+ B lymphocytes were increased in these same individuals. Additionally: 1 CCL28 concentration in BM was associated with longer survival in HIV vertically-infected children; and 2 gastro-intestinal mucosal IgA-ASC were significantly increased in VSV-immunized mice receiving CCL28.CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28-including constructs should be considered in mucosal vaccines to prevent HIV infection of the gastro-intestinal MLP via modulation of IgA-ASC.

  16. The mucosae-associated epithelial chemokine (MEC/CCL28) modulates immunity in HIV infection.

    Science.gov (United States)

    Castelletti, Eleonora; Lo Caputo, Sergio; Kuhn, Louise; Borelli, Manuela; Gajardo, Johanna; Sinkala, Moses; Trabattoni, Daria; Kankasa, Chipepo; Lauri, Eleonora; Clivio, Alberto; Piacentini, Luca; Bray, Dorothy H; Aldrovandi, Grace M; Thea, Donald M; Veas, Francisco; Nebuloni, Manuela; Mazzotta, Francesco; Clerici, Mario

    2007-10-03

    CCL28 (MEC) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASC) in the mucosal lamina propria (MLP). Mucosal HIV-specific IgA are detected in HIV-infection and exposure. The CCL28 circuit was analyzed in HIV-infected and-exposed individuals and in HIV-unexposed controls; the effect of CCL28 administration on gastrointestinal MLP IgA-ASC was verified in a mouse model. CCL28 was augmented in breast milk (BM) plasma and saliva of HIV-infected and -exposed individuals; CCR3+ and CCR10+ B lymphocytes were increased in these same individuals. Additionally: 1) CCL28 concentration in BM was associated with longer survival in HIV vertically-infected children; and 2) gastro-intestinal mucosal IgA-ASC were significantly increased in VSV-immunized mice receiving CCL28. CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28-including constructs should be considered in mucosal vaccines to prevent HIV infection of the gastro-intestinal MLP via modulation of IgA-ASC.

  17. Anti-CCL21 Antibody Attenuates Infarct Size and Improves Cardiac Remodeling After Myocardial Infarction

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    Yi Jiang

    2015-09-01

    Full Text Available Background/Aims: Over-activation of cellular inflammatory effectors adversely affects myocardial function after acute myocardial infarction (AMI. The CC-chemokine CCL21 is, via its receptor CCR7, one of the key regulators of inflammation and immune cell recruitment, participates in various inflammatory disorders, including cardiovascular ones. This study explored the therapeutic effect of an anti-CCL21 antibody in cardiac remodeling after myocardial infarction. Methods and Results: An animal model of AMI generated by left anterior descending coronary artery ligation in C57BL/6 mice resulted in higher levels of circulating CCL21 and cardiac CCR7. Neutralization of CCL21 by intravenous injection of anti-CCL21 monoclonal antibody reduced infarct size after AMI, decreased serum levels of neutrophil and monocyte chemo attractants post AMI, diminished neutrophil and macrophage recruitment in infarcted myocardium, and suppressed MMP-9 and total collagen content in myocardium. Anti-CCL21 treatment also limited cardiac enlargement and improved left ventricular function. Conclusions: Our study indicated that CCL21 was involved in cardiac remodeling post infarction and anti-CCL21 strategies might be useful in the treatment of AMI.

  18. Fusion of CCL21 non-migratory active breast epithelial and breast cancer cells give rise to CCL21 migratory active tumor hybrid cell lines.

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    Benjamin Berndt

    Full Text Available The biological phenomenon of cell fusion has been linked to tumor progression because several data provided evidence that fusion of tumor cells and normal cells gave rise to hybrid cell lines exhibiting novel properties, such as increased metastatogenic capacity and an enhanced drug resistance. Here we investigated M13HS hybrid cell lines, derived from spontaneous fusion events between M13SV1-EGFP-Neo breast epithelial cells exhibiting stem cell characteristics and HS578T-Hyg breast cancer cells, concerning CCL21/CCR7 signaling. Western Blot analysis showed that all cell lines varied in their CCR7 expression levels as well as differed in the induction and kinetics of CCR7 specific signal transduction cascades. Flow cytometry-based calcium measurements revealed that a CCL21 induced calcium influx was solely detected in M13HS hybrid cell lines. Cell migration demonstrated that only M13HS hybrid cell lines, but not parental derivatives, responded to CCL21 stimulation with an increased migratory activity. Knockdown of CCR7 expression by siRNA completely abrogated the CCL21 induced migration of hybrid cell lines indicating the necessity of CCL21/CCR7 signaling. Because the CCL21/CCR7 axis has been linked to metastatic spreading of breast cancer to lymph nodes we conclude from our data that cell fusion could be a mechanism explaining the origin of metastatic cancer (hybrid cells.

  19. CCL3L gene copy number and survival in an HIV-1 infected Zimbabwean population

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Wegner, Lise Thørner; Zinyama, Rutendo

    2012-01-01

    and progression to AIDS, but these results have been inconsistent. We examined a Zimbabwean study population for an association of CCL3L CNV with HIV status, progression (CD4 T-cells and viral load), and survival. Another aim was to investigate the possible effects of CCL3L CNV on CCL3 protein concentration....... A treatment-naïve cohort, which included 153 HIV infected and 159 HIV uninfected individuals, was followed for up to 4.3 years. The CNV of the CCL3L was determined by duplex real-time polymerase chain reaction. We found no association between four CCL3L CNV strata and HIV status (P=0.7), CD4 T-cell count (P=0...

  20. Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, T.L.; Sellebjerg, F; Jensen, C.V.

    2001-01-01

    leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9...... patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials....... Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls...

  1. Antioksidan Ekstrak Air Biji Kopi Robusta Lampung dalam Menghambat Degenerasi Sel Hati Tikus Model Hepatitis yang Diinduksi CCL4

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    Asep Sukohar

    2012-09-01

    Full Text Available Liver plays an important role in maintaining homeostasis and is critical for physiological functions of other organs. Morphological changes of the liver will have an impact on changes in liver function and may appear as clinical manifestations. Hepatitis is a serious disorder that causes inflammation of the liver cells and is caused by viruses, chemicals and toxins. Reactions that occur in the form of oxidative stress, free radicals dominant condition of antioxidants. Traditionally coffee is used as an everyday beverage and known as antioxidants because it contains flavonoids (chlorogenic acid. This study aim was to determine the hepatoprotective/antioxidant effect of coffee growing in Pesawaran Lampung, on the description of hepatocyte cell damage in Wistar rats hepatitis model induced with carbon tetrachloride (CCl4. Laboratory experimental research has been conducted in Pharmacology >Department, Faculty Medicine Padjadjaran University Bandung and pathology examinations was performed at the Hospital Abdoel Moeloek Lampung in December 2008–July 2009, using 15 male Wistar rats divided in three groups, the negative control group, positive control as a model of hepatitis, and hepatitis model that received the water extract of robusta coffee beans 25 mg/kgBW/days for 7 days and then received CCl4 induction. The results were analyzed by analysis of variance and independent t test. Administration of water extract of robusta coffee beans can prevented damage to the liver cell degeneration picture from 58.4±7.09 to 34.4±5.85, these results differed significantly (p≤0.05 compared with positive and negative control. In conclusion, water extract of robusta coffee beans has the potential to prevent interference with the effects of liver function as antioxidants in the ra model of hepatitis which has been inducted with CCL4.

  2. Glial- and Neuronal-Specific Expression of CCL5 mRNA in the Rat Brain

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    Maria Fe Lanfranco

    2018-01-01

    Full Text Available Chemokine (C-C motif ligand 5 (CCL5 belongs to a group of chemokines that play a role in the peripheral immune system, mostly as chemoattractant molecules, and mediate tactile allodynia. In the central nervous system (CNS, CCL5 and its receptors have multiple functions, including promoting neuroinflammation, insulin signaling, neuromodulator of synaptic activity and neuroprotection against a variety of neurotoxins. Evidence has also suggested that this chemokine may regulate opioid response. The multifunctional profile of CCL5 might correlate with its ability to bind different chemokine receptors, as well as with its unique cellular expression. In this work, we have used fluorescence in situ hybridization combined with immunohistochemistry to examine the expression profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular localization. We have observed that the highest expression of CCL5 mRNA occurs in all major fiber tracts, including the corpus callosum, anterior commissure, and cerebral peduncle. In these tracts, CCL5 mRNA was localized in oligodendrocytes, astrocytes and microglia. Astrocytic and microglial expression was also evident in several brain areas including the cerebral cortex, caudate/putamen, hippocampus, and thalamus. Furthermore, using a specific neuronal marker, we observed CCL5 mRNA expression in discrete layers of the cortex and hippocampus. Interestingly, in the midbrain, CCL5 mRNA co-localized with tyrosine hydroxylase (TH positive cells of the ventral tegmental area, suggesting that CCL5 might be expressed by a subset of dopaminergic neurons of the mesolimbic system. The expression of CCL5 mRNA and protein, together with its receptors, in selected brain cell populations proposes that this chemokine could be involved in neuronal/glial communication.

  3. Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression

    Science.gov (United States)

    Amir, Gail; Demma, Jonathan; Vernea, Fiona; Beider, Katia; Shlomai, Zippora; Wald, Hanna; Zamir, Gideon; Shapira, Oz M.; Peled, Amnon; Wald, Ori

    2011-01-01

    Objectives Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. Methods A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. Results CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52–15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. Conclusion Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations. PMID:21949768

  4. In vivo metabolism of CCl4 by rats pretreated with chlordecone, mirex, or phenobarbital

    International Nuclear Information System (INIS)

    Mehendale, H.M.; Klingensmith, J.S.

    1988-01-01

    The propensity of chlordecone (CD) to potentiate hepatotoxic and lethal effects of CCl4 is well established. Mirex (M), a close structural analogue of CD, or phenobarbital (PB), powerful inducers of hepatic microsomal drug metabolizing enzymes, are much weaker potentiators of CCl4 toxicity. The purpose of this study was to test the possibility that CD potentiates the toxicity of CCl4 by increasing the metabolism of CCl4 to a greater degree than either PB or M. We compared the in vivo metabolism of CCl4 in rats pretreated with CD, M, or PB, by measuring the hepatic content of 14CCl4, the expiration of 14CCl4, expiration of 14CCl4-derived 14CO2, and lipid peroxidation. Male Sprague-Dawley rats (250-270 g) were pretreated with a single oral dose of CD (10 mg/kg), M (10 mg/kg), or corn oil vehicle (1 ml/kg). PB pretreatment consisted of an ip injection of sodium PB (80 mg/kg) in saline (0.9%) for 2 successive days. Twenty-four hours later, 14CCl4 (0.1 ml/kg; sp act: 0.04 mCi/mmol) was administered ip in corn oil and the radioactivity present in the expired air was collected for 6 hr. Excretion of the parent compound as represented by the 14C label in the toluene trap was unchanged by any of the pretreatments. Expiration of 14CO2 measured during the 6 hr after CCl4 administration was increased in animals pretreated with PB or CD. In vivo lipid peroxidation measured as diene conjugation in lipids extracted from the livers was increased to a similar extent in animals pretreated with PB and CD, whereas the serum transaminases (ALT, AST) were significantly elevated only in animals pretreated with CD.M did not affect 14CO2 production and was without a significant effect on the lipid peroxidation

  5. In vivo metabolism of CCl4 by gerbils pretreated with chlordecone, phenobarbital, or mirex

    International Nuclear Information System (INIS)

    Cai, Z.; Mehendale, H.M.

    1990-01-01

    Gerbils are known to be much more sensitive to CCl 4 lethality than rats as indicated by 48 hours LD 50 (0.08 vs 2.8 ml/kg). On the other hand, gerbils are refractory to chlordecone (CD) potentiation of CCl 4 toxicity. To investigate the possible mechanism underlying gerbil's high sensitivity to CCl 4 lethality, the authors studied in vivo metabolism of CCl 4 in gerbils pretreated with dietary CD (10 ppm), phenobarbital (PB, 225 ppm) or mirex (M, 10 ppm). The hepatic content of CCl 4 , the expiration of 14 CCl 4 and 14 CCl 4 -derived Co 2 , and lipid peroxidation were measured and the results were compared with our previous data for rats. After 15-day dietary pretreatment, male gerbils (60-80 g) received 14 CCl 4 (80 ml/kg; sp act: 0.04 mCi/mmol) ip in corn oil and the expired air was collected for 6 hours. More than 80% of the dose administered was expired as parent compound in 6 hours regardless of pretreatments. Expiration of 14 CCl 4 derived 14 CO 2 in control gerbils was 3.5-fold more than in control rats and was increased significantly in pretreated gerbils (M>PB>CD). PB and M pretreatments resulted in significant increase of 14 C label bound to non-lipid fraction of hepatic content as compared with CD or control gerbils. The radiolabel present in hepatic content of control gerbils was 5-fold higher than that of control rats. In vivo liquid peroxidation measured as diene conjugation in lipid extracts from the livers was lower in gerbils than in rats, and there were no significant differences among control and pretreated gerbils. These data indicate that the more extensive metabolism of CCl 4 in gerbils may partially explain their high sensitivity to CCl 4 toxicity. However, the significantly enhanced metabolism of CCl 4 found in CD, PB, or M pretreated gerbils did not lead to amplification of CCl 4 hepatotoxic and lethal effects

  6. CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.

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    Zahra Hasan

    Full Text Available BACKGROUND: Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity. METHODOLOGY: We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB and healthy endemic controls (ECs, n = 36. TB patients comprised pulmonary (PTB, n = 34 and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16 or severe disseminated ETB (D-ETB, n = 16. Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined. RESULTS: M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01 as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023, while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005 patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p = 0.04, while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB patients (p = 0.036. TNFalpha mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02 and BCG (p = 0.03. Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups. CONCLUSIONS: The increased CCL2 and TNFalpha in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.

  7. Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort.

    Science.gov (United States)

    Vega, Jorge A; Villegas-Ospina, Simón; Aguilar-Jiménez, Wbeimar; Rugeles, María T; Bedoya, Gabriel; Zapata, Wildeman

    2017-06-01

    Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant. Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

  8. UV and infrared absorption spectra, atmospheric lifetimes, and ozone depletion and global warming potentials for CCl2FCCl2F (CFC-112, CCl3CClF2 (CFC-112a, CCl3CF3 (CFC-113a, and CCl2FCF3 (CFC-114a

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    M. E. Davis

    2016-07-01

    Full Text Available The potential impact of CCl2FCF3 (CFC-114a and the recently observed CCl2FCCl2F (CFC-112, CCl3CClF2 (CFC-112a, and CCl3CF3 (CFC-113a chlorofluorocarbons (CFCs on stratospheric ozone and climate is presently not well characterized. In this study, the UV absorption spectra of these CFCs were measured between 192.5 and 235 nm over the temperature range 207–323 K. Precise parameterizations of the UV absorption spectra are presented. A 2-D atmospheric model was used to evaluate the CFC atmospheric loss processes, lifetimes, ozone depletion potentials (ODPs, and the associated uncertainty ranges in these metrics due to the kinetic and photochemical uncertainty. The CFCs are primarily removed in the stratosphere by short-wavelength UV photolysis with calculated global annually averaged steady-state lifetimes (years of 63.6 (61.9–64.7, 51.5 (50.0–52.6, 55.4 (54.3–56.3, and 105.3 (102.9–107.4 for CFC-112, CFC-112a, CFC-113a, and CFC-114a, respectively. The range of lifetimes given in parentheses is due to the 2σ uncertainty in the UV absorption spectra and O(1D rate coefficients included in the model calculations. The 2-D model was also used to calculate the CFC ozone depletion potentials (ODPs with values of 0.98, 0.86, 0.73, and 0.72 obtained for CFC-112, CFC-112a, CFC-113a, and CFC-114a, respectively. Using the infrared absorption spectra and lifetimes determined in this work, the CFC global warming potentials (GWPs were estimated to be 4260 (CFC-112, 3330 (CFC-112a, 3650 (CFC-113a, and 6510 (CFC-114a for the 100-year time horizon.

  9. CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer's disease.

    Science.gov (United States)

    Cherry, Jonathan D; Stein, Thor D; Tripodis, Yorghos; Alvarez, Victor E; Huber, Bertrand R; Au, Rhoda; Kiernan, Patrick T; Daneshvar, Daniel H; Mez, Jesse; Solomon, Todd M; Alosco, Michael L; McKee, Ann C

    2017-01-01

    CCL11, a protein previously associated with age-associated cognitive decline, is observed to be increased in the brain and cerebrospinal fluid (CSF) in chronic traumatic encephalopathy (CTE) compared to Alzheimer's disease (AD). Using a cohort of 23 deceased American football players with neuropathologically verified CTE, 50 subjects with neuropathologically diagnosed AD, and 18 non-athlete controls, CCL11 was measured with ELISA in the dorsolateral frontal cortex (DLFC) and CSF. CCL11 levels were significantly increased in the DLFC in subjects with CTE (fold change = 1.234, p football (β = 0.426, p = 0.048) independent of age (β = -0.046, p = 0.824). Preliminary analyses of a subset of subjects with available post-mortem CSF showed a trend for increased CCL11 among individuals with CTE (p = 0.069) mirroring the increase in the DLFC. Furthermore, an association between CSF CCL11 levels and the number of years exposed to football (β = 0.685, p = 0.040) was observed independent of age (β = -0.103, p = 0.716). Finally, a receiver operating characteristic (ROC) curve analysis demonstrated CSF CCL11 accurately distinguished CTE subjects from non-athlete controls and AD subjects (AUC = 0.839, 95% CI 0.62-1.058, p = 0.028). Overall, the current findings provide preliminary evidence that CCL11 may be a novel target for future CTE biomarker studies.

  10. The protective effect of Phoenix dactylifera L. seeds against CCl4-induced hepatotoxicity in rats.

    Science.gov (United States)

    Abdelaziz, Dalia H A; Ali, Sahar A

    2014-08-08

    In traditional Egyptian medicine, Phoenix dactylifera L. (date palm) seeds are listed in folk remedies for the management of diabetes, liver diseases and gastrointestinal disorders. The present study was conducted to investigate the protective effect of Phoenix dactylifera L. seeds aqueous suspension against the chemically-induced hepatic injury in rats. Liver injury was achieved by exposing Wistar rats to CCl4 (10% in olive oil; 0.5 mL/rat; IP) twice a week for 4 weeks. Along with CCl4, aqueous suspensions of raw or roasted Phoenix dactylifera seeds (1.0 g/kg) were administered orally in a daily manner. Our results demonstrated that Phoenix dactylifera seeds significantly improved the CCl4-induced alterations in liver function parameters (AST, ALT, ALP and albumin). Moreover, the CCl4-induced oxidative stress, represented by elevated thiobarbituric acid reactive substance (TBARS), nitric oxide and oxidative DNA damage, was ameliorated by Phoenix dactylifera seeds treatment. In addition, Phoenix dactylifera seeds restored the activities of hepatic antioxidant enzymes (superoxide dismutase and glutathione S-transferase) that were declined after CCl4 treatment. Examination of liver histopathology revealed that Phoenix dactylifera seeds attenuate the incidence of liver lesions (including vacuolization and fibroblast proliferation) triggered by CCl4 intoxication. The Phoenix dactylifera seeds could be a promising candidate for protection against the CCl4-induced liver intoxication, and this hepatoprotective effect might be attributed to the antioxidant and free radical scavenging activities. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway

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    Loïc Maillard

    2014-09-01

    Full Text Available The perpetuation of angiogenesis is involved in certain chronic inflammatory diseases. The accelerated neovascularisation may result from an inflammatory status with a response of both endothelial cells and monocytes to inflammatory mediators such as chemokines. We have previously described in vitro and in vivo the pro-angiogenic effects of the chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES/CCL5. The effects of RANTES/CCL5 may be related to its binding to G protein-coupled receptors and to proteoglycans such as syndecan-1 and -4. The aim of this study was to evaluate the functionality of syndecan-4 as a co-receptor of RANTES/CCL5 by the use of mutated syndecan-4 constructs. Our data demonstrate that site-directed mutations in syndecan-4 modify RANTES/CCL5 biological activities in endothelial cells. The SDC4S179A mutant, associated with an induced protein kinase C (PKCα activation, leads to higher RANTES/CCL5 pro-angiogenic effects, whereas the SDC4L188QQ and the SDC4A198del mutants, leading to lower phosphatidylinositol 4,5-bisphosphate (PIP2 binding or to lower PDZ protein binding respectively, are associated with reduced RANTES/CCL5 cellular effects. Moreover, our data highlight that the intracellular domain of SDC-4 is involved in RANTES/CCL5-induced activation of the PKCα signaling pathway and biological effect. As RANTES/CCL5 is involved in various physiopathological processes, the development of a new therapeutic strategy may be reliant on the mechanism by which RANTES/CCL5 exerts its biological activities, for example by targeting the binding of the chemokine to its proteoglycan receptor.

  12. Variations in CCL3L gene cluster sequence and non-specific gene copy numbers

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    Edberg Jeffrey C

    2010-03-01

    Full Text Available Abstract Background Copy number variations (CNVs of the gene CC chemokine ligand 3-like1 (CCL3L1 have been implicated in HIV-1 susceptibility, but the association has been inconsistent. CCL3L1 shares homology with a cluster of genes localized to chromosome 17q12, namely CCL3, CCL3L2, and, CCL3L3. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the CCL3L1 gene. Findings Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with CCL3L1 and CCL3L3 being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only CCL3L1. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence. Conclusions This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.

  13. Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization

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    Dilektasli AG

    2017-01-01

    Full Text Available Asli Gorek Dilektasli,1 Ezgi Demirdogen Cetinoglu,1 Esra Uzaslan,1 Ferah Budak,2 Funda Coskun,1 Ahmet Ursavas,1 Ilker Ercan,3 Ercument Ege1 1Department of Pulmonary Disesaes, 2Department of Immunology, 3Department of Biostatistics, Uludag University Faculty of Medicine, Bursa, Turkey Introduction: Chemokine (C-C motif ligand 18 (CCL-18 has been shown to be elevated in chronic obstructive pulmonary disease (COPD patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. Materials and methods: Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. Results: Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, P<0.0001. CCL-18 level was significantly correlated with the number of exacerbations (r=0.30, P=0.026, although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL subgroups did not achieve statistical significance (P=0.09. Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92. Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, P<0

  14. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

    Science.gov (United States)

    Mitchell, Duane A; Batich, Kristen A; Gunn, Michael D; Huang, Min-Nung; Sanchez-Perez, Luis; Nair, Smita K; Congdon, Kendra L; Reap, Elizabeth A; Archer, Gary E; Desjardins, Annick; Friedman, Allan H; Friedman, Henry S; Herndon, James E; Coan, April; McLendon, Roger E; Reardon, David A; Vredenburgh, James J; Bigner, Darell D; Sampson, John H

    2015-03-19

    After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.

  15. CCL3 and CCL20-recruited dendritic cells modified by melanoma antigen gene-1 induce anti-tumor immunity against gastric cancer ex vivo and in vivo.

    Science.gov (United States)

    He, Songbing; Wang, Liang; Wu, Yugang; Li, Dechun; Zhang, Yanyun

    2010-04-27

    To investigate whether dendritic cell (DC) precursors, recruited by injection of chemokine ligand 3 (CCL3) and CCL20, induce anti-tumor immunity against gastric cancer induced by a DC vaccine expressing melanoma antigen gene-1 (MAGE-1) ex vivo and in vivo. B6 mice were injected with CCL3 and CCL20 via the tail vein. Freshly isolated F4/80-B220-CD11c+ cells cultured with cytokines were analyzed by phenotype analysis and mixed lymphocyte reaction (MLR). For adenoviral (Ad)-mediated gene transduction, cultured F4/80-B220-CD11c+ cells were incubated with Ad-MAGE-1. Vaccination of stimulated DC induced T lymphocytes. The killing effect of these T cells against gastric carcinoma cells was assayed by MTT. INF-gamma production was determined with an INF-gamma ELISA kit. In the solid tumor and metastases model, DC-based vaccines were used for immunization after challenge with MFC cells. Tumor size, survival of mice, and number of pulmonary metastatic foci were used to assess the therapeutic effect of DC vaccines. F4/80-B220-CD11c+ cell numbers increased after CCL3 and CCL20 injection. Freshly isolated F4/80-B220-CD11c+ cells cultured with cytokines were phenotyically identical to typical DC and gained the capacity to stimulate allogeneic T cells. These DCs were transduced with Ad-MAGE-1, which were prepared for DC vaccines expressing tumor antigen. T lymphocytes stimulated by DCs transduced with Ad-MAGE-1 exhibited specific killing effects on gastric carcinoma cells and produced high levels of INF-gamma ex vivo. In vivo, tumor sizes of the experimental group were much smaller than both the positive control group and the negative control groups (P anti-tumor immunity specific to gastric cancer ex vivo and in vivo. This system may prove to be an efficient strategy for anti-tumor immunotherapy.

  16. The porcine skin associated T-cell homing chemokine CCL27: molecular cloning and mRNA expression in piglets infected experimentally with Staphylococcus hyicus

    DEFF Research Database (Denmark)

    Johnsen, C. K.; Jensen, Annette Nygaard; Ahrens, P.

    2003-01-01

    . In this paper, we report the cloning of porcine CCL27 cDNA and investigation of CCL27 mRNA expression in Staphylococcus hyicus infected piglets. At the protein level, 77 and 74% homology was found to human and mouse CCL27 sequences, respectively. The results of the expression analyses show that CCL27 m...

  17. Chemokine CCL2 and chemokine receptor CCR2 in early active multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Strieter, R M

    2004-01-01

    The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2 have been strongly implicated in disease pathogenesis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on the CCL2-CCR2 axis are scarce in MS. We studied...... the expression of CCR2 on leukocytes in blood and cerebrospinal fluid (CSF) from patients with monosymptomatic optic neuritis and MS, and the concentration of CCL2 in the CSF from these patients. Results were compared with the results in non-inflammatory neurological controls and were correlated with other...... parameters (magnetic resonance imaging and CSF data). Our findings suggest a limited role for CCL2/CCR2 in early active MS....

  18. Local elevation of CCL22: A new trend in immunotherapy (skin model

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    Omer Yahia Elhussein Mohamed

    2016-11-01

    Full Text Available Many evidences supported the suggestion that one of the reasons for the failure of immunosuppressant like Corticosteroides, Calcinurine inhibitors and VitD3 in reestablishing skin immune tolerance is relying on inhibition of CCL22 expression from skin dendritic cells. Inhibition of CCL22 decreases CD4+ CD25+ FoxP3+ regulatory T cells homing to macular area and reduces the suppression capacity of these cells that make a sort of an imbalance between effector and regulatory T cells. Addition of CCL22 into the skin lesion from external sources could change the ratio between effector and regulatory T cells which dramatically alter immune system and reestablish immune tolerance. This action can't be established by the later immunosuppressant (e.g. corticosteroids and calcinurine inhibitors alone which give CCL22 an important role in the treatment of skin autoimmune and graft rejection diseases.

  19. Association of CCR2-CCR5 haplotypes and CCL3L1 copy number with Kawasaki Disease, coronary artery lesions, and IVIG responses in Japanese children.

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    Manju Mamtani

    Full Text Available BACKGROUND: The etiology of Kawasaki Disease (KD is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5 and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL and response to intravenous immunoglobulin (IVIG in Japanese children, who have the highest incidence of KD, is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., four copies was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR=2.25, p=0.004 and OR=6.26, p=0.089, respectively. Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR=0.21, p=0.026 and CAL development (OR=0.44, p=0.071. CONCLUSIONS/SIGNIFICANCE: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.

  20. CCL3 and CCL20-recruited dendritic cells modified by melanoma antigen gene-1 induce anti-tumor immunity against gastric cancer ex vivo and in vivo

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    Zhang Yanyun

    2010-04-01

    Full Text Available Abstract Background To investigate whether dendritic cell (DC precursors, recruited by injection of chemokine ligand 3 (CCL3 and CCL20, induce anti-tumor immunity against gastric cancer induced by a DC vaccine expressing melanoma antigen gene-1 (MAGE-1 ex vivo and in vivo. Methods B6 mice were injected with CCL3 and CCL20 via the tail vein. Freshly isolated F4/80-B220-CD11c+ cells cultured with cytokines were analyzed by phenotype analysis and mixed lymphocyte reaction (MLR. For adenoviral (Ad-mediated gene transduction, cultured F4/80-B220-CD11c+ cells were incubated with Ad-MAGE-1. Vaccination of stimulated DC induced T lymphocytes. The killing effect of these T cells against gastric carcinoma cells was assayed by MTT. INF-γ production was determined with an INF-γ ELISA kit. In the solid tumor and metastases model, DC-based vaccines were used for immunization after challenge with MFC cells. Tumor size, survival of mice, and number of pulmonary metastatic foci were used to assess the therapeutic effect of DC vaccines. Results F4/80-B220-CD11c+ cell numbers increased after CCL3 and CCL20 injection. Freshly isolated F4/80-B220-CD11c+ cells cultured with cytokines were phenotyically identical to typical DC and gained the capacity to stimulate allogeneic T cells. These DCs were transduced with Ad-MAGE-1, which were prepared for DC vaccines expressing tumor antigen. T lymphocytes stimulated by DCs transduced with Ad-MAGE-1 exhibited specific killing effects on gastric carcinoma cells and produced high levels of INF-γ ex vivo. In vivo, tumor sizes of the experimental group were much smaller than both the positive control group and the negative control groups (P P Conclusions CCL3 and CCL20-recruited DCs modified by adenovirus-trasnsduced, tumor-associated antigen, MAGE-1, can stimulate anti-tumor immunity specific to gastric cancer ex vivo and in vivo. This system may prove to be an efficient strategy for anti-tumor immunotherapy.

  1. BACTERIAL CLEARANCE IN SEPTIC MICE IS MODULATED BY MCP-1/CCL2 AND NITRIC OXIDE

    Science.gov (United States)

    Gomes, Rachel N.; Teixeira-Cunha, Mariana G. A.; Figueiredo, Rodrigo T.; Almeida, Patricia E.; Alves, Silvio C.; Bozza, Patrícia T.; Bozza, Fernando A.; Bozza, Marcelo T.; Zimmerman, Guy A.; Castro-Faria-Neto, Hugo C.

    2013-01-01

    Bacterial clearance is one of the most important beneficial consequences of the innate immune response. Chemokines are important mediators controlling leukocyte trafficking and activation, whereas reactive oxygen and nitrogen species are effectors in bacterial killing. In the present work, we used in vivo and in vitro models of infections to study the role of monocyte chemoattractant protein 1 (MCP-1)/CCL2 and nitric oxide (NO) in the bacterial clearance in sepsis. Our results show that MCP-1/CCL2 and NO levels are increased in the peritoneal cavity of mice 6 h after sepsis induced by cecal ligation and puncture. Pretreatment with anti–MCP-1/CCL2 monoclonal antibodies increased the number of colony-forming units (CFUs) recovered in the peritoneal lavage fluid. Moreover, CFU counts were increased in the peritoneal fluid of CCR2−/− mice subjected to cecal ligation and puncture. In vitro stimulation of peritoneal macrophages with recombinant MCP-1/CCL2 reduced CFU counts in the supernatant after challenge with Escherichia coli. Conversely, treatment with anti–MCP-1/CCL2 increased CFU counts under the same experimental condition. Stimulation of cultured macrophages with MCP-1/CCL2 and interferon had a synergistic effect on NO production. Macrophages from CCL2−/− mice showed a consistent decrease in NO production when compared with wild-type controls after stimulation with LPS + interferon. Finally, we showed incubation of macrophages with E. coli, and the ERK inhibitor U0126 increased CFU numbers and decreased intracellular levels of NO. In conclusion, we demonstrated for the first time that MCP-1/CCL2 has a crucial role in the clearance of bacteria by mechanisms involving increased expression of inducible NO synthase and production of NO by ERK signaling pathways. PMID:23247123

  2. Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

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    Kuznitzky Raquel

    2004-04-01

    Full Text Available Abstract Background Expression of murine CCL21 by dermal lymphatic endothelial cells (LEC has been demonstrated to be one of the most important steps in Langerhans cell emigration from skin. Previously, our group and others have found that this chemokine is up-regulated in different human inflammatory skin diseases mediated by diverse specific immune responses. This study was carried out to investigate the involvement of CCL21 in human skin after challenge with irritant agents responsible for inducing Irritant Contact Dermatitis (ICD. Results Eleven normal individuals were challenged with different chemical or physical irritants. Two patients with Allergic Contact Dermatitis (ACD were also challenged with the relevant antigen in order to have a positive control for CCL21 expression. Macroscopic as well as microscopic responses were evaluated. We observed typical ICD responses with mostly mononuclear cells in perivascular areas, but a predominance of polymorphonuclear cells away from the inflamed blood vessels and in the epidermis at 24 hours. Immunohistochemical studies showed up-regulation of CCL21 by lymphatic endothelial cells in all the biopsies taken from ICD and ACD lesions compared to normal skin. Kinetic study at 10, 48, 96 and 168 hours after contact with a classical irritant (sodium lauryl sulphate showed that the expression of CCL21 was increased in lymphatic vessels at 10 hours, peaked at 48 hours, and then gradually declined. There was a strong correlation between CCL21 expression and the macroscopic response (r = 0.69; p = 0.0008, but not between CCL21 and the number of infiltrating cells in the lesions. Conclusions These results provide new evidence for the role of CCL21 in inflammatory processes. Since the up-regulation of this chemokine was observed in ICD and ACD, it is tempting to speculate that this mechanism operates independently of the type of dermal insult, facilitating the emigration of CCR7+ cells.

  3. CCL2-ethanol interactions and hippocampal synaptic protein expression in a transgenic mouse model

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    Donna eGruol

    2014-04-01

    Full Text Available Chronic exposure to ethanol produces a number of detrimental effects on behavior. Neuroadaptive changes in brain structure or function underlie these behavioral changes and may be transient or persistent in nature. Central to the functional changes are alterations in the biology of neuronal and glial cells of the brain. Recent data show that ethanol induces glial cells of the brain to produce elevated levels of neuroimmune factors including CCL2, a key innate immune chemokine. Depending on the conditions of ethanol exposure, the upregulated levels of CCL2 can be transient or persistent and outlast the period of ethanol exposure. Importantly, results indicate that the upregulated levels of CCL2 may lead to CCL2-ethanol interactions that mediate or regulate the effects of ethanol on the brain. Glial cells are in close association with neurons and regulate many neuronal functions. Therefore, effects of ethanol on glial cells may underlie some of the effects of ethanol on neurons. To investigate this possibility, we are studying the effects of chronic ethanol on hippocampal synaptic function in a transgenic mouse model that expresses elevated levels of CCL2 in the brain through enhanced glial expression, a situation know to occur in alcoholics. Both CCL2 and ethanol have been reported to alter synaptic function in the hippocampus. In the current study, we determined if interactions are evident between CCL2 and ethanol at level of hippocampal synaptic proteins. Two ethanol exposure paradigms were used; the first involved ethanol exposure by drinking and the second involved ethanol exposure in a paradigm that combines drinking plus ethanol vapor. The first paradigm does not produce dependence on ethanol, whereas the second paradigm is commonly used to produce ethanol dependence. Results show modest effects of both ethanol exposure paradigms on the level of synaptic proteins in the hippocampus of CCL2 transgenic mice compared with their non

  4. CCL5 rs2107538 Polymorphism Increased the Risk of Tuberculosis in a Sample of Iranian Population

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    Hamid Reza Kouhpayeh

    2016-01-01

    Full Text Available Cysteine-cysteine chemokine ligand 5 (CCL5 with immunoregulatory and inflammatory activities has an important role in granuloma formations that activates and stimulates T-cells and macrophages. Cysteine-cysteine chemokine receptor 5 (CCR5 is a chemokine receptor, which is important for migration of immune cells to site of infection. In the present study we investigated the possible association between CCL5 –403G/A (rs2107538, CCL5 –28C/G (rs2280788 and CCR5 Δ32 polymorphisms and pulmonary tuberculosis (PTB in an Iranian population. This case-control study was performed on 160 patients with pulmonary tuberculosis and 160 unrelated healthy subjects. The CCL5 –403G/A, CCL5 –28C/G and CCR5 Δ32 polymorphisms were genotyped by allele-specific polymerase chain reaction (AS-PCR, tetra amplification refractory mutation system polymerase chain reaction (T-ARMS PCR and PCR, respectively. Our results showed that GA as well as GA+AA genotypes of CCL5 –403G/A (rs2107538 increased the risk of PTB in comparison with GG genotype (OR=1.70, 95% CI=1.03–2.81, P=0.038 and OR=1.64, 95% CI=1.00–2.68, P=0.049, respectively. No significant association was found between CCL5 –28C/G as well as CCR5 Δ32 polymorphism and PTB risk. In conclusion, our findings proposed that CCL5 –403G>A polymorphism may be a risk factor for susceptibility to PTB in our population. Larger sample sizes with different ethnicities are required to validate our findings.

  5. Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats.

    Science.gov (United States)

    Eidi, Akram; Mortazavi, Pejman; Moghadam, Jalal Zarringhalam; Mardani, Parisa Mousavi

    2015-07-01

    Purslane (Portulaca oleracea L., Portulacaceae) has been traditionally used in folk medicine to afford protection against liver injury, although its actual efficacy remains uncertain. To evaluate purslane as a hepatoprotective agent, we investigated the protective effect of its ethanol extract against carbon tetrachloride (CCl4)-induced hepatic toxicity in rats. A total of 108 male Wistar rats were randomly divided into 12 groups. The first group was maintained as normal control, whereas CCl4 (0.5 ml/kg bw, 50% CCl4 in olive oil, i.p.), purslane extract (0.005, 0.01, 0.05, 0.1, and 0.15 g/kg bw, intragastrically), and purslane extract (five doses as above) along with CCl4 were administered to the Groups II, III-VII, and VIII-XII, respectively. The rats were sacrificed on the 30th day, and blood was withdrawn by cardiac puncture. Liver damage was assessed by measuring hepatic marker enzymes (ALT, AST, ALP, GGT, and SOD) and histopathological observation. Treatment with CCl4 resulted in increased serum activities of marker enzymes with a concomitant decrease in SOD. Histological alterations were also observed in the liver tissue upon CCl4 treatment. Administration of purslane extract (0.01, 0.05, 0.1, and 0.15 g/kg b.w.) significantly showed a marked tendency towards normalization of all measured biochemical parameters in CCl4-treated rats. Histopathological changes also paralleled the detected alteration in markers of liver function. These results demonstrate that purslane exerts protective effects against CCl4-induced damage in rat liver and supports a potential therapeutic use of purslane as an alternative for patients with liver diseases.

  6. Restorative effect of Eclipta alba in CCl4 induced hepatotoxicity in male albino rats

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    T Thirumalai

    2011-12-01

    Full Text Available Objective: To elucidate the restorative effect of the aqueous leaf extract (85% of the traditional medicinal plant Eclipta alba (E. alba against CCl4 induced hepatotoxicity in male albino rats. Methods: Restorative activity was assessed using CCl4-induced hepatic injury in rats by monitoring biochemical parameters. Biochemical markers of hepatic damage such as aspartate transaminase (AST, alanine transaminase (ALT and alkaline phosphatase (ALP were assessed in serum. The oxidative stress was evaluated by measuring the levels of thiobarbutric acid reactive substance (TBARS, hydroperoxides, activity levels of enzymes viz. superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPX and glutathione-s-transferase (GST in hepatic tissue. Results: CCl 4 and olive oil mixture (1:1 dosage of 1 mL/kg b.w. induced oxidative stress was indicated by elevated levels of TBARS and hydroperoxides, and augmented levels of serum AST, ALT and ALP. The depleted activity levels of antioxidant enzymes such as SOD, CAT, GPX and GST were found in CCl 4 induced animals. The aqueous leaf extract of E. alba (250 mg/kg b.w. ameliorated the effects of CCl 4 and returned the alter levels of the biochemical markers near to the normal levels. Conclusions: The study indicates that aqueous leaf extract of E. alba has potential restorative effect on CCl4 induced hepatotoxicity in male albino rats.

  7. Chlorination of uranium oxides with CCl4 using a mechanochemical method

    Science.gov (United States)

    Kitawaki, Shinichi; Nagai, Takayuki; Sato, Nobuaki

    2013-08-01

    A chlorination method for uranium oxides at low temperature was investigated by using a mechanochemical method. In particular, the possibility of the chlorination of uranium oxides, such as UO2 and U3O8, via mechanochemical reaction with CCl4 was studied using a planetary ball mill. Mechanochemical experiments were conducted to evaluate the effect of milling time, CCl4/uranium oxide molar ratio, and revolution speed on the reaction. The synthesized products were then subjected to X-ray diffraction analysis, and it was found that the chlorination of U3O8 with CCl4 to UOCl2, UCl4, and U2O2Cl5 proceeded. However, the chlorination reaction could not be observed when using UO2 powder as the raw material. The chlorination reaction could not be observed when using UO2 powder as the raw material. The chlorination of U3O8 with CCl4 to form UOCl2, UCl4, and U2O2Cl5 via mechanochemical reaction occurs at room temperature. The ratio of chlorination increases with milling time when the appropriate amount of CCl4 is employed. However, the use of excess liquid CCl4 decreases the mechanochemical effect.

  8. Transgenic mice with increased astrocyte expression of CCL2 show altered behavioral effects of alcohol.

    Science.gov (United States)

    Bray, Jennifer G; Roberts, Amanda J; Gruol, Donna L

    2017-06-23

    Emerging research provides strong evidence that activation of CNS glial cells occurs in neurological diseases and brain injury and results in elevated production of neuroimmune factors. These factors can contribute to pathophysiological processes that lead to altered CNS function. Recently, studies have also shown that both acute and chronic alcohol consumption can produce activation of CNS glial cells and the production of neuroimmune factors, particularly the chemokine ligand 2 (CCL2). The consequences of alcohol-induced increases in CCL2 levels in the CNS have yet to be fully elucidated. Our studies focus on the hypothesis that increased levels of CCL2 in the CNS produce neuroadaptive changes that modify the actions of alcohol on the CNS. We utilized behavioral testing in transgenic mice that express elevated levels of CCL2 to test this hypothesis. The increased level of CCL2 in the transgenic mice involves increased astrocyte expression. Transgenic mice and their non-transgenic littermate controls were subjected to one of two alcohol exposure paradigms, a two-bottle choice alcohol drinking procedure that does not produce alcohol dependence or a chronic intermittent alcohol procedure that produces alcohol dependence. Several behavioral tests were carried out including the Barnes maze, Y-maze, cued and contextual conditioned fear test, light-dark transfer, and forced swim test. Comparisons between alcohol naïve, non-dependent, and alcohol-dependent CCL2 transgenic and non-transgenic mice show that elevated levels of CCL2 in the CNS interact with alcohol in tests for alcohol drinking, spatial learning, and associative learning. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. STRATIGRAPHIC CONTROL ON CCL4 AND CHCL3 CONCENTRATIONS IN THE 200 WEST AREA, HANFORD SITE

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    Winsor, K.; Last, G.V.

    2008-01-01

    An extensive subsurface contaminant plume of carbon tetrachloride (CCl4) is the focus of a remedial effort in the 200 West Area of the U.S. Department of Energy’s Hanford Site in eastern Washington. Remediation requires a high-resolution understanding of the region’s spatially variable lithofacies and of the effect these lithofacies have on CCl4 migration through the unconfi ned aquifer. To increase the level of detail of our current understanding, a transect was chosen along the primary groundwater fl ow path in the most heavily contaminated area. Borehole logs of wells along this 3.7 km-long transect were standardized and used to create a cross section displaying the depth and continuity of lithofacies. Natural and spectral gamma geophysical logs were examined to pinpoint the depths of geologic units. Depth discrete concentrations of CCl4 and its reductive dechlorination product, chloroform (CHCl3), were overlain on this cross section. Comparison of stratigraphy to contaminant levels shows that peaks in CCl4 concentration occur in thin, fine-grained layers and that other fine-grained layers frequently form lower boundaries to regions of high concentration. Peaks in CCl4 concentrations are frequently located at different depths from those of CHCl3, suggesting that these concentrations are affected by dechlorination of CCl4. Transformation of CCl4 to CHCl3 appears to be more prevalent within reduced, iron-containing sediments. The infl uence of thin, fine-grained layers within the larger aquifer unit indicates that characterization of contamination in this locality should consider subsurface geology with at least as much resolution as provided in this study.

  10. Chitin elicits CCL2 from airway epithelial cells and induces CCR2-dependent innate allergic inflammation in the lung

    Science.gov (United States)

    Roy, René M.; Wüthrich, Marcel; Klein, Bruce S.

    2012-01-01

    Chitin exposure in the lung induces eosinophilia and alternative activation of macrophages, and is correlated with allergic airway disease. However, the mechanism underlying chitin-induced polarization of macrophages is poorly understood. Here, we show that chitin induces alternative activation of macrophages in vivo, but does not do so directly in vitro. We further show that airway epithelial cells bind chitin in vitro and produce CCL2 in response to chitin both in vitro and in vivo. Supernatants of chitin exposed epithelial cells promoted alternative activation of macrophages in vitro, whereas antibody neutralization of CCL2 in the supernate abolished the alternative activation of macrophages. CCL2 acted redundantly in vivo, but mice lacking the CCL2 receptor, CCR2, showed impaired alternative activation of macrophages in response to chitin, as measured by arginase I, CCL17 and CCL22 expression. Furthermore, CCR2KO mice exposed to chitin had diminished ROS products in the lung, blunted eosinophil and monocyte recruitment, and impaired eosinophil functions as measured by expression of CCL5, IL13 and CCL11. Thus, airway epithelial cells secrete CCL2 in response to chitin and CCR2 signaling mediates chitin-induced alternative activation of macrophages and allergic inflammation in vivo. PMID:22851704

  11. Semen lactoferrin promotes CCL20 production by epithelial cells: Involvement in HIV transmission

    Science.gov (United States)

    Lourenço, Alan Grupioni; Komesu, Marilena Chinalli; Machado, Alcyone Artioli; Quintana, Silvana Maria; Bourlet, Thomas; Pozzetto, Bruno; Delézay, Olivier

    2014-01-01

    AIM: To study the effect of seminal plasma on Chemokine (C-C motif) ligand 20 (CCL20) production by epithelial cells and its relationship with lactoferrin. METHODS: HEC-1A cells, a cell line derived from a monostratified endocervical epithelium, were incubated with samples of seminal plasma (diluted 1:10 in culture medium) recovered from human immunodeficiency virus (HIV) seronegative (HIV-) or HIV seropositive (HIV+) subjects. Recombinant human interleukin 1 beta (IL-1β) was used as positive control, and culture medium only as negative control. The measurement of CCL20 production in the supernatants of HEC-1A cells and of lactoferrin in seminal plasma was determined by enzyme-linked immunosorbent assay techniques. A fractionation of seminal plasma proteins was performed by ion exchange chromatography on a pool of seminal plasma specimens from HIV- subjects. Each fraction was tested for its ability to stimulate the production of CCL20 by HEC-1A cells and for its lactoferrin concentration. The HIV viral load in seminal plasma samples from HIV+ patients was measured using the HIV-Monitor kit (Roche Diagnostic Systems, Branchburg, NJ, United States). RESULTS: The positive control IL-1β was responsible for an increase of 11.36 ± 3.36 times in the production of CCL20. Stimulation of HEC-1A cells was performed in 34 seminal plasma samples (22 from HIV+ subjects and 12 from HIV- subjects). The mean production of CCL20 by HEC-1A in presence of seminal plasma from HIV- and HIV+ subjects was respectively 5.38 ± 0.91 and 7.57 ± 3.26 times higher than that obtained with the untreated cells (P < 0.05 between the two groups). Using the same 34 specimens of seminal plasma, no correlation was observed between the concentration of total proteins in seminal plasma and their ability to stimulate the secretion of CCL20 by HEC-1 cells. In contrast, the ability to produce CCL20 by HEC-1A cells correlated to the concentration of lactoferrin in the seminal plasma samples (r

  12. CCL2/MCP-1 modulation of microglial activation and proliferation

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    Garcia-Bueno Borja

    2011-07-01

    Full Text Available Abstract Background Monocyte chemoattractant protein (CCL2/MCP-1 is a chemokine that attracts cells involved in the immune/inflammatory response. As microglia are one of the main cell types sustaining inflammation in brain, we proposed here to analyze the direct effects of MCP-1 on cultured primary microglia. Methods Primary microglia and neuronal cultures were obtained from neonatal and embryonic Wistar rats, respectively. Microglia were incubated with different concentrations of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring incorporation of bromodeoxyuridine (BrdU. Nitrite accumulation was measured using the Griess assay. The expression and synthesis of different proteins was measured by RT-PCR and ELISA. Cell death was quantified by measuring release of LDH into the culture medium. Results MCP-1 treatment (50 ng/ml, 24 h did not induce morphological changes in microglial cultures. Protein and mRNA levels of different cytokines were measured, showing that MCP-1 was not able to induce proinflammatory cytokines (IL-1β, IL6, MIP-1α, either by itself or in combination with LPS. A similar lack of effect was observed when measuring inducible nitric oxide synthase (NOS2 expression or accumulation of nitrites in the culture media as a different indicator of microglial activation. MCP-1 was also unable to alter the expression of different trophic factors that were reduced by LPS treatment. In order to explore the possible release of other products by microglia and their potential neurotoxicity, neurons were co-cultured with microglia: no death of neurons could be detected when treated with MCP-1. However, the presence of MCP-1 induced proliferation of microglia, an effect opposite to that observed with LPS. Conclusion These data indicate that, while causing migration and proliferation of microglia, MCP-1 does not appear to directly activate an inflammatory response in this cell type, and therefore, other factors may be

  13. A single acute hepatotoxic dose of CCl4 causes oxidative stress in the rat brain

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    K.R. Ritesh

    2015-01-01

    Full Text Available Carbon tetrachloride (CCl4, a hepatotoxic agent is widely used to study the toxic mechanisms in experimental animals. We have investigated whether oxidative stress is induced in the brain at a single hepatotoxic dosage (1 ml/kg bw of CCl4. Increased lipid peroxidation (LPO, protein carbonyls (PC content and glutathione (GSH depletion were observed in the brain regions of rats treated with CCl4 which was higher than that of liver. A drastic reduction in the activity of glutathione-S-transferase (GST was seen in the brain regions which was higher than that of liver. Similarly, activities of glutathione peroxidase (GPx, glutathione reductase (GR, superoxide dismutase (SOD, catalase (CAT, NADH- and NADPH-dehydrogenase were reduced in the brain regions similar to that of liver. Higher induction of oxidative stress in the brain compared to that of liver implies vulnerability of the brain for CCl4 neurotoxicity. Our study shows that a single hepatotoxic dose of CCl4 is equally neurotoxic to rats.

  14. Efficacy of Hibiscus sabdariffa and Telfairia occidentalis in the attenuation of CCl4-mediated oxidative stress.

    Science.gov (United States)

    Victor, Ikpeme Ekei; Ugorji, Udensi Ogbuagu; Adeyinka, Adetayo

    2014-09-01

    To assess the efficacy of Hibiscus sabdariffa (H. sabdariffa) and Telfairia occidentalis (T. occidentalis) extracts in the attenuation of CCl4-mediated oxidative stress. Seventy-two healthy matured male albino rats weighing between (120±20) g were divided into 6 groups (A-F) in a 2×6 factorial experiment using completely randomized design. Rats in Group A received only water, B received 1 mL/kg CCl4, C received 300 mg/kg, D received 600 mg/kg, E received CCl4+300 mg/kg while F received CCl4+600 mg/kg for each of the extract, respectively. Semen from epididymes was obtained for sperm analysis while blood was obtained through cardiac puncture for biochemical analysis, after the treatment regimen. Our results showed that CCl4 induction elevated aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total protein, globulin levels significantly (Psabdariffa and T. occidentalis extracts at the doses of 300 and 600 mg/kg caused the reversal of these effects significantly. Implicitly, the implication of our results is that H. sabdariffa and T. occidentalis extracts might be ted and optimized for the management of oxidative stress-related organ injuries, including infertility, though further researches are needed. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  15. Drinking of Salvia officinalis tea increases CCl(4)-induced hepatotoxicity in mice.

    Science.gov (United States)

    Lima, Cristovao F; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

    2007-03-01

    In a previous study, the drinking of a Salvia officinalis tea (prepared as an infusion) for 14 days improved liver antioxidant status in mice and rats where, among other factors, an enhancement of glutathione-S-transferase (GST) activity was observed. Taking in consideration these effects, in the present study the potential protective effects of sage tea drinking against a situation of hepatotoxicity due to free radical formation, such as that caused by carbon tetrachloride (CCl(4)), were evaluated in mice of both genders. Contrary to what was expected, sage tea drinking significantly increased the CCl(4)-induced liver injury, as seen by increased plasma transaminase levels and histology liver damage. In accordance with the previous study, sage tea drinking enhanced significantly GST activity. Additionally, glutathione peroxidase was also significantly increased by sage tea drinking. Since CCl(4) toxicity results from its bioactivation mainly by cytochrome P450 (CYP) 2E1, the expression level of this protein was measured by Western Blot. An increase in CYP 2E1 protein was observed which may explain, at least in part, the potentiation of CCl(4)-induced hepatotoxicity conferred by sage tea drinking. The CCl(4)-induced hepatotoxicity was higher in females than males. In conclusion, our results indicate that, although sage tea did not have toxic effects of its own, herb-drug interactions are possible and may affect the efficacy and safety of concurrent medical therapy with drugs that are metabolized by phase I enzymes.

  16. Inhibitory effect of TCCE on CCl4-induced overexpression of IL-6 in acute liver injury.

    Science.gov (United States)

    Gao, Jing; Dou, Huan; Tang, Xin-Hui; Xu, Li-Zhi; Fan, Yi-Mei; Zhao, Xiao-Ning

    2004-11-01

    Terminalia catappa L. leaves have been shown to protect against acute liver injury produced by some hepatotoxicants, but the active components and mechanisms are not clear. This study was designed to characterize the protective effects of the chloroform fraction of the ethanol extract of T. catappa leaves (TCCE) against carbon tetrachloride (CCl4)-induced hepatotoxicity in mice, and analyze the changes in expression level of interleukin-6 (IL-6) in the process. It was found that TCCE pretreatment (10 or 30 mg/kg, ig) protected mice from CCl4 toxicity, as evidenced by the reversed alterations in serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) activities. Additionally liver tissues were subjected to RT-PCR, Western blot and immunohistochemistry to analyze changes in IL-6 expression. It was found that TCCE markedly suppressed the CCl4-induced over-transcription of IL-6 gene. Consistent with the result, the expression of IL-6 protein was also blocked by TCCE in CCl4-stimulated mice, especially in the area around central vein on liver tissue section. In conclusion, TCCE is effective in protecting mice from the hepatotoxicity produced by CCl4, and the mechanisms underlying its protective effects may be related to the inhibition on the overexpression of IL-6 mainly around terminal hepatic vein.

  17. CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of neurocognitive dysfunction.

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    Tomomi Kiyota

    2009-07-01

    Full Text Available The linkages between neuroinflammation and Alzheimer's disease (AD pathogenesis are well established. What is not, however, is how specific immune pathways and proteins affect the disease. To this end, we previously demonstrated that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a Swedish beta-amyloid (Abeta precursor protein mutant.We now report that CCL2 transgene expression accelerates deficits in spatial and working memory and hippocampal synaptic transmission in beta-amyloid precursor protein (APP mice as early as 2-3 months of age. This is followed by increased numbers of microglia that are seen surrounding Abeta oligomers. CCL2 does not suppress Abeta degradation. Rather, CCL2 and tumor necrosis factor-alpha directly facilitated Abeta uptake, intracellular Abeta oligomerization, and protein secretion.We posit that CCL2 facilitates Abeta oligomer formation in microglia and propose that such events accelerate memory dysfunction by affecting Abeta seeding in the brain.

  18. The essential oil of Artemisia capillaris protects against CCl4-induced liver injury in vivo

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    Qinghan Gao

    Full Text Available Abstract To study the hepatoprotective effect of the essential oil of Artemisia capillaris Thunb., Asteraceae, on CCl4-induced liver injury in mice, the levels of serum aspartate aminotransferase and alanine aminotransferase, hepatic levels of reduced glutathione, activity of glutathione peroxidase, and the activities of superoxide dismutase and malondialdehyde were assayed. Administration of the essential oil of A. capillaris at 100 and 50 mg/kg to mice prior to CCl4 injection was shown to confer stronger in vivo protective effects and could observably antagonize the CCl4-induced increase in the serum alanine aminotransferase and aspartate aminotransferase activities and malondialdehyde levels as well as prevent CCl4-induced decrease in the antioxidant superoxide dismutase activity, glutathione level and glutathione peroxidase activity (p < 0.01. The oil mainly contained β-citronellol, 1,8-cineole, camphor, linalool, α-pinene, β-pinene, thymol and myrcene. This finding demonstrates that the essential oil of A. capillaris can protect hepatic function against CCl4-induced liver injury in mice.

  19. Theoretical study of CCl(4) adsorption and hydrogenation on a Pt (111) surface.

    Science.gov (United States)

    Lu, Guiwu; Lan, Jianhui; Li, Chunxi; Wang, Wenchuan; Wang, Chunlei

    2006-12-07

    The adsorption and hydrogenation of carbon tetrachloride (CCl(4)) on a Pt (111) surface have been investigated using density functional theory (DFT). We have performed calculations on the adsorption energies and structures of CCl(4) on four different adsorption sites of a Pt (111) surface using the full adsorbate geometry optimization method. The results show that the adsorption energy of all of the potential sites is less than -17 kcal/mol, which indicates that CCl(4) is physiosorbed on a Pt (111) surface through van der Waals interactions. The dissociation and hydrogenation pathways were investigated by a transition state search. For the Pt(15), Pt(19), and Pt(25) cluster surfaces, the activation energies of dissociation obtained in this work are 15.69, 16.94, and 16.77 kcal/mol, respectively. The hydrogenation of CCl(3). was studied at the on-top site of the Pt(15) cluster, and the calculated activation energy is 5.06 kcal/mol. The small activation energies indicate that the Pt (111) surface has high catalytic activity for the CCl(4) hydrogenation reaction. In addition, the Hirshfeld population analysis reveals that the charge transfer from the Pt (111) surface to the adsorbates occurs in both the dissociation and hydrogenation pathways.

  20. Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

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    Ping-Chun Li

    2012-01-01

    Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

  1. Pistacia chinensis: A Potent Ameliorator of CCl4 Induced Lung and Thyroid Toxicity in Rat Model

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    Kiran Naz

    2014-01-01

    Full Text Available In the current study protective effect of ethanol extract of Pistacia chinensis bark (PCEB was investigated in rats against CCl4 induced lung and thyroid injuries. PCEB dose dependently inhibited the rise of thiobarbituric acid-reactive substances, hydrogen peroxide, nitrite, and protein content and restored the levels of antioxidant enzymes, that is, catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, γ-glutamyl transpeptidase, and quinone reductase in both lung and thyroid tissues of CCl4 treated rats. Decrease in number of leukocytes, neutrophils, and hemoglobin and T3 and T4 content as well as increase in monocytes, eosinophils, and lymphocytes count with CCl4 were restored to normal level with PCEB treatment. Histological study of CCl4 treated rats showed various lung injuries like rupture of alveolar walls and bronchioles, aggregation of fibroblasts, and disorganized Clara cells. Similarly, histology of CCl4 treated thyroid tissues displayed damaged thyroid follicles, hypertrophy, and colloidal depletion. However, PCEB exhibited protective behaviour for lungs and thyroid, with improved histological structure in a dose dependant manner. Presence of three known phenolic compounds, that is, rutin, tannin, and gallic acid, and three unknown compounds was verified in thin layer chromatographic assessment of PCEB. In conclusion, P. chinensis exhibited antioxidant activity by the presence of free radical quenching constituents.

  2. Chlorination of uranium oxides with CCl4 using a mechanochemical method

    International Nuclear Information System (INIS)

    Kitawaki, Shinichi; Nagai, Takayuki; Sato, Nobuaki

    2013-01-01

    Highlights: • UCl 4 or UOCl 2 could be synthesized from U 3 O 8 with CCl 4 by using a planetary ball mill. • The chlorination could not be observed when using UO 2 powder as the starting material. • Extension of milling time was effective for chlorinating U 3 O 8 with the appropriate amount of CCl 4 . -- Abstract: A chlorination method for uranium oxides at low temperature was investigated by using a mechanochemical method. In particular, the possibility of the chlorination of uranium oxides, such as UO 2 and U 3 O 8 , via mechanochemical reaction with CCl 4 was studied using a planetary ball mill. Mechanochemical experiments were conducted to evaluate the effect of milling time, CCl 4 /uranium oxide molar ratio, and revolution speed on the reaction. The synthesized products were then subjected to X-ray diffraction analysis, and it was found that the chlorination of U 3 O 8 with CCl 4 to UOCl 2 , UCl 4 , and U 2 O 2 Cl 5 proceeded. However, the chlorination reaction could not be observed when using UO 2 powder as the raw material

  3. Chlorination of uranium oxides with CCl{sub 4} using a mechanochemical method

    Energy Technology Data Exchange (ETDEWEB)

    Kitawaki, Shinichi, E-mail: kitawaki.shinichi@jaea.go.jp [Nuclear Fuel Cycle Engineering Laboratories, Japan Atomic Energy Agency, 4-33 Muramatsu, Tokai, Naka, Ibaraki 319-1194 (Japan); Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba, Sendai, Miyagi 980-8577 (Japan); Nagai, Takayuki [Nuclear Fuel Cycle Engineering Laboratories, Japan Atomic Energy Agency, 4-33 Muramatsu, Tokai, Naka, Ibaraki 319-1194 (Japan); Sato, Nobuaki [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba, Sendai, Miyagi 980-8577 (Japan)

    2013-08-15

    Highlights: • UCl{sub 4} or UOCl{sub 2} could be synthesized from U{sub 3}O{sub 8} with CCl{sub 4} by using a planetary ball mill. • The chlorination could not be observed when using UO{sub 2} powder as the starting material. • Extension of milling time was effective for chlorinating U{sub 3}O{sub 8} with the appropriate amount of CCl{sub 4}. -- Abstract: A chlorination method for uranium oxides at low temperature was investigated by using a mechanochemical method. In particular, the possibility of the chlorination of uranium oxides, such as UO{sub 2} and U{sub 3}O{sub 8}, via mechanochemical reaction with CCl{sub 4} was studied using a planetary ball mill. Mechanochemical experiments were conducted to evaluate the effect of milling time, CCl{sub 4}/uranium oxide molar ratio, and revolution speed on the reaction. The synthesized products were then subjected to X-ray diffraction analysis, and it was found that the chlorination of U{sub 3}O{sub 8} with CCl{sub 4} to UOCl{sub 2}, UCl{sub 4}, and U{sub 2}O{sub 2}Cl{sub 5} proceeded. However, the chlorination reaction could not be observed when using UO{sub 2} powder as the raw material.

  4. CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance

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    Milton-Omar Guzmán-Ornelas

    2016-01-01

    Full Text Available Genetic susceptibility has been described in insulin resistance (IR. Chemokine (C-C motif ligand-2 (CCL2 is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2. The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2, metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.. Phenotype carriers CCL2 (A+ displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+ phenotype. The double-polymorphic phenotype carriers (A+/Ile+ exhibited higher sCCL2 than double-wild-type phenotype carriers (A−/Ile−. The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.

  5. Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.

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    Erickson, Michelle A; Morofuji, Yoichi; Owen, Joshua B; Banks, William A

    2014-06-01

    Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

  6. Protective effects of Launaea procumbens on rat testis damage by CCl4

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    Khan Rahmat

    2012-08-01

    Full Text Available Abstract Background Traditionally various human diseases of kidneys, hormonal imbalance and sexual diseases are treated with Launaea procumbens (L. In the present study protective effects of methanolic extract of Launaea procumbens (LPME was evaluated against CCl4-induced oxidative damages in rat testis. Methods To examine the protective effects of Launaea procumbens on testis against oxidative stress of carbon tetrachloride in male rat, 30 male albino rats were equally divided into 5 groups (6 rats. First group was given standard diet and drinking water. Second group received CCl4 3 ml/kg intraperitoneally (30% in olive oil. Third and forth were given orally 100; 200 mg/kg b.w., in 99.8% dimethyl sulphooxide (DMSO, Launaea procumbens methanolic extracts (LPME after 48 h of CCl4 treatment twice a week and sixth group received only LPME in DMSO at a dose of 200 mg/kg b.w., for four weeks. Protective effects of Launaea procumbens were observed on sperm concentration, motility and morphology, serum reproductive hormonal level, activity of antioxidant enzymes, lipid peroxidation (TBARS and DNA damages. Results Results of the present study revealed that treatment of CCl4 significantly (p  reduced sperm concentration and motility comparatively to controls. Level of testosterone, luteinizing hormone and follicle stimulating hormone, were depleted markedly (p with treatment of CCl4. In addition, CCl4 induction in rats reduced activities of antioxidant enzymes while increased lipid peroxidation and DNA damages. Co-administration of LPME significantly (p improved these alterations in improving of hormonal level, activities of antioxidant enzymes and lipid peroxidation near to control rats. Conclusion From the results it is suggested that Launaea procumbens methanolic extract has the ability to protect testis against oxidative damages, possibly through antioxidant effects of its bioactive compounds.

  7. Rhinovirus-bacteria coexposure synergistically induces CCL20 production from human bronchial epithelial cells.

    Science.gov (United States)

    Maciejewski, Barbara A; Jamieson, Kyla C; Arnason, Jason W; Kooi, Cora; Wiehler, Shahina; Traves, Suzanne L; Leigh, Richard; Proud, David

    2017-05-01

    Exacerbations of chronic obstructive pulmonary disease are triggered by viral or bacterial pathogens, with human rhinovirus (HRV) and nontypeable Hemophilus influenzae (NTHI) among the most commonly detected pathogens. Patients who suffer from concomitant viral and bacterial infection have more severe exacerbations. The airway epithelial cell is the initial site of viral and bacterial interactions, and CCL20 is an epithelial chemokine that attracts immature dendritic cells to the airways and can act as an antimicrobial. As such, it contributes to innate and adaptive immune responses to infection. We used primary cultures of human bronchial epithelial cells and the BEAS-2B cell line to examine the effects of bacterial-viral coexposure, as well as each stimulus alone, on epithelial expression of CXCL8 and, in particular, CCL20. HRV-bacterial coexposure induced synergistic production of CXCL8 and CCL20 compared with the sum of each stimulus alone. Synergistic induction of CCL20 did not require viral replication and occurred with two different HRV serotypes that use different viral receptors. Synergy was also seen with either NTHI or Pseudomonas aeruginosa Synergistic induction of CCL20 was transcriptionally regulated. Although NF-κB was required for transcription, it did not regulate synergy, but NF-IL-6 did appear to contribute. Among MAPK inhibitors studied, neither SB203580 nor PD98059 had any effect on synergy, whereas U0126 prevented synergistic induction of CCL20 by HRV and bacteria, apparently via "off-target" effects. Thus bacterial-viral coexposure synergistically increases innate immune responses compared with individual infections. We speculate that this increased inflammatory response leads to worse clinical outcomes. Copyright © 2017 the American Physiological Society.

  8. CCl4 distribution derived from MIPAS ESA v7 data: intercomparisons, trend, and lifetime estimation

    Science.gov (United States)

    Valeri, Massimo; Barbara, Flavio; Boone, Chris; Ceccherini, Simone; Gai, Marco; Maucher, Guido; Raspollini, Piera; Ridolfi, Marco; Sgheri, Luca; Wetzel, Gerald; Zoppetti, Nicola

    2017-08-01

    Atmospheric emissions of carbon tetrachloride (CCl4) are regulated by the Montreal Protocol due to its role as a strong ozone-depleting substance. The molecule has been the subject of recent increased interest as a consequence of the so-called mystery of CCl4, the discrepancy between atmospheric observations and reported production and consumption. Surface measurements of CCl4 atmospheric concentrations have declined at a rate almost 3 times lower than its lifetime-limited rate, suggesting persistent atmospheric emissions despite the ban. In this paper, we study CCl4 vertical and zonal distributions in the upper troposphere and lower stratosphere (including the photolytic loss region, 70-20 hPa), its trend, and its stratospheric lifetime using measurements from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS), which operated onboard the ENVISAT satellite from 2002 to 2012. Specifically, we use the MIPAS data product generated with Version 7 of the Level 2 algorithm operated by the European Space Agency.The CCl4 zonal means show features typical of long-lived species of anthropogenic origin that are destroyed primarily in the stratosphere, with larger quantities in the troposphere and a monotonic decrease with increasing altitude in the stratosphere. MIPAS CCl4 measurements have been compared with independent measurements from other satellite and balloon-borne remote sounders, showing a good agreement between the different datasets.CCl4 trends are calculated as a function of both latitude and altitude. Negative trends of about text">-10 to -15 pptv decade-1 (-10 to -30 % decade-1) are found at all latitudes in the upper troposphere-lower stratosphere region, apart from a region in the southern midlatitudes between 50 and 10 hPa where the trend is positive with values around 5-10 pptv decade-1 (15-20 % decade-1). At the lowest altitudes sounded by MIPAS, we find trends consistent with those determined on the basis of long-term ground

  9. Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis

    Directory of Open Access Journals (Sweden)

    Luzia Maria de-Oliveira-Pinto

    2012-02-01

    Full Text Available Dengue virus (DENV and parvovirus B19 (B19V infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL-1 receptor antagonist (Ra, CXCL10/inducible protein-10 (IP-10, CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1 were determined by multiplex immunoassay in serum samples obtained from B19V (37 and DENV-infected (36 patients and from healthy individuals (7. Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1β, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

  10. Ab Initio Theoretical Studies on the Kinetics of Hydrogen Abstraction Type Reactions of Hydroxyl Radicals with CH3CCl2F and CH3CClF2

    Science.gov (United States)

    Saheb, Vahid; Maleki, Samira

    2018-03-01

    The hydrogen abstraction reactions from CH3Cl2F (R-141b) and CH3CClF2 (R-142b) by OH radicals are studied theoretically by semi-classical transition state theory. The stationary points for the reactions are located by using KMLYP density functional method along with 6-311++G(2 d,2 p) basis set and MP2 method along with 6-311+G( d, p) basis set. Single-point energy calculations are performed by the CBS-Q and G4 combination methods on the geometries optimized at the KMLYP/6-311++G(2 d,2 p) level of theory. Vibrational anharmonicity coefficients, x ij , which are needed for semi-classical transition state theory calculations, are computed at the KMLYP/6-311++G(2 d,2 p) and MP2/6-311+G( d, p) levels of theory. The computed barrier heights are slightly sensitive to the quantum-chemical method. Thermal rate coefficients are computed over the temperature range from 200 to 2000 K and they are shown to be in accordance with available experimental data. On the basis of the computed rate coefficients, the tropospheric lifetime of the CH3CCl2F and CH3CClF2 are estimated to be about 6.5 and 12.0 years, respectively.

  11. Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients...

  12. Transgenic mouse model harboring the transcriptional fusion ccl20-luciferase as a novel reporter of pro-inflammatory response.

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    Martina Crispo

    Full Text Available The chemokine CCL20, the unique ligand of CCR6 functions as an attractant of immune cells. Expression of CCL20 is induced by Toll-like Receptor (TLR signaling or proinflammatory cytokine stimulation. However CCL20 is also constitutively produced at specific epithelial sites of mucosa. This expression profile is achieved by transcriptional regulation. In the present work we characterized regulatory features of mouse Ccl20 gene. Transcriptional fusions between the mouse Ccl20 promoter and the firefly luciferase (luc encoding gene were constructed and assessed in in vitro and in vivo assays. We found that liver CCL20 expression and luciferase activity were upregulated by systemic administration of the TLR5 agonist flagellin. Using shRNA and dominant negative form specific for mouse TLR5, we showed that this expression was controlled by TLR5. To address in situ the regulation of gene activity, a transgenic mouse line harboring a functional Ccl20-luc fusion was generated. The luciferase expression was highly concordant with Ccl20 expression in different tissues. Our data indicate that the transgenic mouse model can be used to monitor activation of innate response in vivo.

  13. Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria.

    LENUS (Irish Health Repository)

    Sibartie, Shomik

    2009-01-01

    BACKGROUND: Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-kappaB activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-kappaB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-kappaB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis-induced CCL20 secretion. CONCLUSION: This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens.

  14. A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.

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    Kristi Huik

    Full Text Available The role of CC chemokine receptor 5 (CCR5 and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID from Estonia.Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% co-infected. Four CCL5 haplotypes (A-D were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789 typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis.Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40, which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29. An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively compared to those who did not possess these haplotypes, respectively.Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV.

  15. Misbalanced CXCL12 and CCL5 Chemotactic Signals in Vitiligo Onset and Progression.

    Science.gov (United States)

    Rezk, Ahmed F; Kemp, Daria Marley; El-Domyati, Moetaz; El-Din, Wael Hosam; Lee, Jason B; Uitto, Jouni; Igoucheva, Olga; Alexeev, Vitali

    2017-05-01

    Generalized nonsegmental vitiligo is often associated with the activation of melanocyte-specific autoimmunity. Because chemokines play an important role in the maintenance of immune responses, we examined chemotactic signatures in cultured vitiligo melanocytes and skin samples of early (≤2 months) and advanced (≥6 months) vitiligo. Analysis showed that melanocytes in early lesions have altered expression of several chemotaxis-associated molecules, including elevated secretion of CXCL12 and CCL5. Higher levels of these chemokines coincided with prominent infiltration of the skin with antigen presenting cells (APCs) and T cells. Most of the intralesional APCs expressed the CD86 maturation marker and co-localized with T cells, particularly in early vitiligo lesions. These observations were confirmed by in vivo animal studies showing preferential recruitment of APCs and T cells to CXCL12- and CCL5-expressing transplanted melanocytes, immunotargeting of the chemokine-positive cells, continuous loss of the pigment-producing cells from the epidermis, and development of vitiligo-like lesions. Taken together, our studies show that melanocyte-derived CXCL12 and CCL5 support APC and T-cell recruitment, antigen acquisition, and T-cell activation in early vitiligo and reinforce the role of melanocyte-derived CXCL12 and CCL5 in activation of melanocyte-specific immunity and suggest inhibition of these chemotactic axes as a strategy for vitiligo stabilization. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Serum amyloid P down-regulates CCL-1 expression, and inhibits ...

    African Journals Online (AJOL)

    MAPK pathway in the development of breast cancer (BC) via regulation of chemokine (CC motif) ligand 1 (CCL-1). Methods: Breast cancer (BC) and metastasis models were established using SAP-Tg transgenic mice and WT C57BL/6 mice.

  17. Effect of extracts from araticum (Annona crassiflora on CCl4-induced liver damage in rats

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    Roberta Roesler

    2011-03-01

    Full Text Available The influence of ethanolic extracts of Annona crassiflora on the activities of hepatic antioxidant enzymes was examined. Extracts of A. crassiflora seeds and peel were administered orally (50 mg of galic acid equivalents.kg-1 to Wistar rats for 14 consecutive days followed by a single oral dose of carbon tetrachloride (CCl4, 2 g.kg-1. Lipid peroxidation and the activities of hepatic catalase (CAT, cytochromes P450 (CP450 and b5, glutathione peroxidase (GPx, glutathione reductase (GRed, superoxide dismutase (SOD, and the content of glutathione equivalents (GSH were evaluated. The treatment with CCl4 increased lipid peroxidation, the level of GSH equivalents and the content of cytochrome b5 by 44, 140 and 32%, respectively, with concomitant reductions of 23, 34 and 39% in the activities of CAT, SOD, and CP450, respectively. The treatment with A. crassiflora seeds and peel extracts alone inhibited lipid peroxidation by 27 and 22%, respectively without affecting the CP450 content. The pretreatment with the A. crassiflora extracts prevented the lipid peroxidation, the increase in GSH equivalents and the decrease in CAT activity caused by CCl4, but it had no effect on the CCl4-mediated changes in CP450 and b5 and SOD. These results show that A. crassiflora seeds and peel contain antioxidant activity in vivo that could be of potential therapeutic use.

  18. Potent hepatoprotective effect in CCl4-induced hepatic injury in mice of phloroacetophenone from Myrcia multiflora

    Science.gov (United States)

    Ferreira, Eduardo Antonio; Gris, Eliana Fortes; Felipe, Karina Bettega; Correia, João Francisco Gomes; Cargnin-Ferreira, Eduardo; Wilhelm Filho, Danilo; Pedrosa, Rozangela Curi

    2010-01-01

    Background This study investigated the hepatoprotective effect and antioxidant properties of phloroacetophenone (2′,4′,6′-trihydroxyacetophenone – THA), an acetophenone derived from the plant Myrcia multiflora. Material & Method The free radical scavenging activity in vitro and induction of oxidative hepatic damage by carbon tetrachloride (CCl4) (0.5 ml/kg, i.p.) were tested in male Swiss mice (25±5 g). Results This compound exhibited in vitro antioxidant effects on FeCl2–ascorbate-induced lipid peroxidation (LPO) in mouse liver homogenate, scavenging hydroxyl and superoxide radicals, and 2,2-diphenyl-1-picrylhydrazyl. The in vivo assays showed that THA significantly (pthese observations, THA pre-treatment normalized the activities of antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, and increased the levels of reduced glutathione (GSH) in CCl4-treated mice. In addition, THA treatment significantly prevented the elevation of serum enzymatic activities of alanine amino transferase, aspartate amino transferase, and lactate dehydrogenase, as well as histological alterations induced by CCl4. Silymarin (SIL) (24 mg/kg), a known hepatoprotective drug used for comparison, led to a significant decrease (ptheses enzymes in way very similar to that observed in pre-treatment with THA. Conclusion These results suggest that the protective effects are due to reduction of oxidative damage induced by CCl4 resulting from the antioxidant properties of THA. PMID:21483585

  19. Association of CCL11 promoter polymorphisms with schizophrenia in a Korean population.

    Science.gov (United States)

    Kang, Won Sub; Kim, Young Jong; Park, Hae Jeong; Kim, Su Kang; Paik, Jong-Woo; Kim, Jong Woo

    2018-05-20

    Immunological alterations and dysregulation of the inflammatory response have been suggested to play a crucial role in schizophrenia pathophysiology. Growing evidence supports the involvement of chemokines in brain development, thus many chemokines have been studied in relation with schizophrenia. The C-C motif chemokine ligand 11 (CCL11) has been shown to be related with synaptic plasticity and neurogenesis. Moreover, altered levels of CCL11 have been observed in schizophrenia patients. Therefore, we examined whether single nucleotide polymorphisms (SNPs) of the CCL11 in the promoter region contribute to susceptibility to schizophrenia. Four promoter SNPs [rs17809012 (-384T>C), rs16969415 (-426C>T), rs17735961 (-488C>A), and rs4795896 (576G>A)] were genotyped in 254 schizophrenia patients and 405 control subjects using Fluidigm SNPtype assays. The genotype frequency of CCL11 rs4795896 (-576G>A) showed significant association with schizophrenia in a recessive model (AA vs. GG/AG, p schizophrenia (p schizophrenia (p = 0.0044, p schizophrenia in a Korean population. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Antioxidant and protective effect of inulin and catechin grafted inulin against CCl4-induced liver injury.

    Science.gov (United States)

    Liu, Jun; Lu, Jian-feng; Wen, Xiao-yuan; Kan, Juan; Jin, Chang-hai

    2015-01-01

    In this study, the antioxidant activity and hepatoprotective effect of inulin and catechin grafted inulin (catechin-g-inulin) against carbon tetrachloride (CCl4)-induced acute liver injury were investigated. Results showed that both inulin and catechin-g-inulin had moderate scavenging activity on superoxide radical, hydroxyl radical and H2O2, as well as lipid peroxidation inhibition effect. The antioxidant activity decreased in the order of Vc > catechin >catechin-g-inulin > inulin. Administration of inulin and catechin-g-inulin could significantly reduce the elevated levels of serum aspartate transaminase, alanine transaminase and alkaline phosphatase as compared to CCl4 treatment group. Moreover, inulin and catechin-g-inulin significantly increased the levels of hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione and total antioxidant capacity, whereas markedly decreased the malondialdehyde level when compared with CCl4 treatment group. Notably, catechin-g-inulin showed higher hepatoprotective effect than inulin. In addition, the hepatoprotective effect of catechin-g-inulin was comparable to positive standard of silymarin. Our results suggested that catechin-g-inulin had potent antioxidant activity and potential protective effect against CCl4-induced acute liver injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Plasma chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis

    NARCIS (Netherlands)

    Boot, Rolf G.; Hollak, Carla E. M.; Verhoek, Marri; Alberts, C.; Jonkers, René E.; Aerts, Johannes M.

    2010-01-01

    BACKGROUND: Accumulation of macrophages in multiple organs is a common feature of sarcoidosis and Gaucher disease. The vast number of storage macrophages in Gaucher patients has facilitated the discovery of suitable plasma markers like chitotriosidase and CCL18. METHODS: Plasma specimens of patients

  2. Functional role of CCL5/RANTES for HCC progression during chronic liver disease

    NARCIS (Netherlands)

    Mohs, Antje; Kuttkat, Nadine; Reissing, Johanna; Zimmermann, Henning Wolfgang; Sonntag, Roland; Proudfoot, Amanda; Youssef, Sameh A.; de Bruin, Alain; Cubero, Francisco Javier; Trautwein, Christian

    Background & Aims: During liver inflammation, triggering fibrogenesis and carcinogenesis immune cells play a pivotal role. In the present study we investigated the role of CCL5 in human and in murine models of chronic liver inflammation leading to hepatocellular carcinoma (HCC) development. Methods:

  3. Hepatoprotection of emodin and Polygonum multiflorum against CCl(4)-induced liver injury.

    Science.gov (United States)

    Lee, Bao-Hong; Huang, Ya-Yin; Duh, Pin-Der; Wu, She-Ching

    2012-03-01

    Polygonum multiflorum is known as a medicinal plant. It has been used as a folk medicine which showed antioxidative property. Protective effects of the water extracts (w/v:1/10) from fresh P. multiflorum (WEP) on carbon tetrachloride (CCl(4))-induced liver damage in rats were investigated. CCl(4) was used for inducing liver damage of SD rats, and WEP and emodin were fed for eight consecutive weeks. We found that emodin levels in fresh WEP was higher than that in ripening WEP. Rats were administered WEP and emodin, the main active compound, for 56 consecutive days. WEP significantly lowered the serum levels of hepatic enzyme markers, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and reduced the generation of malonaldehyde. Treatment with WEP recovered glutathione S-transferase and catalase activity in rats as compared to treatment with CCl(4) alone. In addition, serum tumor necrosis factor-α, an inflammatory marker, was found to decrease in rats treated with WEP. In histopathological evaluation, fatty degeneration and necrosis were found to be significantly decreased in the CCl(4) plus WEP treatment group. WEP may be effective in attenuating liver damage by reducing lipid peroxidation as well as by positively modulating inflammation.

  4. Hepatoprotective activity of Mentha arvensis Linn. leaves against CCL4 induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Kalpana Patil

    2012-05-01

    Full Text Available Objective: To study the Hepatoprotective activity of ethanol, chloroform and aqueous extracts of Mentha arvensis leaves against CCL4 induced liver damage in rats. Methods: Hepatotoxicity was induced by CCL4 and the biochemical parameters such as serum glutamate pyruvate transminase (sGPT, serum glutamate oxaloacetate transaminase (sGOT, alkaline phosphatase (sALP, serum bilirubin (sB and histopathological changes in liver were studied along with silymarin as standard Hepatoprotective agents. Results: The Phytochemical investigation of the extracts showed presence of flavonoids, steroids, triterpenoids, alkaloids, glycosides, carbohydrates, tannins, phenolic compounds. Treatment of the rats with chloroform, ethanol and aqueous extract with CCL 4 administration caused a significant reduction in the values of sGOT, sGPT, sALP and sB (P<0.01 almost comparable to the silymarin. The Hepatoprotective was confirmed by histopathological examination of the liver tissue of control and treated animals. Conclusions: From the results it can be concluded that Mentha arvensis possesses Hepatoprotective effect against CCL4 induced liver damage in rats.

  5. Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat

    Directory of Open Access Journals (Sweden)

    Khan Rahmat A

    2011-06-01

    Full Text Available Abstract Background Carissa opaca (Apocynaceae leaves possess antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative in hepatic disorders. The effect produced by methanolic extract of Carissa opaca leaves (MCL was investigated on CCl4-induced liver damages in rat. Methods 30 rats were divided into five groups of six animals of each, having free access to food and water ad libitum. Group I (control was given olive oil and DMSO, while group II, III and IV were injected intraperitoneally with CCl4 (0.5 ml/kg as a 20% (v/v solution in olive oil twice a week for 8 weeks. Animals of group II received only CCl4. Rats of group III were given MCL intragastrically at a dose of 200 mg/kg bw while that of group IV received silymarin at a dose of 50 mg/kg bw twice a week for 8 weeks. However, animals of group V received MCL only at a dose of 200 mg/kg bw twice a week for 8 weeks. The activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP, lactate dehydrogenase (LDH and γ-glutamyltransferase (γ-GT were determined in serum. Catalase (CAT, peroxidase (POD, superoxide dismutase (SOD, glutathione-S-transferase (GST, glutathione peroxidase (GSH-Px, glutathione reductase (GSR and quinone reductase (QR activity was measured in liver homogenates. Lipid peroxidation (thiobarbituric acid reactive substances; TBARS, glutathione (GSH and hydrogen peroxide (H2O2 concentration was also assessed in liver homogenates. Phytochemicals in MCL were determined through qualitative and high performance liquid chromatography (HPLC analysis. Results Hepatotoxicity induced with CCl4 was evidenced by significant increase in lipid peroxidation (TBARS and H2O2 level, serum activities of AST, ALT, ALP, LDH and γ-GT. Level of GSH determined in liver was significantly reduced, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GSR, GST and QR. On cirrhotic animals treated with

  6. Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons.

    Science.gov (United States)

    Huang, Chung-Yu; Chen, Ying-Ling; Li, Allen H; Lu, Juu-Chin; Wang, Hung-Li

    2014-01-10

    Several lines of evidence suggest that CCL2 could initiate the hyperalgesia of neuropathic pain by causing central sensitization of spinal dorsal horn neurons and facilitating nociceptive transmission in the spinal dorsal horn. The cellular and molecular mechanisms by which CCL2 enhances spinal pain transmission and causes hyperalgesia remain unknown. The substantia gelatinosa (lamina II) of the spinal dorsal horn plays a critical role in nociceptive transmission. An activated spinal microglia, which is believed to release pro-inflammatory cytokines including TNF-α, plays an important role in the development of neuropathic pain, and CCL2 is a key mediator for spinal microglia activation. In the present study, we tested the hypothesis that spinal CCL2 causes the central sensitization of substantia gelatinosa neurons and enhances spinal nociceptive transmission by activating the spinal microglia and augmenting glutamatergic transmission in lamina II neurons. CCL2 was intrathecally administered to 2-month-old male rats. An intrathecal injection of CCL2 induced heat hyperalgesia, which was assessed using the hot plate test. Whole-cell voltage-clamp recordings substantia gelatinosa neurons in spinal cord slices were performed to record glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs). The hot plate test showed that 1 day after the intrathecal injection of CCL2 (1 μg), the latency of hind-paw withdrawal caused by a heat stimulus was significantly reduced in rats. One day after the intrathecal administration of CCL2, the amplitude of the evoked glutamatergic EPSCs and the frequency of spontaneous glutamatergic miniature EPSCs (mEPSCs) were significantly increased in outer lamina II neurons. Intrathecal co-injection of minocycline, a specific inhibitor of microglial activation, and CCL2 blocked the CCL2-induced reduction in the latency of hind-paw withdrawal and thermal hyperalgesia. Following intrathecal co

  7. Protective effect of Cucurbita pepo fruit peel against CCl4 induced neurotoxicity in rat.

    Science.gov (United States)

    Zaib, Sania; Khan, Muhammad Rashid

    2014-11-01

    Cucurbita pepo is a common vegetable used all over the world. In folk medicine it is used in gastroenteritis, hepatorenal and in brain anomalies. In the present study, protective effect of Cucurbita pepo fruit peel against CCl4-induced neurotoxicity in rats was investigated. In this study, 36 Sprague-Dawley female rats (190±15 g) were randomly divided into 6 groups of 6 rats each. Group I was given 1 ml/kg bw (body weight) of corn oil intraperotoneally (i.p); Group II, III and IV were treated with 20% CCl4 in corn oil (1ml/kg bw i.p.). However, animals of Group III and IV were also treated with CPME (methanol extract of C. pepo fruit peel) at 200 and 400mg/kg bw respectively. Animals of Group V and VI were administered only with CPME at 200 and 400mg/kg bw respectively. These treatments were administered 3 days a week for two weeks. Administration of CCl4 cause acute neurotoxicity as depicted by significant depletion (p<0.05) in the activities of antioxidant enzymes; catalase, superoxide dismutase, peroxidase, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, quinone reductase, while enhanced the γ-glutamyl transferase level in brain samples. CCl4 intoxication decreased the reduced glutathione (GSH) level whereas markedly (p<0.05) enhanced lipid peroxidation in brain samples. Co-treatment of CPME significantly (p<0.05) protected the brain tissues against CCl4 constituted injuries by restoring activities of antioxidant enzymes and ameliorated lipid peroxidation in a dose dependent fashion. These neuroprotective effects might be due to the presence of antioxidant constituents.

  8. Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats

    Directory of Open Access Journals (Sweden)

    Das Mahasweta

    2011-10-01

    Full Text Available Abstract Background Traumatic brain injury (TBI evokes a systemic immune response including leukocyte migration into the brain and release of pro-inflammatory cytokines; however, the mechanisms underlying TBI pathogenesis and protection are poorly understood. Due to the high incidence of head trauma in the sports field, battlefield and automobile accidents identification of the molecular signals involved in TBI progression is critical for the development of novel therapeutics. Methods In this report, we used a rat lateral fluid percussion impact (LFPI model of TBI to characterize neurodegeneration, apoptosis and alterations in pro-inflammatory mediators at two time points within the secondary injury phase. Brain histopathology was evaluated by fluoro-jade (FJ staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL assay, polymerase chain reaction (qRT PCR, enzyme linked immunosorbent assay (ELISA and immunohistochemistry were employed to evaluate the CCL20 gene expression in different tissues. Results Histological analysis of neurodegeneration by FJ staining showed mild injury in the cerebral cortex, hippocampus and thalamus. TUNEL staining confirmed the presence of apoptotic cells and CD11b+ microglia indicated initiation of an inflammatory reaction leading to secondary damage in these areas. Analysis of spleen mRNA by PCR microarray of an inflammation panel led to the identification of CCL20 as an important pro-inflammatory signal upregulated 24 h after TBI. Although, CCL20 expression was observed in spleen and thymus after 24h of TBI, it was not expressed in degenerating cortex or hippocampal neurons until 48 h after insult. Splenectomy partially but significantly decreased the CCL20 expression in brain tissues. Conclusion These results demonstrate that the systemic inflammatory reaction to TBI starts earlier than the local brain response and suggest that spleen- and/ or thymus-derived CCL20 might play a role in

  9. CCL5–Glutamate Cross-Talk in Astrocyte-Neuron Communication in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Anna Pittaluga

    2017-09-01

    Full Text Available The immune system (IS and the central nervous system (CNS are functionally coupled, and a large number of endogenous molecules (i.e., the chemokines for the IS and the classic neurotransmitters for the CNS are shared in common between the two systems. These interactions are key elements for the elucidation of the pathogenesis of central inflammatory diseases. In recent years, evidence has been provided supporting the role of chemokines as modulators of central neurotransmission. It is the case of the chemokines CCL2 and CXCL12 that control pre- and/or post-synaptically the chemical transmission. This article aims to review the functional cross-talk linking another endogenous pro-inflammatory factor released by glial cells, i.e., the chemokine Regulated upon Activation Normal T-cell Expressed and Secreted (CCL5 and the principal neurotransmitter in CNS (i.e., glutamate in physiological and pathological conditions. In particular, the review discusses preclinical data concerning the role of CCL5 as a modulator of central glutamatergic transmission in healthy and demyelinating disorders. The CCL5-mediated control of glutamate release at chemical synapses could be relevant either to the onset of psychiatric symptoms that often accompany the development of multiple sclerosis (MS, but also it might indirectly give a rationale for the progression of inflammation and demyelination. The impact of disease-modifying therapies for the cure of MS on the endogenous availability of CCL5 in CNS will be also summarized. We apologize in advance for omission in our coverage of the existing literature.

  10. Effects of MgCl2 supplementation on blood parameters and kidney injury of rats exposed to CCl4

    Directory of Open Access Journals (Sweden)

    Mbarki Sakhria

    2016-01-01

    Full Text Available The purpose of this study was to evaluate the beneficial effects of magnesium (Mg supplementation upon carbon tetrachloride (CCl4 toxicity. Our study was carried out on 24 Wistar male rats divided into 4 batches. During a 6 week period, one group served as a control, two groups received Mg (after 4 weeks one of these groups was then treated with CCl4, and a final group was treated with CCl4 only. Under our experimental conditions, CCl4 poisoning resulted in oxidative stress indicated by a significant increase in lipid peroxidation level in renal tissues. The blood levels of creatinine and urea increased while the blood level of uric acid and proteins decreased. CCl4 also induced an increase in superoxide dismutase (SOD and glutathione peroxidase (GPX activity in kidneys, in the number of red blood cells (RBC, and in hemoglobin content (Hb and mean cell hemoglobin concentration (MCHC. However, white blood cell count (WBC, platelet count (Pl and catalase activity (CAT all decreased significantly. Treatment with Mg was found to alleviate most of CCl4-induced damage by decreasing lipid peroxidation and by correcting changed hematological parameters, and catalase, glutathione peroxidase and superoxide-dismutase activities. The results provide strong evidence that Mg supplementation is beneficial in protecting the kidneys from CCl4 toxicity.

  11. Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria.

    Directory of Open Access Journals (Sweden)

    Kyler B Pallister

    Full Text Available In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis.

  12. Prevention of carbon tetrachloride (CCl4)-induced toxicity in testes of rats treated with Physalis peruviana L. fruit.

    Science.gov (United States)

    Abdel Moneim, Ahmed E

    2016-06-01

    Treatment of rats with carbon tetrachloride (CCl4; 2 ml/kg body weight) once a week for 12 weeks caused a significant decrease in serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. These decreases in sex hormones were reduced with Physalis peruviana L. (Cape gooseberry) juice supplementation. In addition, testicular activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase suppressed with CCl4 were elevated after P. peruviana juice supplements. P. peruviana juice supplementation significantly increased the testicular glutathione and significantly decreased the level of lipid peroxidation and the nitric oxide production compared with the CCl4 group. In addition, the decline in the activity of antioxidant enzymes after CCl4 was ameliorated by P. peruviana Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl4 injections were prevented with the supplementation of P. peruviana juice. Furthermore, P. peruviana juice attenuated CCl4-induced apoptosis in testes tissue by inhibition of caspase-3 activity. The results clearly demonstrate that P. peruviana juice augments the antioxidants defense mechanism against CCl4-induced reproductive toxicity and provides evidence that the juice may have a therapeutic role in free radical-mediated diseases and infertility. © The Author(s) 2014.

  13. CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer’s disease

    Science.gov (United States)

    Stein, Thor D.; Tripodis, Yorghos; Alvarez, Victor E.; Huber, Bertrand R.; Au, Rhoda; Kiernan, Patrick T.; Daneshvar, Daniel H.; Mez, Jesse; Solomon, Todd M.; Alosco, Michael L.; McKee, Ann C.

    2017-01-01

    CCL11, a protein previously associated with age-associated cognitive decline, is observed to be increased in the brain and cerebrospinal fluid (CSF) in chronic traumatic encephalopathy (CTE) compared to Alzheimer’s disease (AD). Using a cohort of 23 deceased American football players with neuropathologically verified CTE, 50 subjects with neuropathologically diagnosed AD, and 18 non-athlete controls, CCL11 was measured with ELISA in the dorsolateral frontal cortex (DLFC) and CSF. CCL11 levels were significantly increased in the DLFC in subjects with CTE (fold change = 1.234, p football (β = 0.426, p = 0.048) independent of age (β = -0.046, p = 0.824). Preliminary analyses of a subset of subjects with available post-mortem CSF showed a trend for increased CCL11 among individuals with CTE (p = 0.069) mirroring the increase in the DLFC. Furthermore, an association between CSF CCL11 levels and the number of years exposed to football (β = 0.685, p = 0.040) was observed independent of age (β = -0.103, p = 0.716). Finally, a receiver operating characteristic (ROC) curve analysis demonstrated CSF CCL11 accurately distinguished CTE subjects from non-athlete controls and AD subjects (AUC = 0.839, 95% CI 0.62–1.058, p = 0.028). Overall, the current findings provide preliminary evidence that CCL11 may be a novel target for future CTE biomarker studies. PMID:28950005

  14. High CCL27 immunoreactivity in 'supratumoral' epidermis correlates with better prognosis in patients with cutaneous malignant melanoma.

    Science.gov (United States)

    Martinez-Rodriguez, Miguel; Thompson, Alec K; Monteagudo, Carlos

    2017-01-01

    It has been proposed that the expression of chemokines and chemokine receptors by melanoma cells may have a role in tumour immune escape. Chemokine CCL27 is reported to be expressed specifically on the epidermal keratinocytes. The implication of CCL27 in cutaneous melanomas is currently unresolved. It has been suggested that CCL27 expression in melanomas can induce antitumoral immunity, and that CCL27 may suppress tumour growth probably due to the local lymphocyte recruitment. We studied CCL27 chemokine expression in three different concentric epidermal areas covering the primary cutaneous melanoma in patients with a long clinical follow-up. Our study included 91 cases of primary melanomas of the skin diagnosed during the 10-year period 1992-2002, and a minimum clinical follow-up of 10 years. We evaluated three different concentric and easily reproducible areas in the epidermis: the area covering melanoma (which we called 'supratumoral'), the area adjacent to the tumour ('peritumoral') and the most peripheral epidermal area ('peripheral'). Only CCL27 expression in supratumoral epidermis correlated with clinical outcome. Our study showed that a higher immunostaining of CCL27 in supratumoral epidermis is associated with longer progression-free interval and melanoma-specific survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. CCL5 promotes proliferation of MCF-7 cells through mTOR-dependent mRNA translation

    Energy Technology Data Exchange (ETDEWEB)

    Murooka, Thomas T.; Rahbar, Ramtin [Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Ont. (Canada); Department of Immunology, University of Toronto, Ont. (Canada); Fish, Eleanor N., E-mail: en.fish@utoronto.ca [Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Ont. (Canada); Department of Immunology, University of Toronto, Ont. (Canada)

    2009-09-18

    The proliferative capacity of cancer cells is regulated by factors intrinsic to cancer cells and by secreted factors in the microenvironment. Here, we investigated the proto-oncogenic potential of the chemokine receptor, CCR5, in MCF-7 breast cancer cell lines. At physiological levels, CCL5, a ligand for CCR5, enhanced MCF-7.CCR5 proliferation. Treatment with the mTOR inhibitor, rapamycin, inhibited this CCL5-inducible proliferation. Because mTOR directly modulates mRNA translation, we investigated whether CCL5 activation of CCR5 leads to increased translation. CCL5 induced the formation of the eIF4F translation initiation complex through an mTOR-dependent process. Indeed, CCL5 initiated mRNA translation, shown by an increase in high-molecular-weight polysomes. Specifically, we show that CCL5 mediated a rapid up-regulation of protein expression for cyclin D1, c-Myc and Dad-1, without affecting their mRNA levels. Taken together, we describe a mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs, thereby providing CCR5-positive breast cancer cells with a proliferative advantage.

  16. Estrogen-dependent regulation of human uterine natural killer cells promotes vascular remodelling via secretion of CCL2.

    Science.gov (United States)

    Gibson, D A; Greaves, E; Critchley, H O D; Saunders, P T K

    2015-06-01

    Does intrauterine biosynthesis of estrogen play an important role in early pregnancy by altering the function of uterine natural killer (uNK) cells? Estrogens directly regulate the function of human uNK cells by increasing uNK cell migration and secretion of uNK cell-derived chemokine (C-C motif) ligand 2 (CCL2) that critically facilitates uNK-mediated angiogenesis. uNK cells are a phenotypically distinct population of tissue-resident immune cells that regulate vascular remodelling within the endometrium and decidua. Recently we discovered that decidualisation of human endometrial stromal cells results in the generation of an estrogen-rich microenvironment in areas of decidualised endometrium. We hypothesize that intrauterine biosynthesis of estrogens plays an important role in early pregnancy by altering the function of uNK cells. This laboratory-based study used primary human uNK cells which were isolated from first trimester human decidua (n = 32). Primary uNK cells were isolated from first trimester human decidua using magnetic cell sorting. The impact of estrogens on uNK cell function was assessed. Isolated uNK cells were treated with estrone (E1, 10(-8) M) or estradiol (E2, 10(-8) M) alone or in combination with the anti-estrogen ICI 182 780 (ICI, 10(-6) M). uNK cell motility was assessed by transwell migration assay and time-lapse microscopy. Expression of chemokine receptors was assessed by quantitative PCR (qPCR) and immunohistochemistry, and angiogenic factors were assessed by qPCR and cytokine array. Concentrations of CCL2 in supernatants were measured by enzyme-linked immunosorbent assay. Angiogenesis was assessed in a human endometrial endothelial cell network formation assay. Treatment with either E1 or E2 increased uNK cell migration (P = 0.0092 and P = 0.0063, respectively) compared with control. Co-administration of the anti-estrogen ICI blocked the effects of E1 and E2 on cell migration. Concentrations of C-X-C chemokine receptor type 4 (CXCR4) m

  17. Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion.

    Science.gov (United States)

    Sun, Chan; Zhang, Yuan-Yuan; Tang, Chuan-Ling; Wang, Song-Cun; Piao, Hai-Lan; Tao, Yu; Zhu, Rui; Du, Mei-Rong; Li, Da-Jin

    2013-10-01

    Spontaneous abortion is the most common complication of pregnancy. Immune activation and the subsequent inflammation-induced tissue injury are often observed at the maternal-fetal interface as the final pathological assault in recurrent spontaneous abortion. However, the precise mechanisms responsible for spontaneous abortion involving inflammation are not fully understood. Chemokine CCL28 and its receptors CCR3 and CCR10 are important regulators in inflammatory process. Here, we examined the expression of CCL28 and its receptors in decidual stromal cells (DSCs) by immunochemistry and flow cytometry (FCM), and compared their expression level in DSCs from normal pregnancy versus spontaneous abortion, and their relationship to inflammatory cytokines production by DSCs. We further analyzed regulation of the pro-inflammatory cytokines on CCL28 expression in DSCs by real-time polymerase chain reaction, In-cell Western and FCM. The effects of CCL28-CCR3/CCR10 interaction on DSC apoptosis was investigated by Annexin V staining and FCM analysis or DAPI staining and nuclear morphology. Higher levels of the inflammatory cytokines interleukin (IL)-1β, IL-17A and tumor necrosis factor-α, and increased CCR3/CCR10 expression were observed in DSCs from spontaneous abortion compared with normal pregnancy. Treatment with inflammatory cytokines differently affected CCL28 and CCR3/CCR10 expression in DSCs. Human recombinant CCL28 promoted DSC apoptosis, which was eliminated by pretreatment with neutralizing antibodies against CCR3/CCR10 and CCL28. However, CCL28 did not affect DSC growth. These results suggest that the inflammation-promoted up-regulation of CCL28 and its receptors interaction in DSCs is involved in human spontaneous abortion via inducing DSC apoptosis.

  18. Testosterone increases CCL-2 expression in visceral adipose tissue from obese women of reproductive age.

    Science.gov (United States)

    Crisosto, Nicolás; Flores, Cristián; Maliqueo, Manuel; Echiburú, Bárbara; Vásquez, Jaime; Maluenda, Fernando; Sir-Petermann, Teresa

    2017-03-15

    Hyperandrogenic states and obesity in women are associated with insulin-resistance. Androgens reduce glucose uptake in adipose cells and increase TNFα production in peripheral monocytes. Inflammatory cytokines have a known detrimental effect on insulin resistance. The aim of the present study was to explore the role of testosterone in local cytokine production in visceral adipose tissue from women of reproductive age. Twenty-four women 18-40 years old, undergoing elective abdominal surgery for benign and non-inflammatory conditions, were recruited for the study. Women with clinical hyperandrogenism, diabetes, hepatic or renal dysfunction, hypothyroidism, BMI> 40 or drugs known to interfere with hormonal levels or fat metabolism were excluded. Women were classified into two groups according to BMI, non-obese (NO; BMI obese (O; BMI 30-40). A basal blood sample was drawn at the time of surgery for the measurement of glucose, insulin, total testosterone, lipid profile and circulating CCL-2, IL-6 and total adiponectin. Omental fat tissue (10 g) was obtained in all women. Samples of 300 mg of minced adipose tissue were incubated with vehicle (CTL) or testosterone (T) 10 -9  M to 10 -6  M for 24, 48 or 72 h. CCL-2, IL-6, TNFα, androgen Receptor (AR) mRNA levels were measured by Real Time quantitative polymerase chain reaction (qPCR) and normalized to GAPDH expression. Secretion of CCL-2 and IL-6 was measured in conditioned media by ELISA. Expression of CCL-2 and IL-6 at 24 h in CTLs was significantly higher in the obese group compared to the non-obese group (2.81 ± 0.43 fold for CCL-2; p = 0.005 and 3.26 ± 0.73 fold for IL-6; p = 0.03). At 48 and 72 h there were no differences between both groups in any of the markers. In the total group without T stimulation (CTL) there were significant correlations between: TNFα expression at 24 h and BMI (r = 0.708; p = 0.005), TGC levels (r = 0.904; p = 0.004), total Cholesterol (r = 0.904; p = 0

  19. Transforming Growth Factor-β and Interleukin-1β Signaling Pathways Converge on the Chemokine CCL20 Promoter.

    Science.gov (United States)

    Brand, Oliver J; Somanath, Sangeeta; Moermans, Catherine; Yanagisawa, Haruhiko; Hashimoto, Mitsuo; Cambier, Stephanie; Markovics, Jennifer; Bondesson, Andrew J; Hill, Arthur; Jablons, David; Wolters, Paul; Lou, Jianlong; Marks, James D; Baron, Jody L; Nishimura, Stephen L

    2015-06-05

    CCL20 is the only chemokine ligand for the chemokine receptor CCR6, which is expressed by the critical antigen presenting cells, dendritic cells. Increased expression of CCL20 is likely involved in the increased recruitment of dendritic cells observed in fibroinflammatory diseases such as chronic obstructive pulmonary disease (COPD). CCL20 expression is increased by the proinflammatory cytokine IL-1β. We have determined that IL-1β-dependent CCL20 expression is also dependent on the multifunctional cytokine TGF-β. TGF-β is expressed in a latent form that must be activated to function, and activation is achieved through binding to the integrin αvβ8 (itgb8). Here we confirm correlative increases in αvβ8 and IL-1β with CCL20 protein in lung parenchymal lysates of a large cohort of COPD patients. How IL-1β- and αvβ8-mediated TGF-β activation conspire to increase fibroblast CCL20 expression remains unknown, because these pathways have not been shown to directly interact. We evaluate the 5'-flanking region of CCL20 to determine that IL-1β-driven CCL20 expression is dependent on αvβ8-mediated activation of TGF-β. We identify a TGF-β-responsive element (i.e. SMAD) located on an upstream enhancer of the human CCL20 promoter required for efficient IL-1β-dependent CCL20 expression. By chromatin immunoprecipitation, this upstream enhancer complexes with the p50 subunit of NF-κB on a NF-κB-binding element close to the transcriptional start site of CCL20. These interactions are confirmed by electromobility shift assays in nuclear extracts from human lung fibroblasts. These data define a mechanism by which αvβ8-dependent activation of TGF-β regulates IL-1β-dependent CCL20 expression in COPD. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    International Nuclear Information System (INIS)

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik

    2014-01-01

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via

  1. Protective effect of Curcuma longa L. extract on CCl4-induced acute hepatic stress.

    Science.gov (United States)

    Lee, Geum-Hwa; Lee, Hwa-Young; Choi, Min-Kyung; Chung, Han-Wool; Kim, Seung-Wook; Chae, Han-Jung

    2017-02-01

    The Curcuma longa L. (CLL) rhizome has long been used to treat patients with hepatic dysfunction. CLL is a member of the ginger family of spices that are widely used in China, India, and Japan, and is a common spice, coloring, flavoring, and traditional medicine. This study was performed to evaluate the hepatoprotective activity of CLL extract and its active component curcumin in an acute carbon tetrachloride (CCl 4 )-induced liver stress model. Acute hepatic stress was induced by a single intraperitoneal injection of CCl 4 (0.1 ml/kg body weight) in rats. CLL extract was administered once a day for 3 days at three dose levels (100, 200, and 300 mg/kg/day) and curcumin was administered once a day at the 200 mg/kg/day. We performed alanine transaminase (ALT) and aspartate transaminase (AST). activity analysis and also measured total lipid, triglyceride, and cholesterol levels, and lipid peroxidation. At 100 g CLL, the curcuminoid components curcumin (901.63 ± 5.37 mg/100 g), bis-demethoxycurcumin (108.28 ± 2.89 mg/100 g), and demethoxycurcumin (234.85 ± 1.85 mg/100 g) were quantified through high liquid chromatography analysis. In CCl 4 -treated rats, serum AST and ALT levels increased 2.1- and 1.2-fold compared with the control. AST but not ALT elevation induced by CCl 4 was significantly alleviated in CLL- and curcumin-treated rats. Peroxidation of membrane lipids in the liver was significantly prevented by CLL (100, 200, and 300 mg/kg/day) on tissue lipid peroxidation assay and immunostaining with anti-4HNE antibody. We found that CLL extract and curcumin exhibited significant protection against liver injury by improving hepatic superoxide dismutase (p < 0.05) and glutathione peroxidase activity, and glutathione content in the CCl 4 -treated group (p < 0.05), leading to a reduced lipid peroxidase level. Our data suggested that CLL extract and curcumin protect the liver from acute CCl 4 -induced injury in a rodent model by suppressing

  2. Human CCL3L1 copy number variation, gene expression, and the role of the CCL3L1-CCR5 axis in lung function [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Adeolu B. Adewoye

    2018-02-01

    Full Text Available Background: The CCL3L1-CCR5 signaling axis is important in a number of inflammatory responses, including macrophage function, and T-cell-dependent immune responses. Small molecule CCR5 antagonists exist, including the approved antiretroviral drug maraviroc, and therapeutic monoclonal antibodies are in development. Repositioning of drugs and targets into new disease areas can accelerate the availability of new therapies and substantially reduce costs. As it has been shown that drug targets with genetic evidence supporting their involvement in the disease are more likely to be successful in clinical development, using genetic association studies to identify new target repurposing opportunities could be fruitful. Here we investigate the potential of perturbation of the CCL3L1-CCR5 axis as treatment for respiratory disease. Europeans typically carry between 0 and 5 copies of CCL3L1 and this multi-allelic variation is not detected by widely used genome-wide single nucleotide polymorphism studies.  Methods: We directly measured the complex structural variation of CCL3L1 using the Paralogue Ratio Test and imputed (with validation CCR5del32 genotypes in 5,000 individuals from UK Biobank, selected from the extremes of the lung function distribution, and analysed DNA and RNAseq data for CCL3L1 from the 1000 Genomes Project. Results: We confirmed the gene dosage effect of CCL3L1 copy number on CCL3L1 mRNA expression levels.  We found no evidence for association of CCL3L1 copy number or CCR5del32 genotype with lung function. Conclusions: These results suggest that repositioning CCR5 antagonists is unlikely to be successful for the treatment of airflow obstruction.

  3. NOAA JPSS Visible Infrared Imaging Radiometer Suite (VIIRS) Cloud Cover Layer (CCL) Environmental Data Record (EDR) from IDPS

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset contains a high quality Environmental Data Record (EDR) of Cloud Cover Layers (CCL) from the Visible Infrared Imaging Radiometer Suite (VIIRS)...

  4. Serum amyloid P down-regulates CCL-1 expression, and inhibits ...

    African Journals Online (AJOL)

    2A, B, P<0.01). Using H&E staining, the total number of metastatic nodules inside of lungs were counted, which was also lower in SAP-Tg mice compared with the. C57BL/6 group (Figure 2C, p < 0.01). SAP regulates CCL-1 secretion by macrophages. We collected the orbital blood and obtained the serum by centrifugation.

  5. Hepatoprotective and antioxidant effects of single clove garlic against CCl4-induced hepatic damage in rabbits.

    Science.gov (United States)

    Naji, Khalid Mohammed; Al-Shaibani, Elham Shukri; Alhadi, Fatima A; Al-Soudi, Safa'a Abdulrzaq; D'souza, Myrene R

    2017-08-17

    The increase in demand and consumption of single clove garlic or 'Solo garlic' (Allium sativum) has resulted in an increase in research on its therapeutic properties. The present study aims to evaluate the antioxidant activities, oxidant-scavenging efficiency and preventive effects of SCG (single clove garlic) and MCG (multi clove garlic) on CCl 4 -induced acute hepatotoxicity in male rabbits. For this purpose, rabbits were orally administered with 3 ml of CCl 4 /kg of body weight, followed by 0.8 g of MCG or SCG/kg twice a week for three successive weeks. Oxidative hepatotoxicity was then assessed. SCG extracts exhibited higher antioxidant capacity than the MCG extract. Scavenging ability of SCG showed significant (p garlic storage constituents varies with the number of cloves present. CCl 4 -induced hepatotoxicity demonstrated histological changes including severe damage in the structure of liver tissues which correlated well to oxidative stress levels. Simultaneously, administration of SCG resulted in a significant reduction of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TB) levels in addition to improvement in some histological parameters. Low levels of lipid peroxidation (malondialdehyde, MDA) (p < 0.001), along with a huge reduction in peroxidase (POx) (p < 0.001) revealed protection against oxidative toxicity in the liver homogenate. Higher levels of catalase (CAT) (p < 0.001) and superoxide dismutase (SOD) (p < 0.05) when compared to the MCG test (TM) group indicates that removal of H 2 O 2 is based on CAT activity in SCG test (TS) group rather than the POx activity demonstrated in the former group. The present study indicates that SCG possesses more protective ability than MCG against CCl 4 -induced liver injury and might be an effective alternative medicine against acute oxidative liver toxicity.

  6. Drinking of Salvia officinalis tea increases CCl4-induced hepatotoxicity in mice

    OpenAIRE

    Lima, Cristóvão F.; Ferreira, Manuel Fernandes; Wilson, Cristina Pereira

    2007-01-01

    In a previous study, the drinking of a Salvia officinalis tea (prepared as an infusion) for 14 days improved liver antioxidant status in mice and rats where, among other factors, an enhancement of glutathione-S-transferase (GST) activity was observed. Taking in consideration these effects, in the present study the potential protective effects of sage tea drinking against a situation of hepatotoxicity due to free radical formation, such as that caused by carbon tetrachloride (CCl4), were evalu...

  7. CCL21 and IP-10 as blood biomarkers for pulmonary involvement in systemic lupus erythematosus patients.

    Science.gov (United States)

    Odler, B; Bikov, A; Streizig, J; Balogh, C; Kiss, E; Vincze, K; Barta, I; Horváth, I; Müller, V

    2017-05-01

    Biomarkers for pulmonary manifestations in systemic lupus erythematosus (SLE) are missing. Plasma samples of nine SLE patients with known pulmonary involvement (SLE pulm ) and nine SLE patients without pulmonary involvement (SLE) were tested by multiplex microarray analysis for various cyto- and chemokines. Significantly decreased lung function paramters for forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity for carbon monoxide (DL CO ) and diffusion of CO corrected on lung volume (KL CO ) were observed in SLE pulm as compared to SLE patients. CC chemokine ligand 21 (CCL21) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in SLE pulm , than in patients without pulmonary manifestations. CCL21 correlated negatively with DL CO ( r = -0.73; p < 0.01) and KL CO ( r = -0.62; p < 0.01), while IP-10 with FVC and forced expiratory volume one second. Receiver Operating Characteristics (ROC) analysis confirmed high sensitivity and specificity for the separation of SLE patients with and without pulmonary involvement for the chemokines CCL21 (Area Under Curve (AUC): 0.85; sensitivity%: 88.90; specificity%: 75.00; p < 0.01) and IP-10 (AUC: 0.82; sensitivity%: 66.67, specificity%: 100; p < 0.01). Pleuropulmonary manifestations in SLE patients associated with lung functional and DL CO /KL CO changes and were associated with significant increase in CCL21 and IP-10. These chemokines might serve as potential biomarkers of lung involvement in SLE patients.

  8. CCL2 is Upregulated by Decreased miR-122 Expression in Iron-Overload-Induced Hepatic Inflammation

    Directory of Open Access Journals (Sweden)

    Yuxiao Tang

    2017-11-01

    Full Text Available Background/Aims: Iron overload (IO is accompanied by hepatic inflammation. The chemokine (C-C motif ligand 2 (CCL2 mediates inflammation, and its overexpression is associated with IO. However, whether IO results in CCL2 overexpression in the liver and the underlying mechanisms are unclear. Methods: We subjected mice to IO by administering intraperitoneal injections of dextran-iron or by feeding mice a 3% dextran-iron diet to observe the effects of IO on miR-122/CCL2 expression through real-time qPCR and Western blot analysis. We also used indicators, including the expression of the inflammatory cytokine, the inflammation score based on H&E staining and the serum content of ALT and AST to evaluate the effects of IO on hepatic inflammation. Meanwhile, we observed the effects of vitamin E on IO-induced hepatic inflammation. In cells, we used 100 µΜ FeSO4 or 30 µΜ Holo-Tf to produce IO and observed the roles of miR-122 in regulating CCL2 expression by using miR-122 mimics or inhibitors to overexpress or inhibit miR-122. Then, we used a dual-luciferase reporter assay to prove that miR-122 regulates CCL2 expression through direct binding to its complementary sequence in the CCL2 mRNA 3’UTR. Results: IO induces the downregulation of miR-122 and the upregulation of CCL2, as well as inflammatory responses both in vitro and in vivo. Although IO-induced oxidative stress is eliminated by the antioxidant vitamin E, IO-induced hepatic inflammation still exists, which probably can be explained by the fact that vitamin E has no effects on the miR-122/CCL2 pathway. In in vitro experiments, the overexpression and inhibition of miR-122 significantly reduced and increased CCL2 expression, respectively. The dual-luciferase reporter assay indicates that miR-122 binds CCL2 mRNA 3’UTR. Conclusion: We propose the roles of miR-122/CCL2 in IO-induced hepatic inflammation. Our studies should provide a new clue for developing clinical strategies for patients with IO.

  9. Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats

    Directory of Open Access Journals (Sweden)

    Mohammed Al-Yahya

    2013-01-01

    Full Text Available The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH on carbon tetrachloride (CCl4 induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β-carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2′,7′-dichlorofluorescein (DCF toxicity in ex vivo test.

  10. Inflammatory Monocytes Promote Perineural Invasion via CCL2-Mediated Recruitment and Cathepsin B Expression.

    Science.gov (United States)

    Bakst, Richard L; Xiong, Huizhong; Chen, Chun-Hao; Deborde, Sylvie; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William; Lee, Sei-Young; Olson, Oakley C; Leiner, Ingrid M; Marcadis, Andrea R; Keith, James W; Al-Ahmadie, Hikmat A; Katabi, Nora; Gil, Ziv; Vakiani, Efsevia; Joyce, Johanna A; Pamer, Eric; Wong, Richard J

    2017-11-15

    Perineural invasion (PNI) is an ominous event strongly linked to poor clinical outcome. Cells residing within peripheral nerves collaborate with cancer cells to enable PNI, but the contributing conditions within the tumor microenvironment are not well understood. Here, we show that CCR2-expressing inflammatory monocytes (IM) are preferentially recruited to sites of PNI, where they differentiate into macrophages and potentiate nerve invasion through a cathepsin B-mediated process. A series of adoptive transfer experiments with genetically engineered donors and recipients demonstrated that IM recruitment to nerves was driven by CCL2 released from Schwann cells at the site of PNI, but not CCL7, an alternate ligand for CCR2. Interruption of either CCL2-CCR2 signaling or cathepsin B function significantly impaired PNI in vivo Correlative studies in human specimens demonstrated that cathepsin B-producing macrophages were enriched in invaded nerves, which was associated with increased local tumor recurrence. These findings deepen our understanding of PNI pathogenesis and illuminate how PNI is driven in part by corruption of a nerve repair program. Further, they support the exploration of inhibiting IM recruitment and function as a targeted therapy for PNI. Cancer Res; 77(22); 6400-14. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Oxidative stress modulation by Rosmarinus officinalis in CCl4-induced liver cirrhosis.

    Science.gov (United States)

    Gutiérrez, Rosalinda; Alvarado, José L; Presno, Manuel; Pérez-Veyna, Oscar; Serrano, Carmen J; Yahuaca, Patricia

    2010-04-01

    Rosmarinus officinalis (Lamiaceae) possesses antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative for chronic liver disease. The effect produced by a methanolic extract of Rosmarinus officinalis on CCl(4)-induced liver cirrhosis in rats was investigated using both prevention and reversion models. Over the course of the development of cirrhosis, the increased enzymatic activities of gamma-glutamyl transpeptidase and alanine aminotransferase, and the rise in bilirubin levels caused by CCl(4) administration, were prevented by Rosmarinus officinalis co-administration. When the cirrhosis by oxidative stress was evaluated as an increase on liver lipoperoxidation, total lipid peroxides, nitric oxide in serum, and loss of erythrocyte plasma membrane stability, R. officinalis was shown to prevent such alterations. On cirrhotic animals treated with CCl(4), histological studies showed massive necrosis, periportal inflammation and fibrosis which were modified by R. officinalis. These benefits on experimental cirrhosis suggest a potential therapeutic use for R. officinalis as an alternative for liver cirrhosis. Copyright (c) 2009 John Wiley & Sons, Ltd.

  12. mTOR Overactivation in Mesenchymal cells Aggravates CCl4- Induced liver Fibrosis.

    Science.gov (United States)

    Shan, Lanlan; Ding, Yan; Fu, You; Zhou, Ling; Dong, Xiaoying; Chen, Shunzhi; Wu, Hongyuan; Nai, Wenqing; Zheng, Hang; Xu, Wanfu; Bai, Xiaochun; Jia, Chunhong; Dai, Meng

    2016-11-07

    Hepatic stellate cells are of mesenchymal cell type located in the space of Disse. Upon liver injury, HSCs transactivate into myofibroblasts with increase in expression of fibrillar collagen, especially collagen I and III, leading to liver fibrosis. Previous studies have shown mTOR signaling is activated during liver fibrosis. However, there is no direct evidence in vivo. The aim of this study is to examine the effects of conditional deletion of TSC1 in mesenchymal on pathogenesis of liver fibrosis. Crossing mice bearing the floxed TSC1 gene with mice harboring Col1α2-Cre-ER(T) successfully generated progeny with a conditional knockout of TSC1 (TSC1 CKO) in collagen I expressing mesenchymal cells. TSC1 CKO and WT mice were subjected to CCl 4 , oil or CCl 4 + rapamycin treatment for 8 weeks. TSC1 CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene. Absence of TSC1 in mesenchymal cells induced proliferation and prevented apoptosis in activated HSCs. However, there were no significant differences in oil-treated TSC1 CKO and WT mice. Rapamycin, restored these phenotypic changes by preventing myofibroblasts proliferation and enhancing their apoptosis. These findings revealed mTOR overactivation in mesenchymal cells aggravates CCl 4 - induced liver fibrosis and the rapamycin prevent its occurance.

  13. Diethylcarbamazine Reduces Chronic Inflammation and Fibrosis in Carbon Tetrachloride- (CCl4- Induced Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Sura Wanessa Santos Rocha

    2014-01-01

    Full Text Available This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl4 0.5 μL/g of body weight through two injections a week for 6 weeks. DEC (50 mg/kg was administered by gavage for 12 days before finishing the CCl4 induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1β, MDA, TGF-β, and αSMA immunopositivity, besides exhibiting decreased IL1β, COX-2, NFκB, IFNγ, and TGFβ expressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.

  14. Attenuation of CCl4-Induced Oxidative Stress and Hepatonephrotoxicity by Saudi Sidr Honey in Rats

    Science.gov (United States)

    Al-Yahya, Mohammed; Mothana, Ramzi; Al-Said, Mansour; Al-Dosari, Mohammed; Al-Musayeib, Nawal; Al-Sohaibani, Mohammed; Parvez, Mohammad Khalid; Rafatullah, Syed

    2013-01-01

    The present study was undertaken to investigate the possible protective effect of Saudi Sidr honey (SSH) on carbon tetrachloride (CCl4) induced oxidative stress and liver and kidney damage in rat. Moreover, the antioxidant activity and the phenolic and flavonoidal contents were determined. The hepatorenal protective activity of the SSH was determined by assessing biochemical, hematological, and histological parameters. Serum transaminases, ALP, GGT, creatinine, bilirubin urea, uric acid, and MDA level in liver and kidney tissues were significantly elevated, and the antioxidant status of nonprotein sulfhydryls, albumin, and total protein levels in liver and kidney were declined significantly in CCl4 alone treated animals. Pretreatment with SSH and silymarin prior to the administration of CCl4 significantly prevented the increase of the serum levels of enzyme markers and reduced oxidative stress. SSH also exhibited a significant lipid-lowering effect and caused an HDL-C enhanced level in serum. The histopathological evaluation of the liver and kidney also revealed that honey protected incidence of both liver and kidney lesions. Moreover, SSH showed a strong antioxidant activity in DPPH and β-carotene-linoleic acid assays. SSH was found to contain phenolic compounds. Additionally, the SSH supplementation restored the hepatocytes viability against 2′,7′-dichlorofluorescein (DCF) toxicity in ex vivo test. PMID:23533498

  15. CCL5 expression in panniculitic T-cell dyscrasias and its potential role in adipocyte tropism.

    Science.gov (United States)

    Magro, Cynthia M; Wang, Xuan

    2013-05-01

    Subcutaneous panniculitis-like T-cell lymphoma and gamma/delta T-cell lymphoma involving fat are unique among the hematologic dyscrasias because of their almost exclusive involvement of the subcutaneous fat with little tendency toward extracutaneous dissemination. The systemic manifestations associated with this lymphoma are largely the sequelae of cytokine production by neoplastic T cells found within the subcutaneous fat. We hypothesized that the basis of this localization could be due to an interactive microenvironment between the neoplastic cells and the adipocytes. Given the expression of CCR5 in adipocytes, we explored the expression of its ligand CCL5 in the subcutaneous infiltrates in subcutaneous panniculitis-like T-cell lymphoma, gamma/delta T-cell lymphoma and compared it with those in lupus erythematosus profundus (LEP). We found that CCL5 was expressed in a significantly higher percentage of lymphocytes in lymphomas compared with those in LEP (P tropism may reflect a unique interaction between CCL5-positive lymphocytes and CCR5 positive adipocytes. Given the known pharmacologic inhibitors of CCR5-expression one might propose that using such inhibitors (ie, anti-CCR5) could be of therapeutic value in select cases.

  16. BMP-2 promotes oral squamous carcinoma cell invasion by inducing CCL5 release.

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    Mi-joo Kim

    Full Text Available Bone morphogenetic protein-2 (BMP-2-containing bone grafts are useful regenerative materials for oral and maxillofacial surgery; however, several in vitro and in vivo studies previously reported cancer progression-related adverse effects caused by BMP-2. In this study, by quantifying the rhBMP-2 content released from bone grafts, the rhBMP-2 concentration that did not show cytotoxicity in each cell line was determined and applied to the in vitro monoculture or coculture model in the invasion assay. Our results showed that 1 ng/ml rhBMP-2, while not affecting cancer cell viability, significantly increased the invasion ability of the cancer cells cocultured with fibroblasts. Cocultured medium with rhBMP-2 also contained increased levels of matrix metalloproteinases. rhBMP-2-treated cocultured fibroblasts did not show a prominent difference in mRNA expression profile. Some cytokines, however, were detected in the conditioned medium by a human cytokine antibody array. Among them, the cancer invasion-related factor CCL5 was quantified by ELISA. Interestingly, CCL5 neutralizing antibodies significantly reduced the invasion of oral cancer cells. In conclusion, our results suggest that 1 ng/ml rhBMP-2 may induce invasion of oral squamous cell carcinoma (OSCC cells by CCL5 release in coculture models. Therefore, we propose that a careful clinical examination before the use of rhBMP-2-containing biomaterials is indispensable for using rhBMP-2 treatment to prevent cancer progression.

  17. Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization.

    Science.gov (United States)

    Tejchman, Anna; Lamerant-Fayel, Nathalie; Jacquinet, Jean-Claude; Bielawska-Pohl, Aleksandra; Mleczko-Sanecka, Katarzyna; Grillon, Catherine; Chouaib, Salem; Ugorski, Maciej; Kieda, Claudine

    2017-05-09

    Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL21/CCR7 chemokine/receptor axis in a hypoxia-dependent manner. In the present model, breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3 cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor environment. In addition to its known effect on migration, CCL21/CCR7 interaction was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression undergoes a reduction of adhesion, making it an anti-adhesion molecule in the absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231 cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia-dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which influence PDPN expression.

  18. Association between a Single Donor TARC/CCL17 Promotor Polymorphism and Obstructive Chronic Lung Allograft Dysfunction after Lung Transplantation

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    Kevin Budding

    2017-09-01

    Full Text Available Lung transplantation (LTx outcome is hampered by development of chronic rejection, often manifested as the bronchiolitis obliterans syndrome (BOS. Low serum levels of thymus and activation-regulated chemokine (TARC/CCL17, a chemoattractant, measured during the first month post-LTx are predictive for BOS development. Since TARC/CCL17 promotor polymorphisms correlate with serum TARC/CCL17 levels, we investigated seven single-nucleotide polymorphisms (SNPs within this region and their potential association with LTx outcome. We analyzed donor and patient SNP configurations and haplotypes and observed a trend between a donor SNP (rs223899 configuration and patient TARC/CCL17 serum levels post-LTx (p = 0.066. Interestingly, this SNP configuration in patients did not show any correlation with pre-LTx TARC/CCL17 serum levels (p = 0.776. Survival analysis showed that receiving a graft from a donor heterozygous for rs223899 has a disadvantageous impact on transplantation outcome. When stratified per donor SNP genotype, patients receiving a transplant from a heterozygous donor showed a lower BOS-free survival (p = 0.023 and survival rate (p = 0.0079. Since rs223899 is located within a NFκB binding site, heterozygosity at this position could result in a reduced TARC/CCL17 expression. Our data indicate that a single TARC/CCL17 promotor SNP in the donor correlates with lower serum TARC/CCL17 levels measured 1 month after LTx and affects clinical outcome after LTx.

  19. Association between a Single Donor TARC/CCL17 Promotor Polymorphism and Obstructive Chronic Lung Allograft Dysfunction after Lung Transplantation

    Science.gov (United States)

    Budding, Kevin; van Setten, Jessica; van de Graaf, Eduard A.; van Rossum, Oliver A.; Kardol-Hoefnagel, Tineke; Oudijk, Erik-Jan D.; Hack, C. Erik; Otten, Henderikus G.

    2017-01-01

    Lung transplantation (LTx) outcome is hampered by development of chronic rejection, often manifested as the bronchiolitis obliterans syndrome (BOS). Low serum levels of thymus and activation-regulated chemokine (TARC/CCL17), a chemoattractant, measured during the first month post-LTx are predictive for BOS development. Since TARC/CCL17 promotor polymorphisms correlate with serum TARC/CCL17 levels, we investigated seven single-nucleotide polymorphisms (SNPs) within this region and their potential association with LTx outcome. We analyzed donor and patient SNP configurations and haplotypes and observed a trend between a donor SNP (rs223899) configuration and patient TARC/CCL17 serum levels post-LTx (p = 0.066). Interestingly, this SNP configuration in patients did not show any correlation with pre-LTx TARC/CCL17 serum levels (p = 0.776). Survival analysis showed that receiving a graft from a donor heterozygous for rs223899 has a disadvantageous impact on transplantation outcome. When stratified per donor SNP genotype, patients receiving a transplant from a heterozygous donor showed a lower BOS-free survival (p = 0.023) and survival rate (p = 0.0079). Since rs223899 is located within a NFκB binding site, heterozygosity at this position could result in a reduced TARC/CCL17 expression. Our data indicate that a single TARC/CCL17 promotor SNP in the donor correlates with lower serum TARC/CCL17 levels measured 1 month after LTx and affects clinical outcome after LTx. PMID:28932229

  20. Astrocyte-derived CCL2 participates in surgery-induced cognitive dysfunction and neuroinflammation via evoking microglia activation.

    Science.gov (United States)

    Xu, Jiawen; Dong, Hongquan; Qian, Qingqing; Zhang, Xiang; Wang, Yiwei; Jin, Wenjie; Qian, Yanning

    2017-08-14

    Neuroinflammation induced by peripheral trauma plays a key role in the development of postoperative cognitive dysfunction (POCD). Substantial evidence points to reactive glia as a pivotal factor during the inflammation process. However, little is known about the functional interactions between astrocytes and microglia. Recent evidence suggests the involvement of the CCL2-CCR2 pathway in CNS inflammation-related diseases. Our previous studies have suggested that astrocyte-derived CCL2 can induce microglial activation in vitro. Within this context, we sought to determine if the CCL2/CCR2 axis is involved in the crosstalk between astrocytes and microglia, contributing to increased neuroinflammation. Here, we show that tibial fracture surgery promoted CCL2 upregulation in activated astrocytes, increased CCR2 expression in activated microglia, and induced deficits in learning and memory. Site-directed pre-injection of RS504393, a CCR2 antagonist, inhibited this effect by reducing microglial activation, M1 polarization, inflammatory cytokines, and neuronal injury and death and improving cognitive function. Taken together, these data implicate CCL2-CCR2 signaling in astrocyte-mediated microglial activation in central nervous system (CNS) inflammation and suggest that interference with CCL2 signaling could constitute another potential therapeutic target for POCD. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Preventive and curative effects of Cocculus hirsutus (Linn. Diels leaves extract on CCl4 provoked hepatic injury in rats

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    Lavanya Goodla

    2017-12-01

    Full Text Available The present study was designed to estimate the protective or curative potency of an extract from Cocculus hirsutus leaves against CCl4 intoxication via its antioxidant property in rats. Liver enzyme markers (SGOT, SGPT, ALP, LDH, and bilirubin and oxidative stress markers {lipid peroxidation (LPO, enzymatic antioxidants [superoxide dismutase, catalase and glutathione peroxidase] and non-enzymatic antioxidants [reduced glutathione, vitamin C and E]} were analyzed by spectrophotometry. Histopathological studies on hepatic tissue were also performed by the method of Hematoxylin and Eosin staining. Rats administrated with 30% CCl4 in olive oil intraperitoneally resulted in significant increase in the levels of SGOT, SGPT, ALP, LDH, and bilirubin compared to control rats. Significant elevation of hepatic LPO and depletion of enzymatic and non-enzymatic antioxidants levels were observed in CCl4 induced rats. When CCl4 induced rats were co-treated with C. hirsutus at doses of 250 and 500 mg/kg b·wt, all the altered levels of liver marker enzymes and oxidative stress markers were restored to near control values. Histopathological studies provided direct evidence of the hepatoprotective effect of C. hirsutus. In conclusion, extract from C. hirsutus could protect the liver from CCl4-induced oxidative damage, by scavenging the free radicals generated during the metabolism of CCl4. Keywords: Antioxidants, Carbon tetrachloride, Cocculus hirsutus, Hepatoprotective effect, Lipid peroxidation

  2. CC-Chemokine CCL15 Expression and Possible Implications for the Pathogenesis of IgE-Related Severe Asthma

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    Yasuo Shimizu

    2012-01-01

    Full Text Available Airway inflammation is accompanied by infiltration of inflammatory cells and an abnormal response of airway smooth muscle. These cells secrete chemokines and express the cell surface chemokine receptors that play an important role in the migration and degranulation of inflammatory cells. Omalizumab is a monoclonal antibody directed against immunoglobulin E, and its blocking of IgE signaling not only reduces inflammatory cell infiltration mediated by the Th2 immune response but also inhibits other immune responses. The chemokine CCL15 is influenced by omalizumab, and the source of CCL15 has been reported to be airway smooth muscle cells and basophils. CCL15 binds to its receptor CCR1, which has been reported to be expressed by various inflammatory cells and also by airway smooth muscle cells. Therefore, CCL15/CCR1 signaling could be a target for the treatment of asthma. We review the role of CCL15 in the pathogenesis of asthma and also discuss the influence of IgE-mediated immunomodulation via CCL15 and its receptor CCR1.

  3. The Increased Expression of CCL20 and CCR6 in Rectal Mucosa Correlated to Severe Inflammation in Pediatric Ulcerative Colitis

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    Keiichi Uchida

    2015-01-01

    Full Text Available Background/Aims. The aim of this study is to clarify the differences of CCL20 and CCR6 expression, chemokine correlated to intestinal homeostasis, between pediatric and adult ulcerative colitis (UC patients. Methods. Onehundred forty-one patients who underwent proctocolectomy were divided to two groups including childhood-onset UC (CUC, <16 years old, n=24 and adult-onset UC (AUC, ≧16 years old, n=117. A total of 141 formalin-fixed, paraffin-embedded tissue samples of rectum were obtained from these patients. Histological inflammation of rectum in resected specimen was evaluated by using Geboes histological assessment. In immunohistochemistry study, the CCL20 expression was evaluated by intensity and the stained area, and the CCR6 expression was evaluated by lymphocytes infiltration pattern. Results. CCL20 score and CCR6 positive lymphocytes infiltration pattern were statistically significantly correlated with histological inflammation severity of UC in all patients (P<0.05. CCL20 and CCR6 expression in CUC were statistically significantly higher than that in AUC in all or pathologically severe cases (P<0.05. Conclusions. CCL20 and CCR6 may play a significant role in local damage and pathological changes in UC especially pediatric patients. In the future, our understanding of the differences in CCL-CCR6 interaction between adults and children may lead to the pathogenesis of IBD.

  4. Evolution of CCL11: genetic characterization in lagomorphs and evidence of positive and purifying selection in mammals.

    Science.gov (United States)

    Neves, Fabiana; Abrantes, Joana; Esteves, Pedro J

    2016-07-01

    The interactions between chemokines and their receptors are crucial for differentiation and activation of inflammatory cells. CC chemokine ligand 11 (CCL11) binds to CCR3 and to CCR5 that in leporids underwent gene conversion with CCR2. Here, we genetically characterized CCL11 in lagomorphs (leporids and pikas). All lagomorphs have a potentially functional CCL11, and the Pygmy rabbit has a mutation in the stop codon that leads to a longer protein. Other mammals also have mutations at the stop codon that result in proteins with different lengths. By employing maximum likelihood methods, we observed that, in mammals, CCL11 exhibits both signatures of purifying and positive selection. Signatures of purifying selection were detected in sites important for receptor binding and activation. Of the three sites detected as under positive selection, two were located close to the stop codon. Our results suggest that CCL11 is functional in all lagomorphs, and that the signatures of purifying and positive selection in mammalian CCL11 probably reflect the protein's biological roles. © The Author(s) 2016.

  5. Slow CCL2-dependent translocation of biopersistent particles from muscle to brain.

    Science.gov (United States)

    Khan, Zakir; Combadière, Christophe; Authier, François-Jérôme; Itier, Valérie; Lux, François; Exley, Christopher; Mahrouf-Yorgov, Meriem; Decrouy, Xavier; Moretto, Philippe; Tillement, Olivier; Gherardi, Romain K; Cadusseau, Josette

    2013-04-04

    Long-term biodistribution of nanomaterials used in medicine is largely unknown. This is the case for alum, the most widely used vaccine adjuvant, which is a nanocrystalline compound spontaneously forming micron/submicron-sized agglomerates. Although generally well tolerated, alum is occasionally detected within monocyte-lineage cells long after immunization in presumably susceptible individuals with systemic/neurologic manifestations or autoimmune (inflammatory) syndrome induced by adjuvants (ASIA). On the grounds of preliminary investigations in 252 patients with alum-associated ASIA showing both a selective increase of circulating CCL2, the major monocyte chemoattractant, and a variation in the CCL2 gene, we designed mouse experiments to assess biodistribution of vaccine-derived aluminum and of alum-particle fluorescent surrogates injected in muscle. Aluminum was detected in tissues by Morin stain and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho) were used. Intramuscular injection of alum-containing vaccine was associated with the appearance of aluminum deposits in distant organs, such as spleen and brain where they were still detected one year after injection. Both fluorescent materials injected into muscle translocated to draining lymph nodes (DLNs) and thereafter were detected associated with phagocytes in blood and spleen. Particles linearly accumulated in the brain up to the six-month endpoint; they were first found in perivascular CD11b+ cells and then in microglia and other neural cells. DLN ablation dramatically reduced the biodistribution. Cerebral translocation was not observed after direct intravenous injection, but significantly increased in mice with chronically altered blood-brain-barrier. Loss/gain-of-function experiments consistently implicated CCL2 in systemic diffusion of Al-Rho particles captured by monocyte-lineage cells and in their subsequent neurodelivery

  6. Hepatoprotective effects of Micromeria croatica ethanolic extract against CCl4-induced liver injury in mice.

    Science.gov (United States)

    Vladimir-Knežević, Sanda; Cvijanović, Olga; Blažeković, Biljana; Kindl, Marija; Štefan, Maja Bival; Domitrović, Robert

    2015-07-15

    Micromeria croatica (Pers.) Schott is an aromatic plant from Lamiaceae family previously found to possess potent in vitro antioxidant activity which is mainly attributed to the high level of polyphenolic substances. The aim of this study was to investigate the hepatoprotective activity and possible underlying mechanisms of Micromeria croatica ethanolic extract (MC) using a model of carbon tetrachloride (CCl4)-induced liver injury in mice. Male BALB/cN mice were randomly divided into seven groups: control group received saline, MC group received ethanolic extract of M. croatica in 5% DMSO (100 mg/kg b.w., p.o.), and CCl4 group was administered CCl4 dissolved in corn oil (2 mL/kg, 10% v/v, ip). MC50, MC200 and MC400 groups were treated with MC orally at doses of 50, 200 and 400 mg/kg once daily for 2 consecutive days, respectively, 6 h after CCl4 intoxication. The reference group received silymarin at dose of 400 mg/kg. At the end of experiment, blood and liver samples were collected for biochemical, histopathological, immunohistochemical and Western blot analyses. In addition, major phenolic compounds in MC were quantified by HPLC-DAD. CCl4 intoxication resulted in liver cells damage and oxidative stress and triggered inflammatory response in mice livers. MC treatment decreased ALT activity and prevented liver necrosis. Improved hepatic antioxidant status was evident by increased Cu/Zn SOD activity and decreased 4-hydroxynonenal (4-HNE) formation in the livers. Concomitantly, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were overexpressed. The hepatoprotective activity of MC was accompanied by the increase in nuclear factor-kappaB (NF-κB) activation and tumor necrosis factor-alpha (TNF-α) expression, indicating amelioration of hepatic inflammation. Additionally, MC prevented tumor growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression, suggesting the potential for suppression of hepatic fibrogenesis. These

  7. TNF-α and IL-1β Dependent Induction of CCL3 Expression by Nucleus Pulposus Cells Promotes Macrophage Migration through CCR1

    Science.gov (United States)

    Wang, Jianru; Tian, Ye; Phillips, Kate L.E.; Chiverton, Neil; Haddock, Gail; Bunning, Rowena A.; Cross, Alison K.; Shapiro, Irving M.; LeMaitre, Christine L.; Risbud, Makarand V.

    2012-01-01

    Objective To investigate TNF-α and IL-1β regulation of CCL3 expression in nucleus pulposus (NP) cells and in macrophage migration. Methods qRT-PCR and immunohistochemistry were used to measure CCL3 expression in NP cells. Transfections were used to determine the role of NF-κB, C/EBP-β and MAPK on cytokine mediated CCL3 promoter activity. Effect of NP-conditioned medium on macrophage migration was measured using a transwell system. Results An increase in CCL3 expression and promoter activity was observed in NP cells after TNF-α or IL-1β treatment. Treatment of cells with NF-κB and MAPK inhibitors abolished the effect of the cytokines on CCL3 expression. The inductive effect of p65 and C/EBP-β on CCL3 promoter was confirmed through gain- and loss-of-function studies. Noteworthy, co-transfection of p50 completely blocked cytokine and p65 dependent induction. In contrast, c-Rel and RelB had little effect on promoter activity. Lentiviral transduction with Sh-p65 and Sh-Ikkβ significantly decreased TNF-α dependent increase in CCL3 expression. Analysis of degenerate human NP tissues showed that CCL3, but not CCL4 expression correlated positively with the grade of tissue degeneration. Importantly, treatment of macrophages with conditioned medium of NP cells treated with TNF-α or IL-1β promoted their migration; pretreatment of macrophages with antagonist to CCR1, primary receptor for CCL3 and CCL4, blocked cytokine mediated migration. Conclusions By controlling the activation of MAPK, NF-κB and C/EBPβ signaling, TNF-α and IL-1β modulate the expression of CCL3 in NP cells. The CCL3-CCR1 axis may play an important role in promoting macrophage infiltration in degenerate, herniated discs. PMID:23233369

  8. Benzopyrene promotes lung cancer A549 cell migration and invasion through up-regulating cytokine IL8 and chemokines CCL2 and CCL3 expression.

    Science.gov (United States)

    Zhang, Jin; Chang, Li; Jin, Hanyu; Xia, Yaoxiong; Wang, Li; He, Wenjie; Li, Wenhui; Chen, Hong

    2016-08-01

    Tobacco-sourced carcinogen including benzopyrene (B[a]P) in lung cancer metastasis has not been fully reported. In this study, lung carcinoma A549 cell line was used to investigate the potential roles of tobacco-sourced B[a]P on cell metastasis and invasion and to assess its underlying mechanism. Effects of tobacco-sourced carcinogen on A549 cell proliferation, metastasis, and invasion were analyzed using MTT assay, Transwell assay, and scratch method, respectively. The effects of tobacco-sourced carcinogen on cytokines and chemokines secretion were detected using enzyme-linked immunosorbent assay. Moreover, correlation between inflammatory factor expression and cancer cell migration and invasion was assessed using siRNA-mediated gene silencing. Data showed that both B[a]P and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone either at high or low dose performed no significant difference on A549 cell proliferation with time increasing. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone performed no significant difference on A549 cell migration and invasion while B[a]P significantly increased A549 cell migration and invasion compared to the control group (P A549 cells were significantly decreased compared to the control, respectively (P < 0.05), while silenced IL-8 drastically decreased the migrated and invasive cells compared to the control (P < 0.01). Taken together, this study illustrated that there may be significant correlation between smoking and lung cancer metastasis. B[a]P maybe an excellent contributor for lung cancer metastasis through up-regulating IL-8, CCL-2, and CCL-3 expression. © 2016 by the Society for Experimental Biology and Medicine.

  9. Theory and computational science

    International Nuclear Information System (INIS)

    Durham, P.

    1985-01-01

    The theoretical and computational science carried out at the Daresbury Laboratory in 1984/5 is detailed in the Appendix to the Daresbury Annual Report. The Theory, Computational Science and Applications Groups, provide support work for the experimental projects conducted at Daresbury. Use of the FPS-164 processor is also described. (U.K.)

  10. Protective effects of Carissa opaca fruits against CCl4-induced oxidative kidney lipid peroxidation and trauma in rat

    Directory of Open Access Journals (Sweden)

    Sumaira Sahreen

    2015-09-01

    Full Text Available Background: Carbon tetrachloride (CCl4 is a potent nephrotoxin, as it causes acute as well as chronic toxicity in kidneys. Therefore, this study was carried out to assess the pharmacological potential of different fractions of Carissa opaca fruits on CCl4-induced oxidative trauma in the kidney. Methods: The parameters studied in this respect were the kidney function tests viz, serum profile, urine profile, genotoxicity, characteristic morphological findings, and antioxidant enzymatic level of kidneys. Result: The protective effects of various fractions of C. opaca fruits against CCl4 administration were reviewed by rat renal function alterations. Chronic toxicity caused by 8-week treatment of CCl4 to the rats significantly decreased the pH level, activities of antioxidant enzymes, and glutathione contents, whereas a significant increase was found in the case of specific gravity, red blood cells, white blood cells, level of urea, and lipid peroxidation in comparison to control group. Administration of various fractions of C. opaca fruit with CCl4 showed protective ability against CCl4 intoxication by restoring the urine profile, activities of antioxidant enzymes, and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and glomerular atrophy by means of dilation, disappearance of Bowmen's space, congestion in the capillary loops, dilation in renal tubules, and foamy look of epithelial cells of tubular region, which were restored by co-admiration of various fractions of C. opaca. Conclusion: Results revealed that the methanolic fractions of C. opaca are the most potent and helpful in kidney trauma.

  11. 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.

  12. Role of Interleukin-17A on the Chemotactic Responses to CCL7 in a Murine Allergic Rhinitis Model.

    Science.gov (United States)

    Zhang, Yu-Lian; Han, Doo Hee; Kim, Dong-Young; Lee, Chul Hee; Rhee, Chae-Seo

    2017-01-01

    The proinflammatory cytokine interleukin (IL)-17A is associated with eosinophil infiltration into the nasal mucosa in a mouse model of ovalbumin-induced allergic rhinitis. Chemotaxis of eosinophils is mediated primarily through C-C chemokine receptor type 3 (CCR3). However, the mechanism underlying the IL-17A-mediated enhancement of eosinophil recruitment via chemoattractants/chemokines remains unknown. In this study, we assessed the contribution of IL-17A to eosinophil-related inflammation via the CCL7/CCR3 pathway in experimental allergic rhinitis. IL-17A knockout (KO) and wild-type (WT) BALB/c mice were injected intraperitoneally and challenged intranasally with OVA to induce allergic rhinitis. Various parameters of the allergic response were evaluated, and mRNA and protein levels of CCL7 and CCR3 in nasal tissue and serum were compared between the two groups. The chemotactic response to CCL7 with or without IL-17A in bone marrow-derived eosinophils (bmEos) from BALB/c mice was measured. In the allergic rhinitis model, IL-17A deficiency significantly decreased nasal symptoms, serum IgE levels, and eosinophil recruitment to the nasal mucosa. CCL7 and CCR3 mRNA and protein levels were decreased in the nasal mucosa of IL-17A KO mice compared with the WT mice. BmEos showed a significantly increased chemotactic response to -low concentration of CCL7 in the presence of IL-17A compared with its absence. The suppression of nasal inflammation due of IL-17A deficiency in allergic rhinitis is partly responsible for the regulation of CCL7 secretion and eosinophil infiltration, which may be regulated via the CCL7/CCR3 pathway.

  13. Effects of venom immunotherapy on serum level of CCL5/RANTES in patients with Hymenoptera venom allergy.

    Science.gov (United States)

    Gawlik, Radoslaw; Glück, Joanna; Jawor, Barbara; Rogala, Barbara

    2015-01-01

    Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction to Hymenoptera venom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91 ± 7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5 ± 322.77 versus 387.27 ± 85.11 pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5 ± 322.77 versus 567.32 ± 92.16 pg/ml). CCL5/RANTES serum doesn't correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced by Hymenoptera venom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy.

  14. CCL3 Enhances Antitumor Immune Priming in the Lymph NodeviaIFNγ with Dependency on Natural Killer Cells.

    Science.gov (United States)

    Allen, Frederick; Rauhe, Peter; Askew, David; Tong, Alexander A; Nthale, Joseph; Eid, Saada; Myers, Jay T; Tong, Caryn; Huang, Alex Y

    2017-01-01

    Lymph node (LN) plays a critical role in tumor cell survival outside of the primary tumor sites and dictates overall clinical response in many tumor types (1, 2). Previously, we and others have demonstrated that CCL3 plays an essential role in orchestrating T cell-antigen-presenting cell (APC) encounters in the draining LN following vaccination, and such interactions enhance the magnitude of the memory T cell pool (3-5). In the current study, we investigate the cellular responses in the tumor-draining lymph nodes (TDLNs) of a CCL3-secreting CT26 colon tumor (L3TU) as compared to wild-type tumor (WTTU) during the priming phase of an antitumor response (≤10 days). In comparison to WTTU, inoculation of L3TU resulted in suppressed tumor growth, a phenomenon that is accompanied by altered in vivo inflammatory responses on several fronts. Autologous tumor-derived CCL3 (aCCL3) secretion by L3TU bolstered the recruitment of T- and B-lymphocytes, tissue-migratory CD103 + dendritic cells (DCs), and CD49b + natural killer (NK) cells, resulting in significant increases in the differentiation and activation of multiple Interferon-gamma (IFNγ)-producing leukocytes in the TDLN. During this early phase of immune priming, NK cells constitute the major producers of IFNγ in the TDLN. CCL3 also enhances CD8+ T cell proliferation and differentiation by augmenting DC capacity to drive T cell activation in the TDLN. Our results revealed that CCL3-dependent IFNγ production and CCL3-induced DC maturation drive the priming of effective antitumor immunity in the TDLN.

  15. CCL3 Enhances Antitumor Immune Priming in the Lymph Node via IFNγ with Dependency on Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Frederick Allen

    2017-10-01

    Full Text Available Lymph node (LN plays a critical role in tumor cell survival outside of the primary tumor sites and dictates overall clinical response in many tumor types (1, 2. Previously, we and others have demonstrated that CCL3 plays an essential role in orchestrating T cell—antigen-presenting cell (APC encounters in the draining LN following vaccination, and such interactions enhance the magnitude of the memory T cell pool (3–5. In the current study, we investigate the cellular responses in the tumor-draining lymph nodes (TDLNs of a CCL3-secreting CT26 colon tumor (L3TU as compared to wild-type tumor (WTTU during the priming phase of an antitumor response (≤10 days. In comparison to WTTU, inoculation of L3TU resulted in suppressed tumor growth, a phenomenon that is accompanied by altered in vivo inflammatory responses on several fronts. Autologous tumor-derived CCL3 (aCCL3 secretion by L3TU bolstered the recruitment of T- and B-lymphocytes, tissue-migratory CD103+ dendritic cells (DCs, and CD49b+ natural killer (NK cells, resulting in significant increases in the differentiation and activation of multiple Interferon-gamma (IFNγ-producing leukocytes in the TDLN. During this early phase of immune priming, NK cells constitute the major producers of IFNγ in the TDLN. CCL3 also enhances CD8+ T cell proliferation and differentiation by augmenting DC capacity to drive T cell activation in the TDLN. Our results revealed that CCL3-dependent IFNγ production and CCL3-induced DC maturation drive the priming of effective antitumor immunity in the TDLN.

  16. Increased CCL24/eotaxin-2 with postnatal ozone exposure in allergen-sensitized infant monkeys is not associated with recruitment of eosinophils to airway mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Debbie L.; Gerriets, Joan E. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Schelegle, Edward S.; Hyde, Dallas M. [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States); Miller, Lisa A., E-mail: lmiller@ucdavis.edu [California National Primate Research Center, UC Davis, Davis, CA 95616 (United States); Department of Anatomy, Physiology, and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616 (United States)

    2011-12-15

    Epidemiology supports a causal link between air pollutant exposure and childhood asthma, but the mechanisms are unknown. We have previously reported that ozone exposure can alter the anatomic distribution of CD25+ lymphocytes in airways of allergen-sensitized infant rhesus monkeys. Here, we hypothesized that ozone may also affect eosinophil trafficking to allergen-sensitized infant airways. To test this hypothesis, we measured blood, lavage, and airway mucosa eosinophils in 3-month old monkeys following cyclical ozone and house dust mite (HDM) aerosol exposures. We also determined if eotaxin family members (CCL11, CCL24, CCL26) are associated with eosinophil location in response to exposures. In lavage, eosinophil numbers increased in animals exposed to ozone and/or HDM. Ozone + HDM animals showed significantly increased CCL24 and CCL26 protein in lavage, but the concentration of CCL11, CCL24, and CCL26 was independent of eosinophil number for all exposure groups. In airway mucosa, eosinophils increased with exposure to HDM alone; comparatively, ozone and ozone + HDM resulted in reduced eosinophils. CCL26 mRNA and immunofluorescence staining increased in airway mucosa of HDM alone animals and correlated with eosinophil volume. In ozone + HDM animal groups, CCL24 mRNA and immunofluorescence increased along with CCR3 mRNA, but did not correlate with airway mucosa eosinophils. Cumulatively, our data indicate that ozone exposure results in a profile of airway eosinophil migration that is distinct from HDM mediated pathways. CCL24 was found to be induced only by combined ozone and HDM exposure, however expression was not associated with the presence of eosinophils within the airway mucosa. -- Highlights: Black-Right-Pointing-Pointer Ozone can modulate the localization of eosinophils in infant allergic airways. Black-Right-Pointing-Pointer Expression of eotaxins within the lung is affected by ozone and allergen exposure. Black-Right-Pointing-Pointer CCL24 induction by

  17. Mechanism of the Inhibitory Effects of Eucommia ulmoides Oliv. Cortex Extracts (EUCE in the CCl4-Induced Acute Liver Lipid Accumulation in Rats

    Directory of Open Access Journals (Sweden)

    Chang-Feng Jin

    2013-01-01

    Full Text Available Eucommia ulmoides Oliv. (EU has been used for treatment of liver diseases. The protective effects of Eucommia Ulmoides Oliv. cortex extracts (EUCE on the carbon tetrachloride- (CCl4- induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4 decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4 treatment decreased glutathione (GSH and increased malondialdehyde (MDA accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4 treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4 reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.

  18. Elucidating a Key Anti-HIV-1 and Cancer-Associated Axis: The Structure of CCL5 (Rantes) in Complex with CCR5

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A.

    2014-06-01

    CCL5 (RANTES) is an inflammatory chemokine which binds to chemokine receptor CCR5 and induces signaling. The CCL5:CCR5 associated chemotactic signaling is of critical biological importance and is a potential HIV-1 therapeutic axis. Several studies provided growing evidence for the expression of CCL5 and CCR5 in non-hematological malignancies. Therefore, the delineation of the CCL5:CCR5 complex structure can pave the way for novel CCR5-targeted drugs. We employed a computational protocol which is primarily based on free energy calculations and molecular dynamics simulations, and report, what is to our knowledge, the first computationally derived CCL5:CCR5 complex structure which is in excellent agreement with experimental findings and clarifies the functional role of CCL5 and CCR5 residues which are associated with binding and signaling. A wealth of polar and non-polar interactions contributes to the tight CCL5:CCR5 binding. The structure of an HIV-1 gp120 V3 loop in complex with CCR5 has recently been derived through a similar computational protocol. A comparison between the CCL5 : CCR5 and the HIV-1 gp120 V3 loop : CCR5 complex structures depicts that both the chemokine and the virus primarily interact with the same CCR5 residues. The present work provides insights into the blocking mechanism of HIV-1 by CCL5.

  19. FOXA2 alleviates CCl4-induced liver fibrosis by protecting hepatocytes in mice

    OpenAIRE

    Wang, Wei; Yao, Li-Jia; Shen, Weifeng; Ding, Kai; Shi, Pei-Mei; Chen, Fei; He, Jin; Ding, Jin; Zhang, Xin; Xie, Wei-Fen

    2017-01-01

    The liver-enriched transcription factor Forkhead Box A2 (FOXA2) has been reported to be involved in bile acid homeostasis and bile duct development. However, the role of FOXA2 in liver fibrogenesis remains undefined. In this study, we found that the abundance of FOXA2 was significantly lower in fibrotic livers of patients and mice treated with CCl4 than in controls. Interestingly, the expression level of FOXA2 decreased in hepatocytes, whereas FOXA2 was elevated in hepatic stellate cells (HSC...

  20. The hepatoprotective action of ten herbal extracts in CCl4 intoxicated liver.

    Science.gov (United States)

    Rusu, M A; Tamas, M; Puica, C; Roman, Ioana; Sabadas, Mihaela

    2005-09-01

    The effect of ten phytotherapeutic products on CCl(4) intoxicated liver in albino male Wistar rats was investigated. Biochemical parameters, including serum transaminase activity (GPT and GOT), histoenzymological measurements (lactate dehydrogenase, LDH; succinate dehydrogenase, SDH, cytochromoxidase, CyOx; Mg(2+)-dependent adenosine triphosphatase, ATP-ase) and histochemical (Sudan black) and histological examinations (haematoxylin-eosin staining) of the liver were investigated. Some positive effects such as the reduction of hepatocytolysis and steatosis, and a return to normal values of the activity of some enzymes in the following plants: Chrysanthemum balsamita, Echinacea pallida, Calendula officinalis and Corylus avelana were obtained. Copyright 2005 John Wiley & Sons, Ltd.

  1. Ultrasonic assisted synthesis of gem-dichloroaziridine derivatives using Mg/CCl4 under neutral conditions.

    Science.gov (United States)

    Rabiei, Khadijeh; Naeimi, Hossein

    2015-05-01

    A novel and convenient method for synthesis of gem-dichloroaziridine derivatives was reported in that was utilized Mg powder with CCl4 for dichlorocarbene generation under ultrasonic irradiation. In this clean and efficient reaction procedure, the desired products were purely obtained in excellent yields. The other advantages of this method are availability of reagents, very short reaction times, simplicity of the method, easily work up, neutral reaction medium and high purity of products. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Genetic and bibliographic information: CCL3L1 [GenLibi

    Lifescience Database Archive (English)

    Full Text Available CCL3L1 chemokine (C-C motif) ligand 3-like 1 human HIV Infections (MeSH); HIV-1 Virus Diseases...ctions (C02.782.815.616) > HIV Infections (C02.782.815.616.400) Virus Diseases (C02) > Sexually Transmitted Diseases... (C02.800) > Sexually Transmitted Diseases, Viral (C02.800.801) > HIV Inf...ections (C02.800.801.400) Immune System Diseases (C20) > Immunologic Deficiency Syndromes (C20.673) > HIV Infections (C20.673.480) 05A0287080 ...

  3. Protective Effect of γ-Irradiated Dried Powder of Artichoke Leaves against CCl4 Oxidative Stress Induced in Rat Liver

    International Nuclear Information System (INIS)

    Hamza, R.G.; El shahat, A.N.; Mekawey, H.M.S.

    2012-01-01

    Liver injuries are one of the most degenerative worldwide diseases and can lead to different complications. Artichoke (Cynara scolymus L.) is full of natural antioxidants and has hepato protective effect against liver toxicity. Gamma irradiation has been widely used as a first choice sterilization method of raw medicinal plants to be used in the phytotherapic industry worldwide .This study was designed to investigate the effect of dietary supplementation with γ- irradiated artichoke against carbon tetrachloride (CCl 4 )-induced oxidative stress and hepatotoxicity. The results of high performance liquid chromatography (HPLC) analysis of artichoke leaves indicated that the value of some of the main phenolic constituents was elevated under the effect of γ-irradiation (10 KGy). CCl 4 administration resulted in significant increase in the activity of serum alkaline phosphatase, gamma glutamyl transferase and transaminase in addition to an increase in the level of total bilirubine, malondialdehyde (MDA), glucose and the concentration of some lipid contents. Furthermore, CCl 4 administration reduced glutathione content, superoxides dismutase (SOD) and catalase (CAT) activity as well as a remarkable decrease in the level of insulin and high density lipoprotein-cholesterol was observed. In CCl 4 -treated rats dietary supplemented with either raw or γ-irradiated artichoke, a significant amelioration was observed on the adverse effects of the above mentioned parameters induced by CCl 4 administration. The present findings concluded that artichoke may be useful, as dietary supplement and possess phenolic compounds, for the prevention of oxidative stress-induced hepatotoxicity

  4. Levo-Corydalmine Alleviates Neuropathic Cancer Pain Induced by Tumor Compression via the CCL2/CCR2 Pathway

    Directory of Open Access Journals (Sweden)

    Yahui Hu

    2017-06-01

    Full Text Available Background: Tumor compression-induced pain (TCIP is a complex pathological cancer pain. Spinal glial cells play a critical role in maintenance of cancer pain by releasing proinflammatory cytokines and chemokines. In this study, we verified the role of levo-corydalmine (l-CDL on TCIP. Methods: Spontaneous pain, paw withdrawal threshold and latency were assessed using TCIP mouse model. Immunofluorescence was used to identify the reactions of glia. RT-PCR and western blot or ELISA were used to determine mRNA or protein expression of tumor necrosis factor-α (TNF-α, interlukin-1β (IL-1β, CC chemokine ligand 2 (CCL2 and chemotactic cytokine receptor 2 (CCR2 in vivo and in vitro. Results: l-CDL significantly attenuated TCIP hypersensitivity, accompanying with downregulation of TNF-α and IL-1β expression levels and declined astrocytes and microglial activation. It also significantly decreased the expression of the mRNA and protein level for CCL2 and CCR2. Further, l-CDL could suppress TNF-α-induced astrocytes activation and IL-1β expression through downregulating the CCL2/CCR2. Besides, CCL2-induced BV-microglia activation and inflammatory factors secretion were suppressed by l-CDL via CCR2. Conclusions: Suppression of CCL2/CCR2 by l-CDL may contribute to alleviate TCIP, offering an alternative medication for TCIP.

  5. Effect of leaf extracts of Taraxacum officinale on CCl4 induced hepatotoxicity in rats, in vivo study.

    Science.gov (United States)

    Gulfraz, Muhammad; Ahamd, Dawood; Ahmad, Muhammad Sheeraz; Qureshi, Rehmatullah; Mahmood, Raja Tahir; Jabeen, Nyla; Abbasi, Kashif Sarfraz

    2014-07-01

    Taraxacum officinale L is a medicinal plant, which has enormous medicinal values against various types of liver disorders and it has traditionally been used for the treatment of liver problems by people from the South East Asia. Previously we have screened the crude methanolic extract of T. officinale against cytotoxicity induced by CCl4. Present study was designed to compare the protective effect of ethanolic and n-hexane extract of leaves in carbon tetrachloride (CCl4) induced liver toxicity in rats. The extract (200 mg/kg and 400mg/kg body weight) along with silymarin (100 mg/kg) a standard drug was administered to experimental animals. It was observed that ethanolic plant extract has significantly reduced the negative effect of CCl4 as compared to n-hexane extract and effect of extract was increased with increasing dose level. Although both leaf extracts decreased the concentration of TBARS, H2O2 and nitrite contents which enhance due to CCl4 toxicity but effect was higher in ethanolic extract. The results clearly indicated that Taraxacum officinale ethanolic leaves extract has better protective effect against CCl4 induced liver tissues toxicity. This claim was also supported by histopathological results obtained during this study and this might be due to presence of various polar phytochemicals that might be more prevent in this extract.

  6. Acetonic and Methanolic Extracts of Heterotheca inuloides, and Quercetin, Decrease CCl4-Oxidative Stress in Several Rat Tissues

    Science.gov (United States)

    Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Cárdenas-Rodríguez, Noemí; Huerta-Gertrudis, Bernardino; García-Cruz, Mercedes Edna; Montesinos-Correa, Hortencia; Sánchez-González, Dolores Javier; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

    2013-01-01

    The present study was designed to test the hypothesis that the acetonic and methanolic extracts of H. inuloides prevent carbon tetrachloride-(CCl4) induced oxidative stress in vital tissues. Pretreatment with both H. inuloides extracts or quercetin attenuated the increase in serum activity of alkaline phosphatase (ALP), total bilirubin (BB), creatinine (CRE), and creatine kinase (CK), and impeded the decrease of γ-globulin (γ-GLOB) and albumin (ALB) observed in CCl4-induced tissue injury. The protective effect was confirmed by histological analysis with hematoxylin-eosin and periodic acid/Schiff's reagent. Level of lipid peroxidation was higher in the organs of rats exposed to CCl4 than in those of the animals treated with Heterohteca extracts or quercetin, and these showed levels similar to the untreated group. Pretreatment of animals with either of the extracts or quercetin also prevented the increase of 4-hydroxynonenal and 3-nitrotyrosine. Pretreatment with the plant extracts or quercetin attenuated CCl4 toxic effects on the activity of several antioxidant enzymes. The present results strongly suggest that the chemopreventive effect of the extracts used and quercetin, against CCl4 toxicity, is associated with their antioxidant properties and corroborated previous results obtained in liver tissue. PMID:23365610

  7. Human MSCs promotes colorectal cancer epithelial-mesenchymal transition and progression via CCL5/β-catenin/Slug pathway.

    Science.gov (United States)

    Chen, Ke; Liu, Qianqian; Tsang, Lai Ling; Ye, Qiao; Chan, Hsiao Chang; Sun, Yunwei; Jiang, Xiaohua

    2017-05-25

    Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stroma cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) progression and metastasis is controversial. This study was designed to identify the role of inflammation-activated-MSCs in CRC development. Our results show that tumor necrosis factor (TNF)-α-preactivated-hMSCs significantly promote the progression of colon cancer cells by enhancing cell proliferation, epithelial-mesenchymal transition, migration, and invasion. TNF-α-primed-hMSCs secrete high level of CCL5, which interacts with its receptor CCR1 expressed in colon cancer cells. Interestingly, the stimulation of colon cancer cell progression by TNF-α-primed hMSCs is associated with the upregulation of β-catenin signaling pathway. Blocking β-catenin pathway significantly decreases the TNF-α-primed-conditioned medium or CCL5-mediated cancer cell progression by decreasing the enhancement of Slug, suggesting that the CCL5/β-catenin/Slug pathway plays a critical role in hMSC-mediated cancer progression. Furthermore, in vivo model in nude mice confirms the ability of hMSCs to promote the proliferation and progression of colon cancer cells, and the upregulation of CCl5/β-catenin/Slug pathway. Taken together, the present study has demonstrated a novel pathway involving CCl5/CCR1/β-catenin/Slug, via which hMSCs promotes CRC development.

  8. Social stress-enhanced severity of Citrobacter rodentium induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri

    Science.gov (United States)

    Mackos, Amy R.; Galley, Jeffrey D.; Eubank, Timothy D.; Easterling, Robert S.; Parry, Nicola M.; Fox, James G.; Lyte, Mark; Bailey, Michael T.

    2015-01-01

    Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2−/− mice, indicating the effects of the stressor are CCL2-dependent. Additionally, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon, and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through a down-regulation of the chemokine CCL2. PMID:26422754

  9. Genetic polymorphism of CCL2-2510 and susceptibility to enterovirus 71 encephalitis in a Chinese population.

    Science.gov (United States)

    Han, Zhen-liang; Li, Ji-an; Chen, Zong-bo

    2014-09-01

    The study was performed in 36 Chinese patients with enterovirus 71 (EV71) encephalitis and 141 patients with EV71-related hand, foot and mouth disease (HFMD) without encephalitis. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism technique. Patients with EV71 encephalitis had a significantly higher frequency of the CCL2-2510GG genotypes when compared to patients with EV71-related HFMD without encephalitis (66.7% vs. 41.8%, p=0.028). The frequency of CCL2-2510G alleles was also significantly higher among the patients with EV71 encephalitis than among patients with EV71-related HFMD without encephalitis (79.2% vs. 64.9%, OR=2.1, 95% CI=1.1-3.8, P=0.023). Significant differences were found in gender, age, fever days, white blood cell count, C-reactive protein level, blood glucose concentration, and CCL2 level among genotypes of CCL2-2510A/G in EV71-infected patients, but no significant differences were found in alanine aminotransferase, aspartate aminotransferase, or creatine kinase myocardial isozyme levels or in cerebrospinal fluid evaluations (except monocytes) in patients with EV71 encephalitis. These findings suggest that the CCL2-2510G allele is associated with susceptibility to EV71 encephalitis in Chinese patients.

  10. Bioassay Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Bioassay Laboratory is an accredited laboratory capable of conducting standardized and innovative environmental testing in the area of aquatic ecotoxicology. The...

  11. HYDROMECHANICS LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — Naval Academy Hydromechanics LaboratoryThe Naval Academy Hydromechanics Laboratory (NAHL) began operations in Rickover Hall in September 1976. The primary purpose of...

  12. The CCl4 action upon physiological indices in Lepus timidus and the protective role of some substances

    Directory of Open Access Journals (Sweden)

    Alina PAUNESCU

    2009-11-01

    Full Text Available Aim of this study is to demonstrate the hepatoprotective role of grape seed oil and Cynara scolymus leaf extract. This experiment lasted for 12 days performed on male and female rabbit. The animals were intoxicated in the latest day of experiment (day 12th with CCl4 in a dose of 30μl/100g body weight and a group of them was treated for 12 days with 0.4 mg/kg body weight/day of Cynara scolymus (artichoke leaf extract while another group was treated with grape seed oil (1ml/kg body weight/day. Intoxication with CCl4 caused an increase a glycemia and a number of leukocytes, decrease cholesterol, triglycerides value, and a number of erythrocytes. We observed that the extract of Cynara scolymus leaf and the grape seed oil had a protective effect against CCl4 intoxication.

  13. NF-kappaB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Babcock, Alicia A; Owens, Trevor

    2008-01-01

    -regulation and phosphorylation were NF-kappaB -dependent since they did not occur in the lesion-reactive hippocampus of transgenic mice with specific inhibition of NF-kappaB activation in astrocytes. We further showed that lack of NF-kappaB signaling significantly reduced injury-induced CCL2 expression as well as leukocyte...... infiltration. Our results suggest that NF-kappaB signaling in astrocytes controls expression of both STAT2 and CCL2, and thus regulates infiltration of leukocytes into lesion-reactive hippocampus after axonal injury. Taken together, these findings indicate a central role for astrocytes in directing immune...... induces glial response. Astrocytes are the major glial population in the CNS. We examined expression of STATs and the chemokine CCL2 and their relationship to astroglial NF-kappaB signaling in the CNS following axonal transection. Double labeling with Mac-1/CD11b and glial fibrillary acidic protein...

  14. Statins induce regulatory T cell recruitment via a CCL1 dependent pathway.

    Science.gov (United States)

    Mira, Emilia; León, Beatriz; Barber, Domingo F; Jiménez-Baranda, Sonia; Goya, Iñigo; Almonacid, Luis; Márquez, Gabriel; Zaballos, Angel; Martínez-A, Carlos; Stein, Jens V; Ardavín, Carlos; Mañes, Santos

    2008-09-01

    The statins, a group of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are reported to influence a variety of immune system activities through 3-hydroxy-3-methylglutaryl coenzyme A reductase-dependent and -independent mechanisms. How statin treatment regulates immune system function in vivo nonetheless remains to be fully defined. We analyzed the immunomodulatory effects of lovastatin in a Candida albicans-induced delayed-type hypersensitivity reaction in mice. In this model, lovastatin administration reduced the acute inflammatory response elicited by C. albicans challenge. This anti-inflammatory activity of lovastatin was associated with a shift from a Th1 to a Th2 immune response, as well as an increase in the percentage of regulatory T cells at the inflammation site and in the regional draining lymph node. The lovastatin-induced increase in regulatory T cells in the inflamed skin was dependent on expression of CCL1, a chemokine that is locally up-regulated by statin administration. The anti-inflammatory effect of lovastatin was abrogated in CCL1-deficient mice. These results suggest that local regulation of chemokine expression may be an important process in statin-induced modulation of the immune system.

  15. FOXA2 alleviates CCl4-induced liver fibrosis by protecting hepatocytes in mice.

    Science.gov (United States)

    Wang, Wei; Yao, Li-Jia; Shen, Weifeng; Ding, Kai; Shi, Pei-Mei; Chen, Fei; He, Jin; Ding, Jin; Zhang, Xin; Xie, Wei-Fen

    2017-11-14

    The liver-enriched transcription factor Forkhead Box A2 (FOXA2) has been reported to be involved in bile acid homeostasis and bile duct development. However, the role of FOXA2 in liver fibrogenesis remains undefined. In this study, we found that the abundance of FOXA2 was significantly lower in fibrotic livers of patients and mice treated with CCl 4 than in controls. Interestingly, the expression level of FOXA2 decreased in hepatocytes, whereas FOXA2 was elevated in hepatic stellate cells (HSCs) of mouse fibrotic livers. Hepatocyte-specific ablation of FOXA2 in adult mice exacerbated liver fibrosis induced by CCl 4 . Either lentivirus LV-CMV-FOXA2 mediated FOXA2 overexpression in the liver or adeno-associated virus AAV8-TBG-FOXA2-mediated hepatocyte-specific upregulation of FOXA2 alleviated hepatic fibrosis. Overexpression of FOXA2 in HSCs did not obviously affect hepatic fibrogenesis. Additionally, FOXA2 knockout in hepatocytes resulted in aberrant transcription of metabolic genes. Furthermore, hepatocyte-specific knockout of FOXA2 enhanced endoplasmic reticulum stress (ER stress) and the apoptosis of hepatocytes, whereas FOXA2 overexpression in hepatocytes suppressed ER stress and hepatocyte apoptosis in mouse fibrotic livers. In conclusion, our findings suggested that FOXA2-mediated hepatocyte protection has a therapeutic role in hepatic fibrosis, and thus may be a new, promising anti-fibrotic option for treating chronic liver diseases.

  16. Peripheral Neuropathic Facial/Trigeminal Pain and RANTES/CCL5 in Jawbone Cavitation

    Directory of Open Access Journals (Sweden)

    Johann Lechner

    2015-01-01

    Full Text Available Introduction. In this study, we elucidate the possible causative role of chronic subclinical inflammation in jawbone of patients with atypical facial pain (AFP and trigeminal neuralgia (TRN in the local overexpression of the chemokine regulated on activation and normal T-cell expressed and secreted (RANTES/C-C motif ligand 5 CCL5. Neurons contain opioid receptors that transmit antipain reactions in the peripheral and central nervous system. Proinflammatory chemokines like RANTES/CCL5 desensitize μ-opioid receptors in the periphery sensory neurons and it has been suggested that RANTES modifies the nociceptive reaction. Materials and Methods. In 15 patients with AFP/TRN, we examined fatty degenerated jawbone (FDOJ samples for the expression of seven cytokines by multiplex analysis and compared these results with healthy jawbones. Results. Each of these medullary jawbone samples exhibited RANTES as the only highly overexpressed cytokine. The FDOJ cohort with AFP/TRN showed a mean 30-fold overexpression of RANTES compared to healthy jawbones. Conclusions. To the best of our knowledge, no other research has identified RANTES overexpression in silent inflamed jawbones as a possible cause for AFP/TRN. Thus, we hypothesize that the surgical clearing of FDOJ might diminish RANTES signaling pathways in neurons and contribute to resolving chronic neurological pain in AFP/TRN patients.

  17. Neuropathic pain inhibitor, RAP-103, is a potent inhibitor of microglial CCL1/CCR8.

    Science.gov (United States)

    Noda, Mami; Tomonaga, Daichi; Kitazono, Kota; Yoshioka, Yusaku; Liu, Jiadai; Rousseau, Jean-Philippe; Kinkead, Richard; Ruff, Michael R; Pert, Candace B

    2017-12-14

    Chemokine signaling is important in neuropathic pain, with microglial cells expressing chemokine (C-C motif) receptor CCR2, CCR5 and CCR8, all playing key roles. In the previous report (Padi et al., 2012), oral administration of a short peptide, RAP-103, for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rodents. As for the mechanism of the inhibiting effect of RAP-103, it was speculated to be due to dual blockade of CCR2 and CCR5. We report here that RAP-103 exhibits stronger antagonism for CCR8 (half maximal inhibitory concentration [IC 50 ] 7.7 fM) compared to CCR5 (IC 50  < 100 pM) in chemotaxis using primary cultured mouse microglia. In addition, RAP-103 at a concentration of 0.1 pM completely inhibits membrane ruffling and phagocytosis induced by chemokine (C-C motif) ligand 1 (CCL1), an agonist for CCR8. It has been shown that CCL1/CCR8 signaling is important in tactile allodynia induced by nerve ligation. Therefore, CCR8, among other chemokine receptors such as CCR2/CCR5, could be the most potent target for RAP-103. Inhibitory effects of RAP-103 on plural chemokine receptors may play important roles for broad clinical use in neuropathic pain treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Leakage Performance of the GM + CCL Liner System for the MSW Landfill

    Directory of Open Access Journals (Sweden)

    Fan Jingjing

    2014-01-01

    Full Text Available The contaminants in the landfill leachate press pose a grave threat to environment of the soil and the groundwater beneath the landfill. Despite there being strict requirements in relevant provisions of both domestic and foreign countries for the design of the bottom liner system. Pollution of the soil and the groundwater still took place in a number of landfills because of the leakage. To investigate the leakage rate of the liner systems, the minimum design requirements of the liner systems are summarized according to the provisions of four countries, including China, USA, Germany, and Japan. Comparative analyses using one-dimensional transport model are conducted to study the leakage performance of these liner systems composed of geomembrance (GM and compacted clay layer (CCL meeting the relevant minimum design requirements. Then parametric analyses are conducted to study the effects of the hydraulic head, the thickness of GM, the hydraulic conductivity of CCL, and so forth on the leakage performance of the liner system. It is concluded that the liner system designed according to the minimum design requirements of Germany provide the best antileakage performance, while that of Japan performs the lowest. The key parameters affecting the failure time of the liner system are summarized. Finally, some suggestions for the design of the liner systems are made according to the analyses.

  19. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

    Science.gov (United States)

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

    2014-01-09

    Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

  20. Antioxidant Potential of Plumieride against CCl4-Induced Peroxidative Damage in Rats

    Directory of Open Access Journals (Sweden)

    Dharmendra Singh

    2014-11-01

    Full Text Available In search of a new potent as an antioxidant from natural sources, plumieride—an iridoid isolated from the methanol extract of the bark of Plumeria bicolor (family Apocynaceae was evaluated for its antioxidant potential against CCl4-induced peroxidative damage in liver of rats. The antioxidant potential was evaluated by using hepatic tissue for SOD (superoxide dismutase, CAT (catalase, GSH (reduced glutathione, GPx (glutathione peroxidase, GR (glutathione reductase and LPO (lipid peroxidation alongwith the concomitant blood serum for AST & ALT (aspartate and alanine transaminases, GGT (gamma glutamyl transpeptidase, ALP (alkaline phosphatase, total bilirubin and total protein contents. All the biochemical parameters were significantly (p ≤ 0.001 altered by CCl4 (0.3 mL/kg body weight/twice a week, intra-peritoneally for 30 days. Simultaneously, oral treatment with plumieride (5, 10 and 20 mg/kg body weight/day for 30 days, restored all the parameters towards a normal level, remarkably. The histological findings of liver sections further corroborated the antioxidant potential of plumieride compared with standard drug-silymarin. In conclusion, plumieride consists of sugar molecules, which have alcoholic groups. Therefore, the alcoholic groups of sugar increase its antioxidant potential through intermolecular hydrogen bonding along with the thiol(SH group of non-protein thiols and enzymes resulting in the restoration of the antioxidant system. Therefore, it might be considered a natural antioxidant against peroxidative damage in rats.

  1. Protective effect of Spirulina platensis enriched in phenolic compounds against hepatotoxicity induced by CCl4.

    Science.gov (United States)

    Kepekçi, Remziye Aysun; Polat, Sait; Çelik, Ahmet; Bayat, Nuray; Saygideger, Saadet Demirörs

    2013-12-01

    Phenolic compounds make up the major secondary metabolites with high pharmaceutical potential. Microalgae were reported to contain low amounts of phenolic compounds. The present study aimed to investigate the hepatoprotective potential of biomass of Spirulina platensis enriched in phenolic compounds. The protective effects of the biomass of S. platensis with low amounts of phenolics (SP1) and with high amounts of phenolics (SP2) against CCl4-induced acute hepatotoxicity were evaluated in rats. The increased levels of ALT, AST and MDA along with decreased activities of SOD and CAT were significantly (p<0.01) ameliorated by SP2. Histological examinations revealed that SP2 was more potent than SP1 in protecting the liver from toxic injury of CCl4 and preserving the hepatocyte ultrastructure. The lesions including necrosis, lymphocyte infiltration, ballooning degeneration and hepatocyte injury as irregular lamellar organisation, dilations in endoplasmic reticulums and the presence of great number of cytoplasmic vacuolization were healed by SP2. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21.

    Directory of Open Access Journals (Sweden)

    Ana B Sanz

    2010-01-01

    Full Text Available TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFkappaB activation suggestive of engagement of the non-canonical NFkappaB pathway. We now explore TWEAK-induced activation of NFkappaB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFalpha activated different DNA-binding NFkappaB complexes. TWEAK-induced sustained NFkappaB activation was associated with NFkappaB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFalpha used as control, induced a delayed increase in CCL21a mRNA (3.5+/-1.22-fold over control and CCL21 protein (2.5+/-0.8-fold over control, which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFkappaB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFalpha. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h. In vivo, TWEAK induced nuclear NFkappaB2 and RelB translocation and CCL21a mRNA (1.5+/-0.3-fold over control and CCL21 protein (1.6+/-0.5-fold over control expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2+/-0.9 vs 1.3+/-0.6-fold over healthy control or deficiency of TWEAK (2+/-0.9 vs 0.8+/-0.6-fold over healthy control. Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1+/-1.4 vs 1.8+/-1-fold over healthy control. Our results thus identify TWEAK as a regulator of non-canonical NFkappa

  3. NF-kappaB-driven STAT2 and CCL2 expression in astrocytes in response to brain injury

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Babcock, Alicia A; Owens, Trevor

    2008-01-01

    -regulation and phosphorylation were NF-kappaB -dependent since they did not occur in the lesion-reactive hippocampus of transgenic mice with specific inhibition of NF-kappaB activation in astrocytes. We further showed that lack of NF-kappaB signaling significantly reduced injury-induced CCL2 expression as well as leukocyte...... infiltration. Our results suggest that NF-kappaB signaling in astrocytes controls expression of both STAT2 and CCL2, and thus regulates infiltration of leukocytes into lesion-reactive hippocampus after axonal injury. Taken together, these findings indicate a central role for astrocytes in directing immune...

  4. Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate

    Directory of Open Access Journals (Sweden)

    Ju-Ri Sim

    2018-01-01

    Full Text Available Short-chain fatty acids (SCFAs, such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP. Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

  5. Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Hirokazu Nakatsumi

    2017-11-01

    Full Text Available C-C chemokine ligand 2 (CCL2 plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF-κB signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1 but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1 as a downstream target of mTORC1. Activation of mTORC1 induces dephosphorylation of FOXK1, resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-κB and that CCL2 produced by this pathway contributes to tumor progression.

  6. CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals

    Directory of Open Access Journals (Sweden)

    Lin-Lin Lu

    2016-01-01

    Full Text Available Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3β mediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients.

  7. Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate.

    Science.gov (United States)

    Sim, Ju-Ri; Kang, Seok-Seong; Lee, Daesang; Yun, Cheol-Heui; Han, Seung Hyun

    2018-01-01

    Short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect. Enhanced CCL20 secretion was associated with GPR109A activation, and histone deacetylase (HDAC) inhibition. In addition, co-treatment with Shanchol™ and butyrate synergistically increased the secretion of adenosine triphosphate (ATP). Moreover, CCL20 secretion was decreased by inhibiting the extracellular ATP receptor P2X7. However, neither inflammasomes nor caspases were involved in CCL20 production. The culture supernatant of cells treated with Shanchol™ and butyrate augmented human immature dendritic cell migration. Collectively, these results suggest that butyrate enhances Shanchol™-induced CCL20 production in human intestinal epithelial cells via HDAC inhibition and ATP-P2X7 signaling by activating GPR109A. These effects potentially enhance the mucosal immune responses in the gut induced by this oral cholera vaccine.

  8. The CCL3L1-CCR5 genotype influences the development of AIDS, but not HIV susceptibility or the response to HAART

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Tanmoy [Los Alamos National Laboratory; Stanton, Jennifer [NORTHWESTERN UNIV; Kim, Eun - Young [NORTHWESTERN UNIV; Kunstman, Kevin [NORTHWESTERN UNIV; Phair, John [NORTHWESTERN UNIV; Jacobson, Lisa P [JOHNS HOPKINS UNIV; Wolinsky, Steven M [NORTHWESTERN UNIV

    2008-01-01

    A selective advantage against infectious diseases such as HIV/AIDS is associated with differences in the genes relevant to immunity and virus replication. The CC chemokine receptor 5 (CCR5), the principal coreceptor for HIV, and its chemokine ligands, including CCL3L1, influences the CD4+ target cells susceptibility to infection. The CCL3L1 gene is in a region of segmental duplication on the q-arm of human chromosome 17. Increased numbers of CCL3L1 gene copies that affect the gene expression phenotype might have substantial protective effects. Here we show that the population-specific CCL3L1 gene copy number and the CCR5 {Delta}32 protein-inactivating deletion that categorizes the CCL3L1-CCR5 genotype do not influence HIV/AIDS susceptibility or the robustness of immune recovery after the initiation of highly active antiretroviral therapy (HAART).

  9. 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.

  10. Superconducting Super Collider Laboratory coupled-cavity linac mechanical design

    International Nuclear Information System (INIS)

    Starling, W.J.; Cain, T.

    1992-01-01

    A collaboration between the Superconducting Super Collider Laboratory (SSCL) and the Los Alamos National Laboratory (LANL) for the engineering and mechanical design of the SSCL Coupled-Cavity Linac (CCL) has yielded an innovative example of the well known side coupled-cavity type of linear accelerator. The SSCL CCL accelerates an H - beam from 70 MeV to 600 MeV with an rf cavity structure consisting of eight tanks in each of nine modules for a total length of about 112 meters. Magnetically-coupled bridge couplers transfer power from tank to tank within a module. A single rf power input is located at the center bridge coupler of each module. The bridge couplers permit placement along the beam line of combined function focusing/steering electromagnets and diagnostic pods for beam instrumentation. Each tank and bridge coupler is rf frequency stabilized, nominally to 1,283 MHz, by water pumped through integral water passages. Air isolation grooves surround the water passages at each braze joint so that water-to-vacuum interfaces are avoided. Each tank is supported by adjustable spherical bearing rod end struts to permit alignment and accommodate thermal expansion and contraction of the rf structure. Tank struts, electromagnet/diagnostic pod support frames, vacuum manifolds and utilities are all mounted to a girder-and-leg support stand running the full length of the CCL. (Author) tab., fig

  11. Relationship of serum CCL20 and PCDGF levels with recurrence of non-small cell lung cancer after thoracoscopic radical operation

    Directory of Open Access Journals (Sweden)

    Peng-Kun Wang

    2016-09-01

    Full Text Available Objective: To study the relationship of serum CCL20 and PCDGF levels with recurrence of non-small cell lung cancer after thoracoscopic radical operation. Method: A total of 93 patients with non-small cell lung cancer who received thoracoscopic radical operation in our hospital were selected, followed up for 2 years and divided into recurrence group and non-recurrence group, serum was collected before operation as well as 30 d and 90 d after operation to determine CCL20 and PCDGF levels, chest CT perfusion imaging was carried out after recurrence and the perfusion parameters were measured, and recurrent tumor tissue was collected to determine apoptosis molecule levels. Results: Before operation as well as 30 d and 90 d after operation, serum CCL20 and PCDGF levels of recurrence group and nonrecurrence group were not significantly different; 180 d after operation, serum CCL20 and PCDGF levels of recurrence group were significantly higher than those of non-recurrence group, and there were significant differences between two groups. Patients with recurrence were grouped according to serum CCL20 and PCDGF levels 180 d after operation, BF, BV and PS of recurrent patients with high CCL20 and PCDGF levels were sig.nificantly higher than those of recurrent patients with low CCL20 and PCDGF levels while MTT and TTP as well as Caspase-3, -8, -9, pULK, Beclin1, PICKC3, Atg21 and Atg24 levels in tumor tissue were lower than those of recurrent patients with low CCL20 and PCDGF levels. Conclusion: Monitoring of postoperative serum CCL20 and PCDGF levels can provide reference for the evaluation of postoperative non-small cell lung cancer recurrence, and serum CCL20 and PCDGF levels 180 d after operation are closely related to tumor tissue perfusion and cell apoptosis.

  12. Copy number variation of CCL3-like genes affects rate of progression to simian-AIDS in Rhesus Macaques (Macaca mulatta.

    Directory of Open Access Journals (Sweden)

    Jeremiah D Degenhardt

    2009-01-01

    Full Text Available Variation in genes underlying host immunity can lead to marked differences in susceptibility to HIV infection among humans. Despite heavy reliance on non-human primates as models for HIV/AIDS, little is known about which host factors are shared and which are unique to a given primate lineage. Here, we investigate whether copy number variation (CNV at CCL3-like genes (CCL3L, a key genetic host factor for HIV/AIDS susceptibility and cell-mediated immune response in humans, is also a determinant of time until onset of simian-AIDS in rhesus macaques. Using a retrospective study of 57 rhesus macaques experimentally infected with SIVmac, we find that CCL3L CNV explains approximately 18% of the variance in time to simian-AIDS (p<0.001 with lower CCL3L copy number associating with more rapid disease course. We also find that CCL3L copy number varies significantly (p<10(-6 among rhesus subpopulations, with Indian-origin macaques having, on average, half as many CCL3L gene copies as Chinese-origin macaques. Lastly, we confirm that CCL3L shows variable copy number in humans and chimpanzees and report on CCL3L CNV within and among three additional primate species. On the basis of our findings we suggest that (1 the difference in population level copy number may explain previously reported observations of longer post-infection survivorship of Chinese-origin rhesus macaques, (2 stratification by CCL3L copy number in rhesus SIV vaccine trials will increase power and reduce noise due to non-vaccine-related differences in survival, and (3 CCL3L CNV is an ancestral component of the primate immune response and, therefore, copy number variation has not been driven by HIV or SIV per se.

  13. 78 FR 61873 - Revisions to the Export Administration Regulations (EAR) To Make the Commerce Control List (CCL...

    Science.gov (United States)

    2013-10-04

    ...] RIN 0694-AF37 Revisions to the Export Administration Regulations (EAR) To Make the Commerce Control... Revisions to the Export Administration Regulations (EAR) To Make the Commerce Control List (CCL) Clearer... Administration Regulations: Initial Implementation of Export Control Reform; and the July 8, 2013 final rule...

  14. Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model

    DEFF Research Database (Denmark)

    Getschman, A E; Imai, Y; Larsen, O

    2017-01-01

    Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, γδ T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Toget...

  15. Chemokine CCL2 and its receptor CCR2 in the dorsal root ganglion contribute to oxaliplatin-induced mechanical hypersensitivity.

    Science.gov (United States)

    Illias, A M; Gist, A C; Zhang, H; Kosturakis, A K; Dougherty, P M

    2018-03-15

    Activation of innate immune mechanisms within the dorsal root ganglion (DRG) and spinal dorsal horn has been shown to play a key role in the development of neuropathic pain including paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Here we tested whether similar mechanisms are generalizable to oxaliplatin-induced CIPN. After a single intraperitoneal injection of 3mg/kg oxaliplatin, mechanical withdrawal threshold and the expression of C-C chemokine ligand 2 (CCL2) and its receptor, CCR2 in the DRG were measured by behavioral testing and immunohistochemical (IHC) staining, respectively. Mechanical responsiveness increased from the first day after oxaliplatin injection and persisted until day 15, the last day of this experiment. IHC showed that the expression of CCL2/CCR2 started to increase by 4hrs after oxaliplatin treatment, was significantly increased at day 4, and then both signals became normalized by day15. Co-treatment with intrathecal anti-CCL2 antibodies prevented the development of oxaliplatin-induced mechanical hyper-responsiveness, and transiently reversed established hyperalgesia when given 1 week after chemotherapy. This is the first study to demonstrate CCL2/CCR2 signaling in a model of oxaliplatin-related CIPN; and it further shows that blocking of this signal can attenuate the development of oxaliplatin-induced mechanical hyperalgesia. Activation of innate immune mechanisms may therefore be a generalized basis for CIPN irrespective of the specific class of agent.

  16. Polyphenolic screening and protective properties of some vegetables against CCl4 liver damage

    International Nuclear Information System (INIS)

    Salawu, S.O.; Akindahunsi, A.A.

    2007-12-01

    In the present study, we screened for the polyphenolic compounds present in some selected tropical vegetables and the protective effect of the vegetable extract against CCl 4 -induced hepatotoxicity in rats as a way of evaluating their medicinal potential in addition to their nutritional values. The use of HPLC/DAD/MS revealed the presence of some phenolic compounds in the studied vegetables. Crassocephalum crepidioides; caffeoyl derivatives, Talinum triangulare; rutin and kaempferol derivatives, Amaranthus hybridus; caffeoyl derivative, rutin and kaempferol derivative, Hibiscus esculentus; caffeoyl derivative, quercetin derivative and an unidentified flavonoid, Xanthosoma mafaffa; six unidentified flavonoids with similar absorption maximum at different retention times) and Celocia argentia (luteolin derivative and four unidentified flavonoids. Carbon tetrachloride at a dose of 0.5ml/kg body weight (b.w) produced liver damage in rats as manifested by the rise in the levels of ALT (IU/l), AST (IU/l) and total protein (g/l) in the serum (40.60 ± 3.50, 80.60 ± 5.10, 73.20 ± 1.87), in the liver homogenate (1300.00 ± 7.38, 1660.00 ± 13.69, 250.00 ± 7.51) and MDA content (nmol TBARS/mg Liver Protein) in the liver homogenate (82.00 ± 0.02, 82.00 ± 0.07) compared to the control. The result revealed a reduction of the serum marker enzymes (ALT, AST and Total protein), compared with the CCl 4 treated group after the administration of the various polyphenolic extract. In a similar manner, the extract brings about a reduction of the MDA content. It could be concluded that the protective properties exhibited by the vegetables could be amongst other factor due to the presence of some polyphenols. (author)

  17. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

    Directory of Open Access Journals (Sweden)

    Xiaobao Fan

    Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

  18. Kinetics of plasma procalcitonin, soluble CD14, CCL2 and IL-10 after a sublethal infusion of lipopolysaccharide in horses.

    Science.gov (United States)

    Bonelli, Francesca; Meucci, Valentina; Divers, Thomas J; Wagner, Bettina; Intorre, Luigi; Sgorbini, Micaela

    2017-02-01

    Endotoxemia represents a significant clinical and economic problem for the equine industry. This study assesses the kinetics of soluble CD14 (sCD14), chemokine (CC motif) ligand 2 (CCL2), interleukin 10 (IL-10) and plasma procalcitonin (PCT) in healthy horses after the intravenous infusion of lipopolysaccharide (LPS). The aim was to contribute to the basic understanding of the equine species-specific kinetics of these molecules in response to LPS exposure, which could support further findings in clinical studies and identify valuable inflammatory biomarkers for equine practice. Eleven healthy horses were involved in this experimental in vivo study. Horses were classified as healthy before the LPS infusion. After the pre-infusion blood collection (T0), all horses received an infusion of E. coli endotoxin (30ng/kg over 30min). Data and samples were collected 1h (T1), 2 (T2), 3 (T3) and 24h (T24) after infusion. Plasma sCD14, CCL2 and IL-10 were evaluated with a fluorescent bead-based assay, while PCT was evaluated with an equine PCT ELISA assay. A one-way ANOVA test was performed between each blood-sampling time for PCT, sCD14 and IL-10, and a Friedman test was performed for CCL2. Plasma PCT, IL-10 and CCL2 concentrations increased statistically significantly at T1, T2 and T3 compared to T0. No statistically significant differences were found between plasma IL-10 and CCL2 concentrations between T0 vs T24, although plasma PCT values remained high 24h after LPS infusion. Plasma sCD14 concentration showed no statistically significant differences for any of sampling times. Our results demonstrate that LPS injection into healthy horses results in PCT, CCL2 and IL-10 increases in plasma without an increase in sCD14. The increases in PCT, CCL2 and IL-10 are related to the inflammatory response induced by circulating lipopolysaccharide. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. The rs1024611 in the CCL2 gene and risk of gynecological cancer in Asians: a meta-analysis.

    Science.gov (United States)

    He, Shuying; Zhang, Xiuzhen

    2018-02-20

    The -2518A/G (rs1024611) polymorphism of the CCL2 (C-C motif chemokine ligand 2), also known as MCP-1 (monocyte chemotactic protein-1) gene, has been reported to be associated with increased gynecological cancer risk, but the results are conflicting. In this analysis, 1089 cases and 1553 controls from six publications were used to investigate the association between CCL2-2518A/G (rs1024611) polymorphism and the risk of gynecological cancer with a meta-analytic approach. Studies published on EBSCO, EMBASE, Web of Science, PubMed, SpringerLink, ScienceDirect, Weipu, and CNKI databases were identified (last update was on November 3, 2015). Six articles focused on the association between CCL2-2518A/G (rs1024611) polymorphism, and gynecological cancer risk was selected and data were extracted. The cancer type included endometrial cancer (n = 1), breast cancer (n = 2), ovarian cancer (n = 2), and cervical cancer (n = 1). All statistical analyses were performed using the STATA version 12.0 software. The meta-analysis showed that CCL2-2518A/G (rs1024611) polymorphism is associated with risk of gynecological cancer (GG vs AG + AA, OR = 1.55, 95%CI = 1.07-2.24, P < 0.05; AA vs GG, OR = 0.59 95%CI = 0.38-0.92, P < 0.05). Notably, the subgroup analysis demonstrated that the genotype AA is associated with a reduced gynecological cancer risk in Asians, but an increased risk when compared to AG in Europeans. Our data demonstrated the CCL2-2518A/G (rs1024611) polymorphism is significantly associated with risk of gynecological cancer, and the association differs by ethnicity.

  20. The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats.

    Science.gov (United States)

    Al-Seeni, Madeha N; El Rabey, Haddad A; Zamzami, Mazin A; Alnefayee, Abeer M

    2016-11-04

    Liver disease is the major cause of serious health problem leading to morbidity and mortality worldwide and the problem has increased in search for hepatotherapeutic agents from plants. The present study was designed to compare the probable hepatoprotective activity of olive oil and N. sativa oil on CCl 4 induced liver damage in male rats. Forty males of a new model of albino rats (Wistar strain) (175-205 g) were divided into four groups. The 1st Group (G1) was the negative control group, the remaining rats were injected with CCl 4 (1 ml/kg body weight) with equal amount of olive oil on the 1st and 4th day of every week for 4 weeks. The 2nd group (G2) was the positive control, the 3rd group (G3) and the fourth group (G4) were treated orally with N. sativa oil and olive oils using stomach tube. The positive control group showed an increase in hepatic enzymes, total bilirubin, creatinine, uric acid, lipid peroxide total cholesterol, triglyceride, low density lipoprotein, very low density lipoproteins, interleukin-6, and a decrease in antioxidant enzymes, high density lipoprotein cholesterol, a decrease in total protein and albumin an when compared with negative control group. Histology of the CCl 4 treated group revealed inflammation and damage of liver cells. Treating the hepatotoxic rats with olive oil and N. sativa oil showed a significant improvement in all biochemical tests compared with the positive CCl 4 control group. In addition, the liver tissues of olive oil treated group showed mild improvement in inflammatory infiltration and in N. sativa oil treated group showed normal hepatocytes with no evidence of inflammation. This study revealed that olive oil and N. sativa oil have a protective effect against CCl 4 -induced hepatotoxicity in male rats. Nigella sativa oil was more effective than olive oil.

  1. Amniotic fluid stem cells inhibit the progression of bleomycin-induced pulmonary fibrosis via CCL2 modulation in bronchoalveolar lavage.

    Directory of Open Access Journals (Sweden)

    Orquidea Garcia

    Full Text Available The potential for amniotic fluid stem cell (AFSC treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF, is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0 or chronic (day 14 intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL, but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events.

  2. Amniotic Fluid Stem Cells Inhibit the Progression of Bleomycin-Induced Pulmonary Fibrosis via CCL2 Modulation in Bronchoalveolar Lavage

    Science.gov (United States)

    Garcia, Orquidea; Carraro, Gianni; Turcatel, Gianluca; Hall, Marisa; Sedrakyan, Sargis; Roche, Tyler; Buckley, Sue; Driscoll, Barbara; Perin, Laura; Warburton, David

    2013-01-01

    The potential for amniotic fluid stem cell (AFSC) treatment to inhibit the progression of fibrotic lung injury has not been described. We have previously demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney injury through modification of the cytokine environment. Fibrotic lung injury, such as in Idiopathic Pulmonary Fibrosis (IPF), is mediated through pro-fibrotic and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment might inhibit the progression of bleomycin-induced pulmonary fibrosis through cytokine modulation. In particular, we aimed to investigate the effect of AFSC treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased in human IPF patients and is correlated with poor prognoses, advanced disease states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given at acute (day 0) or chronic (day 14) intervention time-points after bleomycin injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen deposition and preserved pulmonary function. CCL2 expression increased in bleomycin-injured bronchoalveolar lavage (BAL), but significantly decreased following AFSC treatment at either day 0 or at day 14. AFSC were observed to localize within fibrotic lesions in the lung, showing preferential targeting of AFSC to the area of fibrosis. We also observed that MMP-2 was transiently increased in BAL following AFSC treatment. Increased MMP-2 activity was further associated with cleavage of CCL2, rendering it a putative antagonist for CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction in BAL following AFSC treatment. Based on this data, we concluded that AFSC have the potential to inhibit the development or progression of fibrosis in a bleomycin injury model during both acute and chronic remodeling events. PMID:23967234

  3. Photometrics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose:The Photometrics Laboratory provides the capability to measure, analyze and characterize radiometric and photometric properties of light sources and filters,...

  4. Blackroom Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Enables evaluation and characterization of materials ranging from the ultraviolet to the longwave infrared (LWIR).DESCRIPTION: The Blackroom Laboratory is...

  5. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  6. Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders.

    Science.gov (United States)

    Carpenter, Danielle; Walker, Susan; Prescott, Natalie; Schalkwijk, Joost; Armour, John Al

    2011-08-18

    Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

  7. Assessment of CCL2 and CXCL8 chemokines in serum, bronchoalveolar lavage fluid and lung tissue samples from dogs affected with canine idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Roels, Elodie; Krafft, Emilie; Farnir, Frederic; Holopainen, Saila; Laurila, Henna P; Rajamäki, Minna M; Day, Michael J; Antoine, Nadine; Pirottin, Dimitri; Clercx, Cecile

    2015-10-01

    Canine idiopathic pulmonary fibrosis (CIPF) is a progressive disease of the lung parenchyma that is more prevalent in dogs of the West Highland white terrier (WHWT) breed. Since the chemokines (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 8 (CXCL8) have been implicated in pulmonary fibrosis in humans, the aim of the present study was to investigate whether these same chemokines are involved in the pathogenesis of CIPF. CCL2 and CXCL8 concentrations were measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) from healthy dogs and WHWTs affected with CIPF. Expression of the genes encoding CCL2 and CXCL8 and their respective receptors, namely (C-C motif) receptor 2 (CCR2) and (C-X-C motif) receptor 2 (CXCR2), was compared in unaffected lung tissue and biopsies from dogs affected with CIPF by quantitative PCR and localisation of CCL2 and CXCL8 proteins were determined by immunohistochemistry. Significantly greater CCL2 and CXCL8 concentrations were found in the BALF from WHWTs affected with CIPF, compared with healthy dogs. Significantly greater serum concentrations of CCL2, but not CXCL8, were found in CIPF-affected dogs compared with healthy WHWTs. No differences in relative gene expression for CCL2, CXCL8, CCR2 or CXCR2 were observed when comparing lung biopsies from control dogs and those affected with CIPF. In affected lung tissues, immunolabelling for CCL2 and CXCL8 was observed in bronchial airway epithelial cells in dogs affected with CIPF. The study findings suggest that both CCL2 and CXCL8 are involved in the pathogenesis of CIPF. Further studies are required to determine whether these chemokines might have a clinical use as biomarkers of fibrosis or as targets for therapeutic intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. The anti-inflammatory effect of low-dose radiation therapy involves a diminished CCL20 chemokine expression and granulocyte/endothelial cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, F. [Dept. of Radiotherapy and Oncology, Univ. of Frankfurt/Main (Germany); Hofmann, D.; Auer, J.; Roellinghoff, M.; Beuscher, H.U. [Inst. of Microbiology and Immunology, Univ. of Erlangen-Nuremberg, Erlangen (Germany); Keilholz, L. [Dept. of Radiotherapy, Clinical Center Bayreuth (Germany); Sauer, R. [Dept. of Radiooncology, Univ. of Erlangen-Nuremberg, Erlangen (Germany)

    2008-01-15

    Background and purpose: low-dose radiotherapy (LD-RT) is known to exert an anti-inflammatory effect, however, the underlying molecular mechanisms are not fully understood. The manipulation of polymorphonuclear neutrophil (PMN) function and/or recruitment may be one mechanism. Chemokines contribute to this process by creating a chemotactic gradient and by activating integrins. This study aimed to characterize the effect of LD-RT on CCL20 chemokine production and PMN/endothelial cell (EC) adhesion. Material and methods: the EC line EA.hy.926 was irradiated with doses ranging from 0 to 3 Gy and was co-cultured with PMNs from healthy donors either by direct cell contact or separated by transwell membrane chambers. CXCL8, CCL18, CCL20 chemokine and tumor necrosis factor-(TNF-){alpha} cytokine levels in supernatants were determined by ELISA and adhesion assays were performed. The functional impact of the cytokines transforming growth factor-(TGF-){beta}{sub 1} and TNF-{alpha} and of the intercellular adhesion molecule-(ICAM-)1 on CCL20 expression was analyzed by using neutralizing antibodies. Results: as compared to CXCL8 and CCL18, CCL20 chemokine secretion was found to be exclusively induced by a direct cell-cell contact between PMNs and EA.hy.926 ECs in a TNF-{alpha}-dependent, but ICAM-1-independent manner. Furthermore, irradiation with doses between 0.5 and 1 Gy resulted in a significant reduction of CCL20 release which was dependent on TGF-{beta}{sub 1} (p < 0.01). The decrease of CCL20 paralleled with a significant reduction in PMN/EA.hy.926 EC adhesion (p < 0.001). Conclusion: the modulation of CCL20 chemokine expression and PMN/EC adhesion adds a further facet to the plethora of mechanisms contributing to the anti-inflammatory efficacy of LD-RT. (orig.)

  9. Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage.

    Directory of Open Access Journals (Sweden)

    Ashraf M Abdel-Moneim

    Full Text Available The present study aims to investigate the hepatoprotective effect of taurine (TAU alone or in combination with silymarin (SIL on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated, toxin control (CCl4 treated, CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-β1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis.

  10. Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice

    Science.gov (United States)

    Zhu, Run-Zhi; Xiang, Di; Xie, Chao; Li, Jing-Jing; Hu, Jian-Jun; He, Hong-Lin; Yuan, Yun-Sheng; Gao, Jin; Han, Wei; Yu, Yan

    2010-01-01

    AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl4). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl4 treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1β, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1β, IL-1Ra and IL-6 expression during CCl4-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl4-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION: rhIL-1Ra could be further developed as a

  11. A New Oleanolic Acid Derivative against CCl4-Induced Hepatic Fibrosis in Rats

    Directory of Open Access Journals (Sweden)

    Hongjun Xiang

    2017-03-01

    Full Text Available A novel hepatoprotective oleanolic acid derivative, 3-oxours-oleana-9(11, 12-dien-28-oic acid (Oxy-Di-OA, has been reported. In previous studies, we found that Oxy-Di-OA presented the anti-HBV (Hepatitis B Virus activity (IC50 = 3.13 µg/mL. Remarkably, it is superior to lamivudine in the inhibition of the rebound of the viral replication rate. Furthermore, Oxy-Di-OA showed good performance of anti-HBV activity in vivo. Some studies showed that liver fibrosis may affiliate with HBV gene mutations. In addition, the anti-hepatic fibrosis activity of Oxy-Di-OA has not been studied. Therefore, we evaluated the protective effect of Oxy-Di-OA against carbon tetrachloride (CCl4-induced liver injury in rats. Daily intraperitoneally administration of Oxy-Di-OA prevented the development of CCl4-induced liver fibrosis, which was evidenced by histological study and immunohistochemical analysis. The entire experimental protocol lasted nine weeks. Oxy-Di-OA significantly suppressed the increases of plasma aspartate aminotransferase (AST and alanine aminotransferase (ALT levels (p < 0.05. Furthermore, Oxy-Di-OA could prevent expression of transforming growth factor β1 (TGF-β1. It is worth noting that the high-dose group Oxy-Di-OA is superior to bifendate in elevating hepatic function. Compared to the model group, Oxy-Di-OA in the high-dose group and low-dose group can significantly reduce the liver and spleen indices (p < 0.05. The acute toxicity test showed that LD50 and a 95% confidence interval (CIs value of Oxy-Di-OA were 714.83 mg/kg and 639.73–798.73 mg/kg via intraperitoneal injection in mice, respectively. The LD50 value of Oxy-Di-OA exceeded 2000 mg/kg via gavage in mice. In addition, a simple and rapid high performance liquid chromatography-ultraviolet (HPLC-UV method was developed and validated to study the pharmacokinetic characteristics of the compound. After single-dose oral administration, time to reach peak concentration of Oxy-Di-OA (Cmax

  12. Differential elastic electron scattering cross sections for CCl4 by 1.5-100 eV energy electron impact

    Science.gov (United States)

    Limão-Vieira, P.; Horie, M.; Kato, H.; Hoshino, M.; Blanco, F.; García, G.; Buckman, S. J.; Tanaka, H.

    2011-12-01

    We report absolute elastic differential, integral and momentum transfer cross sections for electron interactions with CCl4. The incident electron energy range is 1.5-100 eV, and the scattered electron angular range for the differential measurements varies from 15°-130°. The absolute scale of the differential cross section was set using the relative flow technique with helium as the reference species. Comparison with previous total cross sections shows good agreement. Atomic-like behaviour in this scattering system is shown here for the first time, and is further investigated by comparing the CCl4 elastic cross sections to recent results on the halomethanes and atomic chlorine at higher impact energies [H. Kato, T. Asahina, H. Masui, M. Hoshino, H. Tanaka, H. Cho, O. Ingólfsson, F. Blanco, G. Garcia, S. J. Buckman, and M. J. Brunger, J. Chem. Phys. 132, 074309 (2010)], 10.1063/1.3319761.

  13. Laboratory Tests

    Science.gov (United States)

    Laboratory tests check a sample of your blood, urine, or body tissues. A technician or your doctor ... compare your results to results from previous tests. Laboratory tests are often part of a routine checkup ...

  14. National laboratories

    International Nuclear Information System (INIS)

    Moscati, G.

    1983-01-01

    The foundation of a 'National Laboratory' which would support a Research center in synchrotron radiation applications is proposed. The essential features of such a laboratory differing of others centers in Brazil are presented. (L.C.) [pt

  15. Geomechanics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Geomechanics Laboratory allows its users to measure rock properties under a wide range of simulated service conditions up to very high pressures and complex load...

  16. Atmospheric Histories (1765-2015) for CFC-11, CFC-12, CFC-113, CCl4, SF6 and N2O (NCEI Accession 0164584)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The initiation of global atmospheric monitoring programs for CFC-11, CFC-12, CFC-113 and CCl4 began in the late 1970's and early 1980's. Atmospheric concentrations...

  17. In vitro and in vivo antimicrobial activity of a synthetic peptide derived from the C-terminal region of human chemokine CCL13 against Pseudomonas aeruginosa.

    Science.gov (United States)

    Cossio-Ayala, Mayte; Domínguez-López, Mariana; Mendez-Enriquez, Erika; Portillo-Téllez, María Del Carmen; García-Hernández, Enrique

    2017-08-01

    Chemokines are important mediators of immunological responses during inflammation and under steady-state conditions. In addition to regulating cell migration, some chemotactic cytokines have direct effects on bacteria. Here, we characterized the antibacterial ability of the synthetic oligopeptide CCL13 57-75 , which corresponds to the carboxyl-terminal region of the human chemokine CCL13. In vitro measurements indicated that CCL13 57-75 disrupts the cell membrane of Pseudomonas aeruginosa through a mechanism coupled to an unordered-helicoidal conformational transition. In a murine pneumonic model, CCL13 57-75 improved mouse survival and bacterial clearance and decreased neutrophil recruitment, proinflammatory cytokines and lung pathology compared with that observed in untreated infected animals. Overall, our study supports the ability of chemokines and/or chemokine-derived oligopeptides to act as direct defense agents against pathogenic bacteria and suggests their potential use as alternative antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant in CCl4 challenged rats

    Directory of Open Access Journals (Sweden)

    Bhuwan Chandra Joshi

    2015-01-01

    Full Text Available The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant against CCl4-induced hepatotoxicity in-vitro (HepG2 cells and in-vivo (rats model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF, ethyl acetate fraction (EAF, n-butanol fraction (NBF and aqueous fraction (AF were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF was subjected to in-vivo hepatoprotective potential against CCl4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s. Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1H NMR, 13C NMR and MS spectroscopy. Ethyl acetate fraction (EAF of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC50 78.99 ± 0.17 μg/ml and NO (IC50101.39 ± 0.30 μg/ml. The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl4-induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl4 induced hepatotoxicity in-vitro and in-vivo.

  19. Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl4 challenged rats.

    Science.gov (United States)

    Joshi, Bhuwan Chandra; Prakash, Atish; Kalia, Ajudhia N

    2015-01-01

    The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant) against CCl 4 -induced hepatotoxicity in-vitro (HepG2 cells) and in-vivo (rats) model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n -butanol fraction (NBF) and aqueous fraction (AF) were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF) was subjected to in-vivo hepatoprotective potential against CCl 4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s). Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1 H NMR, 13 C NMR and MS spectroscopy. Ethyl acetate fraction (EAF) of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC 50 78.99 ± 0.17 μg/ml) and NO (IC 50 101.39 ± 0.30 μg/ml). The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl 4 -induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF) lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl 4 induced hepatotoxicity in-vitro and in-vivo .

  20. Oligonol Ameliorates CCl4-Induced Liver Injury in Rats via the NF-Kappa B and MAPK Signaling Pathways

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    Jeonghyeon Bak

    2016-01-01

    Full Text Available Oxidative stress is thought to be a key risk factor in the development of hepatic diseases. Blocking or retarding the reactions of oxidation and the inflammatory process by antioxidants could be a promising therapeutic intervention for prevention or treatment of liver injuries. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from lychee fruit. In this study, we investigated the anti-inflammatory effect of oligonol on carbon tetrachloride- (CCl4- induced acute hepatic injury in rats. Oral administration of oligonol (10 or 50 mg/kg reduced CCl4-induced abnormalities in liver histology and serum AST and serum ALT levels. Oligonol treatment attenuated the CCl4-induced production of inflammatory mediators, including TNF-α, IL-1β, cyclooxygenase-2 (COX-2, and inducible nitric oxide synthase (iNOS mRNA levels. Western blot analysis showed that oligonol suppressed proinflammatory nuclear factor-kappa B (NF-κB p65 activation, phosphorylation of extracellular signal-regulated kinase (ERK, c-Jun NH2-terminal kinase (JNK, and p38 mitogen-activated protein kinases (MAPKs as well as Akt. Oligonol exhibited strong antioxidative activity in vitro and in vivo, and hepatoprotective activity against t-butyl hydroperoxide-induced HepG2 cells. Taken together, oligonol showed antioxidative and anti-inflammatory effects in CCl4-intoxicated rats by inhibiting oxidative stress and NF-κB activation via blockade of the activation of upstream kinases including MAPKs and Akt.

  1. CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

    Science.gov (United States)

    Soloski, Mark J.; Rebman, Alison W.; Crowder, Lauren A.; Wagner, Catriona A.; Robinson, William H.; Bechtold, Kathleen T.

    2016-01-01

    Approximately 10% to 20% of patients optimally treated for early Lyme disease develop persistent symptoms of unknown pathophysiology termed posttreatment Lyme disease syndrome (PTLDS). The objective of this study was to investigate associations between PTLDS and immune mediator levels during acute illness and at several time points following treatment. Seventy-six participants with physician-documented erythema migrans and 26 healthy controls with no history of Lyme disease were enrolled. Sixty-four cytokines, chemokines, and inflammatory markers were measured at each visit for a total of 6 visits over 1 year. An operationalized definition of PTLDS incorporating symptoms and functional impact was applied at 6 months and 1 year following treatment completion, and clinical outcome groups were defined as the return-to-health, symptoms-only, and PTLDS groups. Significance analysis of microarrays identified 7 of the 64 immune mediators to be differentially regulated by group. Generalized logit regressions controlling for potential confounders identified posttreatment levels of the T-cell chemokine CCL19 to be independently associated with clinical outcome group. Receiver operating characteristic analysis identified a CCL19 cutoff of >111.67 pg/ml at 1 month following treatment completion to be 82% sensitive and 83% specific for later PTLDS. We speculate that persistently elevated CCL19 levels among participants with PTLDS may reflect ongoing, immune-driven reactions at sites distal to secondary lymphoid tissue. Our findings suggest the relevance of CCL19 both during acute infection and as an immunologic risk factor for PTLDS during the posttreatment phase. Identification of a potential biomarker predictor for PTLDS provides the opportunity to better understand its pathophysiology and to develop early interventions in the context of appropriate and specific clinical information. PMID:27358211

  2. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis

    Science.gov (United States)

    Sanford, Dominic E.; Belt, Brian A.; Panni, Roheena Z.; Mayer, Allese; Deshpande, Anjali D.; Carpenter, Danielle; Mitchem, Jonathan B.; Plambeck-Suess, Stacey M.; Worley, Lori A.; Goetz, Brian D.; Wang-Gillam, Andrea; Eberlein, Timothy J.; Denardo, David G.; Goedegebuure, S. Peter; Linehan, David C.

    2013-01-01

    Purpose To determine the role of the CCL2/CCR2 axis and inflammatory monocytes (IM; CCR2+/CD14+) as immunotherapeutic targets in the treatment of pancreatic cancer (PC). Experimental Design Survival analysis was performed to determine if the prevalence of pre-operative blood monocytes correlates with survival in PC patients following tumor resection. IM prevalence in the blood and bone marrow of PC patients and controls was compared. The immunosuppressive properties of IM and macrophages in the blood and tumors, respectively, of PC patients were assessed. CCL2 expression by human PC tumors was compared to normal pancreas. A novel CCR2 inhibitor (PF-04136309) was tested in an orthotopic model of murine PC. Results Monocyte prevalence in the peripheral blood correlates inversely with survival, and low monocyte prevalence is an independent predictor of increased survival in PC patients with resected tumors. IM are increased in the blood and decreased in the bone marrow of PC patients compared to controls. An increased ratio of IM in the blood versus the bone marrow is a novel predictor of decreased patient survival following tumor resection. Human PC produces CCL2, and immunosuppressive CCR2+ macrophages infiltrate these tumors. Patients with tumors that exhibit high CCL2 expression/low CD8 T cell infiltrate have significantly decreased survival. In mice, CCR2 blockade depletes IM and macrophages from the primary tumor and premetastatic liver resulting in enhanced anti-tumor immunity, decreased tumor growth, and reduced metastasis. Conclusions IM recruitment is critical to PC progression, and targeting CCR2 may be an effective immunotherapeutic strategy in this disease. PMID:23653148

  3. Vitamin D effects on monocytes' CCL-2, IL6 and CD14 transcription in Addison's disease and HLA susceptibility.

    Science.gov (United States)

    Kraus, A U; Penna-Martinez, M; Meyer, G; Badenhoop, K

    2018-03-01

    Addison's disease is a rare autoimmune disorder leading to adrenal insufficiency and life-long glucocorticoid dependency. Vitamin D receptor (VDR) polymorphisms and vitamin D deficiency predispose to Addison's disease. Aim of the current study was, to investigate potential anti-inflammatory vitamin D effects on monocytes in Addison's disease, focusing on inflammatory CCL-2 and IL6, as well on monocyte CD14 markers. Addison's disease is genetically linked to distinct HLA susceptibility alleles. Therefore we analyzed, whether HLA genotypes differed for vitamin D effects on monocyte markers. CD14 + monocytes were isolated from Addison's disease patients (AD, n=13) and healthy controls (HC, n=15) and stimulated with 1,25-dihydroxyvitamin D 3 and IL1β as an inflammatory stimulant. Cells were processed for mRNA expression of CCL-2, IL6 and CD14 and DNA samples were genotyped for major histocompatibility class (MHC) class II-encoded HLA- DQA1-DQB1 haplotypes. We found a downregulation of CCL-2 after vitamin D treatment in IL1β-stimulated monocytes both from AD patients and HC (AD pHLA high-risk haplotypes showed an increased CCL-2 expression after IL1β-induced inflammation compared to intermediate-risk HLA carriers (p=0.05). Also HC monocytes' CD14 transcription after IL1β and vitamin D co-stimulation differed according to HLA risk profile. We show that vitamin D can exert anti-inflammatory effects on AD patients' monocytes which may be modulated by HLA risk genotypes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Tag SNP polymorphism of CCL2 and its role in clinical tuberculosis in Han Chinese pediatric population.

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    Wei-Xing Feng

    Full Text Available BACKGROUND: Chemokine (C-C motif ligand 2 CCL2/MCP-1 is among the key signaling molecules of innate immunity; in particular, it is involved in recruitment of mononuclear and other cells in response to infection, including tuberculosis (TB and is essential for granuloma formation. METHODOLOGY/PRINCIPAL FINDINGS: We identified a tag SNP for the CCL2/MCP-1 gene (rs4586 C/T. In order to understand whether this SNP may serve to evaluate the contribution of the CCL2 gene to the expression of TB disease, we further analysed distribution of its alleles and genotypes in 301 TB cases versus 338 non-infected controls (all BCG vaccinated representing a high-risk pediatric population of North China. In the male TB subgroup, the C allele was identified in a higher rate (P = 0.045, and, acting dominantly, was found to be a risk factor for clinical TB (P = 0.029. Homozygous TT genotype was significantly associated with lower CSF mononuclear leukocyte (ML counts in patients with tuberculous meningitis (TBM (P = 0.001. CONCLUSIONS/SIGNIFICANCE: The present study found an association of the CCL2 tag SNP rs4586 C allele and pediatric TB disease in males, suggesting that gender may affect the susceptibility to TB even in children. The association of homozygous TT genotype with decreased CSF mononuclear leukocyte (ML count not only suggests a clinical significance of this SNP, but indicates its potential to assist in the clinical assessment of suspected TBM, where delay is critical and diagnosis is difficult.

  5. Ab initio ro-vibronic spectroscopy of SiCCl (X{sup ~2}Π)

    Energy Technology Data Exchange (ETDEWEB)

    Brites, Vincent [Université d’Evry Val d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, LAMBE CNRS UMR 8587, Boulevard F. Mitterrand, 91025 Evry Cedex (France); Mitrushchenkov, Alexander O.; Léonard, Céline, E-mail: celine.leonard@u-pem.fr [Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 bd Descartes, 77454 Marne-la-Vallée (France); Peterson, Kirk A. [Department of Chemistry, Washington State University, Pullman, Washington 99164 (United States)

    2014-07-21

    The full dimensional potential energy surfaces of the {sup 2}A{sup ′} and {sup 2}A{sup ′′} electronic components of X{sup ~2}Π SiCCl have been computed using the explicitly correlated coupled cluster method, UCCSD(T)-F12b, combined with a composite approach taking into account basis set incompleteness, core-valence correlation, scalar relativity, and higher order excitations. The spin-orbit and dipole moment surfaces have also been computed ab initio. The ro-vibronic energy levels and absorption spectrum at 5 K have been determined from variational calculations. The influence of each correction on the fundamental frequencies is discussed. An assignment is proposed for bands observed in the LIF experiment of Smith et al. [J. Chem. Phys. 117, 6446 (2002)]. The overall agreement between the experimental and calculated ro-vibronic levels is better than 7 cm{sup −1} which is comparable with the 10–20 cm{sup −1} resolution of the emission spectrum.

  6. Extreme 13C depletion of CCl2F2 in firn air samples from NEEM, Greenland

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    T. Blunier

    2013-01-01

    Full Text Available A series of 12 high volume air samples collected from the S2 firn core during the North Greenland Eemian Ice Drilling (NEEM 2009 campaign have been measured for mixing ratio and stable carbon isotope composition of the chlorofluorocarbon CFC-12 (CCl2F2. While the mixing ratio measurements compare favorably to other firn air studies, the isotope results show extreme 13C depletion at the deepest measurable depth (65 m, to values lower than δ13C = −80‰ vs. VPDB (the international stable carbon isotope scale, compared to present day surface tropospheric measurements near −40‰. Firn air modeling was used to interpret these measurements. Reconstructed atmospheric time series indicate even larger depletions (to −120‰ near 1950 AD, with subsequent rapid enrichment of the atmospheric reservoir of the compound to the present day value. Mass-balance calculations show that this change is likely to have been caused by a large change in the isotopic composition of anthropogenic CFC-12 emissions, probably due to technological advances in the CFC production process over the last 80 yr, though direct evidence is lacking.

  7. Beam Position and Phase Monitors Characterized and Installed in the LANSCE CCL

    Energy Technology Data Exchange (ETDEWEB)

    Gilpatrick, John D [Los Alamos National Laboratory; Kutac, Vincent G. [Los Alamos National Laboratory; Martinez, Derwin [Los Alamos National Laboratory; McCrady, Rodney C. [Los Alamos National Laboratory; O' Hara, James F. [Los Alamos National Laboratory; Olivas, Felix R. [Los Alamos National Laboratory; Shurter, Robert B. [Los Alamos National Laboratory; Watkins, Heath A. [Los Alamos National Laboratory

    2012-04-11

    The Los Alamos Neutron Science Center - Risk Mitigation Project is in the process of replacing older Coupled-Cavity-Linac (CCL) Beam-Position Monitors (BPMs) with newer Beam Position and Phase Monitors (BPPMs) and their associated electronics and cable plants. In many locations, these older BPMs include a separate Delta-T loop for measuring the beam's central phase and energy. Thirty-one BPPMs have been installed and many have monitored the charged particle beam. The installation of these newer BPPMs is the first step to installing complete BPPM measurement systems. Prior to the installation, a characterization of each BPPM took place. The characterization procedure includes a mechanical inspection, a vacuum testing, and associated electrical tests. The BPPM electrical tests for all four electrodes include contact resistance measurements, Time Domain Reflectometer (TDR) measurements, relative 201.25-MHz phase measurements, and finally a set of position-sensitive mapping measurements were performed which included associated fitting routines. This paper will show these data for a typical characterized BPPM.

  8. Organophosphines in Cis-PtP2CCl Derivatives Structural Aspects

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    Milan Melnik

    2018-02-01

    Full Text Available This manuscript summarizes and analyzes X-ray data of monomeric cis-PtP2CCl derivatives. These complexes crystallize in the following crystal systems: tetragonal, P42/n (3, triclinic, Pī (10, orthorhombic, P212121 (prevails(16, and monoclinic, P21/c (prevails (36 examples. There are three sub-groups of the respective complexes: Pt(η1-PL2(η1-CL(η1-Cl; Pt(η2-P2L(η1-CL(η1-Cl and Pt(η1-PL(η2-P,CL(η1-Cl. The chelating P,P-donor ligands form: four-(POP, PCP, five-(PC2P, six-(PC3P, PCNCP, seven-(PC4P and even ten-(PCNCNCNCP membered rings. The chelating P.C-donor ligands create three-(PC, four-(PCC and five-(PC2C membered rings. The mean Pt-L bond distance elongates in the sequence: 2.10 Å (C, trans to P < 2.222 Å (P, trans to Cl < 2.312 Å (P, trans to C < 2.360 Å (Cl, trans to P. There are examples which exist in two isomeric forms, of the distortion isomer type.

  9. Iron Reverses Impermeable Chelator Inhibition of DNA Synthesis in CCl39 Cells

    Science.gov (United States)

    Alcain, Francisco J.; Low, Hans; Crane, Frederick L.

    1994-08-01

    Treatment of Chinese hamster lung fibro-blasts (CCl 39 cells) with the impermeable iron(II) chelator bathophenanthroline disulfonate (BPS) inhibits DNA synthesis when cell growth is initiated with growth factors including epidermal growth factor plus insulin, thrombin, or ceruloplasmin, but not with 10% fetal calf serum. The BPS treatment inhibits transplasma membrane electron transport. The treatment leads to release of iron from the cells as determined by BPS iron(II) complex formation over 90 min. Growth factor stimulation of DNA synthesis and electron transport are restored by addition of di- or trivalent iron to the cells in the form of ferric ammonium citrate, ferrous ammonium sulfate, or diferric transferrin. The effect with BPS differs from the inhibition of growth by hydroxyurea, which acts on the ribonucleotide reductase, or diethylenetriaminepentaacetic acid, which is another impermeable chelating agent, in that these agents inhibit growth in 10% fetal calf serum. The BPS effect is consistent with removal of iron from a site on the cell surface that controls DNA synthesis.

  10. Photolysis of Br2 in CCl4 studied by time-resolved X-ray scattering.

    Science.gov (United States)

    Kong, Qingyu; Lee, Jae Hyuk; Lo Russo, Manuela; Kim, Tae Kyu; Lorenc, Maciej; Cammarata, Marco; Bratos, Savo; Buslaps, Thomas; Honkimaki, Veijo; Ihee, Hyotcherl; Wulff, Michael

    2010-03-01

    A time-resolved X-ray solution scattering study of bromine molecules in CCl(4) is presented as an example of how to track atomic motions in a simple chemical reaction. The structures of the photoproducts are tracked during the recombination process, geminate and non-geminate, from 100 ps to 10 micros after dissociation. The relaxation of hot Br(2)(*) molecules heats the solvent. At early times, from 0.1 to 10 ns, an adiabatic temperature rise is observed, which leads to a pressure gradient that forces the sample to expand. The expansion starts after about 10 ns with the laser beam sizes used here. When thermal artefacts are removed by suitable scaling of the transient solvent response, the excited-state solute structures can be obtained with high fidelity. The analysis shows that 30% of Br(2)(*) molecules recombine directly along the X potential, 60% are trapped in the A/A' state with a lifetime of 5.5 ns, and 10% recombine non-geminately via diffusive motion in about 25 ns. The Br-Br distance distribution in the A/A' state peaks at 3.0 A.

  11. CCL: console command language, RSX11M V4. 0, V7. OC tutorial

    Energy Technology Data Exchange (ETDEWEB)

    Downward, J. G.

    1981-01-01

    The normal user interface to an RSX11M operating system is via MCR (Monitor Console Routine). If terminal input is not specifically requested by a task, all data or commands typed in at a user's terminal, are sent by the terminal driver to MCR for decoding. The MCR task (and its child ...SYS) decode user commands (ACT, ABORT,RUN, DEV, ETC.). Tasks installed with special names of the form ...XYZ are treated as an external MCR command. Hence if a user types, XYZ COMMANDLINE, the commandline in its entirety (or at least up to 79 characters) is sent as input to the task ...XYZ. This is the conventional way of supplying most system commands and controlling the operation of the RSX11M utility program. The limitations of this method are: (1) each task must be installed to get MCR command lines; (2) each installed task uses valuable POOL space; (3) only privileged users can INSTALL and REMOVE tasks; and (4) non-privileged users are restricted to RUNning non-installed tasks. To solve this problem, a user tailorable Console Command Language (CCL) has been implemented which allows each user to have a private task control language to pass command lines to tasks that are not installed in th system as external MCR commands.

  12. Pseudogenization of the MCP-2/CCL8 chemokine gene in European rabbit (genus Oryctolagus, but not in species of Cottontail rabbit (Sylvilagus and Hare (Lepus

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    van der Loo Wessel

    2012-08-01

    Full Text Available Abstract Background Recent studies in human have highlighted the importance of the monocyte chemotactic proteins (MCP in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and HIV-1 infection. In European rabbit (Oryctolagus cuniculus one of the prime MCP targets, the chemokine receptor CCR5 underwent a unique structural alteration. Until now, no homologue of MCP-2/CCL8a, MCP-3/CCL7 or MCP-4/CCL13 genes have been reported for this species. This is interesting, because at least the first two genes are expressed in most, if not all, mammals studied, and appear to be implicated in a variety of important chemokine ligand-receptor interactions. By assessing the Rabbit Whole Genome Sequence (WGS data we have searched for orthologs of the mammalian genes of the MCP-Eotaxin cluster. Results We have localized the orthologs of these chemokine genes in the genome of European rabbit and compared them to those of leporid genera which do (i.e. Oryctolagus and Bunolagus or do not share the CCR5 alteration with European rabbit (i.e. Lepus and Sylvilagus. Of the Rabbit orthologs of the CCL8, CCL7, and CCL13 genes only the last two were potentially functional, although showing some structural anomalies at the protein level. The ortholog of MCP-2/CCL8 appeared to be pseudogenized by deleterious nucleotide substitutions affecting exon1 and exon2. By analyzing both genomic and cDNA products, these studies were extended to wild specimens of four genera of the Leporidae family: Oryctolagus, Bunolagus, Lepus, and Sylvilagus. It appeared that the anomalies of the MCP-3/CCL7 and MCP-4/CCL13 proteins are shared among the different species of leporids. In contrast, whereas MCP-2/CCL8 was pseudogenized in every studied specimen of the Oryctolagus - Bunolagus lineage, this gene was intact in species of the Lepus - Sylvilagus lineage, and was, at least in Lepus, correctly transcribed. Conclusion The biological function of a gene was often

  13. Comparison of hepatic fibrosis models and associated hepatic fibronectin expression in Wistar rats treated by bile duct ligation and CCl4

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    LIU Xiaoya

    2015-02-01

    Full Text Available ObjectiveTo compare serum biochemical parameters, liver pathology, and fibronectin (FN expression in Wister rats with hepatic fibrosis induced by bile duct ligation (BDL and carbon tetrachloride (CCl4. MethodsNinety healthy male Wister rats were assigned to CCl4 model (n=44, CCl4 control (n=6, BDL model (n=30, and BDL control groups (n=10. Animal models of hepatic fibrosis were established by intraperitoneal injection of olive oil solution containing 50% CCl4 in the CCl4 model group and by BDL in the BDL group. General conditions of rats were examined. Expression of serum alanine aminotransferase (ALT, serum aspartate aminotransferase (AST, total bilirubin (TBil, and direct bilirubin (DBil was measured by biochemical analysis. Expression of serum hyaluronic acid (HA and laminin (LN was measured by ELISA assay. Pathological changes in liver tissue were examined through hematoxylin-eosin and Masson staining. Expression of FN was assayed by immunohistochemistry. Comparison between groups was made by t test. ResultsSerum biochemical analysis showed that TBil and DBil levels in BDL model rats increased to and maintained at relatively high levels from day 7 after surgery (P<0.05; these two parameters in CCl4 model rats increased gradually from week 2 and peaked at week 8 after injection (P<0.05. The indicators of hepatic fibrosis, i.e., HA and LN levels, were significantly higher in the BDL model group than in the CCl4 model group. Pathologically, the CCl4 model group showed diffuse fatty degeneration of liver cells, with extremely significant fiber interval formation in the portal area - portal area or the portal area - central vein; the BDL model group showed coexistence of significant intrahepatic bile duct hyperplasia, inflammatory cell infiltration, and fiber interval formation. In the BDL model group, FN expression was dispersive and irregular with thin fibrous tissues; in the CCl4 model group, FN was mostly expressed in the interlobular septa

  14. Red Sea Suberea mollis Sponge Extract Protects against CCl4-Induced Acute Liver Injury in Rats via an Antioxidant Mechanism.

    Science.gov (United States)

    Abbas, Aymn T; El-Shitany, Nagla A; Shaala, Lamiaa A; Ali, Soad S; Azhar, Esam I; Abdel-Dayem, Umama A; Youssef, Diaa T A

    2014-01-01

    Recent studies have demonstrated that marine sponges and their active constituents exhibited several potential medical applications. This study aimed to evaluate the possible hepatoprotective role as well as the antioxidant effect of the Red Sea Suberea mollis sponge extract (SMSE) on carbon tetrachloride- (CCl4-) induced acute liver injury in rats. In vitro antioxidant activity of SMSE was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Rats were orally administered three different concentrations (100, 200, and 400 mg/kg) of SMSE and silymarin (100 mg/kg) along with CCl4 (1 mL/kg, i.p., every 72 hr) for 14 days. Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were also measured. Liver specimens were histopathologically examined. SMSE showed strong scavenging activity against free radicals in DPPH assay. SMSE significantly reduced liver enzyme activities. Moreover, SMSE significantly reduced hepatic MDA formation. In addition, SMSE restored GSH, NO, SOD, GPx, and CAT. The histopathological results confirmed these findings. The results of this study suggested a potent protective effect of the SMSE against CCl4-induced hepatic injury. This may be due to its antioxidant and radical scavenging activity.

  15. Pro-Inflammatory Chemokine CCL2 (MCP-1) Promotes Healing in Diabetic Wounds by Restoring the Macrophage Response

    Science.gov (United States)

    Wood, Stephen; Jayaraman, Vijayakumar; Huelsmann, Erica J.; Bonish, Brian; Burgad, Derick; Sivaramakrishnan, Gayathri; Qin, Shanshan; DiPietro, Luisa A.; Zloza, Andrew; Zhang, Chunxiang; Shafikhani, Sasha H.

    2014-01-01

    Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyper-inflammation characterized by harmful increases in inflammatory leukocytes including macrophages. However, such studies have focused on wounds at later time points (day 10 or older), and very little attention has been given to the dynamics of macrophage responses in diabetic wounds early after injury. Given the importance of macrophages for the process of healing, we studied the dynamics of macrophage response during early and late phases of healing in diabetic wounds. Here, we report that early after injury, the diabetic wound exhibits a significant delay in macrophage infiltration. The delay in the macrophage response in diabetic wounds results from reduced Chemokine (C-C motif) ligand 2 (CCL2) expression. Importantly, one-time treatment with chemoattractant CCL2 significantly stimulated healing in diabetic wounds by restoring the macrophage response. Our data demonstrate that, rather than a hyper-inflammatory state; the early diabetic wound exhibits a paradoxical and damaging decrease in essential macrophage response. Our studies suggest that the restoration of the proper kinetics of macrophage response may be able to jumpstart subsequent healing stages. CCL2 chemokine-based therapy may be an attractive strategy to promote healing in diabetic wounds. PMID:24618995

  16. Pro-inflammatory chemokine CCL2 (MCP-1 promotes healing in diabetic wounds by restoring the macrophage response.

    Directory of Open Access Journals (Sweden)

    Stephen Wood

    Full Text Available Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyper-inflammation characterized by harmful increases in inflammatory leukocytes including macrophages. However, such studies have focused on wounds at later time points (day 10 or older, and very little attention has been given to the dynamics of macrophage responses in diabetic wounds early after injury. Given the importance of macrophages for the process of healing, we studied the dynamics of macrophage response during early and late phases of healing in diabetic wounds. Here, we report that early after injury, the diabetic wound exhibits a significant delay in macrophage infiltration. The delay in the macrophage response in diabetic wounds results from reduced Chemokine (C-C motif ligand 2 (CCL2 expression. Importantly, one-time treatment with chemoattractant CCL2 significantly stimulated healing in diabetic wounds by restoring the macrophage response. Our data demonstrate that, rather than a hyper-inflammatory state; the early diabetic wound exhibits a paradoxical and damaging decrease in essential macrophage response. Our studies suggest that the restoration of the proper kinetics of macrophage response may be able to jumpstart subsequent healing stages. CCL2 chemokine-based therapy may be an attractive strategy to promote healing in diabetic wounds.

  17. Red Sea Suberea mollis Sponge Extract Protects against CCl4-Induced Acute Liver Injury in Rats via an Antioxidant Mechanism

    Directory of Open Access Journals (Sweden)

    Aymn T. Abbas

    2014-01-01

    Full Text Available Recent studies have demonstrated that marine sponges and their active constituents exhibited several potential medical applications. This study aimed to evaluate the possible hepatoprotective role as well as the antioxidant effect of the Red Sea Suberea mollis sponge extract (SMSE on carbon tetrachloride- (CCl4- induced acute liver injury in rats. In vitro antioxidant activity of SMSE was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH assay. Rats were orally administered three different concentrations (100, 200, and 400 mg/kg of SMSE and silymarin (100 mg/kg along with CCl4 (1 mL/kg, i.p., every 72 hr for 14 days. Plasma aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and total bilirubin were measured. Hepatic malondialdehyde (MDA, reduced glutathione (GSH, nitric oxide (NO, superoxide dismutase (SOD, glutathione peroxidase (GPx, and catalase (CAT were also measured. Liver specimens were histopathologically examined. SMSE showed strong scavenging activity against free radicals in DPPH assay. SMSE significantly reduced liver enzyme activities. Moreover, SMSE significantly reduced hepatic MDA formation. In addition, SMSE restored GSH, NO, SOD, GPx, and CAT. The histopathological results confirmed these findings. The results of this study suggested a potent protective effect of the SMSE against CCl4-induced hepatic injury. This may be due to its antioxidant and radical scavenging activity.

  18. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment.

    Science.gov (United States)

    Wunderlich, Claudia M; Ackermann, P Justus; Ostermann, Anna Lena; Adams-Quack, Petra; Vogt, Merly C; Tran, My-Ly; Nikolajev, Alexei; Waisman, Ari; Garbers, Christoph; Theurich, Sebastian; Mauer, Jan; Hövelmeyer, Nadine; Wunderlich, F Thomas

    2018-04-25

    Colorectal cancer (CRC) is one of the most lethal cancers worldwide in which the vast majority of cases exhibit little genetic risk but are associated with a sedentary lifestyle and obesity. Although the mechanisms underlying CRC and colitis-associated colorectal cancer (CAC) remain unclear, we hypothesised that obesity-induced inflammation predisposes to CAC development. Here, we show that diet-induced obesity accelerates chemically-induced CAC in mice via increased inflammation and immune cell recruitment. Obesity-induced interleukin-6 (IL-6) shifts macrophage polarisation towards tumour-promoting macrophages that produce the chemokine CC-chemokine-ligand-20 (CCL-20) in the CAC microenvironment. CCL-20 promotes CAC progression by recruiting CC-chemokine-receptor-6 (CCR-6)-expressing B cells and γδ T cells via chemotaxis. Compromised cell recruitment as well as inhibition of B and γδ T cells protects against CAC progression. Collectively, our data reveal a function for IL-6 in the CAC microenvironment via lymphocyte recruitment through the CCL-20/CCR-6 axis, thereby implicating a potential therapeutic intervention for human patients.

  19. Low Intraprostatic DHT Promotes the Infiltration of CD8+ T Cells in BPH Tissues via Modulation of CCL5 Secretion

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    Yu Fan

    2014-01-01

    Full Text Available Clinical studies suggested thatandrogen might be associated with infiltrating T cells in prostate of benign prostatic hyperplasia (BPH patients, but detail of T-cell subset and mechanism still remained unclear. The present study tested the hypothesis that intraprostatic 5α-dihydrotestosterone (DHT exerts effects on T cells recruitment by BPH epithelial cells. Prostate tissues from 64 cases of BPH patients after transurethral resection of prostate (TURP were divided into 2 groups: (1 no medication history; (2 administration of 5α-reductase type II inhibitor-finasteride 5 mg daily for at least 6 months before surgery. Group 2 presented significantly higher CD8+ T cells infiltration than group 1, but no changes in CD4+ T cells (immunohistochemistry and flow cytometry. In vitro study more CD8+ T cell migrated to the prostate tissue lysates from group 2 and BPH-1 cells in low DHT condition. Transcription of chemokine (C-C motif Ligand 5 (CCL5 mRNA in BPH-1 cells and chemokine (C-C motif receptor 5 (CCR5 mRNA in CD8+ T cells were upregulated in low DHT condition (q-PCR. CCL5 expression was also identified to be higher in group 2 prostate tissues by IHC. This study suggested that intraprostatic DHT may participate in regulating inflammatory response which was induced by human prostatic epithelial cell, via modulating CCL5 secretion.

  20. Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicanaextracts.

    Science.gov (United States)

    Coballase-Urrutia, Elvia; Cárdenas-Rodríguez, Noemí; González-García, María Carolina; Núñez-Ramírez, Eithan; Floriano-Sánchez, Esaú; González-Trujano, María Eva; Fernández-Rojas, Berenice; Pedraza-Chaverrí, José; Montesinos-Correa, Hortencia; Rivera-Espinosa, Liliana; Sampieri, Aristides Iii; Carmona-Aparicio, Liliana

    2017-03-01

    Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl 4 -induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl 4 -treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl 4 -induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

  1. A cross-sectional study: serum CCL3/MIP-1α levels may reflect lumbar intervertebral disk degeneration in Han Chinese people

    Directory of Open Access Journals (Sweden)

    Zhang YL

    2018-03-01

    Full Text Available Yi-Li Zhang,1,2,* Bei Li,1,2,* Zeng-Huan Zhou1 1School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2School of Health Services Management, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Background: The macrophage inflammatory protein-1α (MIP-1α, also named chemokine cytokine ligand 3 (CCL3, has been detected in nucleus pulposus and increased following cytokine stimulation. Objective: The current study was performed to explore the relationship between serum CCL3/MIP-1α levels with lumbar intervertebral disk degeneration (IDD. Patients and methods: A total of 132 disk degeneration patients confirmed by magnetic resonance imaging and 126 healthy controls were enrolled in the current study. Radiological evaluation of the IDD was conducted using a 3.0-T magnetic resonance imaging scanner for entire lumbar vertebra region. Degeneration of intervertebral disk was assessed by Schneiderman criteria. Serum CCL3/MIP-1α levels were investigated using a sandwich enzyme-linked immunosorbent assay. The Visual Analog Scale scores and Oswestry Disability Index index were recorded for clinical severity. Results: Elevated concentrations of CCL3 in serum were found in IDD patients compared with asymptomatic volunteers. The case group included 49 IDD patients with grade 1, 42 with grade 2, and 41 with grade 3. Grade 3 and 2 had significantly higher CCL3 concentrations in serum compared with those with grade 1. The serum CCL3 levels were positively related to the degree of disk degeneration. In addition, the serum CCL3 levels also demonstrated a significant correlation with the clinical severity determined by Visual Analog Scale scores and Oswestry Disability Index index. Conclusion: Serum CCL3 may serve as a biomarker of IDD. Keywords: chemokine cytokine ligand 3, intervertebral disk degeneration, cross

  2. Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

    Science.gov (United States)

    Frossard, Jean Louis; Lenglet, Sébastien; Montecucco, Fabrizio; Steffens, Sabine; Galan, Katia; Pelli, Graziano; Spahr, Laurent; Mach, Francois; Hadengue, Antoine

    2011-05-01

    Acute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4. The severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining. The authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates. These results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.

  3. Increase in chemokines CXCL10 and CCL2 in blood from pigs infected with high compared to low virulence African swine fever virus isolates.

    Science.gov (United States)

    Fishbourne, Emma; Hutet, Evelyne; Abrams, Charles; Cariolet, Roland; Le Potier, Marie-Frédérique; Takamatsu, Haru-H; Dixon, Linda K

    2013-10-01

    Modulation of the expression of chemokines and chemokine receptors in whole blood was compared following infection of pigs with high and low virulence isolates of African swine fever virus. Levels of mRNAs for CCL2, CCL3L1, CCL4, CXCL10, CCR1 and CCR5 were significantly increased in at least one time point following infection in two experiments and CCL5, CCR9 and CXCR4 mRNA were significantly increased in one of the experiments. The results showed that greatest fold increases in mRNAs for CXCL10 and CCL2 were observed following infection of pigs. CXCL10 mRNA was increased by up to 15 fold in infected compared to uninfected pigs. CXCL10 protein was also detected in serum from pigs infected with the high virulence Benin 97/1 isolate. Levels of CCL2 mRNA were increased in pigs infected with high virulence Benin 97/1 isolate compared to low virulence OURT88/3 isolate and this correlated with an increase of greater than 30 fold in levels of CCL2 protein detected in serum from pigs infected with this isolate. An increase in overall chemotaxis active compounds in defibrinated plasma samples from Benin 97/1 infected pigs was observed at 3 days post-infection (dpi) and a decrease by 7 dpi as measured by chemotaxis assay using normal pig leucocytes in vitro. Increased levels of CXCL10 may either contribute to the activation of lymphocyte priming toward the Th1 phenotype or induction of T lymphocyte apoptosis. Increased levels of CCL2, a chemoattractant for macrophages, may result in increased recruitment of monocytes from bone marrow thus increasing the pool of cells susceptible to infection.

  4. CCL20 and Beta-Defensin 2 Production by Human Lung Epithelial Cells and Macrophages in Response to Brucella abortus Infection

    Science.gov (United States)

    Fernández, Andrea G.; Bonetto, Josefina; Giambartolomei, Guillermo H.; Fossati, Carlos A.; Baldi, Pablo C.

    2015-01-01

    Both CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. They are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. Whereas Brucella spp. can infect humans through inhalation, their ability to induce CCL20 and hBD2 in lung cells is unknown. Here we show that B. abortus induces CCL20 expression in human alveolar (A549) or bronchial (Calu-6) epithelial cell lines, primary alveolar epithelial cells, primary human monocytes, monocyte-derived macrophages and the monocytic cell line THP-1. CCL20 expression was mainly mediated by JNK1/2 and NF-kB in both Calu-6 and THP-1 cells. CCL20 secretion was markedly induced in A549, Calu-6 and THP-1 cells by heat-killed B. abortus or a model Brucella lipoprotein (L-Omp19) but not by the B. abortus lipopolysaccharide (LPS). Accordingly, CCL20 production by B. abortus-infected cells was strongly TLR2-dependent. Whereas hBD2 expression was not induced by B. abortus infection, it was significantly induced in A549 cells by conditioned media from B. abortus-infected THP-1 monocytes (CMB). A similar inducing effect was observed on CCL20 secretion. Experiments using blocking agents revealed that IL-1β, but not TNF-α, was involved in the induction of hBD2 and CCL20 secretion by CMB. In the in vitro antimicrobial assay, the lethal dose (LD) 50 of CCL20 for B. abortus (>50 μg/ml) was markedly higher than that against E. coli (1.5 μg/ml) or a B. abortus mutant lacking the O polysaccharide in its LPS (8.7 ug/ml). hBD2 did not kill any of the B. abortus strains at the tested concentrations. These results show that human lung epithelial cells secrete CCL20 and hBD2 in response to B. abortus and/or to cytokines produced by infected monocytes. Whereas these molecules do not seem to exert antimicrobial activity against this pathogen, they could recruit immune cells to the infection site. PMID:26448160

  5. Laboratory Building

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, Joshua M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-01

    This report is an analysis of the means of egress and life safety requirements for the laboratory building. The building is located at Sandia National Laboratories (SNL) in Albuquerque, NM. The report includes a prescriptive-based analysis as well as a performance-based analysis. Following the analysis are appendices which contain maps of the laboratory building used throughout the analysis. The top of all the maps is assumed to be north.

  6. Analytical Laboratory

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    Federal Laboratory Consortium — The Analytical Labspecializes in Oil and Hydraulic Fluid Analysis, Identification of Unknown Materials, Engineering Investigations, Qualification Testing (to support...

  7. Chemistry Laboratory

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    Federal Laboratory Consortium — Purpose: To conduct fundamental studies of highway materials aimed at understanding both failure mechanisms and superior performance. New standard test methods are...

  8. Propulsion Laboratory

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    Federal Laboratory Consortium — The Propulsion Lab simulates field test conditions in a controlled environment, using standardized or customized test procedures. The Propulsion Lab's 11 cells can...

  9. Psychology Laboratory

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    Federal Laboratory Consortium — This facility provides testing stations for computer-based assessment of cognitive and behavioral Warfighter performance. This 500 square foot configurable space can...

  10. Dynamics Laboratory

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    Federal Laboratory Consortium — The Dynamics Lab replicates vibration environments for every Navy platform. Testing performed includes: Flight Clearance, Component Improvement, Qualification, Life...

  11. Visualization Laboratory

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    Federal Laboratory Consortium — FUNCTION: Evaluates and improves the operational effectiveness of existing and emerging electronic warfare systems. By analyzing and visualizing simulation results...

  12. Ameliorative effects of the ethanolic extract of Allium saralicum R.M. Fritsch on CCl4-induced nephrotoxicity in mice: A stereological examination

    Directory of Open Access Journals (Sweden)

    Sherkatolabbasieh Hamidreza

    2017-01-01

    Full Text Available The present study was carried out to investigate the nephroprotective effect of the ethanolic extract of Allium saralicum R.M. Fritsch (ASRMF in mice. Thirty-five male mice were divided into five groups (n=7. Group 1 (positive control received 1 mL/kg olive oil intraperitoneally (i.p. and 0.5 mL distilled water orally; Group 2 (negative control received CCl4 (50% in olive oil, 1 mg/kg; i.p.; Groups 3, 4 and 5 received CCl4 and 200, 800 and 1600 μg/kg of ASRMF extract, respectively. The renal volume and cortex in Groups 1 and 2 were increased by 55% and 62% (p≤0.001 following CCl4 administration, respectively, and were improved after ASRMF administration. The volume of proximal convoluted tubules (PCTs, glomeruli, vessels and interstitial tissue increased 80%, 150%, 83% and 64% (p≤0.05, respectively, in CCl4-treated mice, and decreased significantly with 800 and 1600 μg/kg of ASRMF. The length of PCTs and vessels increased 51% and 45% and decreased (p≤0.05 with 200, 800 and 1600 μg/kg of ASRMF, respectively. CCl4-treated mice lost 22.5% of glomeruli; the loss was inhibited significantly (p≤0.05 by ASRMF. Urea and creatinine concentrations were increased (p≤0.05 in CCl4-induced nephrotoxicity as compared to the controls, whereas different doses of ASRMF restored the levels of these biomarkers compared to the negative controls. In conclusion, ASRMF has a potent nephroprotective property and can improve renal structural and serum biomarkers in CCl4-induced nephrotoxicity in mice.

  13. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

    Directory of Open Access Journals (Sweden)

    Lillard James W

    2011-05-01

    Full Text Available Abstract Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β and forkhead in human rhabdomyosarcoma (FKHR inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.

  14. Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7-CTLA-4 and CCL-CCR pathways.

    Science.gov (United States)

    Gan, Lu; Zhou, Qiaoling; Li, Xiaozhao; Chen, Chen; Meng, Ting; Pu, Jiaxi; Zhu, Mengyuan; Xiao, Chenggen

    2018-04-01

    IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis. Hemolytic streptococcus infection induced an increase in IL-1, IL-6, and TNF-α, resulting in Th22 cell differentiation from T lymphocytes obtained from patients with IgAN, and the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes facilitated Th22 cell chemotaxis. The increased amount of Th22 cells caused an increase in TGF-β1 levels, and anti-CD80, anti-CD86, and CTLA-4Ig treatment reduced TGF-β1 levels by inhibiting Th22 lymphocytosis and secretion of cytokines and chemokines, thus potentially relieving kidney fibrosis. Our data suggest that Th22 cells might be recruited into the kidneys via the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes by mesangial cells and tubular epithelial cells in infection-related IgAN. Th22 cell overrepresentation was attributed to stimulation of the B7-CTLA-4Ig antigen-presenting pathway and IL-1, IL-6, and TNF-α.

  15. Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders

    Directory of Open Access Journals (Sweden)

    Carpenter Danielle

    2011-08-01

    Full Text Available Abstract Background Copy number variation (CNV contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. Results We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. Conclusions Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion.

  16. CCL2 as a trigger of manifestations of compensatory anti-inflammatory response syndrome in mice with severe systemic inflammatory response syndrome.

    Science.gov (United States)

    Takahashi, Hitoshi; Tsuda, Yasuhiro; Kobayashi, Makiko; Herndon, David N; Suzuki, Fujio

    2006-04-01

    Patients with compensatory anti-inflammatory response syndrome (CARS) are at a higher risk for infection with various opportunistic pathogens. CARS develops commonly in association with the manifestation of systemic inflammatory response syndrome (SIRS). In the present study, the role of SIRS-associated soluble factors on the CARS development was examined in mice with pancreatitis, a carrier of typical SIRS. Following the production of SIRS-related cytokines [tumor necrosis factor alpha and interleukin (IL)-1beta], CC chemokine ligand 2 (CCL2), IL-4, and IL-10 (typical CARS cytokines) were detected in the sera of mice with pancreatitis. CCL2 has been described as an essential chemokine for the T helper cell type 2 manifestation. CARS effector cells (cells with an ability to produce IL-4 and IL-10) were not generated from normal T cells after stimulation with SIRS-related cytokines. However, these cells were generated from normal T cells after cultivation with peripheral blood neutrophils (PMN) from SIRS mice in a dual-chamber transwell. Normal T cells did not convert to CARS effector cells after transwell cultures with PMN from normal mice. CCL2 was detected in culture fluids of PMN from SIRS mice, and PMN from normal mice did not produce CCL2 into their culture fluids. CARS effector cells did not appear in PMN-depleted SIRS mice or SIRS mice treated with anti-CCL2 monoclonal antibody, and these cells were demonstrated in PMN-depleted SIRS mice after treatment with recombinant murine CCL2. These results indicate that CCL2 produced by PMN from SIRS mice is an active molecule on the SIRS-associated CARS manifestation.

  17. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

    Science.gov (United States)

    2011-01-01

    Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa) cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU) incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE) assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK)-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β) and forkhead in human rhabdomyosarcoma (FKHR) inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion. PMID:21539750

  18. Antioxidative and cytoprotective effects of andrographolide against CCl4-induced hepatotoxicity in HepG2 cells.

    Science.gov (United States)

    Krithika, R; Verma, R J; Shrivastav, P S

    2013-05-01

    This article describes antioxidative and cytoprotective property of andrographolide, a major active component of the plant Andrographis paniculata (A. paniculata). High yields (2.7%) of andrographolide was isolated from the aerial parts of this plant via silica column chromatography. The purity of the compound was determined by high-performance thin-layer chromatography (HPTLC) and reversed phase high-performance liquid chromatography (HPLC) analysis. The structure was elucidated using techniques such as UV-visible spectrophotometry, elemental analysis, Fourier transform infrared (FT-IR), (1)H nuclear magnetic resonance ((1)H NMR), (13)C nuclear magnetic resonance ((13)C NMR) and mass spectral analysis and the data obtained were comparable with reported results. It was observed that andrographolide exhibited significant antioxidative property (IC50 = 3.2 µg/ml) by its ability to scavenge a stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) as compared to known antioxidants like ascorbic acid, butylated hydroxy toluene (BHT) and the plant extract. The cytoprotective role of andrographolide against carbon tetrachloride (CCl4) toxicity in human hepatoma HepG2 cell line was assessed using trypan blue exclusion test, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, by estimation of various leakage enzymes and by measuring the glutathione levels. The recovery obtained for andrographolide treatment in the presence of CCl4 was two-fold compared to A. paniculata extract for all other related biochemical parameters investigated. The results of the study indicate that andrographolide is a potent inhibitor of CCl4-mediated lipid peroxidation.

  19. Recombinant VP1, an Akt inhibitor, suppresses progression of hepatocellular carcinoma by inducing apoptosis and modulation of CCL2 production.

    Directory of Open Access Journals (Sweden)

    Tai-An Chen

    Full Text Available BACKGROUND: The application of viral elements in tumor therapy is one facet of cancer research. Recombinant capsid protein VP1 (rVP1 of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. Here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (HCC, one of the most common human cancers worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with rVP1 inhibited cell proliferation in two murine HCC cell lines, BNL and Hepa1-6, with IC₅₀ values in the range of 0.1-0.2 µM. rVP1 also induced apoptosis in these cells, which was mediated by Akt deactivation and dissociation of Ku70-Bax, and resulted in conformational changes and mitochondrial translocation of Bax, leading to the activation of caspases-9, -3 and -7. Treatment with 0.025 µM rVP1, which did not affect the viability of normal hepatocytes, suppressed cell migration and invasion via attenuating CCL2 production. The production of CCL2 was modulated by Akt-dependent NF-κB activation that was decreased after rVP1 treatment. The in vivo antitumor effects of rVP1 were assessed in both subcutaneous and orthotopic mouse models of HCC in immune-competent BALB/c mice. Intratumoral delivery of rVP1 inhibited subcutaneous tumor growth as a result of increased apoptosis. Intravenous administration of rVP1 in an orthotopic HCC model suppressed tumor growth, inhibited intra-hepatic metastasis, and prolonged survival. Furthermore, a decrease in the serum level of CCL2 was observed in rVP1-treated mice. CONCLUSIONS/SIGNIFICANCE: The data presented herein suggest that, via inhibiting Akt phosphorylation, rVP1 suppresses the growth, migration, and invasion of murine HCC cells by inducing apoptosis and attenuating CCL2 production both in vitro and in vivo. Recombinant protein VP1 thus has the potential to be developed as a new therapeutic agent for HCC.

  20. UV Absorption Cross Sections of Nitrous Oxide (N2O) and Carbon Tetrachloride (CCl4) Between 210 and 350 K and the Atmospheric Implications

    Science.gov (United States)

    Carlon, Nabilah Rontu; Papanastasiou, Dimitrios K.; Fleming, Eric L.; Jackman, Charles H.; Newman, Paul A.; Burkholder, James B.

    2010-01-01

    Absorption cross sections of nitrous oxide (N2O) and carbon tetrachloride (CCl4) are reported at five atomic UV lines (184.95, 202.548, 206.200, 213.857, and 228.8 nm) at 27 temperatures in the range 210-350 K. In addition, UV absorption spectra of CCl4 are reported between 200-235 nm as a function of temperature (225-350 K). The results from this work are critically compared with results from earlier studies. For N2O, the present results are in good agreement with the current JPL recommendation enabling a reduction in the estimated uncertainty in the N2O atmospheric photolysis rate. For CCl4, the present cross section results are systematically greater than the current recommendation at the reduced temperatures most relevant to stratospheric photolysis. The new cross sections result in a 5-7% increase in the modeled CCl4 photolysis loss, and a slight decrease in the stratospheric lifetime, from 51 to 50 years, for present day conditions. The corresponding changes in modeled inorganic chlorine and ozone in the stratosphere are quite small. A CCl4 cross section parameterization for use in 37 atmospheric model calculations is presented.

  1. TOP1 and 2, polysaccharides from Taraxacum officinale, attenuate CCl(4)-induced hepatic damage through the modulation of NF-kappaB and its regulatory mediators.

    Science.gov (United States)

    Park, Chung Mu; Youn, Hyun Joo; Chang, Hee Kyung; Song, Young Sun

    2010-05-01

    In this work, we estimate the inhibitory effect of two polysaccharides from Taraxacum officinale (TOP) on CCl(4)-induced oxidative stress and inflammation in Sprague-Dawley rats. TOP1 and 2 (304, 92 mg/kg bw) were administered for 7 days via a stomach sonde, and hepatitis was induced by a single dose of CCl(4) (50% CCl(4)/olive oil; 0.5 mL/kg bw) administration. CCl(4) significantly elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Histopathological observation further revealed that CCl(4)-induced moderate levels of inflammatory cell infiltration, centrilobular fatty change, apoptosis, and necrosis. However, TOPs pretreatment markedly decreased AST and ALT activities as well as hepatic lesions. TOPs also increased free radical scavenging activity, as exhibited by a lowered TBARS concentration. TOPs pretreatment also reversed other hepatitis-associated symptoms, including GSH depletion, inhibited anti-oxidative enzyme activities, up-regulation of NF-kappaB and increased expression of its regulatory inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta. These results suggest that TOPs have a hepatoprotective effect by modulating inflammatory responses and ameliorating oxidative stress. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  2. Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2: Further Insights into Molecular, Synaptic, and Cellular Mechanisms.

    Science.gov (United States)

    Xie, Rou-Gang; Gao, Yong-Jing; Park, Chul-Kyu; Lu, Ning; Luo, Ceng; Wang, Wen-Ting; Wu, Sheng-Xi; Ji, Ru-Rong

    2018-02-01

    Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 (C-C motif chemokine ligand 2) has been shown to enhance N-methyl-D-aspartate (NMDA)-induced currents in spinal outer lamina II (IIo) neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expression in excitatory vesicular glutamate transporter subtype 2-positive (VGLUT2 + ) neurons. CCL2 increased NMDA-induced currents in CCR2 + /VGLUT2 + neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin-expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2-expressing excitatory neurons in spinal lamina IIo, and this underlies the generation of central sensitization in pathological pain.

  3. Antifibrotic effects of D-limonene (5(1-methyl-4-[1-methylethenyl]) cyclohexane) in CCl4induced liver toxicity in Wistar rats.

    Science.gov (United States)

    Ahmad, Sheikh Bilal; Rehman, Muneeb U; Fatima, Bilques; Ahmad, Bilal; Hussain, Ishraq; Ahmad, Sheikh Pervaiz; Farooq, Adil; Muzamil, Showkeen; Razzaq, Rahil; Rashid, Shahzada Mudasir; Ahmad Bhat, Showkat; Mir, Manzoor Ur Rahman

    2018-03-01

    This study was designed to assess the potential antifibrotic effect of D-Limonene-a component of volatile oils extracted from citrus plants. D-limonene is reported to have numerous therapeutic properties. CCl 4 -intduced model of liver fibrosis in Wistar rats is most widely used model to study chemopreventive studies. CCl 4 -intoxication significantly increased serum aminotransferases and total cholesterol these effects were prevented by cotreatment with D-Limonene. Also, CCl 4 -intoxication caused depletion of glutathione and other antioxidant enzymes while D-Limonene preserved them within normal values. Hydroxyproline and malondialdehyde content was increased markedly by CCl 4 treatment while D-Limonene prevented these alterations. Levels of TNF-α, TGF-β, and α-SMA were also assessed; CCl 4 increased the expression of α-SMA, NF-κB and other downstream inflammatory cascade while D-Limonene co-treatment inhibited them. Collectively these findings indicate that D-Limonene possesses potent antifibrotic effect which may be attributed to its antioxidant and anti-inflammatory properties. © 2017 Wiley Periodicals, Inc.

  4. Fetally derived CCL3 is not essential for the migration of maternal cells across the blood-placental barrier in the mouse.

    Science.gov (United States)

    Unno, Akihiro; Suzuki, Kazuhiko; Kitoh, Katsuya; Takashima, Yasuhiro

    2010-11-01

    In mammals with a hemochorial placenta (e.g., primates and rodents), the maternal and fetal bloodstreams are separated by the blood-placenta barrier. However, a few maternal cells in the general circulation pass through the barrier during normal pregnancy. So far, the transfer mechanism has not been investigated. In this study, we established a chemokine (C-C motif) ligand 3 (CCL3)-deficient mouse model to examine the effect of fetus-derived chemokine(s) on the migration of maternal cells through the blood-placenta barrier. Using this model, we obtained CCL3-positive and -negative littermates from a mother expressing both CCL3 and green fluorescent protein (GFP). The numbers of GFP positive maternal cells in the lung, liver, spleen and heart of CCL3-positive and -negative fetuses were compared. A few GFP-positive cells were detected in the lung and liver of both types of fetus. These results indicate that maternal cells can migrate through the blood-placenta barrier even in the absence of fetal CCL3.

  5. Theoretical kinetics study of the reactions CHClBr + HBr ⇄ CH2ClBr + Br, CCl2Br + HBr ⇄ CHCl2Br + Br and CClBr2 + HBr ⇄ CHClBr2 + Br

    Science.gov (United States)

    Bracco, Larisa L. B.; Tucceri, María E.; Cobos, Carlos J.

    2018-03-01

    The kinetics of CHClBr + HBr ⇄ CH2ClBr + Br (1, -1), CCl2Br + HBr ⇄ CHCl2Br + Br (2, -2) and CClBr2 + HBr ⇄ CHClBr2 + Br (3, -3) reactions at 293-787 K has been studied by using the canonical transition state theory with molecular information provided by different quantum chemical methods. The obtained rate constants (in cm3 molecule-1 s-1) are k1 = 5.24 × 10-13 exp[-1.47 kcal mol-1/RT], k-1 = 2.70 × 10-11 exp[-10.21 kcal mol-1/RT], k2 = 4.18 × 10-13 exp[-2.49 kcal mol-1/RT], k-2 = 6.96 × 10-12 exp[-7.36 kcal mol-1/RT], k3 = 3.29 × 10-13 exp[-2.20 kcal mol-1/RT], and k-3 = 8.45 × 10-13 exp[-7.10 kcal mol-1/RT]. Rate constants for (2, -2) and (3, -3) are here reported for the first time.

  6. Elastomers Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Primary capabilities include: elastomer compounding in various sizes (micro, 3x5, 8x12, 8x15 rubber mills); elastomer curing and post curing (two 50-ton presses, one...

  7. Laboratory Tests

    Science.gov (United States)

    ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & ... What are lab tests? Laboratory tests are medical devices that are intended for use on samples of blood, urine, or other tissues ...

  8. Audio Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides an environment and facilities for auditory display research. A primary focus is the performance use of binaurally rendered 3D sound in conjunction...

  9. Semiconductor Electrical Measurements Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Semiconductor Electrical Measurements Laboratory is a research laboratory which complements the Optical Measurements Laboratory. The laboratory provides for Hall...

  10. The Cannabinoid Delta-9-tetrahydrocannabinol Mediates Inhibition of Macrophage Chemotaxis to RANTES/CCL5 through the CB2 Receptor

    Science.gov (United States)

    Raborn, Erinn S.; Marciano-Cabral, Francine; Buckley, Nancy E.; Martin, Billy R.; Cabral, Guy A.

    2009-01-01

    The chemotactic response of murine peritoneal macrophages to RANTES/CCL5 was inhibited significantly following pretreatment with delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana. Significant inhibition of this chemokine directed migratory response was obtained also when the full cannabinoid agonist CP55940 was used. The CB2 receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB1 receptor-selective ligand ACEA had a minimal effect. The THC-mediated inhibition was reversed by the CB2 receptor-specific antagonist SR144528 but not by the CB1 receptor-specific antagonist SR141716A. In addition, THC treatment had a minimal effect on the chemotactic response of peritoneal macrophages from CB2 knockout mice. Collectively, these results suggest that cannabinoids act through the CB2 receptor to trans-deactivate migratory responsiveness to RANTES/CCL5. Furthermore, the results suggest that the CB2 receptor may be a constituent element of a network of G protein-coupled receptor signal transductional systems, inclusive of chemokine receptors, that act coordinately to modulate macrophage migration. PMID:18247131

  11. Brucella invasion of human intestinal epithelial cells elicits a weak proinflammatory response but a significant CCL20 secretion.

    Science.gov (United States)

    Ferrero, Mariana C; Fossati, Carlos A; Rumbo, Martín; Baldi, Pablo C

    2012-10-01

    In spite of the frequent acquisition of Brucella infection by the oral route in humans, the interaction of the bacterium with cells of the intestinal mucosa has been poorly studied. Here, we show that different Brucella species can invade human colonic epithelial cell lines (Caco-2 and HT-29), in which only smooth species can replicate efficiently. Infection with smooth strains did not produce a significant cytotoxicity, while the rough strain RB51 was more cytotoxic. Infection of Caco-2 cells or HT-29 cells with either smooth or rough strains of Brucella did not result in an increased secretion of TNF-α, IL-1β, MCP-1, IL-10 or TGF-β as compared with uninfected controls, whereas all the infections induced the secretion of IL-8 and CCL20 by both cell types. The MCP-1 response to flagellin from Salmonella typhimurium was similar in Brucella-infected or uninfected cells, ruling out a bacterial inhibitory mechanism as a reason for the weak proinflammatory response. Infection did not modify ICAM-1 expression levels in Caco-2 cells, but increased them in HT-29 cells. These results suggest that Brucella induces only a weak proinflammatory response in gut epithelial cells, but produces a significant CCL20 secretion. The latter may be important for bacterial dissemination given the known ability of Brucella to survive in dendritic cells. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  12. [Efficacy and safety of heptral, vitamin B6 and folic acid during toxic hepatitis induced by CCL4].

    Science.gov (United States)

    Antelava, N A; Gogoluari, M I; Gogoluari, L I; Pirtskhalaĭshvili, N N; Okudzhava, M V

    2007-09-01

    The aim of this work was to evaluate of efficacy and safety of complex Heptral, Vitamin B6 and Folic Acid in experimental hepatitis therapy compared with monotherapy. Experiments were carried out on pubertal rats. Eperimental hepatitis models were induced by Tetrachlormethane. The tetrachlormethane intoxication was reproduced by subcutaneous injection of CCL(4) 1ml/kg dissolved in 1ml of olive oil. Cytochrome P450, cytochrome b5, reduced glutation,activity of glutationetranspherase and content of ATP in hepatocytes were measured by the spectrophotometric techniques,but content of homocysteine by chromophtography techniques. Under CCL(4) intoxication disturbance of liver detoxication function, energy deficit and surplus of homocysteine were observed. Treatment of the toxic hepatitis with heptral increased the level of cytochrome P450, cytochrome b5, glutation activity of glutationetranspherase glutathione and reduced content of homocysteine. Complex therapy with Heptral and B6 and folic acid reveal more expressive hepatoprotective effect and safety than monotherapy with Heptral. Complex therapy improves not only the parameters of biotransformation (metabolic and conjugation phase), but also normalizes the level of ATP and homocystein. Vitamins B6 and folic acid increases the efficacy and safety of Heptral. This complex was recomended for treatment of hepatitis.

  13. Dihydroisotanshinone I combined with radiation inhibits the migration ability of prostate cancer cells through DNA damage and CCL2 pathway.

    Science.gov (United States)

    Lee, I-Yun; Lin, Yin-Yin; Yang, Yao-Hsu; Lin, Yu-Shin; Lin, Chun-Liang; Lin, Wei-Yu; Cheng, Yu-Ching; Shu, Li-Hsin; Wu, Ching-Yuan

    2018-01-31

    Radiotherapy plays an important role in the treatment of prostate cancer. Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Therefore, the study investigated the effect of dihydroisotanshinone I (DT) and the combination treatment of 5 μM DT and 5Gy irradiation (IR) against the migration ability of prostate cancer cells. DT and the combination treatment were studied for its biological activity against migration ability of prostate cancer cells with transwell migration assay. Subsequently, we tried to explore the underlying mechanism with ELISA, flow cytometry and Western's blotting assay. The results showed that DT and the combination treatment substantially inhibited the migration ability of prostate cancer cells. DT and the combined treatment can decrease the ability of macrophages to recruit prostate cancer cells. Mechanistically, DT and the combination treatment reduced the secretion of chemokine (C-C Motif) Ligand 2 (CCL2) from prostate cancer cells. We also found that DT treatment induced the cell cycle of prostate cancer cells entering S phase and increased the protein expression of DNA damage response proteins (rH2AX and phosphorylated ataxia telangiectasia-mutated [ATM]) in DU145 cells and PC-3 cells. DT displays radiosensitization and antimigration effects in prostate cancer cells by inducing DNA damage and inhibiting CCL2 secretion. We suggest that DT can be used as a novel antimetastatic cancer drug or radiosensitizer in the armamentarium of prostate cancer management.

  14. Accelerated CCl4-induced liver fibrosis in Hjv-/- mice, associated with an oxidative burst and precocious profibrogenic gene expression.

    Directory of Open Access Journals (Sweden)

    Giada Sebastiani

    Full Text Available Hereditary hemochromatosis is commonly associated with liver fibrosis. Likewise, hepatic iron overload secondary to chronic liver diseases aggravates liver injury. To uncover underlying molecular mechanisms, hemochromatotic hemojuvelin knockout (Hjv-/- mice and wild type (wt controls were intoxicated with CCl(4. Hjv-/- mice developed earlier (by 2-4 weeks and more acute liver damage, reflected in dramatic levels of serum transaminases and ferritin and the development of severe coagulative necrosis and fibrosis. These responses were associated with an oxidative burst and early upregulation of mRNAs encoding α1-(I-collagen, the profibrogenic cytokines TGF-β1, endothelin-1 and PDGF and, notably, the iron-regulatory hormone hepcidin. Hence, CCl4-induced liver fibrogenesis was exacerbated and progressed precociously in Hjv-/- animals. Even though livers of naïve Hjv-/- mice were devoid of apparent pathology, they exhibited oxidative stress and immunoreactivity towards α-SMA antibodies, a marker of hepatic stellate cells activation. Furthermore, they expressed significantly higher (2-3 fold vs. wt, p<0.05 levels of α1-(I-collagen, TGF-β1, endothelin-1 and PDGF mRNAs, indicative of early fibrogenesis. Our data suggest that hepatic iron overload in parenchymal cells promotes oxidative stress and triggers premature profibrogenic gene expression, contributing to accelerated onset and precipitous progression of liver fibrogenesis.

  15. Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis.

    Science.gov (United States)

    Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

    2016-12-14

    To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. Liver stiffness was measured in sixty-eight rabbits with CCl 4 -induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. LSM by ElastPQ was significantly correlated with histologic fibrosis stage ( r = 0.85, P splenectomy (especially F1) may delay liver fibrosis progression. ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl 4 -induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy.

  16. Vacuum Ultra-Violet Spectroscopy of Laboratory-Simulated Astrophysical Ices

    Science.gov (United States)

    Davis, M. P.; Dawes, A.; Holtom, P. D.; Mukerji, R. J.; Sivaraman, B.; Webb, S. M.; Hoffmann, S. V.; Shaw, D. A.; Mason, N. J.

    Over recent years it has become clear that solid phase processes in the interstellar medium (ISM) are responsible for a significant amount of molecular formation in these regions. A combination of astronomical spectroscopy and laboratory-based simulations has greatly enhanced our understanding of those molecules which are present in the ISM and provided information on their formation mechanisms. Although infra-red spectroscopy has been widely used in these studies and is a common observational tool other spectroscopic techniques are now being developed. We have carried out a number of experiments looking at the electronic structure of simple molecular ices (such as H2O, NH3, CO, CO2, SO2 and CH4) using vacuum ultra-violet (VUV) spectroscopy. In addition to complementing existing infra-red spectra, knowing the electronic structure of ices allows us to understand the processes which take place during irradiation by ultra-violet photons, a common source of ice surface modification in the interstellar medium. In our experiments we have used synchrotron beam-lines at Daresbury Laboratory (UK) and Aarhus University (Denmark) as the irradiating source providing UV light at wavelengths between 120nm and 350nm. A small ultra-high vacuum chamber with an in-built cryostat system was attached to the beam-line (for more information see Dawes, Holtom & Mason (2003)). A magnesium fluoride or calcium fluoride substrate was cooled to between 20K and 100K allowing the sample molecules to physisorb upon it. Typical ice thicknesses range from 0.1μm and 3μm, depending on the UV absorption properties of the ice involved. In this poster we present VUV spectra of several typical astrochemical molecules showing how the electronic structures of different ice systems are affected by their temperature and deposition speed. The importance of VUV spectroscopy as an astrochemical and possible observation technique will be discussed at the meeting.

  17. Smac Mimetic-Induced Upregulation of CCL2/MCP-1 Triggers Migration and Invasion of Glioblastoma Cells and Influences the Tumor Microenvironment in a Paracrine Manner

    Directory of Open Access Journals (Sweden)

    Carina Lindemann

    2015-06-01

    Full Text Available Second mitochondria-derived activator of caspase (Smac mimetics are considered as promising anticancer therapeutics that are currently under investigation in early clinical trials. They induce apoptosis by antagonizing inhibitor of apoptosis proteins, which are frequently overexpressed in cancer. We previously reported that Smac mimetics, such as BV6, additionally exert non-apoptotic functions in glioblastoma (GBM cells by stimulating migration and invasion in a nuclear factor kappa B (NF-κB-dependent manner. Because NF-κB target genes mediating these effects are largely unknown, we performed whole-genome expression analyses. Here, we identify chemokine (C-C motif ligand 2 (CCL2 as the top-listed NF-κB-regulated gene being upregulated upon BV6 treatment in GBM cells. BV6-induced upregulation and secretion of CCL2 are required for migration and invasion of GBM cells because knockdown of CCL2 in GBM cells abolishes these effects. Co-culture experiments of GBM cells with non-malignant astroglial cells reveal that BV6-stimulated secretion of CCL2 by GBM cells into the supernatant triggers migration of astroglial cells toward GBM cells because CCL2 knockdown in BV6-treated GBM cells impedes BV6-stimulated migration of astroglial cells. In conclusion, we identify CCL2 as a BV6-induced NF-κB target gene that triggers migration and invasion of GBM cells and exerts paracrine effects on the GBM's microenvironment by stimulating migration of astroglial cells. These findings provide novel insights into the biological functions of Smac mimetics with important implications for the development of Smac mimetics as cancer therapeutics.

  18. Variants of C-C motif chemokine 22 (CCL22 are associated with susceptibility to atopic dermatitis: case-control studies.

    Directory of Open Access Journals (Sweden)

    Tomomitsu Hirota

    Full Text Available Atopic dermatitis (AD is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2 cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1(st population, 916 cases and 1,032 controls; 2(nd population 1,034 cases and 1,004 controls. After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10⁻⁶; OR, 0.74; 95% CI, 0.65-0.85. Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.

  19. The effect of CCL3 and CCR1 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice.

    Science.gov (United States)

    Taddei, Silvana R de Albuquerque; Queiroz-Junior, Celso M; Moura, Adriana P; Andrade, Ildeu; Garlet, Gustavo P; Proudfoot, Amanda E I; Teixeira, Mauro M; da Silva, Tarcília A

    2013-01-01

    Bone remodeling is affected by mechanical loading and inflammatory mediators, including chemokines. The chemokine (C-C motif) ligand 3 (CCL3) is involved in bone remodeling by binding to C-C chemokine receptors 1 and 5 (CCR1 and CCR5) expressed on osteoclasts and osteoblasts. Our group has previously demonstrated that CCR5 down-regulates mechanical loading-induced bone resorption. Thus, the present study aimed to investigate the role of CCR1 and CCL3 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice. Our results showed that bone remodeling was significantly decreased in CCL3(-/-) and CCR1(-/-) mice and in animals treated with Met-RANTES (an antagonist of CCR5 and CCR1). mRNA levels of receptor activator of nuclear factor kappa-B (RANK), its ligand RANKL, tumor necrosis factor alpha (TNF-α) and RANKL/osteoprotegerin (OPG) ratio were diminished in the periodontium of CCL3(-/-) mice and in the group treated with Met-RANTES. Met-RANTES treatment also reduced the levels of cathepsin K and metalloproteinase 13 (MMP13). The expression of the osteoblast markers runt-related transcription factor 2 (RUNX2) and periostin was decreased, while osteocalcin (OCN) was augmented in CCL3(-/-) and Met-RANTES-treated mice. Altogether, these findings show that CCR1 is pivotal for bone remodeling induced by mechanical loading during orthodontic tooth movement and these actions depend, at least in part, on CCL3. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Isotope laboratories

    International Nuclear Information System (INIS)

    1978-01-01

    This report from the Dutch Ministry of Health is an advisory document concerned with isotope laboratories in hospitals, in connection with the Dutch laws for hospitals. It discusses which hospitals should have isotope laboratories and concludes that as many hospitals as possible should have small laboratories so that emergency cases can be dealt with. It divides the Netherlands into regions and suggests which hospitals should have these facilities. The questions of how big each lab. is to be, what equipment each has, how each lab. is organised, what therapeutic and diagnostic work should be carried out by each, etc. are discussed. The answers are provided by reports from working groups for in vivo diagnostics, in vitro diagnostics, therapy, and safety and their results form the criteria for the licences of isotope labs. The results of a questionnaire for isotope labs. already in the Netherlands are presented, and their activities outlined. (C.F.)

  1. The fate of atmospheric phosgene and the stratospheric chlorine loadings of its parent compounds: CCl4, C2Cl4, C2HCL3, CH3CCl3, and CHCl3

    Science.gov (United States)

    Kindler, T. P.; Chameides, W. L.; Wine, P. H.; Cunnold, D. M.; Alyea, F. N.; Franklin, J. A.

    1995-01-01

    A study of the tropospheric and stratospheric cycles of phosgene is carried out to determine its fate and ultimate role in controlling the ozone depletion potentials of its parent compounds. Tropospheric phosgene is produced from the OH-initiated oxidation of C2Cl4, CH3CCl3, CHCl3, and C2HCl3. Simulations using a two-dimensional model indicate that these processes produce about 90 pptv/yr of tropospheric phosgene with an average concentration of about 18 pptv, in reasonable agreement with observations. We estimate a residence time of about 70 days for tropospheric phosgene, with the vast majority being removed by hydrolysis in cloudwater. Only about 0.4% of the phosgene produced in the troposphere avoids wet removal and is transported to the stratosphere, where its chlorine can be released to participate in the catalytic destruction of ozone. Stratospheric phosgene is produced from the photochemical degradation of CCl4, C2Cl4, CHCl3, and CH3CCl3 and is removed by photolysis and downward transport to the troposphere. Model calculations, in good agreement with observations, indicate that these processes produce a peak stratospheric concentration of about 25-30 pptv at an altitude of about 25 km. In contrast to tropospheric phosgene, stratospheric phosgene is found to have a lifetime against photochemical removal of the order of years. As a result, a significant portion of the phosgene that is produced in the stratosphere is ultimately returned to the troposphere, where it is rapidly removed by clouds. This phenomenon effectively decreases the amount of reactive chlorine injected into the stratosphere and available for ozone depletion from phosgene's parent compounds. A similar phenomenon due to the downward transport of stratospheric COFCl produced from CFC-11 is estimated to cause a 7% decrease in the amount of reactive chlorine injected into the stratosphere from this compound. Our results are potentially sensitive to a variety of parameters, most notably the rate

  2. Saxton Transportation Operations Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Saxton Transportation Operations Laboratory (Saxton Laboratory) is a state-of-the-art facility for conducting transportation operations research. The laboratory...

  3. Laboratory investigations

    International Nuclear Information System (INIS)

    Handin, J.

    1980-01-01

    Our task is to design mined-repository systems that will adequately secure high-level nuclear waste for at least 10,000 yr and that will be mechanically stable for 50 to 100-yr periods of retrievability during which mistakes could be corrected and a valuable source of energy could be reclaimed, should national policy on the reprocessing of spent fuel ever change. The only credible path for the escape of radionuclides from the repository to the biosphere is through ground-water, and in hard rock, bulk permeability is largely governed by natural and artificial fracture systems. Catastrophic failure of an excavation in hard rock is likely to occur at the weakest links - the discontinuities in the rock mass that is perturbed first by mining and then by radiogenic heating. The laboratory can contribute precise measurements of the pertinent thermomechanical, hydrological and chemical properties and improve our understanding of the fundamental processes through careful experiments under well controlled conditions that simulate the prototype environment. Thus laboratory investigations are necessary, but they are not sufficient, for conventional sample sizes are small relative to natural defects like joints - i.e., the rock mass is not a continuum - and test durations are short compared to those that predictive modeling must take into account. Laboratory investigators can contribute substantially more useful data if they are provided facilities for testing large specimens(say one cubic meter) and for creep testing of all candidate host rocks. Even so, extrapolations of laboratory data to the field in neither space nor time are valid without the firm theoretical foundations yet to be built. Meanwhile in-situ measurements of structure-sensitive physical properties and access to direct observations of rock-mass character will be absolutely necessary

  4. Culham Laboratory

    International Nuclear Information System (INIS)

    1980-06-01

    The report contains summaries of work carried out under the following headings: fusion research experiments; U.K. contribution to the JET project; supporting studies; theoretical plasma physics, computational physics and computing; fusion reactor studies; engineering and technology; contract research; external relations; staff, finance and services. Appendices cover main characteristics of Culham fusion experiments, staff, extra-mural projects supported by Culham Laboratory, and a list of papers written by Culham staff. (U.K.)

  5. Plating laboratory

    International Nuclear Information System (INIS)

    Seamster, A.G.; Weitkamp, W.G.

    1984-01-01

    The lead plating of the prototype resonator has been conducted entirely in the plating laboratory at SUNY Stony Brook. Because of the considerable cost and inconvenience in transporting personnel and materials to and from Stony Brook, it is clearly impractical to plate all the resonators there. Furthermore, the high-beta resonator cannot be accommodated at Stony Brook without modifying the set up there. Consequently the authors are constructing a plating lab in-house

  6. Assessment of the hepatoprotective activity of the seeds of Hunteria umbellata (Hallier F.) on carbon tetrachloride (CCl4) induced liver damage in Wistar albino rats

    Science.gov (United States)

    Ogunlana, Olubanke Olujoke; Ogunlana, Oluseyi Ebenezer; Adelani, Isaacson Bababode; Adebayo, Angie Osariem Igbinoba; David, Opetoritse Laju; Adeleye, Oluwaseye Joseph; Udeogu, Stephanie Adaora; Adeyemi, Alaba Oladipupo; Akinyele, Julie Oluranti

    2018-04-01

    This study was designed to evaluate the hepatoprotective activity of the seeds of Hunteria umbellata (HU) on carbon tetrachloride (CCl4) induced rats. Rats of groups 1 (normal control), 3 and 5 were not treated with CCl4 while rats of groups 2 (negative control), 4 and 6 rats were treated with single dose of CCl4 (2 ml/kg) by intraperitoneal administration. Normal control group 1 rats were given distilled water, groups 3 and 4 rats were given 50 mg/kg of silymarin while groups 5 and 6 rats were given 500 mg/kg of HU. Treatment was administered orally for 28 days and sacrificed on the 29th day after an overnight fast. The weights of the rats were taken before and after the treatment. Blood samples were collected in heparinized tubes and biochemical analysis of liver functions and lipid profile tests were carried out on plasma. There was a significant change (pgroup treated with HU compared to the CCl4 untreated group 2 animals. The results obtained showed that the ethanolic extract of HU has hepatoprotective property.

  7. RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

    NARCIS (Netherlands)

    S. Kathiresan (Sekar); M.P. Reilly (Muredach); N.J. Samani (Nilesh); H. Schunkert (Heribert); J. Erdmann (Jeanette); F.L. Moll (Frans); E.A. Boerwinkle (Eric); A. Hall (Anne); C. Hengstenberg (Christian); I.R. König (Inke); R. Laaksonen (Reijo); R. McPherson (Ruth); J.R. Thompson (John); U. Thorsteinsdottir (Unnur); A. Ziegler (Andreas); W. Koenig (Wolfgang); L. Chen (Li); L.A. Cupples (Adrienne); E. Halperin (Eran); X. Li (Xiaohui); K. Musunuru (Kiran); M. Preuss (Michael); A. Schillert (Arne); G. Thorleifsson (Gudmar); B.F. Voight (Benjamin); G.A. Wells (George); P. Deloukas (Panagiotis); H. Holm (Hilma); R. Roberts (Robert); A.F.R. Stewart (Alexandre); S.P. Fortmann (Stephen); A. Go (Attie); M.A. Hlatky (Mark); C. Iribarren (Carlos); J.W. Knowles (Joshua); R.H. Myers (Richard); T. Quertermous (Thomas); S. Sidney (Steven); N. Risch; H. Tang (Hui); S. Blankenberg (Stefan); T. Zeller (Tanja); P.S. Wild (Philipp); R.B. Schnabel (Renate); C. Sinning (Christoph); K.J. Lackner (Karl); L. Tiret (Laurence); V. Nicaud; F. Cambien (François); H. Bickel (Horst); H.J. Rupprecht; C. Perret (Claire); C. Proust (Carole); T. Munzel (Thomas); M. Barbalic (maja); J.C. Bis (Joshua); I.Y.-D. Chen (Ida Yii-Der); A. Dehghan (Abbas); S. Demissie-Banjaw (Serkalem); A.R. Folsom (Aaron); N.L. Glazer (Nicole); V. Gudnason (Vilmundur); T.B. Harris (Tamara); S.R. Heckbert (Susan); D. Levy (Daniel); T. Lumley (Thomas); K. Marciante (Kristin); A.C. Morrison (Alanna); C.J. O'Donnell (Christopher); B.M. Psaty (Bruce); K. Rice (Kenneth); J.I. Rotter (Jerome); D.S. Siscovick (David); N.L. Smith (Nicholas); G.D. Smith; K.D. Taylor (Kent); C.M. van Duijn (Cornelia); K.A. Volcik (Kelly); J. Whitteman (Jaqueline); V.S. Ramachandran (Vasan); A. Hofman (Albert); A.G. Uitterlinden (André); S. Gretarsdottir (Solveig); J.R. Gulcher (Jeffrey); A. Kong (Augustine); J-A. Zwart (John-Anker); G. Thorgeirsson (Gudmundur); K.K. Andersen (Karl); M. Fischer (Marcus); A. Großhennig (Anika); W. Lieb (Wolfgang); P. Linsel-Nitschke (Patrick); K. Stark (Klaus); S. Schreiber (Stefan); H.E. Wichmann (Heinz Erich); Z. Aherrahrou (Zouhair); P. Bruse (Petra); A. Doering (Angela); T. Illig (Thomas); N. Klopp (Norman); C. Loley (Christina); A. Medack (Anja); C. Meisinger (Christa); T. Meitinger (Thomas); J. Nahrstedt (Janja); A. Peters (Annette); A.K. Wagner (Arnika); C. Willenborg (Christina); B. Böhm; H. Dobnig (Harald); T.B. Grammer (Tanja); M.M. Hoffmann (Michael); M. Kleber (Martina); W. März (Winfried); A. Meinitzer (Andreas); B. Winkelmann; D.T. Pilz (Daniela); W. Renner (Wilfried); H. Scharnagl (Hubert); T. Stojakovic (Tatjana); A. Tomaschitz (Andreas); K. Winkler (Karl); C. Guiducci (Candace); N.P. Burtt (Noël); S.B. Gabriel (Stacey); R. Elosua (Roberto); L. Peltonen (Leena Johanna); V. Salomaa (Veikko); S.M. Schwartz (Stephen); O. Melander (Olle); D. Altshuler (David); S. Dandona (Sonny); O. Jarinova (Olga); L. Qu (Liming); A. Wilensky (Asaf); W. Matthai (William); H. Hakonarson (Hakon); J. Devaney (Joseph); M.S. Burnett; A.D. Pichard; K.M. Kent (Kenneth); L.F. Satler; J.M. Lindsay (Joseph); R. Waksman (Ron); C.W. Knouff (Christopher); D. Waterworth (Dawn); M.C. Walker (Max); V. Mooser (Vincent); S.E. Epstein (Stephen); D.J. Rader (Daniel); P.S. Braund (Peter); C.P. Nelson (Christopher P.); B.J. Wright (Benjamin); A.J. Balmforth (Anthony); S.G. Ball (Stephen)

    2011-01-01

    textabstractBackground: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by

  8. Effect of different levels of marigold (Calendula officinails oil extract on performance, blood parameters and immune response of broiler chickens challenged with CCl4

    Directory of Open Access Journals (Sweden)

    Reyhaneh Vahed

    2016-04-01

    Full Text Available Introduction Although use of antibiotic as growth promoter in poultry and animal nutrition have led to positive effects, researches indicated that antibiotic residues in animal and poultry products caused resistance of bacteria and fungi strains and a resistance to antibiotics as a treatment tool for human diseases. Herbal extracts, probiotics and enzymes are suggested as replacers for antibiotics in animal and poultry nutrition. Plants and their active substances with their variety of functions are used as medicinal plants for years to prevent and treat many diseases in human, animal and poultry. Oil extracts of marigold has many active substances such as saponins, flavonoids and antioxidants and serve as a strong antioxidant to control free radicals. Therefore, the extract of marigold was used to test its curing effects on challenged birds with tetra hydrochloride (CCl4, an inducer for liver damage. Material and methods This experiment was conducted to evaluate the effects of marigold oil extracts (MOE on performance, blood parameters and immune response of broiler chickens in a 42-day period. A total of 200 Ross 308 male broiler chickens were allocated to five dietary treatments with four replicates of 10 birds each. Treatments consisted of 1 control (without marigold extract and CCl4, 2 CCl4, 3-5 150, 300, and 450 mg/kg marigold oil extract as supplement + CCl4 (1 mg/kg body weight. CCl4 was injected intraperitoneally from 21 to 30 days of age in a 2- day intervals. During this period sodium chloride (0.9% was added to control group. At day 33, one chick from each replicate of treatments was selected, and their blood and internal organs were used for different bio assays. Results and Discussion No significant differences detected among treatments for performance. However, the highest and the lowest feed intake at starter and grower periods obtained from the treatments used MOE and control groups, respectively (table 2. The highest and the

  9. Batf3-dependent CD8α+ Dendritic Cells Aggravates Atherosclerosis via Th1 Cell Induction and Enhanced CCL5 Expression in Plaque Macrophages.

    Science.gov (United States)

    Li, Yalin; Liu, Xueyan; Duan, Wei; Tian, Hua; Zhu, Guangming; He, Hao; Yao, Shutong; Yi, Shuying; Song, Wengang; Tang, Hua

    2017-04-01

    Dendritic cells (DCs) play an important role in controlling T cell-mediated adaptive immunity in atherogenesis. However, the role of the basic leucine zipper transcription factor, ATF-like 3 (Batf3)-dependent CD8α + DC subset in atherogenesis remains unclear. Here we show that Batf3 -/- Apoe -/- mice, lacking CD8α + DCs, exhibited a significant reduction in atherogenesis and T help 1 (Th1) cells compared with Apoe -/- controls. Then, we found that CD8α + DCs preferentially induce Th1 cells via secreting interleukin-12 (IL-12), and that the expression of interferon-gamma (IFN-γ)or chemokine (C-C motif) ligand 5 (CCL5) in aorta were significantly decreased in Batf3 -/- Apoe -/- mice. We further demonstrated that macrophages were the major CCL5-expressing cells in the plaque, which was significantly reduced in Batf3 -/- Apoe -/- mice. Furthermore, we found CCL5 expression in macrophages was promoted by IFN-γ. Finally, we showed that Batf3 -/- Apoe -/- mice displayed decreased infiltration of leukocytes in the plaque. Thus, CD8α + DCs aggravated atherosclerosis, likely by inducing Th1 cell response, which promoted CCL5 expression in macrophages and increased infiltration of leukocytes and lesion inflammation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Evaluation of the Effects of Some Brazilian Medicinal Plants on the Production of TNF- α and CCL2 by THP-1 Cells.

    Science.gov (United States)

    Gusman, Grasielle S; Campana, Priscilla R V; Castro, Luciano C; Castilho, Rachel O; Teixeira, Mauro M; Braga, Fernão C

    2015-01-01

    Several plant species are traditionally used in Brazil to treat various inflammatory diseases. Tumor necrosis factor- (TNF-) α and chemokine (C-C motif) ligand 2 (CCL2) are key inflammatory mediators in diseases like rheumatoid arthritis and atherosclerosis, respectively; nevertheless, only a few extracts have been assayed against these targets. We herein report the effect of 19 plant extracts on TNF-α and CCL2 release by lipopolysaccharide- (LPS-) stimulated THP-1 cells, a human monocytic leukemia cell line, along with their radical scavenging activity on DPPH. The extracts of Caryocar brasiliense, Casearia sylvestris, Coccoloba cereifera, and Terminalia glabrescens inhibited TNF-α production in a concentration-dependent manner. Fractionation of these extracts potentiated the anti-TNF-α effect, which was shown to concentrate in polar fractions, mainly composed by polyphenols. Significant CCL2 inhibition was elicited by Lippia sidoides and Terminalia glabrescens extracts, whose fractionation resulted in highly active low polar fractions. All assayed extracts showed strong radical scavenging activity, but antioxidant activity did not correlate with inhibition of TNF-α or CCL2 production. Our results allowed identifying extracts with selective capacity to block cytokine production; therefore, further purification of these extracts may yield molecules that could be useful in the treatment of chronic inflammatory diseases.

  11. CCL20 secreted from IgA1-stimulated human mesangial cells recruits inflammatory Th17 cells in IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Guoyuan Lu

    Full Text Available IgA nephropathy (IgAN is the most common primary glomerulonephritis characterized by human mesangial cells (HMC proliferation and extracellular matrix expansion associated with immune deposits consisting of galactose-deficient IgA1. However, how IgA1 contributes to IgAN has yet to be completely elucidated. In this study, the expression profile of chemokines was more altered in IgA1-treated HMC than in the control group. CCL20 was significantly higher either in the serum of IgAN patients or in IgA1-treated HMC. Further experiments demonstrated that CCR6, the only receptor of CCL20, was highly expressed in activated T cells. Intracellular staining assay and cytokine expression profile implied that CCR6+ T cells produced high IL-17 levels. Transwell experiment immunohistochemistry and immunofluorescence experiments extensively demonstrated that CCL20 could recruit inflammatory Th17 cells to the kidneys. These phenomena caused a series of immune inflammatory responses and further damaged the kidneys. Therefore, HMC stimulated by IgA1 could produce CCL20 and consequently recruit inflammatory Th17 cells to the kidneys to induce further lesion in IgA nephropathy.

  12. Evaluation of the Effects of Some Brazilian Medicinal Plants on the Production of TNF-α and CCL2 by THP-1 Cells

    Directory of Open Access Journals (Sweden)

    Grasielle S. Gusman

    2015-01-01

    Full Text Available Several plant species are traditionally used in Brazil to treat various inflammatory diseases. Tumor necrosis factor- (TNF- α and chemokine (C-C motif ligand 2 (CCL2 are key inflammatory mediators in diseases like rheumatoid arthritis and atherosclerosis, respectively; nevertheless, only a few extracts have been assayed against these targets. We herein report the effect of 19 plant extracts on TNF-α and CCL2 release by lipopolysaccharide- (LPS- stimulated THP-1 cells, a human monocytic leukemia cell line, along with their radical scavenging activity on DPPH. The extracts of Caryocar brasiliense, Casearia sylvestris, Coccoloba cereifera, and Terminalia glabrescens inhibited TNF-α production in a concentration-dependent manner. Fractionation of these extracts potentiated the anti-TNF-α effect, which was shown to concentrate in polar fractions, mainly composed by polyphenols. Significant CCL2 inhibition was elicited by Lippia sidoides and Terminalia glabrescens extracts, whose fractionation resulted in highly active low polar fractions. All assayed extracts showed strong radical scavenging activity, but antioxidant activity did not correlate with inhibition of TNF-α or CCL2 production. Our results allowed identifying extracts with selective capacity to block cytokine production; therefore, further purification of these extracts may yield molecules that could be useful in the treatment of chronic inflammatory diseases.

  13. Luminescence characteristics of Xe2Cl excimer molecules under pumping the dense Xe—CCl4 gas mixtures with a pulsed electron beam

    Science.gov (United States)

    Mis'kevich, A. I.; Jinbo, Guo

    2013-05-01

    Temporal and spectral characteristics of the luminescence of dense Xe—CCl4 gas mixtures of different composition, excited by a 5-ns pulsed electron beam, were measured. The energy of the electrons amounted to 150 keV and the electron beam current pulse amplitude was 5 A. The gas mixtures were used containing Xe (38-700 Torr) and CCl4 (0.03-0.3 Torr). The studies were performed within the wavelength range 200-1200 nm using a MAYA-2000Pro diffraction grating spectrometer and a RIGOL DS 5022 ME fast digital oscilloscope. The luminescence lifetimes of the excimer molecules XeCl* (band with λmax = 308 nm) and Xe2Cl* (band with λmax = 486 nm) were measured, as well as the constants of quenching by the components of the gas mixture for Xe2Cl* molecules. A model of plasma-chemical processes for dense Xe—CCl4 gas mixtures with a very low content of the CCl4 donor is proposed. It is shown that in such 'poor' mixtures Xe2Cl* molecules are mainly produced as a result of recombination of the Xe2+ and Cl- ions.

  14. Luminescence characteristics of Xe{sub 2}Cl excimer molecules under pumping the dense Xe-CCl{sub 4} gas mixtures with a pulsed electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Mis' kevich, A I; Jinbo, Guo [National Research Nuclear University ' Moscow Engineering Physics Institute' , Moscow (Russian Federation)

    2013-05-31

    Temporal and spectral characteristics of the luminescence of dense Xe-CCl{sub 4} gas mixtures of different composition, excited by a 5-ns pulsed electron beam, were measured. The energy of the electrons amounted to 150 keV and the electron beam current pulse amplitude was 5 A. The gas mixtures were used containing Xe (38-700 Torr) and CCl{sub 4} (0.03-0.3 Torr). The studies were performed within the wavelength range 200-1200 nm using a MAYA-2000Pro diffraction grating spectrometer and a RIGOL DS 5022 ME fast digital oscilloscope. The luminescence lifetimes of the excimer molecules XeCl* (band with {lambda}{sub max} = 308 nm) and Xe{sub 2}Cl* (band with {lambda}{sub max} = 486 nm) were measured, as well as the constants of quenching by the components of the gas mixture for Xe{sub 2}Cl* molecules. A model of plasma-chemical processes for dense Xe-CCl{sub 4} gas mixtures with a very low content of the CCl{sub 4} donor is proposed. It is shown that in such 'poor' mixtures Xe{sub 2}Cl* molecules are mainly produced as a result of recombination of the Xe{sub 2}{sup +} and Cl{sup -} ions. (active media)

  15. USING IN VIVO GAS UPDATE STUDIES TO ESTIMATE METABOLIC RATE CONSTANTS FOR CCL CHEMICALS: 1,1-DICHLOROPROPANE AND 2,2-DICHLOROPROPANE

    Science.gov (United States)

    USING IN VIVO GAS UPTAKE STUDIES TO ESTIMATE METABOLIC RATE CONSTANTS FOR CCL CHEMICALS: 1,1-DICHLOROPROPENE AND 2,2-DICHLOROPROPANE. Mitchell, C T, Evans, M V, Kenyon, E M. NHEERL, U.S. EPA, ORD, ETD, RTP, NC The Safe Drinking Water Act Amendments of 1996 required ...

  16. Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Buist, Richard; Sun, Xue-Jun

    2006-01-01

    in the perivascular space in brains of transgenic (Tg) mice that overexpress CCL2 under control of a CNS-specific promoter. The Tg mice show no clinical symptoms, even though leukocytes have crossed the endothelial basement membrane. Pertussis toxin (PTx) given i.p. induced encephalopathy and weight loss in Tg mice...... symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor...... of metalloproteinase-1, metalloproteinase disintegrins-12, MMP-8, and -10 in brains of Tg mice. Levels of the microglial-associated MP MMP-15 were not affected in control or PTx-treated Tg mice. PTx also up-regulated expression of proinflammatory cytokines IL-1beta and TNF-alpha mRNA in Tg CNS. Weight loss...

  17. The harmful effect of exercise on reducing taurine concentration in the tissues of rats treated with CCl4 administration.

    Science.gov (United States)

    Miyazaki, Teruo; Matsuzaki, Yasushi; Ikegami, Tadashi; Miyakawa, Shumpei; Doy, Mikio; Tanaka, Naomi; Bouscarel, Bernard

    2004-06-01

    We have previously reported that oral taurine administration reduced the frequency of painful muscle cramps in patients with liver cirrhosis, and that skeletal muscle taurine concentration was significantly decreased after exercise. The aim of this study was to examine taurine concentration in various tissues of a liver damaged with fibrosis (LD) in a rat model before and after exercise. Rats were divided into normal (NML) and LD groups. The LD group received CCl(4) injection for 10 weeks. Thereafter, both groups were divided into control (NML/CTL, LD/CTL) and exercise (NML/EX, LD/EX) groups, respectively. The rats in the EX groups were subjected to treadmill running. Plasma, liver, brain, heart, and skeletal muscle taurine concentration, as well as plasma and liver lipid peroxidase (LPO) concentration, were measured. The liver, brain, and skeletal muscle taurine concentration in the LD groups was significantly decreased compared to that in the respective NML groups. Furthermore, the taurine concentration in the heart and skeletal muscles in the LD/CTL group was significantly decreased post exercise. The respective plasma and liver LPO concentration in the LD groups was significantly increased compared to that in the corresponding NML group. Moreover, plasma LPO concentration in the LD/EX group was significantly higher than in the LD/CTL group. Tissue taurine concentration, particularly in skeletal muscle, was significantly decreased in the LD model rats induced by CCl(4) administration, and furthermore, the significantly decreased concentration, except for liver, was aggravated by exercise, even though at lower intensity.

  18. Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

    Science.gov (United States)

    Dulek, Daniel E.; Newcomb, Dawn C.; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P.; Blackwell, Timothy S.; Moore, Martin L.; Boyd, Kelli L.; Kolls, Jay K.

    2014-01-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity. PMID:24958709

  19. Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood–brain barrier through paracellular transmigration and ERK activation

    Directory of Open Access Journals (Sweden)

    Sagar Divya

    2012-10-01

    Full Text Available Abstract Background Transmigration of circulating dendritic cells (DCs into the central nervous system (CNS across the blood–brain barrier (BBB has not thus far been investigated. An increase in immune cell infiltration across the BBB, uncontrolled activation and antigen presentation are influenced by chemokines. Chemokine ligand 2 (CCL2 is a potent chemoattractant known to be secreted by the BBB but has not been implicated in the recruitment of DCs specifically at the BBB. Methods Experimental autoimmune encephalomyelitis (EAE was induced in C57BL/6 mice by injection of MOG35–55 peptide and pertussis toxin intraperitoneally. Animals with increasing degree of EAE score were sacrificed and subjected to near-infrared and fluorescence imaging analysis to detect and localize the accumulation of CD11c+-labeled DCs with respect to CCL2 expression. To further characterize the direct effect of CCL2 in DC trafficking at the BBB, we utilized an in vitro BBB model consisting of human brain microvascular endothelial cells to compare migratory patterns of monocyte-derived dendritic cells, CD4+ and CD8+ T cells. Further, this model was used to image transmigration using fluorescence microcopy and to assess specific molecular signaling pathways involved in transmigration. Results Near-infrared imaging of DC transmigration correlated with the severity of inflammation during EAE. Ex vivo histology confirmed the presence of CCL2 in EAE lesions, with DCs emerging from perivascular spaces. DCs exhibited more efficient transmigration than T cells in BBB model studies. These observations correlated with transwell imaging, which indicated a paracellular versus transcellular pattern of migration by DCs and T cells. Moreover, at the molecular level, CCL2 seems to facilitate DC transmigration in an ERK1/2-dependent manner. Conclusion CNS recruitment of DCs correlates with disease severity in EAE via CCL2 chemotaxis and paracellular transmigration across the BBB

  20. Effects of Biphenyldimethyl-dicarboxylate Administration Alone or Combined with Silymarin in the CCL4 Model of Liver Fibrosis in Rats

    Directory of Open Access Journals (Sweden)

    Omar M. E. Abdel-Salam

    2007-01-01

    Full Text Available The effect of biphenyldimethyldicarboxylate (DDB, a synthetic compound, in use for the treatment of chronic hepatitis was studied on hepatic injury caused in rats by administration of carbon tetrachloride (CCl4. Starting at time of administration of the first dose of CCl4, rats received DDB at four dose levels (3, 15, 75 or 375 mg/kg, silymarin (22 mg/kg, a combination of DDB (75 mg/kg and silymarin (22 mg/kg or saline (control once orally daily for 30 days. The administration of DDB in CCl4-treated rats at 75 or 375 mg/kg resulted in 61.2-76.2% decrease in alanine aminotransferase (ALT and 46.9-60.8% decrease in aspartate aminotransferase (AST, respectively compared with the CCl4 control group. Silymarin treatment resulted in 34.6 and 30% decrease in ALT and AST, while DDB (75 mg/kg combined with silymarin (22 mg/kg resulted in 58.2 and 31% decrease in ALT and AST, respectively. Serum creatinine increased by 50% by DDB at 375 mg/kg. After treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin, the development of liver necrosis and fibrosis caused by CCl4 was markedly reduced, while after DDB combined with silymarin no DNA aneuploid cells could be observed. The decrease in glycogen and protein contents in hepatocytes caused by CCl4 was markedly prevented by co-treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin. It is concluded that in the model of hepatic injury caused by chronic administration of CCl4 in rats, the synthetic compound DDB, limits hepatocellular injury and exerts antifibrotic effect. Better improvement in protein, DNA, mucopolysaccharide content was seen after both DDB and silymarin compared to DDB alone. It is suggested, therefore, that DDB alone or in combination with silymarin might prove of benefit in the therapy of chronic liver disease. Monitoring of kidney functions in patients taking DDB is warranted.

  1. Ameliorative and antidyslipidemic potentials of aqueous leaf extract of Gongronema latifolium in CCl4 carbon tetrachloride-induced oxidative stress rats

    Directory of Open Access Journals (Sweden)

    Asiat Na’Allah

    2016-10-01

    Full Text Available Objective: To investigate the effect of leaf aqueous extract from Gongronema latifolium (G. latifolium on CCl4 induced-oxidative stress in Wistar rat. This effect was assessed by measuring liver marker enzymes activity, analyzing the antioxidant parameters, lipid profile estimation and lipid peroxidation by-product following CCl4 induced-oxidative stress. Methods: Milled G. latifolium leaves were subjected to aqueous extraction and the filtrate was evaporated between 40–60 °C under reduced pressure and a calculated volume of the leaf extract was administered at a dose of 500 mg/kg body weight. Thirty-five rats were grouped into seven groups of 5 animals each namely; control and experimental groups. The experimental groups were treated with 2.0 mL/kg body weight CCl4, 25 mg/kg body weight/ day silymarin (a standard hepatoprotective antioxidant, 500 mg/kg body weight aqueous extract of G. latifolium leaves were administered to the CCl4 treated rats for 21 days. Results: Administration of the extract and silymarin increase significantly (P < 0.05 in liver marker enzyme (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase activities in serum, liver and kidney in the treated groups when compared with untreated groups. The antioxidant parameters (catalase, peroxidase and glutathione S-transferase were significantly elevated (P < 0.05 in animals treated with the extract and silymarin in comparison with untreated groups. CCl4 induced oxidative stress mediated variations in total cholesterol, triacylglycerides, high-density lipoprotein cholesterol, low density lipoprotein cholesterol and very low-density lipoprotein cholesterol were restored significantly (P < 0.05 by the extract. Conclusions: The result obtained from this study indicated the antioxidant and antidyslipidemic potentials of the aqueous extract of G. latifolium leaves.

  2. Computational study of the double C-Cl bond activation of dichloromethane and phosphine alkylation at [CoCl(PR3)3].

    Science.gov (United States)

    Algarra, Andrés G; Braunstein, Pierre; Macgregor, Stuart A

    2013-03-28

    Density functional theory calculations have been employed to model the double C-Cl bond activation of CH(2)Cl(2) at [CoCl(PR(3))(3)] to give [CoCl(3)(CH(2)PR(3))(PR(3))(2)]. Calculations incorporating dichloromethane solution (PCM approach) on a [CoCl(PMe(3))(3)] model system showed the two C-Cl cleavage steps to involve different mechanisms. The first C-Cl cleavage step occurs on the triplet surface and proceeds via Cl abstraction with a barrier of 19.1 kcal mol(-1). Radical recombination would then give singlet mer,trans-[CoCl(2)(CH(2)Cl)(PMe(3))(3)] with an overall free energy change of +1.8 kcal mol(-1). Alternative C-Cl activation processes based on nucleophilic attack by the Co centre at dichloromethane with loss of Cl(-) have significantly higher barriers. The second C-Cl cleavage occurs via nucleophilic attack of PMe(3) at the CH(2)Cl ligand with formation of a new P-C bond and displacement of Cl(-). This may either occur in an intermolecular fashion (after prior PMe(3) dissociation) or intramolecularly. Both processes have similar barriers of ca. 12 kcal mol(-1). The comproportionation of [CoCl(3)(CH(2)PMe(3))(PMe(3))(2)] with [CoCl(PMe(3))(3)] to give [CoCl(2)(CH(2)PMe(3))(PMe(3))], [CoCl(2)(PMe(3))(2)] and 2 PMe(3) is computed to be strongly exergonic, consistent with the observation of this process in analogous experimental systems.

  3. Hepatoprotectivitve effect of Iranian grape seed and Jaft (a part of oak fruit extracts against CCL4 induced-liver toxicity in rats

    Directory of Open Access Journals (Sweden)

    Ali Mirzaei

    2011-11-01

    Full Text Available Background: Specialists are more interest to grape seed oil for antioxidant activity. Flavonoid compounds, particularly proanthocyanidin are mainly responsible for antioxidant potential in grape seed oil. In addition, recently the interest in using natural remedies to treat diseases increases the use of herbal drugs.The protective effect of grape seed and Jaft extract (a part of oak fruit was studied on liver toxicity which induced by carbon tetra chloride (CCl4 in rats. Methods: This study carried out on 28 male wistar rats. Mixture of hydroalchoholic grape seed and Jaft extracts was gavaged (200mg/kg in two groups of extract control and experiment groups, daily for 7 days. At the same time, in two groups of CCl4(toxic and treatment, CCl4 in olive oil solution was injected (1ml/kg i.p since third day, daily, for 5 days. In control groups, olive oil injected (0.5ml/kg i.p daily, for 5 days. Results: There was significant (P≤0.05 increase in the hepatic enzyme levels such as Aspartate Transaaminase (AST, Alanine Transaminase (ALT, Alkaline Phosphates (ALP and Bilirubin in toxic group compare to control group. Treat with extract can reduce elevation of liver enzymes AST, ALT, ALP and bilirubin, that caused by CCl4 toxin. The administered of extract only, did not meaningfully alter the enzyme levels when compared to the control groups. Conclusion: According to damage induced by CCl4 and protective potential of extract, we can recommend that mixture of grape seed and Jaft extract has hepatoprotective effect due to antioxidant components.

  4. Effect of selected natural products, thioproline and pegasys on hepatic platelet activating factor (PAF) in CCL4-induced hepatic fibrosis in rats

    International Nuclear Information System (INIS)

    Badria, Farid A.

    2007-01-01

    This study aimed to estimate hepatic levels of platelet activating factor (PAF) in liver fibrosis induced by CCl4 in rats. A group of selected natural products; boswellic acids, curcumin and glycrrhizin (preparation named OMNI; a drug under clinical trials for treatment of hepatitis C virus), Mirazid (a commercially available schistomicidal drug), Thioproline (a commercially available hepatoprotective agent) and Pegasys (peg interferon alpha-2a; a commercially available therapy for treatment of Hepatitis C virus) were examined for their effect on hepatic PAF groups each comprised 9 rats. Group 1 was treated only with CCl4, group 2 to 5 were treated with OMNI, Mirazid, Thioproline and Pegasys, respectively whereas the 6th group was the normal control group (with no treatment, except an injection of the vehicle). Liver damage was induced in all groups except normal control group (groups 1 to 5) by i.p. injection of 40% CCl4 in corn oil (0.375 ml/kg) 3 times a week for 3 weeks. One week after CCl4 intoxication, all tested drugs were injected i.p. daily for 3 weeks. Hepatic PAF concentration was estimated by HPTLC (high performance thin layer chromatography), while levels of serum transminases (ALT, AST), hepatic hydroxyproline (as marker of liver fibrosis), serum malondialdehyde and catalase (as markers of oxidative stress) were estimated sepctrophotometrically. The hepatic PAF levels were significantly higher in CCl4 group (24.24+-2.01 pmol equiv. /mg) (p<0.001). Treatment with OMNI, Mirazid, Thioproline and Pegasys reduced hepatic PAF significantly to be 11.84+-0.22, 14.5+-1.00, 13.17+-0, 54 and 14.26+-1.09pmol equiv. /mg respectively. This study may add further rational to the anti-fibrotic activity of the tested drugs via reduction of hepatic PAF. (author)

  5. Validation of ACE-FTS v2.2 measurements of HCl, HF, CCl3F and CCl2F2 using space-, balloon- and ground-based instrument observations

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    C. Servais

    2008-10-01

    Full Text Available Hydrogen chloride (HCl and hydrogen fluoride (HF are respectively the main chlorine and fluorine reservoirs in the Earth's stratosphere. Their buildup resulted from the intensive use of man-made halogenated source gases, in particular CFC-11 (CCl3F and CFC-12 (CCl2F2, during the second half of the 20th century. It is important to continue monitoring the evolution of these source gases and reservoirs, in support of the Montreal Protocol and also indirectly of the Kyoto Protocol. The Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS is a space-based instrument that has been performing regular solar occultation measurements of over 30 atmospheric gases since early 2004. In this validation paper, the HCl, HF, CFC-11 and CFC-12 version 2.2 profile data products retrieved from ACE-FTS measurements are evaluated. Volume mixing ratio profiles have been compared to observations made from space by MLS and HALOE, and from stratospheric balloons by SPIRALE, FIRS-2 and Mark-IV. Partial columns derived from the ACE-FTS data were also compared to column measurements from ground-based Fourier transform instruments operated at 12 sites. ACE-FTS data recorded from March 2004 to August 2007 have been used for the comparisons. These data are representative of a variety of atmospheric and chemical situations, with sounded air masses extending from the winter vortex to summer sub-tropical conditions. Typically, the ACE-FTS products are available in the 10–50 km altitude range for HCl and HF, and in the 7–20 and 7–25 km ranges for CFC-11 and -12, respectively. For both reservoirs, comparison results indicate an agreement generally better than 5–10% above 20 km altitude, when accounting for the known offset affecting HALOE measurements of HCl and HF. Larger positive differences are however found for comparisons with single profiles from FIRS-2 and SPIRALE. For CFCs, the few coincident measurements available suggest that the differences

  6. Hepatoprotective activities of Antrodia camphorata and its triterpenoid compounds against CCl4-induced liver injury in mice.

    Science.gov (United States)

    Li, Zi-Wei; Kuang, Yi; Tang, Shu-Nan; Li, Kai; Huang, Yun; Qiao, Xue; Yu, Si-Wang; Tzeng, Yew-Min; Lo, Jen-Yu; Ye, Min

    2017-07-12

    Antrodia camphorata (AC) is a rare and precious fungus indigenous to Taiwan used as a traditional medicine for the treatment of liver injury. Triterpenoids are the major bioactive constituents of A. camphorata and have been reported to possess hepatoprotective activities. To meet the increasing demand, artificial cultivation techniques have been developed. This study aims to evaluate the hepatoprotective activities of AC samples derived from different cultivation techniques and to dissect the main active triterpenoid compounds. The ethanol extracts of five batches of AC samples, including wild growing fruiting bodies, cutting wood culture fruiting bodies, dish cultures, cutting wood culture mycelia, and submerged fermentation mycelia were orally administered (50mg/kg or 200mg/kg) to ICR mice for 7 days. On the last day, CCl 4 (0.2%, 7mL/kg, i.p.) was used to induce liver injury, and the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined 24h after the injection. Moreover, a HepG2 cell model treated with CCl 4 (0.35%) was used to screen the protective activities of 29 AC triterpenoids. After incubation for 6h, viabilities of the cells were tested using MTS assay. The in vivo hepatoprotective activities of antcin B and antcin K were further studied on the mice model by ALT and AST tests and histopathologic examinations. To elucidate the mechanisms, the mRNA levels of iNOS, COX2, TNF-α and IL-1β, and the protein levels of NF-κB (p65/p-p65), iNOS and COX2 in liver tissues were determined. The wild growing or cutting wood culture fruiting bodies, and the dish cultures of AC showed more potent activities than the mycelia (Pactivities, increasing HepG2 cell viability from 46% of the CCl 4 group to >90%. Antcin B and antcin K could dose-dependently (10 or 50mg/kg, 7 days, i.g.) decrease the serum levels of ALT and AST, and decrease the incidence of liver necrosis. The effects of 50mg/kg of antcin K or antcin B were

  7. Rate constant for the reaction of OH with CH3CCl2F (HCFC-141b) determined by relative rate measurements with CH4 and CH3CCl3

    Science.gov (United States)

    Huder, Karin; Demore, William B.

    1993-01-01

    Determination of accurate rate constants for OH abstraction is of great importance for the calculation of lifetimes for HCFCs and their impact on the atmosphere. For HCFC-141b there has been some disagreement in the literature for absolute measurements of this rate constant. In the present work rate constant ratios for HCFC-141b were measured at atmospheric pressure in the temperature range of 298-358 K, with CH4 and CH3CCl3 as reference gases. Ozone was photolyzed at 254 nm in the presence of water vapor to produce OH radicals. Relative depletions of 141b and the reference gases were measured by FTIR. Arrhenius expressions for 141b were derived from each reference gas and found to be in good agreement with each other. The combined expression for HCFC-141b which we recommend is 1.4 x 10 exp -12 exp(-1630/T) with k at 298 K being 5.9 x 10 exp -15 cu cm/molec-s. This value is in excellent agreement with the JPL 92-20 recommendation.

  8. C and Cl isotope fractionation of 1,2-dichloroethane displays unique δ¹³C/δ³⁷Cl patterns for pathway identification and reveals surprising C-Cl bond involvement in microbial oxidation.

    Science.gov (United States)

    Palau, Jordi; Cretnik, Stefan; Shouakar-Stash, Orfan; Höche, Martina; Elsner, Martin; Hunkeler, Daniel

    2014-08-19

    This study investigates dual element isotope fractionation during aerobic biodegradation of 1,2-dichloroethane (1,2-DCA) via oxidative cleavage of a C-H bond (Pseudomonas sp. strain DCA1) versus C-Cl bond cleavage by S(N)2 reaction (Xanthobacter autotrophicus GJ10 and Ancylobacter aquaticus AD20). Compound-specific chlorine isotope analysis of 1,2-DCA was performed for the first time, and isotope fractionation (ε(bulk)(Cl)) was determined by measurements of the same samples in three different laboratories using two gas chromatography-isotope ratio mass spectrometry systems and one gas chromatography-quadrupole mass spectrometry system. Strongly pathway-dependent slopes (Δδ13C/Δδ37Cl), 0.78 ± 0.03 (oxidation) and 7.7 ± 0.2 (S(N)2), delineate the potential of the dual isotope approach to identify 1,2-DCA degradation pathways in the field. In contrast to different ε(bulk)(C) values [-3.5 ± 0.1‰ (oxidation) and -31.9 ± 0.7 and -32.0 ± 0.9‰ (S(N)2)], the obtained ε(bulk)(Cl) values were surprisingly similar for the two pathways: -3.8 ± 0.2‰ (oxidation) and -4.2 ± 0.1 and -4.4 ± 0.2‰ (S(N)2). Apparent kinetic isotope effects (AKIEs) of 1.0070 ± 0.0002 (13C-AKIE, oxidation), 1.068 ± 0.001 (13C-AKIE, S(N)2), and 1.0087 ± 0.0002 (37Cl-AKIE, S(N)2) fell within expected ranges. In contrast, an unexpectedly large secondary 37Cl-AKIE of 1.0038 ± 0.0002 reveals a hitherto unrecognized involvement of C-Cl bonds in microbial C-H bond oxidation. Our two-dimensional isotope fractionation patterns allow for the first time reliable 1,2-DCA degradation pathway identification in the field, which unlocks the full potential of isotope applications for this important groundwater contaminant.

  9. Bio Engineering Laboratory

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    Federal Laboratory Consortium — Description/History: Chemistry and biology laboratoriesThe Bio Engineering Laboratory (BeL) is theonly full spectrum biotechnology capability within the Department...

  10. FOOTWEAR PERFORMANCE LABORATORY

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    Federal Laboratory Consortium — This laboratory provides biomechanical and physical analyses for both military and commercial footwear. The laboratory contains equipment that is integral to the us...

  11. Distributed Energy Technology Laboratory

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    Federal Laboratory Consortium — The Distributed Energy Technologies Laboratory (DETL) is an extension of the power electronics testing capabilities of the Photovoltaic System Evaluation Laboratory...

  12. Nanotechnology Characterization Laboratory

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    Federal Laboratory Consortium — The Nanotechnology Characterization Laboratory (NCL) at the Frederick National Laboratory for Cancer Research performs preclinical characterization of nanomaterials...

  13. Physical Sciences Laboratory (PSL)

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    Federal Laboratory Consortium — PNNL's Physical Sciences Laboratory (PSL) houses 22 research laboratories for conducting a wide-range of research including catalyst formulation, chemical analysis,...

  14. Endogenous osteopontin induces myocardial CCL5 and MMP-2 activation that contributes to inflammation and cardiac remodeling in a mouse model of chronic Chagas heart disease.

    Science.gov (United States)

    Caballero, Eugenia Pérez; Santamaría, Miguel H; Corral, Ricardo S

    2018-01-01

    Cardiac dysfunction with progressive inflammation and fibrosis is a hallmark of Chagas disease caused by persistent Trypanosoma cruzi infection. Osteopontin (OPN) is a pro-inflammatory cytokine that orchestrates mechanisms controlling cell recruitment and cardiac architecture. Our main goal was to study the role of endogenous OPN as a modulator of myocardial CCL5 chemokine and MMP-2 metalloproteinase, and its pathological impact in a murine model of Chagas heart disease. Wild-type (WT) and OPN-deficient (spp1 -/-) mice were parasite-infected (Brazil strain) for 100days. Both groups developed chronic myocarditis with similar parasite burden and survival rates. However, spp1 -/- infection showed lower heart-to-body ratio (PChagas heart disease, through the upregulation of myocardial CCL5/MMP-2 expression and activities resulting in pro-inflammatory and pro-hypertrophic events, cardiac remodeling and interstitial fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Two Blood Monocytic Biomarkers (CCL15 and p21 Combined with the Mini-Mental State Examination Discriminate Alzheimer’s Disease Patients from Healthy Subjects

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    Tanja Hochstrasser

    2011-10-01

    Full Text Available Background: Alzheimer’s disease (AD is a progressive neurodegenerative disorder. In AD, monocytes migrate across the blood-brain barrier and differentiate into microglia, are linked to inflammatory responses and display age-dependent decreases in telomere lengths. Methods: Six monocyte-specific chemokines and the (telomere-associated tumor suppressor proteins p53 and p21 were determined by multiplex immunoassay in plasma and monocyte extracts of patients with AD or mild cognitive impairment, and levels were compared between patients and controls (without cognitive impairment. Results: CCL15 (macrophage inflammatory protein-1δ, CXCL9 (monokine-induced by interferon-γ and p21 levels were decreased in monocytes of AD patients compared with controls. Conclusion: The combination of monocytic CCL15 and p21 together with the Mini-Mental State Examination enables to differentiate AD patients from controls with high specificity and sensitivity.

  16. Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4.

    Science.gov (United States)

    Mills, Shirley C; Howell, Lesley; Beekman, Andrew; Stokes, Leanne; Mueller, Anja

    2018-01-01

    Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells. We have confirmed the involvement of Rac1 with the use of a specific Rac1 blocking peptide. We also used a Rac1 inhibitor EHT 1864 and a Rac1-GEF inhibitor NSC23766 to probe the importance of Rac1 in chemotaxis. Both inhibitors did not block CCL3-induced chemotaxis, but they were able to block CXCL12-induced chemotaxis. This confirms that Rac1 activation is not essential for CCL3-induced migration, however NSC23766 might have secondary effects on CXCR4. This small molecule exhibits agonistic features in internalisation and cAMP assays, whereas it acts as an antagonist for CXCR4 in migration and calcium release assays. Our findings strongly suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  17. Comparison of chemokines (CCL-5 and SDF-1), chemokine receptors (CCR-5 and CXCR-4) and IL-6 levels in patients with different severities of depression.

    Science.gov (United States)

    Ogłodek, Ewa A; Szota, Anna; Just, Marek J; Moś, Danuta; Araszkiewicz, Aleksander

    2014-10-01

    Depression can be perceived as a psychoneuroimmunological disorder in which cytokines affecting the body's neurochemical and neuroendocrine functions play an important role. Among cytokines, chemokines participating in activation of the inflammatory response are considered to be crucial. 160 men and women were enrolled in the study. 120 of them were diagnosed with various types of depression. The mean age was 45.2 ± 4.5 years (range: 19-47 years). The control group consisted of 40 healthy individuals. The average age in this group was 42.4 ± 4.1 years. Plasma levels of chemokines and their receptors (CCL-5 - RANTES and CXCR-5, SDF-1 and CXCR-4), as well as of IL-6, were assessed by ELISA. There was an increase in SDF-1 and CCL-5 levels in women and men with different severities of depression, versus the control group. Also, an increase in the IL-6 levels, CXCR4 and CCR-5 receptors was observed in both women and men with all types of depression. Levels of SDF-1 and CCL-5 chemokines, as well as of CCR-5 and CXCR4 chemokine receptors, were higher in women than in men. The results of this study indicate the need for assessment of CCL-5 and SDF-1 chemokines levels, as they are likely markers of developing depression. Early measurement of these chemokines levels may be helpful in choosing the best pharmacotherapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Anti-fibrotic potential of human umbilical cord mononuclear cells and mouse bone marrow cells in CCl4- induced liver fibrosis in mice.

    Science.gov (United States)

    Elmahdy, Nageh Ahmed; Sokar, Samia Salem; Salem, Mohamed Labib; Sarhan, Naglaa Ibrahim; Abou-Elela, Sherin Hamed

    2017-05-01

    Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl 4 ) induced liver fibrosis in mice and compare it with that of silymarin. In the present study, male albino mice (N=60) were divided into six groups (10 mice each), the first group served as the normal control group while the remaining five groups were rendered fibrotic by intraperitoneal injections of CCl 4 and being left for 6 weeks to develop hepatic fibrosis. Thereafter, the mice were divided into CCl 4 group, CCl 4 group receiving MNC or BMC or silymarin or MNC and silymarin combination. After the specified treatment period, animals were then euthanized, blood and tissue samples were collected for measurement of alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), reduced glutathione(GSH), collagen, Laminin, transforming growth factor β1(TGFβ1), tumor necrosis factor alpha(TNFα). MNC, BMC, and the combination therapy showed a significant decrease in ALT, AST, MDA, collagen, Laminin, TGFβ1, and TNFα and a significant increase in GSH. The data displayed a similar regression of fibrosis with the histological and immunohistological parameters. In conclusion, MNC, BMC and the combination therapy showed a potential therapeutic effect against liver fibrosis via reducing oxidative stress, inflammatory mediators, and fibrogenic markers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Recovery of the Cell Cycle Inhibition in CCl4-Induced Cirrhosis by the Adenosine Derivative IFC-305

    Directory of Open Access Journals (Sweden)

    Victoria Chagoya de Sánchez

    2012-01-01

    Full Text Available Introduction. Cirrhosis is a chronic degenerative illness characterized by changes in normal liver architecture, failure of hepatic function, and impairment of proliferative activity. The aim of this study is to know how IFC-305 compound induces proliferation of the liver during reversion of cirrhosis. Methods. Once cirrhosis has been installed by CCl4 treatment for 10 weeks in male Wistar rats, they were divided into four groups: two received saline and two received the compound; all were euthanized at 5 and 10 weeks of treatment. Liver homogenate, mitochondria, and nucleus were used to measure cyclins, CDKs, and cell cycle regulatory proteins PCNA, pRb, p53, E2F, p21, p27, HGF, liver ATP, and mitochondrial function. Results. Diminution and small changes were observed in the studied proteins in the cirrhotic animals without treatment. The IFC-305-treated rats showed a clear increase in most of the proteins studied mainly in PCNA and CDK6, and a marked increased in ATP and mitochondrial function. Discussion/Conclusion. IFC-305 induces a recovery of the cell cycle inhibition promoting recovery of DNA damage through the action of PCNA and p53. The increase in energy and preservation of mitochondrial function contribute to recovering the proliferative function.

  20. Mesenchymal stem cells encapsulated into biomimetic hydrogel scaffold gradually release CCL2 chemokine in situ preserving cytoarchitecture and promoting functional recovery in spinal cord injury.

    Science.gov (United States)

    Papa, S; Vismara, I; Mariani, A; Barilani, M; Rimondo, S; De Paola, M; Panini, N; Erba, E; Mauri, E; Rossi, F; Forloni, G; Lazzari, L; Veglianese, P

    2018-04-03

    Spinal cord injury (SCI) is an acute neurodegenerative disorder caused by traumatic damage of the spinal cord. The neuropathological evolution of the primary trauma involves multifactorial processes that exacerbate the pathology, worsening the neurodegeneration and limiting neuroregeneration. This complexity suggests that multi-therapeutic approaches, rather than any single treatment, might be more effective. Encouraging preclinical results indicate that stem cell-based treatments may improve the disease outcome due to their multi-therapeutic ability. Mesenchymal Stem Cells (MSCs) are currently considered one of the most promising approaches. Significant improvement in the behavioral outcome after MSC treatment sustained by hydrogel has been demonstrated. However, it is still not known how hydrogel contribute to the delivery of factors secreted from MSCs and what factors are released in situ. Among different mediators secreted by MSCs after seeding into hydrogel, we have found CCL2 chemokine, which could account for the neuroprotective mechanisms of these cells. CCL2 secreted from human MSCs is delivered efficaciously in the lesioned spinal cord acting not only on recruitment of macrophages, but driving also their conversion to an M2 neuroprotective phenotype. Surprisingly, human CCL2 delivered also plays a key role in preventing motor neuron degeneration in vitro and after spinal cord trauma in vivo, with a significant improvement of the motor performance of the rodent SCI models. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. The Macrophage Inflammatory Proteins MIP1α (CCL3 and MIP2α (CXCL2 in Implant-Associated Osteomyelitis: Linking Inflammation to Bone Degradation

    Directory of Open Access Journals (Sweden)

    Ulrike Dapunt

    2014-01-01

    Full Text Available Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3 and MIP2α (CXCL2 was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis.

  2. Hepatoprotective Effect of the Aqueous Extract of Simarouba amara Aublet (Simaroubaceae Stem Bark against Carbon Tetrachloride (CCl4-Induced Hepatic Damage in Rats

    Directory of Open Access Journals (Sweden)

    Hélida M. L. Maranhão

    2014-10-01

    Full Text Available Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group. Groups I (vehicle—corn oil, II (control-CCl4, III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver.

  3. Ethanol extract and its dichloromethane fraction of Alpinia oxyphylla Miquel exhibited hepatoprotective effects against CCl4-induced oxidative damage in vitro and in vivo with the involvement of Nrf2.

    Science.gov (United States)

    Zhang, Qiao; Hu, Xiaolong; Hui, Fuhai; Song, Qi; Cui, Can; Wang, Changli; Zhao, Qingchun

    2017-07-01

    Alpinia oxyphylla Miq. (A. oxyphylla), as a kind of medicine which also be used as food, is widely used in East Asian for the treatment of dyspepsia, diarrhea, abdominal pain and deficiency cold of spleen and stomach. This study aimed to investigate the protective effects of ethanol extract (EE) and its dichloromethane fraction (DM) of A. oxyphylla, which are rich in phenolic compounds, against CCl 4 -induced hepatic injury in vitro and in vivo. EE, DM and silymarin ameliorated CCl 4 -induced decrease of cell viability and increase of reactive oxygen species (ROS) in HepG2 cells. The CCl 4 -induced changes of glutathione (GSH) and methane dicarboxylic aldehyde (MDA) levels, and the decrease of superoxide dismutase (SOD) and catalase (CAT) activities were all restored with the pretreatment of EE, DM and silymarin. The results in liver injury model in rats showed that EE, DM and silymarin could significant decrease the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin than the model group. Liver histopathology revealed that EE and DM attenuated the incidence of liver lesions triggered by CCl 4 intoxication. They also effectively relieved CCl 4 -induced oxidative damage. Western blot analysis indicated NF-E2-related factor (Nrf2) pathway played an critical role in the protection of EE and DM against CCl 4 -induced oxidative stress. In conclusion, the extracts from A. oxyphylla might be used as hepatoprotective agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Hepatic Regeneration and Reno-Protection by Fish oil, Nigella sativa Oil and Combined Fish Oil/Nigella sativa Volatiles in CCl4 Treated Rats.

    Science.gov (United States)

    Al-Okbi, Sahar Y; Mohamed, Doha A; Hamed, Thanaa E; Edris, Amr E; Fouda, Karem

    2018-03-01

    The aim of the present research was to investigate the effect of fish oil, crude Nigella sative oil and combined fish oil/Nigella sative volatile oil as hepato-regenerative and renal protective supplements. The oils were administered as emulsions to rat model with liver injury induced by CCl 4 . Plasma activities of transaminases (AST and ALT) were evaluated as liver function indicators, while plasma creatinine and urea and creatinine clearance were determined as markers of kidney function. Plasma malondialdehyde (MDA), nitrite (NO) and tumor necrosis factor-α (TNF-α) were estimated to assess the exposure to oxidative stress and subsequent inflammation. Liver fat was extracted and their fatty acids´ methyl esters were determined using gas chromatography. Results showed that plasma activities of AST and ALT were significantly higher in CCl 4 control group compared to control healthy group. Plasma levels of creatinine and urea increased significantly in CCl 4 control, while creatinine clearance was reduced significantly in the same group. All rat treated groups given the three oil emulsions showed improvement in liver function pointing to the initiation of liver regeneration. The combination of fish oil/Nigella sative volatiles showed the most promising regenerative activity. Oxidative stress and inflammation which were increased significantly in CCl 4 control group showed improvement on administration of the three different oil emulsions. Fatty acids methyl ester of liver fat revealed that rats treated with fish oil/Nigella sative volatile oil presented the highest content of unsaturated fatty acids (45.52% ± 0.81) while fish oil showed the highest saturated fatty acids (53.28% ± 1.68). Conclusion; Oral administration of oil emulsions of native fish oil, Nigella sative crude oil and combined fish oil/Nigella sative volatile oil reduced liver and kidney injury in rat model of CCl 4 through exerting anti-inflammatory and antioxidant activity. Fish oil

  5. Antioxidative effects of pumpkin seed (Cucurbita pepo) protein isolate in CCl4-induced liver injury in low-protein fed rats.

    Science.gov (United States)

    Nkosi, C Z; Opoku, A R; Terblanche, S E

    2006-11-01

    The effects of pumpkin seed (Cucurbita pepo) protein isolate on the plasma activity levels of catalase (CA), superoxide dismutase (SOD), glutathione peroxidase (GSHpx) and total antioxidant capacity (TAC) as well as glucose-6-phosphatase (G6Pase) in liver homogenates and lipid peroxidation (LPO-malondialdehyde-MDA) levels in liver homogenates and liver microsomal fractions against carbon tetrachloride (CCl(4))-induced acute liver injury in low-protein fed Sprague-Dawley rats (Rattus norvegicus) were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl(4) intoxication one of the two subgroups was administered with pumpkin seed protein isolate and thereafter switched onto a 20% pumpkin seed protein isolate diet. The other two groups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all the enzymes as well as antioxidant levels were significantly lower than their counterparts on a normal balanced diet. However, a low-protein diet resulted in significantly increased levels of lipid peroxidation. The CCl(4) intoxicated rats responded in a similar way, regarding all the variables investigated, to their counterparts on a low-protein diet. The administration of pumpkin seed protein isolate after CCl(4) intoxication resulted in significantly increased levels of all the variables investigated, with the exception of the lipid peroxidation levels which were significantly decreased. From the results of the present study it is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein

  6. RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.

    Directory of Open Access Journals (Sweden)

    Christian Herder

    Full Text Available The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events.We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years. Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]. None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls, none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years.High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i RANTES serum levels, (ii CCL5 genotypes and (iii RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a

  7. Protein microarray analysis in patients with asthma: elevation of the chemokine PARC/CCL18 in sputum.

    Science.gov (United States)

    Kim, Hyo-Bin; Kim, Chang-Keun; Iijima, Koji; Kobayashi, Takao; Kita, Hirohito

    2009-02-01

    Microarray technology offers a new opportunity to gain insight into global gene and protein expression profiles in asthma. To identify novel factors produced in the asthmatic airway, we analyzed sputum samples by using a membrane-based human cytokine microarray technology in patients with bronchial asthma (BA). Induced sputum was obtained from 28 BA subjects, 20 nonasthmatic atopic control (AC) subjects, and 38 nonasthmatic nonatopic normal control (NC) subjects. The microarray samples of subjects were randomly selected from nine BA subjects, three AC subjects, and six NC subjects. Sputum supernatants were analyzed using a custom human cytokine array (RayBio Custom Human Cytokine Array; RayBiotech; Norcross, GA) designed to analyze 79 specific cytokines simultaneously. The levels of growth-regulated oncogene (GRO)-alpha, eotaxin-2, and pulmonary and activation-regulated chemokine (PARC)/CCL18 were measured by sandwich enzyme-linked immunosorbent assays (ELISAs), and eosinophil-derived neurotoxin (EDN) was measured by radioimmunoassay. By microarray, the signal intensities for GRO-alpha, eotaxin-2, and PARC were significantly higher in BA subjects than in AC and NC subjects (p = 0.036, p = 0.042, and p = 0.033, respectively). By ELISA, the sputum PARC protein levels were significantly higher in BA subjects than in AC and NC subjects (p < 0.0001). Furthermore, PARC levels correlated significantly with sputum eosinophil percentages (r = 0.570, p < 0.0001) and the levels of EDN (r = 0.633, p < 0.0001), the regulated upon activation, normal T cell expressed and secreted cytokine (r = 0.440, p < 0.001), interleukin-4 (r = 0.415, p < 0.01), and interferon-gamma (r = 0.491, p < 0.001). By a nonbiased screening approach, a chemokine, PARC, is elevated in sputum specimens from patients with asthma. PARC may play important roles in development of airway eosinophilic inflammation in asthma.

  8. Synchrotron radiation

    International Nuclear Information System (INIS)

    Helliwell, J.R.; Walker, R.P.

    1985-01-01

    A detailed account of the research work associated with the Synchrotron Radiation Source at Daresbury Laboratory, United Kingdom, in 1984/85, is presented in the Appendix to the Laboratory's Annual Report. (U.K.)

  9. Denver District Laboratory (DEN)

    Data.gov (United States)

    Federal Laboratory Consortium — Program CapabilitiesDEN-DO Laboratory is a multi-functional laboratory capable of analyzing most chemical analytes and pathogenic/non-pathogenic microorganisms found...

  10. Gun Dynamics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Gun Dynamics Laboratory is a research multi-task facility, which includes two firing bays, a high bay area and a second floor laboratory space. The high bay area...

  11. NASA Space Radiation Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory is a NASA funded facility, delivering heavy ion beams to a target area where scientists...

  12. Advanced Chemistry Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Description/History: Chemistry laboratoryThe Advanced Chemistry Laboratory (ACL) is a unique facility designed for working with the most super toxic compounds known...

  13. Lincoln Laboratory Grid

    Data.gov (United States)

    Federal Laboratory Consortium — The Lincoln Laboratory Grid (LLGrid) is an interactive, on-demand parallel computing system that uses a large computing cluster to enable Laboratory researchers to...

  14. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.

    2008-01-01

    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  15. Distinctive Treg associated CCR4-CCL22 expression profile with altered frequency of Th17/Treg cell in the immunopathogenesis of Pemphigus Vulgaris.

    Science.gov (United States)

    Asothai, R; Anand, Vivek; Das, Dayasagar; Antil, Parul Singh; Khandpur, Sujay; Sharma, V K; Sharma, Alpana

    2015-10-01

    Pemphigus Vulgaris (PV), a relatively common autoimmune blistering disease in India, primarily mediated by anti-Desmoglein 3 (anti-Dsg3) autoantibodies. T-helper 17 (Th17) and T-regulatory (Treg) cells play significant role in regulating immune homeostasis in autoimmune disorders. To understand immunopathogenesis of PV, it is crucial to unfold the phenotypic expression and functional characteristics of these cells along with their specific homing chemokine receptor-ligand. This proposed study aims to unravel the functional expression of Th17 and Treg cells along with their specific homing chemokine receptor-ligand, transcription factors and cytokine levels to better understand the immunopathogenesis of PV. The Flow cytometry results showed decreased frequency of Treg cells and high number of Th17 cells (p<0.001) indicating immune dysregulation in PV. A significant increase (p<0.001) in the serum levels of Th17 associated molecules (IL-17A, CCL-20) and relative expression of RORγt, CCR6 and CCL20 was found in patients. For Treg cells, transcription factor FOXp3 was significantly lowered along with defective CCR4-CCL22 (p<0.05) that might be playing an ambiguous role in Treg generated immune regulation, leading to homing defect at lesional sites. This maiden study revealed the role of defective receptor-ligand interface that might have failed to suppress inflammatory milieu produced by Th17 cells thus promoting inflammation and contributing to immunopathogenesis of PV. This chemokine receptor-ligand can further be explored as potential target for development of novel therapies in PV. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Targeting both viral and host determinants of human immunodeficiency virus entry, using a new lentiviral vector coexpressing the T20 fusion inhibitor and a selective CCL5 intrakine.

    Science.gov (United States)

    Petit, Nicolas; Dorgham, Karim; Levacher, Béatrice; Burlion, Aude; Gorochov, Guy; Marodon, Gilles

    2014-08-01

    Numerous strategies targeting early and late steps of the HIV life cycle have been proposed for gene therapy. However, targeting viral and host determinants of HIV entry is the only strategy that would prevent viral DNA-mediated CD4(+) cell death while diminishing the possibility for the virus to escape. To this end, we devised a bicistronic lentiviral vector expressing the membrane-bound form of the T20 fusion inhibitor, referred to as the C46 peptide, and a CCR5 superagonist, modified to sequester CCR5 away from the cell surface, referred to as the P2-CCL5 intrakine. We tested the effects of the vector on HIV infection and replication, using the human CEMR5 cell line expressing CD4 and CCR5, and primary human T cells. Transduced cells expressed the C46 peptide, detected with the 2F5 monoclonal antibody by flow cytometry. Expression of the P2-CCL5 intrakine correlates with lower levels of cell surface CCR5. Complete protection against HIV infection could be observed in cells expressing the protective transgenes. Importantly, we show that the combination of the transgenes was more potent than either transgene alone, showing the interest of expressing two entry inhibitors to inhibit HIV infection. Last, genetically modified cells possessed a selective advantage over nonmodified cells on HIV challenge in vitro, showing that modified cells were protected from HIV-induced cell death. Our results demonstrate that lentiviral vectors coexpressing the T20 fusion inhibitor and the P2-CCL5 intrakine represent promising tools for HIV gene therapy.

  17. The MCP-1, CCL-5 and SDF-1 chemokines as pro-inflammatory markers in generalized anxiety disorder and personality disorders.

    Science.gov (United States)

    Ogłodek, Ewa A; Szota, Anna M; Just, Marek J; Moś, Danuta M; Araszkiewicz, Aleksander

    2015-02-01

    The co-occurrence of generalized anxiety disorder and personality disorders suggests the existence of association between the neurobiological predispositions leading to the development of these disorders and activation of cytokine system. Pro-inflammatory chemokines such as CCL-5/RANTES (regulated upon activation normal T cell expressed and secreted) and CXCL12/SDF-1 (stromal derived factor) play an important role in immune response. A total of 160 participants were enrolled in the study, 120 of whom comprised the study group (people with the dual diagnosis of personality disorder and generalized anxiety disorder). The mean age was 41.4 ± 3.5 years (range: 20-44 years). The control group consisted of 40 healthy individuals in the mean age of 40.8 ± 3.1 years (range: 20-43 years). A blood sample was collected from each participant and the plasma levels of the CCL-2/MCP-1 (monocyte chemoattractant protein-1), RANTES and SDF-1 chemokines were determined by ELISA. Increased levels of MCP-1 and SDF-1 were found both in women and in men versus the control group for all types of personality disorders. The levels of CCL-5 in men were significantly increased versus the control group and significantly higher in women than in men. Neither women nor men with avoidant or obsessive-compulsive personality disorder showed any significant differences in MCP-1 or SFD-1 levels. In subjects with borderline personality disorder, the levels of the study chemokines were higher in women than in men. Our study has shown the need for determination of proinflammatory interleukins which are considered as biomarkers of personality disorders and generalized anxiety disorders. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Inhibition of CCl formation during the combustion of MSW gasification syngas: An experimental study on the synergism and competition between oxidation and chlorination.

    Science.gov (United States)

    Zhang, Rui-Zhi; Yin, Ren-Hao; Luo, Yong-Hao

    2018-03-17

    For the safe disposal of MSW, a four-step gasification-combustion conversion process is proposed in this work, consisting of material gasification, ash melting, syngas conversion and combustion. Based on the control method of dioxin in gasification process which has been studied previously, experiments of tar chlorination process under oxidative atmospheres were carried out in a homogeneous flow reaction system, using benzene as the tar model compound, to find a way for the inhibition of CCl formation during the syngas combustion process. Results indicated that Cl 2 reacts with benzene more easily than O 2 under low temperatures, and has a positive effect on both oxidative cracking and polymerization. For chlorination reactions, high temperature enhances the chlorination degree and leads to the formation of perchlorinated hydrocarbons, but also promotes the rupture of the weak CCl bonds. With the rise of temperature, hexachlorobenzene became the major product, the amounts of all chlorinated hydrocarbons decreased rapidly, and the conversion direction depended on the amount of O 2 . O 2 generally promotes the formation of hydrogen chloride, and inhibits the chlorination of hydrocarbons. At a temperature above 900 °C, the total amount of chlorinated hydrocarbons was very low under oxidative atmospheres, even only with a equivalence ratio of 0.2. However, during the oxidation process under low temperatures, CCl can also be formed on cyclopentadienyl and 1,3-butadienyl radicals, whose chlorination products were observed. The synergistic and competitive effects between oxidation and chlorination are concluded and the major benzene conversion pathways are summarized according to the products detected. Copyright © 2018. Published by Elsevier Ltd.

  19. Serum VEGF-A and CCL5 levels as candidate biomarkers for efficacy and toxicity of regorafenib in patients with metastatic colorectal cancer

    Science.gov (United States)

    Suenaga, Mitsukuni; Mashima, Tetsuo; Kawata, Naomi; Wakatsuki, Takeru; Horiike, Yuki; Matsusaka, Satoshi; Dan, Shingo; Shinozaki, Eiji; Seimiya, Hiroyuki; Mizunuma, Nobuyuki; Yamaguchi, Kensei; Yamaguchi, Toshiharu

    2016-01-01

    Regorafenib is an oral multi-kinase inhibitor used as salvage therapy for metastatic colorectal cancer (mCRC). We tested whether serum cytokine levels are associated with clinical outcome in the mCRC patients receiving regorafenib. Serum samples were collected before treatment start, day 21, and progressive disease, and eleven angiogenic and inflammatory cytokine serum levels were examined. Fifty-four patients of a total of 62 enrolled patients were eligible for the analyses. The chemokine ligand 5 (CCL5) levels ≤ cut-off value (59959 pg/ml) at baseline was associated with relative tumor shrinkage (P = 0.021), better progression-free survival (PFS) (P = 0.036) and overall survival (OS) (P = 0.019). Vascular endothelial growth factor A (VEGF-A) levels showing a decrease on day 21 were significantly associated with a better PFS (P = 0.021). CCL5 levels ≤ cut-off was associated with any grade hand-foot skin reaction (HFSR) (P = 0.025) and thrombocytopenia (P = 0.013). Low chemokine ligand 2 levels at baseline were associated with grade 2 ≤ HFSR. High angiopoietin-2 and basic fibroblast growth factor (bFGF) levels at baseline were associated with grade 3 ≤ total bilirubin increase and transaminases increase, respectively. Low bFGF levels at baseline were associated with grade 3 ≤ hypertension. No correlation with severe events was observed. Baseline serum CCL5 levels and decrease of the serum VEGF-A levels may serve as potential predictive markers for survival or treatment-specific toxicities in mCRC patients receiving regorafenib. PMID:27166185

  20. Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats

    Directory of Open Access Journals (Sweden)

    Wang Yu

    2012-06-01

    Full Text Available Abstract Introduction Adipose derived mesenchymal stem cells (ADMSCs, carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4 in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway. Methods ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4-induced liver fibrosis rats. Computed tomography (CT perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated. Results CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein. Conclusions ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.

  1. 'Ashvagandharishta' prepared using yeast consortium from Woodfordia fruticosa flowers exhibit hepatoprotective effect on CCl4 induced liver damage in Wistar rats.

    Science.gov (United States)

    Bhondave, Prashant D; Devarshi, Prasad P; Mahadik, Kakasaheb R; Harsulkar, Abhay M

    2014-01-01

    [corrected] Consortium of yeasts sourced from traditionally used Woodfordia fruticosa flowers proved to be beneficial for fermenting Ashvagandharishta. It resulted in faster fermentation, acceptable organoleptic properties and demonstrable hepatoprotective potential in CCl4 induced hepatotoxicity. To formulate Ashvagandharishta using consortium of yeasts and to investigate its physiochemical parameters. Standardize the formulation with the help of standard withaferin-A and withanolide-A and to evaluate its hepatoprotective potential in CCl4 induced hepatotoxicity in the rat model. Ashvagandharishta was prepared using a 5% consortium of yeasts and ascertained its quality through physiochemical and phytochemical investigation. Withaferin-A and withanolide-A was simultaneously estimated by HPLC for standardization. Hepatoprotective potential was evaluated by administering 2.31 and 1.15 ml/kg doses while considering biochemical parameters like serum AST, ALT, ALP and lipid profile. Gene expression study was carried out for the expression of antioxidant and inflammatory genes such as CAT, GPx and proinflammatory gene IL-6. Histopathology of liver was also studied with the help of H&E staining. Ashvagandharishta was found organolepticaly acceptable with optimized physiochemical parameters. Withaferin-A and withanolide-A in Ashvagandharishta estimated as 0.3711, 0.7426 (%w/v), respectively. In the CCl4 induced hepato-toxicity model, Ashvagandharishta-2.31ml/kg dose showed significant decrease in elevated hepatic level of AST(pWoodfordia fruticosa flowers showed better fermentation pattern for Ashvagandharishta produced with acceptable organoleptic properties. Hepatoprotection shown by Ashvagandharishta was mainly through prevention of oxidative damage. Up-regulation of CAT and GPx genes and corresponding down regulation of proinflammatory IL6 gene was revealed as possible mechanism of its action. © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Chemokine Ligand 5 (CCL5 and chemokine receptor (CCR5 genetic variants and prostate cancer risk among men of African Descent: a case-control study

    Directory of Open Access Journals (Sweden)

    Kidd LaCreis R

    2012-11-01

    Full Text Available Abstract Background Chemokine and chemokine receptors play an essential role in tumorigenesis. Although chemokine-associated single nucleotide polymorphisms (SNPs are associated with various cancers, their impact on prostate cancer (PCA among men of African descent is unknown. Consequently, this study evaluated 43 chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of variant chemokine-associated alleles may lead to alterations in PCA susceptibility, presumably due to variations in antitumor immune responses. Methods Sequence variants were evaluated in germ-line DNA samples from 814 African-American and Jamaican men (279 PCA cases and 535 controls using Illumina’s Goldengate genotyping system. Results Inheritance of CCL5 rs2107538 (AA, GA+AA and rs3817655 (AA, AG, AG+AA genotypes were linked with a 34-48% reduction in PCA risk. Additionally, the recessive and dominant models for CCR5 rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained significant for the Jamaican and U.S. subgroups, respectively. Conclusions In summary, CCL5 (rs2107538, rs3817655 and CCR5 (rs1799988 sequence variants significantly modified PCA susceptibility among men of African descent, even after adjusting for age and multiple comparisons. Our findings are only suggestive and require further evaluation and validation in relation to prostate cancer risk and ultimately disease progression, biochemical/disease recurrence and mortality in larger high-risk subgroups. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent.

  3. Laboratory of Chemical Physics

    Data.gov (United States)

    Federal Laboratory Consortium — Current research in the Laboratory of Chemical Physics is primarily concerned with experimental, theoretical, and computational problems in the structure, dynamics,...

  4. Combustion Research Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Combustion Research Laboratory facilitates the development of new combustion systems or improves the operation of existing systems to meet the Army's mission for...

  5. Semiconductor Laser Measurements Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Semiconductor Laser Measurements Laboratory is equipped to investigate and characterize the lasing properties of semiconductor diode lasers. Lasing features such...

  6. Optical Remote Sensing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Optical Remote Sensing Laboratory deploys rugged, cutting-edge electro-optical instrumentation for the collection of various event signatures, with expertise in...

  7. Embedded Processor Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Embedded Processor Laboratory provides the means to design, develop, fabricate, and test embedded computers for missile guidance electronics systems in support...

  8. Thermogravimetric Analysis Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — At NETL’s Thermogravimetric Analysis Laboratory in Morgantown, WV, researchers study how chemical looping combustion (CLC) can be applied to fossil energy systems....

  9. Geospatial Services Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: To process, store, and disseminate geospatial data to the Department of Defense and other Federal agencies.DESCRIPTION: The Geospatial Services Laboratory...

  10. [Theme: Using Laboratories.

    Science.gov (United States)

    Pritchard, Jack; Braker, Clifton

    1982-01-01

    Pritchard discusses the opportunities for applied learning afforded by laboratories. Braker describes the evaluation of cognitive, affective, and psychomotor skills in the agricultural mechanics laboratory. (SK)

  11. Wireless Emulation Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Wireless Emulation Laboratory (WEL) is a researchtest bed used to investigate fundamental issues in networkscience. It is a research infrastructure that emulates...

  12. Coatings and Corrosion Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The mission of the Coatings and Corrosion Laboratory is to develop and analyze the effectiveness of innovative coatings test procedures while evaluating the...

  13. Space Weather Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Space Weather Computational Laboratory is a Unix and PC based modeling and simulation facility devoted to research analysis of naturally occurring electrically...

  14. Vehicle Development Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Supports the development of prototype deployment platform vehicles for offboard countermeasure systems.DESCRIPTION: The Vehicle Development Laboratory is...

  15. Fuels Processing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — NETL’s Fuels Processing Laboratory in Morgantown, WV, provides researchers with the equipment they need to thoroughly explore the catalytic issues associated with...

  16. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  17. FOOD SAFETY TESTING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory develops screening assays, tests and modifies biosensor equipment, and optimizes food safety testing protocols for the military and civilian sector...

  18. ANALYTICAL MICROBIOLOGY LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory contains equipment that performs a broad array of microbiological analyses for pathogenic and spoilage microorganisms. It performs challenge studies...

  19. Advanced Manufacturing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Manufacturing Laboratory at the University of Maryland provides the state of the art facilities for realizing next generation products and educating the...

  20. COGNITIVE PERFORMANCE LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory conducts basic and applied human research studies to characterize cognitive performance as influenced by militarily-relevant contextual and physical...

  1. Environmental Microbiology Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Environmental Microbiology Laboratory, located in Bldg. 644 provides a dual-gas respirometer for measurement of oxygen consumption and carbon dioxide evolution...

  2. Photovoltaic Characterization Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — NIST's PV characterization laboratory is used to measure the electrical performance and opto-electronic properties of solar cells and modules. This facility consists...

  3. Virtual Training Devices Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Virtual Training Devices (VTD) Laboratory at the Life Cycle Software Engineering Center, Picatinny Arsenal, provides a software testing and support environment...

  4. Tactical Systems Integration Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Tactical Systems Integration Laboratory is used to design and integrate computer hardware and software and related electronic subsystems for tactical vehicles....

  5. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  6. Acoustic Technology Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory contains an electro-magnetic worldwide data collection and field measurement capability in the area of acoustic technology. Outfitted by NASA Langley...

  7. Atmospheric Measurements Laboratory (AML)

    Data.gov (United States)

    Federal Laboratory Consortium — The Atmospheric Measurements Laboratory (AML) is one of the nation's leading research facilities for understanding aerosols, clouds, and their interactions. The AML...

  8. Sandia National Laboratories

    Data.gov (United States)

    Federal Laboratory Consortium — For more than 60 years, Sandia has delivered essential science and technology to resolve the nation's most challenging security issues.Sandia National Laboratories...

  9. Composites Characterization Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The purpose of the Composites Characterization Laboratory is to investigate new and/or modified matrix materials and fibers for advanced composite applications both...

  10. Research Combustion Laboratory (RCL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Research Combustion Laboratory (RCL) develops aerospace propulsion technology by performing tests on propulsion components and materials. Altitudes up to 137,000...

  11. Intelligent Optics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Intelligent Optics Laboratory supports sophisticated investigations on adaptive and nonlinear optics; advancedimaging and image processing; ground-to-ground and...

  12. Wind Structural Testing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This facility provides office space for industry researchers, experimental laboratories, computer facilities for analytical work, and space for assembling components...

  13. Central Laboratories Services

    Data.gov (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  14. CCL3 and MMP-9 are induced by TL1A during death receptor 3 (TNFRSF25)-dependent osteoclast function and systemic bone loss.

    Science.gov (United States)

    Collins, Fraser L; Williams, Jessica O; Bloom, Anja C; Singh, Ravinder K; Jordan, Lauren; Stone, Michael D; McCabe, Laura R; Wang, Eddie C Y; Williams, Anwen S

    2017-04-01

    Reduced bone density and secondary osteoporosis, resulting in increased risk of fracture, is a significant complicating factor in the inflammatory arthritides. While the exact etiology of systemic bone loss is not fully elucidated, recent insights into the tumor necrosis factor super family (TNFSF) revealed a potential role for death receptor 3 (DR3/TNFRSF25) and one of its ligands, TNF-like protein 1A (TL1A/TNFSF15). The mechanisms by which DR3/TL1A signalling modulates bone loss are unclear. We investigated the effect of DR3/TL1A signalling upon osteoclast-dependent chemokine and MMP production to unravel novel mechanisms whereby this pathway regulates OC formation and OC-dependent bone resorption. Collagen induced arthritis (CIA) was established in DR3 wt and DR3 ko mice, joints were sectioned and analysed histologically for bone damage while systemic trabecular bone loss distal to the affected joints was compared by micro-CT. Ablation of DR3 protected DBA/1 mice against the development and progression of CIA. In DR3 ko , joints of the ankle and mid-foot were almost free of bone erosions and long bones of mice with CIA were protected against systemic trabecular bone loss. In vitro, expression of DR3 was confirmed on primary human CD14 + osteoclast precursors by flow cytometry. These cells were treated with TL1A in osteoclast differentiation medium and TRAP + osteoclasts, bone resorption, levels of osteoclast-associated chemokines (CCL3, CCL2 and CXCL8) and MMP-9 measured. TL1A intensified human osteoclast differentiation and bone resorption and increased osteoclast-associated production of CCL3 and MMP-9. Our data reveals the DR3 pathway as an attractive therapeutic target to combat adverse bone pathology associated with inflammatory arthritis. We demonstrate that DR3 is critical in the pathogenesis of murine CIA and associated secondary osteoporosis. Furthermore, we identify a novel mechanism by which the DR3/TL1A pathway directly enhances human OC formation

  15. Laboratory quality assurance

    International Nuclear Information System (INIS)

    Delvin, W.L.

    1977-01-01

    The elements (principles) of quality assurance can be applied to the operation of the analytical chemistry laboratory to provide an effective tool for indicating the competence of the laboratory and for helping to upgrade competence if necessary. When used, those elements establish the planned and systematic actions necessary to provide adequate confidence in each analytical result reported by the laboratory (the definition of laboratory quality assurance). The elements, as used at the Hanford Engineering Development Laboratory (HEDL), are discussed and they are qualification of analysts, written methods, sample receiving and storage, quality control, audit, and documentation. To establish a laboratory quality assurance program, a laboratory QA program plan is prepared to specify how the elements are to be implemented into laboratory operation. Benefits that can be obtained from using laboratory quality assurance are given. Experience at HEDL has shown that laboratory quality assurance is not a burden, but it is a useful and valuable tool for the analytical chemistry laboratory

  16. Application of gas chromatography to the study of the chemical effects produced by the radiolysis and the 35Cl(n,p)35S reaction on the CCl4

    International Nuclear Information System (INIS)

    Davila R, J.I.

    1980-01-01

    In this work the gas radiochromatography, which is essential in the hot atom chemistry is used. By means of this technique the chemical effects of the 35 Cl(n,p) 35 S, and the radiolysis of liquid CCl 4 were studied. The samples of liquid CCl 4 were capsulated in cuarzo bulbs and were deaereated by several cycles of freeze and pumping in a vacuum line. The sample's irradiation was made in the Triga Mark III Salazar reactor with an approximated flux of 10 12 n-cm 2 -s -1 during ten hours. The sample's analysis was made using a gas radiochromatographer composed of a gas chromatographer, proportional flux detector and an adequate electronic system. In this form were obtained the radiochromatographics of the 35 S labelled compounds possibly formed by hot atom chemistry and at the same time the hexachloroetane formed by the secondary radiolytic effect of the ionizing radiation on the CCl 4 was identified. (author)

  17. Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4-induced cirrhosis: protective role of adenosine administration.

    Science.gov (United States)

    Hernández-Muñoz, R; Díaz-Muñoz, M; López, V; López-Barrera, F; Yáñez, L; Vidrio, S; Aranda-Fraustro, A; Chagoya de Sánchez, V

    1997-11-01

    Oxidative stress and its consequent lipid peroxidation (LP) exert harmful effects, which have been currently involved in the generation of carbon tetrachloride-induced cirrhosis. However, the recent report that "physiological" LP can be associated with liver regeneration (LR) makes it necessary to discriminate between oxidative stress-induced and LR-associated LP. In rats rendered cirrhotic by continuous CCl4 administration for 4 weeks, moderate cell necrosis and fine fatty infiltration were found. The histological abnormalities were accompanied by increased LP, mainly accounted for by the microsomal and cytosolic fractions and evidence of oxidative stress (decreased hepatic glutathione content and changes in xanthine oxidase and pentose phosphate pathway activities). After 8 weeks, a micronodular cirrhosis developed, but oxidative stress was greatly attenuated, only persisting in the enhanced LP confined to microsomes. Simultaneous administration of adenosine, a reliable hepatoprotector that readily prevents the onset of liver fibrosis, was able to block the oxidative stress induced by the long-term CCl4 treatment but elicited a selective subcellular distribution of increased LP, similar to that found during LR. The adenosine-induced changes in liver LP (mainly in the nuclear fraction) correlated with an increased activity of thymidine kinase. Therefore, data suggest that adenosine-mediated preservation of energy availability and mitochondrial function could participate in preventing the onset of oxidative stress in cirrhotic rats. The latter could induce a successful liver recovery, curtailing the sequence of events leading to fibrogenesis.

  18. CX3CL1/CX3CR1 and CCL2/CCR2 Chemokine/Chemokine Receptor Complex in Patients with AMD

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    PURPOSE: The chemokine receptors CX3CR1 and CCR2 have been implicated in the development of age-related macular degeneration (AMD). The evidence is mainly derived from experimental cell studies and murine models of AMD. The purpose of this study was to investigate the association between expression...... of CX3CR1 and CCR2 on different leukocyte subsets and AMD. Furthermore we measured the plasma levels of ligands CX3CL1 and CCL2. METHODS: Patients attending our department were asked to participate in the study. The diagnosis of AMD was based on clinical examination and multimodal imaging techniques...... positive correlation between CCR2 and CX3CR1 expression on CD8+ cells (r = 0.727, p = 0.0001). We found no difference in plasma levels of CX3CL1 and CCL2 among the groups. CONCLUSIONS: Our results show a down regulation of CX3CR1 on CD8+ cells; this correlated to a low expression of CCR2 on CD8+ cells...

  19. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4 Induced Hepatic Fibrosis in Mice.

    Directory of Open Access Journals (Sweden)

    Leola N Chow

    Full Text Available Modulation of chemokine CXCL12 and its receptor CXCR4 has been implicated in attenuation of bleomycin (BLM-induced pulmonary fibrosis and carbon tetrachloride (CCl4-induced hepatic injury. In pulmonary fibrosis, published reports suggest that collagen production in the injured lung is derived from fibrocytes recruited from the circulation in response to release of pulmonary CXCL12. Conversely, in hepatic fibrosis, resident hepatic stellate cells (HSC, the key cell type in progression of fibrosis, upregulate CXCR4 expression in response to activation. Further, CXCL12 induces HSC proliferation and subsequent production of collagen I. In the current study, we evaluated AMD070, an orally bioavailable inhibitor of CXCL12/CXCR4 in alleviating BLM-induced pulmonary and CCl4-induced hepatic fibrosis in mice. Similar to other CXCR4 antagonists, treatment with AMD070 significantly increased leukocyte mobilization. However, in these two models of fibrosis, AMD070 had a negligible impact on extracellular matrix deposition. Interestingly, our results indicated that CXCL12/CXCR4 signaling has a role in improving mortality associated with BLM induced pulmonary injury, likely through dampening an early inflammatory response and/or vascular leakage. Together, these findings indicate that the CXCL12-CXCR4 signaling axis is not an effective target for reducing fibrosis.

  20. Evaluation of the Effectiveness of Piper cubeba Extract in the Amelioration of CCl4-Induced Liver Injuries and Oxidative Damage in the Rodent Model

    Directory of Open Access Journals (Sweden)

    Mansour AlSaid

    2015-01-01

    Full Text Available Background. Liver diseases still represent a major health burden worldwide. Moreover, medicinal plants have gained popularity in the treatment of several diseases including liver. Thus, the present study was to evaluate the effectiveness of Piper cubeba fruits in the amelioration of CCl4-induced liver injuries and oxidative damage in the rodent model. Methods. Hepatoprotective activity was assessed using various biochemical parameters like SGOT, SGPT, γ-GGT, ALP, total bilirubin, LDH, and total protein. Meanwhile, in vivo antioxidant activities as LPO, NP-SH, and CAT were measured in rat liver as well as mRNA expression of cytokines such as TNFα, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. The extent of liver damage was also analyzed through histopathological observations. Results. Treatment with PCEE significantly and dose dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, PCEE significantly reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant enzymes NP-SH and CAT towards normal levels. The administration of PCEE significantly downregulated the CCl4-induced proinflammatory cytokines TNFα and IL-6 mRNA expression in dose dependent manner, while it upregulated the IL-10 and induced hepatoprotective effect by downregulating mRNA expression of iNOS and HO-1 gene.

  1. Effects of undenatured whey protein supplementation on CXCL12- and CCL21-mediated B and T cell chemotaxis in diabetic mice

    Directory of Open Access Journals (Sweden)

    Badr Gamal

    2011-11-01

    Full Text Available Abstract Background Long and persistent uncontrolled diabetes tends to degenerate the immune system and leads to an increased incidence of infection. Whey proteins (WPs enhance immunity during early life and have a protective role in some immune disorders. In this study, the effects of camel WP on the chemotaxis of B and T cells to CXCL12 and CCL21 in diabetic mice were investigated. Results Flow cytometric analysis of the surface expressions of CXCR4 (CXCL12 receptor and CCR7 (CCL21 receptor on B and T cells revealed that the surface expressions of CXCR4 and CCR7 were not significantly altered in diabetic and WP-supplemented diabetic mice compared with control mice. Nevertheless, B and T lymphocytes from diabetic mice were found to be in a stunned state, with a marked and significant (P Conclusion Our data revealed the benefits of WP supplementation in enhancing cytoskeletal rearrangement and chemotaxis in B and T cells, and subsequently improving the immune response in diabetic mice.

  2. Genetic Variations in the Receptor-Ligand Pair CCR5 and CCL3L1 Are Important Determinants of Susceptibility to Kawasaki Disease

    Science.gov (United States)

    Burns, Jane C.; Shimizu, Chisato; Gonzalez, Enrique; Kulkarni, Hemant; Patel, Sukeshi; Shike, Hiroko; Sundel, Robert S.; Newburger, Jane W.; Ahuja, Sunil K.

    2010-01-01

    Kawasaki disease (KD) is an enigmatic, self-limited vasculitis of childhood that is complicated by development of coronary-artery aneurysms. The high incidence of KD in Asian versus European populations prompted a search for genetic polymorphisms that are differentially distributed among these populations and that influence KD susceptibility. Here, we demonstrate a striking, inverse relationship between the worldwide distribution of CCR5-Δ32 allele and the incidence of KD. In 164 KD patient-parent trios, 4 CCR5 haplotypes including the CCR5-Δ32 allele were differentially transmitted from heterozygous parents to affected children. However, the magnitude of the reduced risk of KD associated with the CCR5-Δ32 allele and certain CCR5 haplotypes was significantly greater in individuals who also possessed a high copy number of the gene encoding CCL3L1, the most potent CCR5 ligand. These findings, derived from the largest genetic study of any systemic vasculitis, suggest a central role of CCR5-CCL3L1 gene-gene interactions in KD susceptibility and the importance of gene modifiers in infectious diseases. PMID:15962231

  3. Rhizoma coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFB-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Andrew Remppis

    2010-01-01

    Full Text Available Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. Results. Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP-1 production in RAW cells. Activation of the transcription factors AP-1 and NFB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. Conclusions. Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine.

  4. Rhizoma Coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFκB-Dependent Pathway

    Science.gov (United States)

    Remppis, Andrew; Bea, Florian; Greten, Henry Johannes; Buttler, Annette; Wang, Hongjie; Zhou, Qianxing; Preusch, Michael R.; Enk, Ronny; Ehehalt, Robert; Katus, Hugo; Blessing, Erwin

    2010-01-01

    Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFκB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. Results. Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP)-1 production in RAW cells. Activation of the transcription factors AP-1 and NFκB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. Conclusions. Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFκB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine. PMID:20652055

  5. Energy Materials Research Laboratory (EMRL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Energy Materials Research Laboratory at the Savannah River National Laboratory (SRNL) creates a cross-disciplinary laboratory facility that lends itself to the...

  6. Comparison of CCL28, interleukin-8, interleukin-1β and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis.

    Science.gov (United States)

    Ertugrul, A S; Sahin, H; Dikilitas, A; Alpaslan, N; Bozoglan, A

    2013-02-01

    Cytokines produced by various cells are strong local mediators of inflammation. Mucosa-associated epithelial chemokine (CCL28), interleukin-8 (IL-8), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) are major cytokines that play important roles in the periodontal inflammatory process. In this study we aimed to compare the levels of CCL28, IL-8, IL-1β and TNF-α in the gingival crevicular fluid of both periodontally healthy subjects and in subjects diagnosed with gingivitis, chronic periodontitis and generalized aggressive periodontitis. A total of 84 subjects participated in the study: 21 subjects had gingivitis, 21 subjects had chronic periodontitis, 21 subjects had generalized aggressive periodontitis and 21 were periodontally healthy. The levels of CCL28, IL-8, IL-1β and TNF-α were analyzed using enzyme-linked immune sorbent assay (ELISA). The total levels of CCL28 and IL-8 in the gingival crevicular fluid of the generalized aggressive periodontitis group (324.74 ± 42.62 pg/30 s, 487.62 ± 49.21 pg/30 s) were significantly higher than those of the chronic periodontitis group (268.81 ± 28.64 pg/30 s, 423.65 ± 35.24 pg/30 s), the gingivitis group (146.35 ± 17.46 pg/30 s, 310.24 ± 48.20 pg/30 s) and the periodontally healthy group (92.46 ± 22.04 pg/30 s, 148.41 ± 24.64 pg/30 s). Similarly, the total levels of IL-1β and TNF-α in the generalized aggressive periodontitis group (110.23 ± 9.20 pg/30 s, 1284.46 ± 86.32 pg/30 s) were significantly higher than those in the chronic periodontitis group (423.65 ± 35.24 pg/30 s, 82.64 ± 9.12 pg/30 s), the gingivitis group (52.10 ± 7.15 pg/30 s, 824.24 ± 44.68 pg/30 s) and the periodontally healthy group (36.44 ± 8.86 pg/30 s, 628.26 ± 34.61 pg/30 s). CCL28, IL-8, IL-1β and TNF-α may play key roles in the host response to inflammation in periodontal diseases. As the severity of periodontal diseases increases, destruction of periodontal tissues also increases. Inflammation is one among

  7. CCL5, CCR1 and CCR5 in murine glioblastoma: immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5

    OpenAIRE

    Pham, Kien; Luo, Defang; Liu, Che; Harrison, Jeffrey K.

    2012-01-01

    Glioblastoma multiforme (GBM) is the most malignant brain tumor. Microglia/macrophages are found within human GBM where they likely promote tumor progression. We report that CCL5, CCR1, and CCR5 are expressed in glioblastoma. Individual deletion of CCR1 or CCR5 had little to no effect on survival of tumor bearing mice, or numbers of glioblastoma-infiltrated microglia/macrophages or lymphocytes. CCL5 promoted in vitro migration of wild type, CCR1- or CCR5-deficient microglia/macrophages that w...

  8. Radiochemical Processing Laboratory (RPL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Radiochemical Processing Laboratory (RPL)�is a scientific facility funded by DOE to create and implement innovative processes for environmental clean-up and...

  9. Geological Services Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Researchers use computed tomography (CT) scanners at NETL’s Geological Services Laboratory in Morgantown, WV, to peer into geologic core samples to determine how...

  10. Aircraft Fire Protection Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Navy Aircraft Protection Laboratory provides complete test support for all Navy air vehicle fire protection systems.The facility allows for the simulation of a...

  11. Los Alamos National Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Lab has a proud history and heritage of almost 70 years of science and innovation. The people at the Laboratory work on advanced technologies to provide the best...

  12. FLEXIBLE FOOD PACKAGING LABORATORY

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory contains equipment to fabricate and test prototype packages of many types and sizes (e.g., bags, pouches, trays, cartons, etc.). This equipment can...

  13. Neutral Buoyancy Laboratory (NBL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Neutral Buoyancy Laboratory (NBL) is an astronaut training facility and neutral buoyancy pool operated by NASA and located at the Sonny Carter Training Facility,...

  14. Energetics Laboratory Facilities

    Data.gov (United States)

    Federal Laboratory Consortium — These energetic materials laboratories are equipped with explosion proof hoods with blow out walls for added safety, that are certified for safe handling of primary...

  15. Product Evaluation Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory offers the services of highly trained and experienced specialists that have a full complement of measuring equipment. It is equipped with two optical...

  16. Philadelphia District Laboratory (PHI)

    Data.gov (United States)

    Federal Laboratory Consortium — Program CapabilitiesPHI-DO Pharmaceutical Laboratory specializes in the analyses of all forms and types of drug products.Its work involves nearly all phases of drug...

  17. Building the Korogwe Laboratory

    DEFF Research Database (Denmark)

    Knudsen, Jakob; von Seidlein, Lorenz; Richard, Jean Pierre

    2011-01-01

    An illustrated description of the building of a biomedical research laboratory in Korogwe, Tanzania.......An illustrated description of the building of a biomedical research laboratory in Korogwe, Tanzania....

  18. Detroit District Laboratory (DET)

    Data.gov (United States)

    Federal Laboratory Consortium — Program CapabilitiesDET-DO Laboratory is equipped with the usual instrumentation necessary to perform a wide range of analyses of food, drugs and cosmetics. Program...

  19. Geometric Design Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The mission of the Geometric Design Laboratory (GDL) is to support the Office of Safety Research and Development in research related to the geometric design...

  20. Electro-Deposition Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The electro-deposition laboratory can electro-deposit various coatings onto small test samples and bench level prototypes. This facility provides the foundation for...

  1. Superfund Contract Laboratory Program

    Science.gov (United States)

    The Contract Laboratory Program (CLP) is a national network of EPA personnel, commercial laboratories, and support contractors whose primary mission is to provide data of known and documented quality to the Superfund program.

  2. Aquatic Research Laboratory (ARL)

    Data.gov (United States)

    Federal Laboratory Consortium — Columbia River and groundwater well water sources are delivered to the Aquatic Research Laboratory (ARL), where these resources are used to conduct research on fish...

  3. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  4. Protective Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory is a 40 by 28 by 9 foot facility that is equipped with tools for the development of various items of control technology related to the transmission...

  5. High Bay Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory is a specially constructed facility with elevated (37 feet) ceilings and an overhead catwalk, and which is dedicated to research efforts in reducing...

  6. Clinical Laboratory Fee Schedule

    Data.gov (United States)

    U.S. Department of Health & Human Services — Outpatient clinical laboratory services are paid based on a fee schedule in accordance with Section 1833(h) of the Social Security Act. The clinical laboratory fee...

  7. Laboratory of Biological Modeling

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to a...

  8. Laboratory Demographics Lookup Tool

    Data.gov (United States)

    U.S. Department of Health & Human Services — This website provides demographic information about laboratories, including CLIA number, facility name and address, where the laboratory testing is performed, the...

  9. Los Alamos National Laboratory.

    Science.gov (United States)

    Hammel, Edward F., Jr.

    1982-01-01

    Current and post World War II scientific research at the Los Alamos National Laboratory (New Mexico) is discussed. The operation of the laboratory, the Los Alamos consultant program, and continuation education, and continuing education activities at the laboratory are also discussed. (JN)

  10. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.

    2008-01-01

    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  11. The Canfranc Underground Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Amare, J. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Beltran, B. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Carmona, J.M. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Cebrian, S. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Garcia, E. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Irastorza, I.G. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Gomez, H. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Luzon, G. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Martinez, M. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Morales, J. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Ortiz de Solorzano, A. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Pobes, C. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Puimedon, J. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Rodriguez, A. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Ruz, J. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Sarsa, M.L. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Torres, L. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain); Villar, J.A. [Laboratory of Nuclear and High Energy Physics, University of Zaragoza. 50009 Zaragoza (Spain)

    2005-06-15

    This paper describes the forthcoming enlargement of the Canfranc Underground Laboratory (LSC) which will allow to host new international Astroparticle Physics experiments and therefore to broaden the European underground research area. The new Canfranc Underground Laboratory will operate in coordination (through the ILIAS Project) with the Gran Sasso (Italy), Modane (France) and Boulby (UK) underground laboratories.

  12. Underground laboratory in China

    Science.gov (United States)

    Chen, Heshengc

    2012-09-01

    The underground laboratories and underground experiments of particle physics in China are reviewed. The Jinping underground laboratory in the Jinping mountain of Sichuan, China is the deepest underground laboratory with horizontal access in the world. The rock overburden in the laboratory is more than 2400 m. The measured cosmic-ray flux and radioactivities of the local rock samples are very low. The high-purity germanium experiments are taking data for the direct dark-matter search. The liquid-xenon experiment is under construction. The proposal of the China National Deep Underground Laboratory with large volume at Jinping for multiple discipline research is discussed.

  13. SCAI expert consensus statement: Evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (Endorsed by the Cardiological Society of India, and Sociedad Latino Americana de Cardiologıa Intervencionista).

    Science.gov (United States)

    Iliescu, Cezar; Grines, Cindy L; Herrmann, Joerg; Yang, Eric H; Cilingiroglu, Mehmet; Charitakis, Konstantinos; Hakeem, Abdul; Toutouzas, Konstantinos; Leesar, Massoud A; Marmagkiolis, Konstantinos

    2016-04-01

    In the United States alone, there are currently approximately 14.5 million cancer survivors, and this number is expected to increase to 20 million by 2020. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), stroke, critical limb ischemia, arrhythmias, and heart failure, independently from the direct myocardial or pericardial damage from the malignancy itself. Consequently, the need for invasive evaluation and management in the cardiac catheterization laboratory (CCL) for such patients has been increasing. In recognition of the need for a document on special considerations for cancer patients in the CCL, the Society for Cardiovascular Angiography and Interventions (SCAI) commissioned a consensus group to provide recommendations based on the published medical literature and on the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients. © 2015 Wiley Periodicals, Inc.

  14. SCAI Expert consensus statement: Evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (endorsed by the cardiological society of india, and sociedad Latino Americana de Cardiologıa intervencionista).

    Science.gov (United States)

    Iliescu, Cezar A; Grines, Cindy L; Herrmann, Joerg; Yang, Eric H; Cilingiroglu, Mehmet; Charitakis, Konstantinos; Hakeem, Abdul; Toutouzas, Konstantinos P; Leesar, Massoud A; Marmagkiolis, Konstantinos

    2016-04-01

    In the United States alone, there are currently approximately 14.5 million cancer survivors, and this number is expected to increase to 20 million by 2020. Cancer therapies can cause significant injury to the vasculature, resulting in angina, acute coronary syndromes (ACS), stroke, critical limb ischemia, arrhythmias, and heart failure, independently from the direct myocardial or pericardial damage from the malignancy itself. Consequently, the need for invasive evaluation and management in the cardiac catheterization laboratory (CCL) for such patients has been increasing. In recognition of the need for a document on special considerations for cancer patients in the CCL, the Society for Cardiovascular Angiography and Interventions (SCAI) commissioned a consensus group to provide recommendations based on the published medical literature and on the expertise of operators with accumulated experience in the cardiac catheterization of cancer patients. © 2016 Wiley Periodicals, Inc.

  15. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia

    Directory of Open Access Journals (Sweden)

    Victor Manuel Blanco-Alvarez

    2015-01-01

    Full Text Available Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO. Male rats were grouped as follows: (1 Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days; (2 Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3 CCAO, rats with CCAO only; (4 Sham group, rats with mock CCAO; and (5 untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

  16. Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF-1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia.

    Science.gov (United States)

    Blanco-Alvarez, Victor Manuel; Soto-Rodriguez, Guadalupe; Gonzalez-Barrios, Juan Antonio; Martinez-Fong, Daniel; Brambila, Eduardo; Torres-Soto, Maricela; Aguilar-Peralta, Ana Karina; Gonzalez-Vazquez, Alejandro; Tomás-Sanchez, Constantino; Limón, I Daniel; Eguibar, Jose R; Ugarte, Araceli; Hernandez-Castillo, Jeanett; Leon-Chavez, Bertha Alicia

    2015-01-01

    Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

  17. Course of SP-D, YKL-40, CCL18 and CA 15-3 in adult patients hospitalised with community-acquired pneumonia and their association with disease severity and aetiology: A post-hoc analysis.

    Directory of Open Access Journals (Sweden)

    Simone M C Spoorenberg

    Full Text Available SP-D, YKL-40, CCL18 and CA 15-3 are pulmonary markers that have been extensively investigated in different chronic pulmonary diseases. However, in acute pulmonary diseases, such as community-acquired pneumonia (CAP, little is known about the course of these markers and their relationship with the aetiological agent. The aim of this study was to investigate the course of these four markers in CAP and to study influence of disease severity, aetiology and antibiotic use prior to admission on their course.We included 291 adult patients hospitalised with CAP and 20 healthy controls. Measurements were performed in serum of day 0, 2, and 4, and at least 30 days after admission.Our most important results were: 1 At all time-points, including 30 days after admission, YKL-40 and CCL18 levels were higher in CAP patients compared to healthy controls; and 2 Patients with CAP caused by an intracellular, atypical bacterium had lower YKL-40 and especially CCL18 levels on and during admission in comparison with other or unknown CAP aetiology.Our findings suggest that these pulmonary markers could be useful to assess CAP severity and, especially YKL-40 and CCL18 by helping predict CAP caused by atypical pathogens.

  18. Course of SP-D, YKL-40, CCL18 and CA 15-3 in adult patients hospitalised with community-acquired pneumonia and their association with disease severity and aetiology: A post-hoc analysis.

    Science.gov (United States)

    Spoorenberg, Simone M C; Vestjens, Stefan M T; Voorn, G P; van Moorsel, Coline H M; Meek, Bob; Zanen, Pieter; Rijkers, Ger T; Bos, Willem Jan W; Grutters, Jan C

    2018-01-01

    SP-D, YKL-40, CCL18 and CA 15-3 are pulmonary markers that have been extensively investigated in different chronic pulmonary diseases. However, in acute pulmonary diseases, such as community-acquired pneumonia (CAP), little is known about the course of these markers and their relationship with the aetiological agent. The aim of this study was to investigate the course of these four markers in CAP and to study influence of disease severity, aetiology and antibiotic use prior to admission on their course. We included 291 adult patients hospitalised with CAP and 20 healthy controls. Measurements were performed in serum of day 0, 2, and 4, and at least 30 days after admission. Our most important results were: 1) At all time-points, including 30 days after admission, YKL-40 and CCL18 levels were higher in CAP patients compared to healthy controls; and 2) Patients with CAP caused by an intracellular, atypical bacterium had lower YKL-40 and especially CCL18 levels on and during admission in comparison with other or unknown CAP aetiology. Our findings suggest that these pulmonary markers could be useful to assess CAP severity and, especially YKL-40 and CCL18 by helping predict CAP caused by atypical pathogens.

  19. Flavanones from Sedum sarmentosum Bunge Alleviate CCl4-Induced Liver Fibrosis in Rats by Targeting TGF-β1/TβR/Smad Pathway In Turn Inhibiting Epithelial Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Yuancan Lin

    2018-01-01

    Full Text Available Objective. The aim of the study is to evaluate the therapeutic effects of flavanones from Sedum sarmentosum Bunge (FSSB on CCl4-induced liver fibrosis in rats and the underlying mechanisms of action. Methods. An experimental model of liver fibrosis was established by subcutaneous injection of rats with CCl4 (40% v/v, 3 ml/kg twice per week for six weeks. FSSB (100, 200, and 400 mg/kg was intragastrically administered once per day consecutively for five weeks. Results. Our results showed that FSSB significantly attenuated CCl4-induced liver fibrosis as evidenced by reducing the elevated levels of serum biochemical indexes and improving the histological changes, including decreasing the elevation in serum alanine transaminase (ALT, aspartate transaminase (AST, hyaluronic acid (HA, and laminin (LN level, reducing infiltration of inflammatory cells and collagen fibers in liver tissue. In addition, compared to the model group, FSSB markedly downregulated the protein and mRNA expression of TGF-β1, TGF-β1 receptors I and II (TβRI and TβRII, Smad2, Smad3, and Vimentin in liver tissue, at the mean time upregulating the expression of Smad7 and E-cadherin. Conclusions. The results suggest that FSSB alleviated CCl4-induced liver fibrosis probably through inhibition of TGF-β/TβR/Smad pathway in turn inhibiting epithelial mesenchymal transition.

  20. Biosynthesis of silver nanoparticles from Premna serratifolia L. leaf and its anticancer activity in CCl4-induced hepato-cancerous Swiss albino mice

    Science.gov (United States)

    Arockia John Paul, J.; Karunai Selvi, B.; Karmegam, N.

    2015-11-01

    In this study, we report the biosynthesis of silver nanoparticles using the ethanolic leaf powder extract of Premna serratifolia L. and its anticancer activity in carbon tetra chloride (CCl4)-induced liver cancer in Swiss albino mice (Balb/c). The synthesized silver nanoparticles were characterized by SEM, FTIR and XRD analyses. The Debye-Scherrer equation was used to calculate particle size and the average size of silver nanoparticles synthesized from P. serratifolia leaf extract was 22.97 nm. The typical pattern revealed that the sample contained cubic structure of silver nanoparticles. FTIR analysis confirmed that the bioreduction of silver ions to silver nanoparticles is due to reduction by capping material of the plant extract. The silver nanoparticles of P. serratifolia leaf extract were effective in treating liver cancer in Swiss albino mice when compared with P. serratifolia leaf extract with isoleucine.

  1. Ozone generation in oxygen-fed wire-to-cylinder ozonizer: effect of CH2Cl2, CHCl3 and CCl4 diluents

    Science.gov (United States)

    Skalný, J. D.; Ráheľ, J.; Holubčík, Ľ.

    1999-03-01

    The inhibition effect of methylene chloride CH2Cl2, chloroform CHCl3 and carbon tetrachloride CCl4 on the ozone generation process from oxygen by negative corona discharge was experimentally investigated. The experiments were performed in a system of coaxial cylindrical electrodes at total gas pressure of 900 mbar and ambient temperature of gaseous mixtures. The rate of ozone generation as well as ozone concentration apparently decreases with a rising number of substituted chlorine atoms in the methane molecule at constant specific energy consumption dissipated in the discharge and at constant concentration of gaseous impurities in oxygen. In addition to experimental results, the paper presents theoretical considerations aimed at identifying the main process responsible for inhibition of ozone generation. The consumption of considerable fraction of oxygen atoms by CH x Cl y-1 radicals formed in discharge, is likely the most important mechanism responsible for the deleterious effect of such compounds on the efficiency of ozone production.

  2. Characterizing the Laboratory Market

    Energy Technology Data Exchange (ETDEWEB)

    Shehabi, Arman [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Ganeshalingam, Mohan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DeMates, Lauren [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mathew, Paul [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sartor, Dale [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-04-11

    Laboratories are estimated to be 3-5 times more energy intensive than typical office buildings and offer significant opportunities for energy use reductions. Although energy intensity varies widely, laboratories are generally energy intensive due to ventilation requirements, the research instruments used, and other health and safety concerns. Because the requirements of laboratory facilities differ so dramatically from those of other buildings, a clear need exists for an initiative exclusively targeting these facilities. The building stock of laboratories in the United States span different economic sectors, include governmental and academic institution, and are often defined differently by different groups. Information on laboratory buildings is often limited to a small subsection of the total building stock making aggregate estimates of the total U.S. laboratories and their energy use challenging. Previous estimates of U.S. laboratory space vary widely owing to differences in how laboratories are defined and categorized. A 2006 report on fume hoods provided an estimate of 150,000 laboratories populating the U.S. based in part on interviews of industry experts, however, a 2009 analysis of the 2003 Commercial Buildings Energy Consumption Survey (CBECS) generated an estimate of only 9,000 laboratory buildings. This report draws on multiple data sources that have been evaluated to construct an understanding of U.S. laboratories across different sizes and markets segments. This 2016 analysis is an update to draft reports released in October and December 2016.

  3. Personalized laboratory medicine

    DEFF Research Database (Denmark)

    Pazzagli, M.; Malentacchi, F.; Mancini, I.

    2015-01-01

    Developments in "omics" are creating a paradigm shift in Laboratory Medicine leading to Personalised Medicine. This allows the increasing in diagnostics and therapeutics focused on individuals rather than populations. In order to investigate whether Laboratory Medicine is able to implement new...... diagnostic tools and expertise and commands proper state-of-the-art knowledge about Personalized Medicine and Laboratory Medicine in Europe, the joint Working Group "Personalized Laboratory Medicine" of the EFLM and ESPT societies compiled and conducted the Questionnaire "Is Laboratory Medicine ready...... for the era of Personalized Medicine?". 48 laboratories from 18 European countries participated at this survey. The answers of the participating Laboratory Medicine professionals indicate that they are aware that Personalized Medicine can represent a new and promising health model. Whereas they are aware...

  4. Transformation of Contaminant Candidate List (CCL3) compounds during ozonation and advanced oxidation processes in drinking water: Assessment of biological effects.

    Science.gov (United States)

    Mestankova, Hana; Parker, Austa M; Bramaz, Nadine; Canonica, Silvio; Schirmer, Kristin; von Gunten, Urs; Linden, Karl G

    2016-04-15

    The removal of emerging contaminants during water treatment is a current issue and various technologies are being explored. These include UV- and ozone-based advanced oxidation processes (AOPs). In this study, AOPs were explored for their degradation capabilities of 25 chemical contaminants on the US Environmental Protection Agency's Contaminant Candidate List 3 (CCL3) in drinking water. Twenty-three of these were found to be amenable to hydroxyl radical-based treatment, with second-order rate constants for their reactions with hydroxyl radicals (OH) in the range of 3-8 × 10(9) M(-1) s(-1). The development of biological activity of the contaminants, focusing on mutagenicity and estrogenicity, was followed in parallel with their degradation using the Ames and YES bioassays to detect potential changes in biological effects during oxidative treatment. The majority of treatment cases resulted in a loss of biological activity upon oxidation of the parent compounds without generation of any form of estrogenicity or mutagenicity. However, an increase in mutagenic activity was detected by oxidative transformation of the following CCL3 parent compounds: nitrobenzene (OH, UV photolysis), quinoline (OH, ozone), methamidophos (OH), N-nitrosopyrolidine (OH), N-nitrosodi-n-propylamine (OH), aniline (UV photolysis), and N-nitrosodiphenylamine (UV photolysis). Only one case of formation of estrogenic activity was observed, namely, for the oxidation of quinoline by OH. Overall, this study provides fundamental and practical information on AOP-based treatment of specific compounds of concern and represents a framework for evaluating the performance of transformation-based treatment processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Increased generation of HIV-1 gp120-reactive CD8+ T cells by a DNA vaccine construct encoding the chemokine CCL3.

    Directory of Open Access Journals (Sweden)

    Inger Øynebråten

    Full Text Available DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC could increase the immune response to surface envelope glycoprotein (Env gp120 from Human Immunodeficiency Virus type 1 (HIV-1. To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv specific for the major histocompatibility complex (MHC class II I-E molecules, and the CC chemokine ligand 3 (CCL3. The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8+ T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.

  6. The innate immune response to lower respiratory tract E. Coli infection and the role of the CCL2-CCR2 axis in neonatal mice.

    Science.gov (United States)

    McGrath-Morrow, Sharon A; Ndeh, Roland; Collaco, Joseph M; Poupore, Amy K; Dikeman, Dustin; Zhong, Qiong; Singer, Benjamin D; D'Alessio, Franco; Scott, Alan

    2017-09-01

    Neonates have greater morbidity/mortality from lower respiratory tract infections (LRTI) compared to older children. Lack of conditioning of the pulmonary immune system due to limited environmental exposures and/or infectious challenges likely contributes to the increase susceptibility in the neonate. In this study, we sought to gain insights into the nature and dynamics of the neonatal pulmonary immune response to LRTI using a murine model. Wildtype (WT) and Ccr2 -/- C57BL/6 neonatal and juvenile mice received E. coli or PBS by direct pharyngeal aspiration. Flow cytometry was used to measure immune cell dynamics and identify cytokine-producing cells. Real-time PCR and ELISA were used to measure cytokine/chemokine expression. Innate immune cell recruitment in response to E. coli-induced LRTI was delayed in the neonatal lung compared to juvenile lung. Lung clearance of bacteria was also significantly delayed in the neonate. Ccr2 -/- neonates, which lack an intact CCL2-CCR2 axis, had higher mortality after E. coli challenged than Ccr2 +/+ neonates. A greater percentage of CD8 + T cells and monocytes from WT neonates challenged with E. coli produced TNF compared to controls. The pulmonary immune response to E. coli-induced LRTI differed significantly between neonatal and juvenile mice. Neonates were more susceptible to increasing doses of E. coli and exhibited greater mortality than juveniles. In the absence of an intact CCL2-CCR2 axis, susceptibility to LRTI-induced mortality was further increased in neonatal mice. Taken together these findings underscore the importance of age-related differences in the innate immune response to LRTI during early stages of postnatal life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. CD4+ T cells elicit host immune responses to MHC class II-negative ovarian cancer through CCL5 secretion and CD40-mediated licensing of dendritic cells.

    Science.gov (United States)

    Nesbeth, Yolanda C; Martinez, Diana G; Toraya, Seiko; Scarlett, Uciane K; Cubillos-Ruiz, Juan R; Rutkowski, Melanie R; Conejo-Garcia, Jose R

    2010-05-15

    T cell adoptive transfer strategies that have produced clinical remissions against specific tumors have so far produced disappointing results against ovarian cancer. Recent evidence suggests that adoptively transferred CD4(+) T cells can trigger endogenous immune responses in particular patients with ovarian cancer through unknown mechanisms. However, conflicting reports suggest that ovarian cancer-infiltrating CD4(+) T cells are associated with negative outcomes. In this study, we elucidate the phenotypic attributes that enable polyclonal CD4(+) T cells briefly primed against tumor Ags to induce therapeutically relevant endogenous antitumor immune responses. Our results unveil a therapeutic mechanism whereby tumor-primed CD4(+) T cells transferred into ovarian cancer-bearing mice secrete high levels of CCL5, which recruits endogenous CCR5(+) dendritic cells to tumor locations and activate them through CD40-CD40L interactions. These newly matured dendritic cells are then able to prime tumor-specific endogenous CD8(+) T cells, which mediate long-term protection. Correspondingly, administration of tumor-primed CD4(+) T cells significantly delayed progression of MHC class II(-) ovarian cancers, similarly to CD8(+) T cells only, and directly activated wild-type but not CD40-deficient dendritic cells recruited to the tumor microenvironment. Our results unveil a CCL5- and CD40L-dependent mechanism of transferring immunity from exogenously activated CD4(+) T cells to tumor-exposed host cells, resulting in sustained antitumor effects. Our data provide a mechanistic rationale for incorporating tumor-reactive CD4(+) T cells in adoptive cell transfer immunotherapies against ovarian cancer and underscore the importance of optimizing immunotherapeutic strategies for the specific microenvironment of individual tumors.

  8. Genetic polymorphism rs3760396 of the chemokine (C-C motif) ligand 2 gene (CCL2) associated with the susceptibility of lung cancer in a pathological subtype-specific manner in Han-ancestry Chinese: a case control study

    International Nuclear Information System (INIS)

    Li, Xu; Lin, Fangcai; Zhou, Hong

    2016-01-01

    Chemokines are well known inflammatory factors critical for tumor development in diverse tissues, including lung cancer. Chemokine (C-C motif) Ligand 2 (CCL2) was one of such chemokines important for both primary tumor development and metastasis of various cancers. Polymorphism at rs3760396 of CCL2 genes is associated with the prognosis of non-small cell lung cancer (NSCLC). The goal of our study was to examine the relationship of genetic polymorphisms rs3760396 with the susceptibility of lung cancer and its pathological subtypes in Han-ancestry Chinese population. rs3760396 G/C polymorphism of CCL2 was genotyped using PCR in 394 patients with lung cancer and 545 cancer-free controls from the same Northeast region of China. After controlling for gender, age and smoking status, no significant association was observed between rs3760396 polymorphism and overall lung cancer. However, minor allele G of rs3760396 polymorphism was significantly associated with increased risk of adenosquamous lung carcinoma with either allelic genetic model (OR = 5.29, P < 0.001), or dominant genetic model (OR = 9.88, P < 0.001), or genotypic model (GC genotype vs. CC genotype, OR = 10.73, P < 0.001). Although rs3760396 polymorphism was not significantly associated with increased risk of adenocarcinoma subtype, it was nominally associated with the pooled outcome of either adenocarcinoma or adenosquamous carcinoma under allelic genetic model (OR = 1.54, P = 0.023) or dominant genetic model (OR = 1.57, P = 0.031). Our study suggested rs3760396 polymorphism of CCL2 is associated not only with prognosis of NSCLC, but also with risk of lung cancer in a subtype-specific manner. Our results further supported previous evidence of the important role of CCL2 in lung cancer development

  9. Optics/Optical Diagnostics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Optics/Optical Diagnostics Laboratory supports graduate instruction in optics, optical and laser diagnostics and electro-optics. The optics laboratory provides...

  10. Heat Flux Instrumentation Laboratory (HFIL)

    Data.gov (United States)

    Federal Laboratory Consortium — Description: The Heat Flux Instrumentation Laboratory is used to develop advanced, flexible, thin film gauge instrumentation for the Air Force Research Laboratory....

  11. COMMERCIALLY ORIENTED CLINICAL LABORATORIES

    Science.gov (United States)

    Chapman, W. Max

    1964-01-01

    Out-of-state flat-rate mail order contract laboratories operating from states which have little or no legal control over them can do business in California without obedience to regulations that govern laboratories located within the state. The flat-rate contract principle under which some out-of-state laboratories operate is illegal in California. The use of such laboratories increases physician liability. Legislation for the control of these laboratories is difficult to construct, and laws which might result would be awkward to administer. The best remedy is for California physicians not to use an out-of-state laboratory offering contracts or conditions that it could not legally offer if it were located in California. PMID:14165875

  12. Applied Neuroscience Laboratory Complex

    Data.gov (United States)

    Federal Laboratory Consortium — Located at WPAFB, Ohio, the Applied Neuroscience lab researches and develops technologies to optimize Airmen individual and team performance across all AF domains....

  13. Sediment Core Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides instrumentation and expertise for physical and geoacoustic characterization of marine sediments.DESCRIPTION: The multisensor core logger measures...

  14. Shallow Water Acoustic Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Supports experimental research where high-frequency acoustic scattering and surface vibration measurements of fluid-loaded and non-fluid-loaded structures...

  15. GSPEL - Fuel Cell Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Fuel Cell Lab (FCL)Established to investigate, integrate, testand verifyperformance and technology readiness offuel cell systems and fuel reformers for use with...

  16. Interactive virtual optical laboratories

    Science.gov (United States)

    Liu, Xuan; Yang, Yi

    2017-08-01

    Laboratory experiences are essential for optics education. However, college students have limited access to advanced optical equipment that is generally expensive and complicated. Hence there is a need for innovative solutions to expose students to advanced optics laboratories. Here we describe a novel approach, interactive virtual optical laboratory (IVOL) that allows unlimited number of students to participate the lab session remotely through internet, to improve laboratory education in photonics. Although students are not physically conducting the experiment, IVOL is designed to engage students, by actively involving students in the decision making process throughout the experiment.

  17. Biochemical Neuroscience Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This biochemistry lab is set up for protein analysis using Western blot, enzyme linked immunosorbent assays, immunohistochemistry, and bead-based immunoassays. The...

  18. Head Impact Laboratory (HIL)

    Data.gov (United States)

    Federal Laboratory Consortium — The HIL uses testing devices to evaluate vehicle interior energy attenuating (EA) technologies for mitigating head injuries resulting from head impacts during mine/...

  19. Flying Electronic Warfare Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides NP-3D aircraft host platforms for Effectiveness of Navy Electronic Warfare Systems (ENEWS) Program antiship missile (ASM) seeker simulators used...

  20. Sandia National Laboratories

    Science.gov (United States)

    Gilliom, Laura R.

    1992-01-01

    Sandia National Laboratories has identified technology transfer to U.S. industry as a laboratory mission which complements our national security mission and as a key component of the Laboratory's future. A number of technology transfer mechanisms - such as CRADA's, licenses, work-for-others, and consortia - are identified and specific examples are given. Sandia's experience with the Specialty Metals Processing Consortium is highlighted with a focus on the elements which have made it successful. A brief discussion of Sandia's potential interactions with NASA under the Space Exploration Initiative was included as an example of laboratory-to-NASA technology transfer. Viewgraphs are provided.