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

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David Christopher Nieman

2016-09-01

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

Combined use of serum MCP-1/IL-10 ratio and uterine artery Doppler index significantly improves the prediction of preeclampsia.

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Cui, Shihong; Gao, Yanan; Zhang, Linlin; Wang, Yuan; Zhang, Lindong; Liu, Pingping; Liu, Ling; Chen, Juan

2017-10-01

Monocyte chemotactic protein-1 (MCP-1, or CCL2) is a member of the chemokine subfamily involved in recruitment of monocytes in inflammatory tissues. IL-10 is a key regulator for maintaining the balance of anti-inflammatory and pro-inflammatory milieu at the feto-maternal interface. Doppler examination has been routinely performed for the monitoring and management of preeclampsia patients. This study evaluates the efficiency of these factors alone, or in combination, for the predication of preeclampsia. The serum levels of MCP-1 and IL-10 in 78 preeclampsia patients and 143 age-matched normal controls were measured. The Doppler ultrasonography was performed and Artery Pulsatility Index (PI) and Resistance Index (RI) were calculated for the same subjects. It was found that while the second-trimester serum MCP-1, IL-10, MCP-1/IL-10 ratio, PI, and RI showed some power in predicting preeclampsia, the combination of MCP-1/IL-10 and PI and RI accomplishes the highest efficiency, achieving an AUC of 0.973 (95% CI, 0.000-1.000, Ppreeclampsia. Future studies using a larger sample can be conducted to construct an algorithm capable of quantitative assessment on the risk of preeclampsia. Copyright © 2016 Elsevier B.V. All rights reserved.

p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation.

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Singh, Nikhlesh K; Janjanam, Jagadeesh; Rao, Gadiparthi N

2017-08-25

Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)-induced vascular wall remodeling. We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs). Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migration and proliferation. Consistent with these observations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid arteries, and siRNA-mediated down-regulation of its levels substantially attenuated BI-induced smooth muscle cell migration and proliferation, resulting in reduced neointima formation. Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling. Our findings also show that protein kinase N1 (PKN1) downstream of Rac1-cyclin D1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling axis is involved in the modulation of vascular wall remodeling. Of note, we also observed that CCR2-G i/o -Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation. These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and proliferation in vitro and for injury-induced neointima formation in vivo by modulating Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Crystallization and crystallographic analysis of the ligand-binding domain of the Pseudomonas putida chemoreceptor McpS in complex with malate and succinate

International Nuclear Information System (INIS)

Gavira, J. A.; Lacal, J.; Ramos, J. L.; García-Ruiz, J. M.; Krell, T.; Pineda-Molina, E.

2012-01-01

The crystallization of the ligand-binding domain of the methyl-accepting chemotaxis protein chemoreceptor McpS (McpS-LBD) is reported. Methyl-accepting chemotaxis proteins (MCPs) are transmembrane proteins that sense changes in environmental signals, generating a chemotactic response and regulating other cellular processes. MCPs are composed of two main domains: a ligand-binding domain (LBD) and a cytosolic signalling domain (CSD). Here, the crystallization of the LBD of the chemoreceptor McpS (McpS-LBD) is reported. McpS-LBD is responsible for sensing most of the TCA-cycle intermediates in the soil bacterium Pseudomonas putida KT2440. McpS-LBD was expressed, purified and crystallized in complex with two of its natural ligands (malate and succinate). Crystals were obtained by both the counter-diffusion and the hanging-drop vapour-diffusion techniques after pre-incubation of McpS-LBD with the ligands. The crystals were isomorphous and belonged to space group C2, with two molecules per asymmetric unit. Diffraction data were collected at the ESRF synchrotron X-ray source to resolutions of 1.8 and 1.9 Å for the malate and succinate complexes, respectively

Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently

NARCIS (Netherlands)

de Waard, Vivian; Bot, Ilze; de Jager, Saskia C. A.; Talib, Sara; Egashira, Kensuke; de Vries, Margreet R.; Quax, Paul H. A.; Biessen, Erik A. L.; van Berkel, Theo J. C.

2010-01-01

Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice

Increased cerebrospinal fluid levels of cytokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in patients with amyotrophic lateral sclerosis.

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Martínez, H R; Escamilla-Ocañas, C E; Camara-Lemarroy, C R; González-Garza, M T; Moreno-Cuevas, J; García Sarreón, M A

2017-10-10

Neuroinflammation has recently been described in amyotrophic lateral sclerosis (ALS). However, the precise role of such proinflammatory cytokines as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in ALS has not yet been determined. In this study, we determined cerebrospinal fluid (CSF) MCP-1 and MIP-1β levels and assessed their association with the duration and severity of ALS. Concentrations of MCP-1 and MIP-1β were determined in the CSF of 77 patients diagnosed with ALS and 13 controls. Cytokine levels were analysed in relation to ALS duration (12months) and severity (30points on the ALS Functional Rating Scale administered at hospital admission). Higher CSF MIP-1β (10.68pg/mL vs. 4.69pg/mL, P<.0001) and MCP-1 (234.89pg/mL vs. 160.95pg/mL, P=.011) levels were found in the 77 patients with ALS compared to controls. There were no differences in levels of either cytokine in relation to disease duration or severity. However, we did observe a significant positive correlation between MIP-1β and MCP-1 in patients with ALS. The increase in MIP-1β and MCP-1 levels suggests that these cytokines may have a synergistic effect on ALS pathogenesis. However, in our cohort, no association was found with either the duration or the clinical severity of the disease. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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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.

Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3.

Czech Academy of Sciences Publication Activity Database

Potměšil, Petr; Holý, Antonín; Kmoníčková, Eva; Křížková, Jana; Zídek, Zdeněk

2007-01-01

Roč. 14, č. 1 (2007), s. 59-66 ISSN 1021-7770 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z40550506 Keywords : Acyclic nucleoside phosponate * HIV * Monocyte chemotactic protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.024, year: 2007

Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man

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Palasubramaniam Dharshan

2011-09-01

Full Text Available Abstract Background Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a and monocyte chemotactic factor 1(MCP-1 are detectable in peripheral blood after myocardial infarction (MI. It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium. Methods Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous blood from patients with normal coronary arteries, stable coronary artery disease (CAD, unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI. Results Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model. Conclusions SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.

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

PEG-albumin plasma expansion increases expression of MCP-1 evidencing increased circulatory wall shear stress: an experimental study.

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C Makena Hightower

Full Text Available Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS, decreasing endothelial nitric oxide (NO production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer's lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1, a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity.

MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing.

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Masahiro Ishikawa

Full Text Available OBJECTIVE: The purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models. METHODS: The expression profiles of chemokines were examined during fracture healing in wild-type (WT mice using a polymerase chain reaction array and histological staining. The functional effect of monocyte chemotactic protein-1 (MCP-1 on primary mouse bone marrow stromal cells (mBMSCs was evaluated using an in vitro migration assay. MCP-1-/- and C-C chemokine receptor 2 (CCR2-/- mice were fractured and evaluated by histological staining and micro-computed tomography (micro-CT. RS102895, an antagonist of CCR2, was continuously administered in WT mice before or after rib fracture and evaluated by histological staining and micro-CT. Bone graft exchange models were created in WT and MCP-1-/- mice and were evaluated by histological staining and micro-CT. RESULTS: MCP-1 and MCP-3 expression in the early phase of fracture healing were up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1-/- and CCR2-/- mice was delayed compared with WT mice on day 21. Administration of RS102895 in the early, but not in the late phase, caused delayed fracture healing. Transplantation of WT-derived graft into host MCP-1-/- mice significantly increased new bone formation in the bone graft exchange models. Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum was observed around the WT-derived graft in the host MCP-1-/- mouse. Conversely, transplantation of MCP-1-/- mouse-derived grafts into host WT mice markedly decreased new bone formation. CONCLUSIONS: MCP-1/CCR2 signaling in the periosteum and endosteum is essential for the recruitment of mesenchymal progenitor cells in the early phase of fracture healing.

Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

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Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

2017-01-01

The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

Curcumin as a natural regulator of monocyte chemoattractant protein-1.

Science.gov (United States)

Karimian, Maryam Saberi; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

2017-02-01

Monocyte chemoattractant/chemotactic protein-1 (MCP-1), a member of the CC chemokine family, is one of the key chemokines that regulate migration and tissue infiltration of monocytes/macrophages. Its role in the pathophysiology of several inflammatory diseases has been widely recognized, thus making MCP-1 a possible target for anti-inflammatory treatments. Curcumin (diferuloylmethane) is a natural polyphenol derived from the rhizomes of Curcuma Longa L. (turmeric). Anti-inflammatory action underlies numerous pharmacological effects of curcumin in the control and prevention of several diseases. The purpose of this review is to evaluate the effects of curcumin on the regulation of MCP-1 as a key mediator of chemotaxis and inflammation, and the biological consequences thereof. In vitro studies have shown that curcumin can decrease MCP-1 production in various cell lines. Animal studies have also revealed that curcumin can attenuate MCP-1 expression and improve a range of inflammatory diseases through multiple molecular targets and mechanisms of action. There is limited data from human clinical trials showing the decreasing effect of curcumin on MCP-1 concentrations and improvement of the course of inflammatory diseases. Most of the in vitro and animal studies confirm that curcumin exert its MCP-1-lowering and anti-inflammatory effects by down-regulating the mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway. As yet, there is limited data from human clinical trials showing the effect of curcumin on MCP-1 levels and improvement of the course of inflammatory diseases. More evidence, especially from human studies, is needed to better assess the effects of curcumin on circulating MCP-1 in different human diseases and the role of this modulatory effect in the putative anti-inflammatory properties of curcumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Monocyte chemoattractant protein 1 (MCP-1) in temporal arteritis and polymyalgia rheumatica

DEFF Research Database (Denmark)

Ellingsen, T; Elling, P; Olson, A

2000-01-01

was localised to the vessel wall in patients with TA. In TA, PMR, and healthy controls MCP-1 was quantified by enzyme linked immunosorbent assay (ELISA) in plasma. RESULTS: MCP-1 was localised to the majority of mononuclear cells, some smooth muscle cells, and giant cells in the arterial biopsy specimens from...

Thioredoxin reductase 1 upregulates MCP-1 release in human endothelial cells

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Liu, Zhen-Bo [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China); Shen, Xun, E-mail: shenxun@sun5.ibp.ac.cn [Institute of Biophysics, Chinese Academy of Sciences, and Graduate School of the Chinese Academy of Sciences, Beijing (China)

2009-09-04

To know if thioredoxin reductase 1 (TrxR1) plays a role in antioxidant defense mechanisms against atherosclerosis, effect of TrxR1 on expression/release of monocyte chemoattractant protein (MCP-1) was investigated in activated human endothelial-like EAhy926 cells. The MCP-1 release and expression, cellular generation of reactive oxygen species (ROS), nuclear translocation and DNA-binding activity of NF-{kappa}B subunit p65 were assayed in cells either overexpressing recombinant TrxR1 or having their endogenous TrxR1 knocked down. It was found that overexpression of TrxR1 enhanced, while knockdown of TrxR1 reduced MCP-1 release and expression. Upregulation of MCP-1 by TrxR1 was associated with increasing generation of intracellular ROS generation, enhanced nuclear translocation and DNA-binding activity of NF-{kappa}B. Assay using NF-{kappa}B reporter revealed that TrxR1 upregulated transcriptional activity of NF-{kappa}B. This study suggests that TrxR1 enhances ROS generation, NF-{kappa}B activity and subsequent MCP-1 expression in endothelial cells, and may promote rather than prevent vascular endothelium from forming atherosclerotic plaque.

MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner

International Nuclear Information System (INIS)

Miyamoto, Kana; Ninomiya, Ken; Sonoda, Koh-Hei; Miyauchi, Yoshiteru; Hoshi, Hiroko; Iwasaki, Ryotaro; Miyamoto, Hiroya

2009-01-01

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a critical role in the recruitment and activation of leukocytes. Here, we describe that multinuclear osteoclast formation was significantly inhibited in cells derived from MCP-1-deficient mice. MCP-1 has been implicated in the regulation of osteoclast cell-cell fusion; however defects of multinuclear osteoclast formation in the cells from mice deficient in DC-STAMP, a seven transmembrane receptor essential for osteoclast cell-cell fusion, was not rescued by recombinant MCP-1. The lack of MCP-1 in osteoclasts resulted in a down-regulation of DC-STAMP, NFATc1, and cathepsin K, all of which were highly expressed in normal osteoclasts, suggesting that osteoclast differentiation was inhibited in MCP-1-deficient cells. MCP-1 alone did not induce osteoclastogenesis, however, the inhibition of osteoclastogenesis in MCP-1-deficient cells was restored by addition of recombinant MCP-1, indicating that osteoclastogenesis was regulated in an autocrine/paracrine manner by MCP-1 under the stimulation of RANKL in osteoclasts.

Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia.

Science.gov (United States)

Chuang, Li-Pang; Chen, Ning-Hung; Lin, Yuling; Ko, Wen-Shan; Pang, Jong-Hwei S

2016-03-01

Obstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. Monocyte chemoattractant protein-1 (MCP-1), as a critical factor for monocyte infiltration, is known to play a role in the development of atherosclerosis. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the MCP-1 expression of monocytes. Peripheral blood was sampled from 61 adults enrolled for suspected OSA. RNA was prepared from the isolated monocytes for the analysis of MCP-1. The effect of in vitro intermittent hypoxia on the regulation and function of MCP-1 was investigated on THP-1 monocytic cells and human monocytes. The mRNA and secreted protein levels were investigated by RT/real-time PCR and enzyme-linked immunosorbent assay, respectively. Monocytic MCP-1 gene expression was found to be increased significantly in severe OSA patients. In vitro intermittent hypoxia was demonstrated to increase the mRNA and protein expression levels of MCP-1 dose- and time-dependently in THP-1 monocytic cells. The MCP-1 mRNA expression in monocytes isolated from OSA patient was induced to a much higher level compared to that from normal control. Pre-treatment with inhibitor for p42/44 MAPK or p38 MAPK suppressed the activation of MCP-1 expression by intermittent hypoxia. This is the first study to demonstrate the increase of MCP-1 gene expression in monocytes of severe OSA patients. In addition, monocytic MCP-1 gene expression can be induced under intermittent hypoxia.

Associations between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes.

Science.gov (United States)

Mansour, S G; Puthumana, J; Reese, P P; Hall, I E; Doshi, M D; Weng, F L; Schröppel, B; Thiessen-Philbrook, H; Bimali, M; Parikh, C R

2017-07-01

Existing methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help predict allograft outcomes. We conducted a sub-study of the multicenter prospective Deceased Donor Study cohort, which evaluated deceased kidney donors from five organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated GFR (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR. AKI occurred in 111 (9%) donors. Median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared to donors without AKI (1.35 [0.41-3.93] ng/ml vs. 0.32 [0.11-0.80] ng/ml, p<0.001). DGF occurred in 756 (31%) recipients, but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with higher 6-month eGFR in those without DGF [0.77 (0.10, 1.45) ml/min/1.73m 2 per doubling of uMCP1]. However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of about 2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR. Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.

The human MCP-2 gene (SCYA8): Cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2

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Van Coillie, E.; Fiten, P.; Van Damme, J.; Opdenakker, G. [Univ. of Leuven (Belgium)] [and others

1997-03-01

Monocyte chemotactic proteins (MCPs) form a subfamily of chemokines that recruit leukocytes to sites of inflammation and that may contribute to tumor-associated leukocyte infiltration and to the antiviral state against HIV infection. With the use of degenerate primers that were based on CC chemokine consensus sequences, the known MIP-1{alpha}/LD78{alpha}, MCP-1, and MCP-3 genes and the previously unidentified eotaxin and MCP-2 genes were isolated from a YAC contig from human chromosome 17q11.2. The amplified genomic MCP-2 fragment was used to isolate an MCP-2 cosmid from which the gene sequence was determined. The MCP-2 gene shares with the MCP-1 and MCP-3 genes a conserved intron-exon structure and a coding nucleotide sequence homology of 77%. By Northern blot analysis the 1.0-kb MCP-2 mRNA was predominantly detectable in the small intestine, peripheral blood, heart, placenta, lung, skeletal muscle, ovary, colon, spinal cord, pancreas, and thymus. Transcripts of 1.5 and 2.4 kb were found in the testis, the small intestine, and the colon. The isolation of the MCP-2 gene from the chemokine contig localized it on YAC clones of chromosome 17q11.2, which also contain the eotaxin, MCP-1, MCP-3, and NCC-1/MCP-4 genes. The combination of using degenerate primer PCR and YACs illustrates that novel genes can efficiently be isolated from gene cluster contigs with less redundancy and effort than the isolation of novel ESTs. 42 refs., 5 figs., 2 tabs.

Intermittent pneumatic leg compressions acutely upregulate VEGF and MCP-1 expression in skeletal muscle.

Science.gov (United States)

Roseguini, Bruno T; Mehmet Soylu, S; Whyte, Jeffrey J; Yang, H T; Newcomer, Sean; Laughlin, M Harold

2010-06-01

Application of intermittent pneumatic compressions (IPC) is an extensively used therapeutic strategy in vascular medicine, but the mechanisms by which this method works are unclear. We tested the hypothesis that acute application (150 min) of cyclic leg compressions in a rat model signals upregulation of angiogenic factors in skeletal muscle. To explore the impact of different pressures and frequency of compressions, we divided rats into four groups as follows: 120 mmHg (2 s inflation/2 s deflation), 200 mmHg (2 s/2 s), 120 mmHg (4 s/16 s), and control (no intervention). Blood flow and leg oxygenation (study 1) and the mRNA expression of angiogenic mediators in the rat tibialis anterior muscle (study 2) were assessed after a single session of IPC. In all three groups exposed to the intervention, a modest hyperemia (approximately 37% above baseline) between compressions and a slight, nonsignificant increase in leg oxygen consumption (approximately 30%) were observed during IPC. Compared with values in the control group, vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) mRNA increased significantly (P < 0.05) only in rats exposed to the higher frequency of compressions (2 s on/2 s off). Endothelial nitric oxide synthase, matrix metalloproteinase-2, and hypoxia-inducible factor-1alpha mRNA did not change significantly following the intervention. These findings show that IPC application augments the mRNA content of key angiogenic factors in skeletal muscle. Importantly, the magnitude of changes in mRNA expression appeared to be modulated by the frequency of compressions such that a higher frequency (15 cycles/min) evoked more robust changes in VEGF and MCP-1 compared with a lower frequency (3 cycles/min).

MCP1 haplotypes associated with protection from pulmonary tuberculosis

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Owusu-Dabo Ellis

2011-04-01

Full Text Available Abstract Background The monocyte chemoattractant protein 1 (MCP-1 is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB case-control study group, associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the MCP1 gene in order to determine causal variants or haplotypes genetically and functionally. Results A 14 base-pair deletion in the first MCP1 intron, int1del554-567, was strongly associated with protection against pulmonary TB (OR = 0.84, CI 0.77-0.92, Pcorrected = 0.00098. Compared to the wildtype combination, a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone (OR = 0.78, CI 0.69-0.87, Pnominal = 0.00002; adjusted Pglobal = 0.0028. In a luciferase reporter gene assay, a significant reduction of luciferase gene expression was observed in the two constructs carrying the MCP1 mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype (P = 0.02 and P = 0.006. The associated variants, in particular the haplotypes composed of these latter variants, result in decreased MCP-1 expression and a decreased risk of pulmonary TB. Conclusions In addition to the results of the previous study of the Ghanaian TB case-control sample, we have now identified the haplotype combination -2581G/-362C/int1del554-567 that mediates considerably stronger protection than does the MCP1 -362C allele alone (OR = 0.78, CI 0.69-0.87 vs OR = 0.83, CI 0.76-0.91. Our findings in both the genetic analysis and the reporter gene study further indicate a largely negligible role of the

Study on MCP-1 related to inflammation induced by biomaterials

International Nuclear Information System (INIS)

Ding Tingting; Sun Jiao; Zhang Ping

2009-01-01

The study of inflammation is important for understanding the reaction between biomaterials and the human body, in particular, the interaction between biomaterials and immune system. In the current study, rat macrophages were induced by multiple biomaterials with different biocompatibilities, including polyvinyl chloride (PVC) containing 8% of organic tin, a positive control material with cellular toxicity. Human umbilical vein endothelial cells (ECV-304), cultured with PRMI-1640, were detached from cells cultured with the supernatant of macrophages containing TNF-α and IL-1β because of stimulation by biomaterials. The cells were then treated with different biomaterials. Then both TNF-α and IL-1β in macrophages were detected by ELISA. Levels of monocyte chemoattractant protein-1 (MCP-1) were measured by RT-PCR. The results suggested that the expression of TNF-α and IL-1β was elevated by polytetrafluoroethylene (PTFE), polylactic-co-glycolic acid (PLGA) and American NPG alloy (p < 0.001). The level of MCP-1 cultured in supernatant of macrophages was higher than in PRMI-1640 with the same biomaterials. And the exposure to PTFE, PLGA and NPG resulted in the high expression of MCP-1 (p < 0.001) following cytokine stimulation. MCP-1 was also significantly expressed in β-tricalcium phosphate (β-TCP) and calcium phosphate cement samples (CPC) (p < 0.01). Thus, TNF-α, IL-1β and MCP-1 had played an important role in the immune reaction induced by biomaterials and there was a close relationship between the expression of cytokines and biomcompatibility of biomaterials. Furthermore, these data suggested that MCP-1 was regulated by TNF-α and IL-1β, and activated by both cytokines and biomaterials. The data further suggested that the expression of MCP-1 could be used as a marker to indicate the degree of immune reaction induced by biomaterials.

Stimulation of Alpha7 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Upregulation of MMP, MCP-1, and RANTES through Modulating ERK1/2/AP-1 Signaling Pathway in RAW264.7 and MOVAS Cells

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Liping Liu

2017-01-01

Full Text Available Vagus nerve stimulation through alpha7 nicotine acetylcholine receptors (α7-nAChR signaling had been demonstrated attenuation of inflammation. This study aimed to determine whether PNU-282987, a selective α7-nAChR agonist, affected activities of matrix metalloproteinase (MMP and inflammatory cytokines in nicotine-treatment RAW264.7 and MOVAS cells and to assess the underlying molecular mechanisms. RAW264.7 and MOVAS cells were treated with nicotine at different concentrations (0, 1, 10, and 100 ng/ml for 0–120 min. Nicotine markedly stimulated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2 and c-Jun in RAW264.7 cells. Pretreatment with U0126 significantly suppressed phosphorylation of ERK1/2 and further attenuated nicotine-induced activation of c-Jun and upregulation of MMP-2, MMP-9, monocyte chemotactic protein- (MCP- 1, and regulated upon activation normal T cell expressed and secreted (RANTES. Similarly, nicotine treatment also increased phosphorylation of c-Jun and expressions of MMP-2, MMP-9, MCP-1, and RANTES in MOVAS cells. When cells were pretreated with PNU-282987, nicotine-induced activations of ERK1/2 and c-Jun in RAW264.7 cells and c-Jun in MOVAS cells were effectively inhibited. Furthermore, nicotine-induced secretions of MMP-2, MMP-9, MCP-1, and RANTES were remarkably downregulated. Treatment with α7-nAChR agonist inhibits nicotine-induced upregulation of MMP and inflammatory cytokines through modulating ERK1/2/AP-1 signaling in RAW264.7 cells and AP-1 in MOVAS cells, providing a new therapeutic for abdominal aortic aneurysm.

Anti-inflammatory effect of resveratrol on TNF-α-induced MCP-1 expression in adipocytes

International Nuclear Information System (INIS)

Zhu Jian; Yong Wei; Wu Xiaohong; Yu Ying; Lv Jinghuan; Liu Cuiping; Mao Xiaodong; Zhu Yunxia; Xu Kuanfeng; Han Xiao; Liu Chao

2008-01-01

Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-α-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-α-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-α-induced MCP-1 transcription. Nuclear factor (NF)-κB was determined to play a major role in the TNF-α-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-κB complex and subsequently suppressed NF-κB transcriptional activity in TNF-α-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies

Combined effects of 1-methyl cyclopropene (1-MCP) and modified ...

African Journals Online (AJOL)

1-MCP-treated fruits delayed two different harvest maturity, persimmon fruits flesh firmness, and combination of 1-MCP with MAPA and MAPB reduced the ethylene production rate during storage. Treatment of 1-MCP improved storability of persimmon fruits more effectively than MAP storage. However, the results indicated ...

Radiation-Induced Thymidine Phosphorylase Upregulation in Rectal Cancer Is Mediated by Tumor-Associated Macrophages by Monocyte Chemoattractant Protein-1 From Cancer Cells

International Nuclear Information System (INIS)

Kim, Tae-Dong; Li Ge; Song, Kyoung-Sub; Kim, Jin-Man; Kim, Jun-Sang; Kim, Jong-Seok; Yun, Eun-Jin; Park, Jong-Il; Park, Hae-Duck; Hwang, Byung-Doo; Lim, Kyu; Yoon, Wan-Hee

2009-01-01

Purpose: The mechanisms of thymidine phosphorylase (TP) regulation induced by radiation therapy (XRT) in various tumors are poorly understood. We investigated the effect and mechanisms of preoperative XRT on TP expression in rectal cancer tissues. Methods and Materials: TP expression and CD68 and monocyte chemoattractant protein-1 (MCP-1) levels in rectal cancer tissues and cancer cell lines were evaluated before and after XRT in Western blotting, immunohistochemistry, enzyme-linked immunoassay, and reverse transcription-polymerase chain reaction studies. Isolated peripheral blood monocytes were used in the study of chemotaxis under the influence of MCP-1 released by irradiated colon cancer cells. Results: Expression of TP was significantly elevated by 9 Gy of XRT in most rectal cancer tissues but not by higher doses of XRT. In keeping with the close correlation of the increase in both TP expression and the number of tumor-associated macrophages (TAMs), anti-TP immunoreactivity was found in the CD68-positive TAMs and not the neoplastic cells. Expression of MCP-1 was increased in most cases after XRT, and this increase was strongly correlated with TP expression. However, this increase in MCP-1 expression occurred in tumor cells and not stromal cells. The XRT upregulated MCP-1 mRNA and also triggered the release of MCP-1 protein from cultured colon cancer cells. The supernatant of irradiated colon cancer cells showed strong chemotactic activity for monocyte migration, but this activity was completely abolished by neutralizing antibody. Conclusions: Use of XRT induces MCP-1 expression in cancer cells, which causes circulating monocytes to be recruited into TAMs, which then upregulate TP expression in rectal cancer tissues

An unusual protein kinase phosphorylates the chemotactic receptor of Dictystelium discoideum

International Nuclear Information System (INIS)

Meier, K.; Klein, C.

1988-01-01

The authors report the cAMP-dependent phosphorylation of the chemotactic receptor of Dictyostelium discoideum in partially purified plasma membranes. The protein kinase responsible for receptor phosphorylation is associated with this fraction and preferentially phosphorylates the ligand-occupied form of the receptor. 8-Azido[ 32 P]cAMP labeling of the cell surface has shown that the cAMP receptor exists in two forms. A 45-kDa protein is predominant on unstimulated cells. cAMP stimulation results in an increased receptor phosphorylation such that the receptor migrates on NaDodSO 4 /PAGE as a 47-kDa protein. Phosphorylation of the chemotactic receptor is not detected in membrane preparations unless cAMP is added to the incubation mixture. Only under those conditions is the phosphorylated 47-kDa form observed. The requirement for cAMP reflects the fact that the kinase involved preferentially uses the ligand-occupied receptor as a substrate. In vitro phosphorylation of the receptor does not involve tyrosine residues. The enzyme does not appear to be a cAMP- or cGMP-dependent protein kinase nor is it sensitive to guanine nucleotides, Ca 2+ /calmodulin, Ca 2+ /phospholipid, or EGTA. Similarities with the β-adrenergic receptor protein kinase are discussed

Expression and divalent cation binding properties of the novel chemotactic inflammatory protein psoriasin

DEFF Research Database (Denmark)

Vorum, H; Madsen, Peder; Rasmussen, H H

1996-01-01

Psoriasin is a novel chemotactic inflammatory protein that possesses weak similarity to the S100 family members of Ca(2+)-binding proteins, and that is highly up-regulated in hyperproliferative psoriatic keratinocytes. Here we have used the psoriasin cDNA to express recombinant human (rh) psorias...

MCP-1 in urine as biomarker of disease activity in Systemic Lupus Erythematosus.

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Barbado, Julia; Martin, Debora; Vega, Luisa; Almansa, Raquel; Gonçalves, Lisbeth; Nocito, Mercedes; Jimeno, Antonio; Ortiz de Lejarazu, Raúl; Bermejo-Martin, Jesus F

2012-11-01

Conventional clinical parameters are not sensitive or specific enough for detecting ongoing disease activity in the Systemic Lupus Erythematosus (SLE). Measurement of cytokines in urine is an encouraging approach to detection of early flares in this disease. Here we have profiled 27 different cytokines, chemokines and celular growth factors in the urine of 48 patients previously diagnosed of SLE as potential biomarkers of disease activity. Correlation analysis with Bonferroni correction showed that MCP-1 was the only immune mediator which levels in urine correlated directly with the SLE Disease Activity Index 2000 (SLEDAI-2K) score (correlation coefficient, p): MCP-1 (0.45,0.003). MCP-1 correlated inversely with levels of C3 complement protein in serum (-0.50,0.001). MCP-1 showed significant higher levels in patients with severe disease activity in comparison with those exhibiting mild activity. Levels of this chemokine were also higher in patients with severe disease activity in comparison with patients with inactive disease and healthy controls. Areas under receiver operating characteristic curves (AUROC) for detection of severe disease (SLEDAI⩾8) was as follows for MCP-1: [AUROC, (IC95%), p]: [0.81 (0.65-0.96) 0.003]. In addition, MCP-1 showed a good result in the AUROC analysis for detecting renal involvement [0.70 (0.52-0.87) 0.050]. When correlation analysis were repeated excluding those patients with active renal disease (n=14), levels of MCP-1 in urine kept on showing a significant positive association with SLEDAI-2K score. In conclusion, multiplex-based cytokine profiling in urine demonstrated the superiority of MCP-1 over a wide range of cytokines as biomarker of disease activity in SLE. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain.

Science.gov (United States)

Gao, Yong-Jing; Zhang, Ling; Samad, Omar Abdel; Suter, Marc R; Yasuhiko, Kawasaki; Xu, Zhen-Zhong; Park, Jong-Yeon; Lind, Anne-Li; Ma, Qiufu; Ji, Ru-Rong

2009-04-01

Our previous study showed that activation of c-jun-N-terminal kinase (JNK) in spinal astrocytes plays an important role in neuropathic pain sensitization. We further investigated how JNK regulates neuropathic pain. In cultured astrocytes, tumor necrosis factor alpha (TNF-alpha) transiently activated JNK via TNF receptor-1. Cytokine array indicated that the chemokine CCL2/MCP-1 (monocyte chemoattractant protein-1) was strongly induced by the TNF-alpha/JNK pathway. MCP-1 upregulation by TNF-alpha was dose dependently inhibited by the JNK inhibitors SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) and D-JNKI-1. Spinal injection of TNF-alpha produced JNK-dependent pain hypersensitivity and MCP-1 upregulation in the spinal cord. Furthermore, spinal nerve ligation (SNL) induced persistent neuropathic pain and MCP-1 upregulation in the spinal cord, and both were suppressed by D-JNKI-1. Remarkably, MCP-1 was primarily induced in spinal cord astrocytes after SNL. Spinal administration of MCP-1 neutralizing antibody attenuated neuropathic pain. Conversely, spinal application of MCP-1 induced heat hyperalgesia and phosphorylation of extracellular signal-regulated kinase in superficial spinal cord dorsal horn neurons, indicative of central sensitization (hyperactivity of dorsal horn neurons). Patch-clamp recordings in lamina II neurons of isolated spinal cord slices showed that MCP-1 not only enhanced spontaneous EPSCs but also potentiated NMDA- and AMPA-induced currents. Finally, the MCP-1 receptor CCR2 was expressed in neurons and some non-neuronal cells in the spinal cord. Together, we have revealed a previously unknown mechanism of MCP-1 induction and action. MCP-1 induction in astrocytes after JNK activation contributes to central sensitization and neuropathic pain facilitation by enhancing excitatory synaptic transmission. Inhibition of the JNK/MCP-1 pathway may provide a new therapy for neuropathic pain management.

Anti-inflammatory and anti-chemotactic effects of dietary flaxseed oil on CD8(+) T cell/adipocyte-mediated cross-talk.

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Monk, Jennifer M; Liddle, Danyelle M; Brown, Morgan J; Zarepoor, Leila; De Boer, Anna A; Ma, David W L; Power, Krista A; Robinson, Lindsay E

2016-03-01

CD8(+) T cell/adipocyte paracrine interactions represent a critical step in the development of the obese inflammatory phenotype that is disrupted by long-chain n-3 PUFA. Our objective was to determine the effect of flaxseed-derived n-3 PUFA (α-linolenic acid) on these paracrine interactions. C57BL/6 mice were fed 3.5% flaxseed oil (FX) + 3.5% corn oil diet w/w or an isocaloric 7% corn oil w/w control diet (CON) for 3 wk. 3T3-L1 adipocytes and purified primary splenic CD8(+) T cells were cocultured at an obese cellular ratio (10% CD8(+) T cells) and LPS-stimulated (10 ng/mL mimicking obese circulating endotoxin levels) for 24 h. FX cocultures reduced (i) secreted IL-6, tumor necrosis factor α (TNF-α), macrophage chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), and RANTES (regulated on activation, normal T cell expressed and secreted) levels; (ii) activation of inflammatory transcription factors NFκB (nuclear factor kappa-light-chain-enhancer of activated B cell) p65 and signal transducer and activator of transcription-3 (STAT3); and (iii) RAW264.7 macrophage chemotaxis versus CON (p ≤ 0.05). Coculture of pre-inflamed adipocytes (10 ng/mL LPS, 24 h prior to CD8(+) T-cell addition) resulted in reduced secretion of IL-6, IL-1β, MCP-1, MCP-3, MIP-1β, and RANTES in FX cocultures versus CON (p ≤ 0.05). FX exerts an anti-chemotactic and anti-inflammatory effect on CD8(+) T cell/adipocyte paracrine interactions (cross-talk), which has the potential to mitigate macrophage chemotaxis which drives components of the obese phenotype. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

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Murea Mariana

2012-11-01

Full Text Available Abstract Background Monocyte chemoattractant protein-1 (MCP-1 plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD were assessed in African Americans (AAs with type 2 diabetes (T2D. Methods Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR, estimated glomerular filtration rate (eGFR, and atherosclerotic calcified plaque (CP in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. Results Participants were 57% female, with mean ± SD (median age 55.6±9.5 (55.0 years, diabetes duration 10.3±8.2 (8.0 years, urine ACR 149.7±566.7 (14.0 mg/g, CKD-EPI eGFR 92.4±23.3 (92.0 ml/min/1.73m2, MCP-1 262.9±239.1 (224.4 pg/ml, coronary artery CP 280.1±633.8 (13.5, carotid artery CP 47.1±132.9 (0, and aorta CP 1616.0±2864.0 (319.0. Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04 and negatively associated with eGFR (parameter estimate −0.0003, P=0.001. MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. Conclusions Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.

Correlation of urinary monocyte chemo-attractant protein-1 with other parameters of renal injury in type-II diabetes mellitus

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Ibrahim Salwa

2008-01-01

Full Text Available Diabetic nephropathy (DN is the leading cause of end-stage renal disease in the western world. Increased number of interstitial macrophages has been observed in biopsies from patients with DN. Monocyte chemo-attractant protein-1 (MCP-1 is the strongest known chemo-tactic factor for monocytes and is upregulated in DN. We examined urinary levels of MCP-1 in patients with type-2 diabetes mellitus (DM to assess its possible correlation with other para-meters of renal injury. The urinary MCP-1 level was assessed in 75 patients with type-2 DM (25 patients each with no microalbuminuria, with macroalbuminuria and, with renal impairment and compared them with matched healthy control subjects. The HbA1c and estimated glomerular fil-tration rate (eGFR derived from the abbreviated Modification of Diet in Renal Disease (MDRD equation were examined in the study groups in relation to the urinary MCP-1. The urinary MCP-1 level was significantly higher in patients with micro and macroalbuminuria (167.41 ± 50.23 and 630.87 ± 318.10 ng/gm creatinine respectively as compared with normoalbuminuric patients and healthy controls (63.85 ± 21.15 and 61.50 ± 24.81 ng/gm creatinine, p< 0.001. MCP-1 correlated positively with urine albumin/creatinine ratio (ACR (r= 0.75, p< 0.001, HbA1c (r= 0.55, p< 0.001 and inversely with eGFR (r=-0.60, p< 0.001. Our findings suggest that hyperglycemia is associated with increased urinary levels of MCP-1 that is closely linked to renal damage as reflected by proteinuria and eGFR levels. Collectively, these findings suggest that MCP-1 is in-volved in the pathogenesis of diabetic nephropathy through its various stages.

The association between MCP-1, VEGF polymorphisms and their serum levels in patients with diabetic foot ulcer.

Science.gov (United States)

Li, Xiaolei

2018-06-01

The purpose of the present study was to investigate distribution of monocyte chemoattractant protein-1 (MCP-1) -2518A/G and vascular endothelial growth factor (VEGF) -634G/C polymorphisms in type 2 diabetes melitus patients (T2DM) presenting diabetic foot ulcer (DFU). Additionally, we evaluated the effects of these 2 polymorphisms on serum levels of MCP-1 and VEGF in the study population.Patients diagnosed with T2DM without or with DFU were recruited in the study. The distribution of MCP-1 -2518A/G and VEGF -634G/C polymorphisms was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the protein levels of MCP-1 and VEGF. The comparisons of protein levels in DFU patients were performed by student t test according to their genotypes.The frequencies of GG genotype and G allele of MCP-1 -2518A/G was increased in DFU patients, compared with T2DM patients (odds ratio [OR] = 2.60, 95% confidence interval [CI] = 1.23-5.50, P = .011 and OR = 1.72, 95% CI = 1.18-2.50, P = .005, respectively). Moreover, the increased frequency of GG was significantly associated with up-regulated MCP-1 level in DFU patients (P < .001). Analysis for VEGF -634G/C polymorphisms indicated that the prevalence of CC genotype and C allele of the polymorphisms was decreased in DFU patients, compared with T2DM patients (OR = 0.36, 95% CI = 0.17-0.77, P = .008 and OR = 0.63, 95% CI = 0.43-0.91, P = .015, respectively). DFU patients carrying CC genotype had a higher level of VEGF than those with other genotypes (P = .007).MCP-1 -2518A/G and VEGF -634G/C polymorphisms may involve in occurrence and progress of DFU through regulating transcription activity of the genes.

Deficiency of the Chemotactic Factor Inactivator in Human Sera with α1-Antitrypsin Deficiency

Science.gov (United States)

Ward, Peter A.; Talamo, Richard C.

1973-01-01

As revealed by appropriate fractionation procedures, human serum deficient in α1-antitrypsin (α1-AT) is also deficient in the naturally occurring chemotactic factor inactivator. These serum donors had severe pulmonary emphysema. Serum from patients with clinically similar pulmonary disease, but with presence of α1-AT in the serum, showed no such deficiency of the chemotactic factor inactivator. When normal human serum and α1-AT-deficient human sera are chemotactically activated by incubation with immune precipitates, substantially more chemotactic activity is generated in α1-AT-deficient serum. These data indicate that in α1-AT-deficient serum there is an imbalance in the generation and control of chemotactic factors. It is suggested that the theory regarding development of pulmonary emphysema in patients lacking the α1-antitrypsin in their serum should be modified to take into account a deficiency of the chemotactic factor inactivator. PMID:4683887

Impact of MCP-1 and CCR-2 gene polymorphisms on coronary artery disease susceptibility.

Science.gov (United States)

Lin, Hsiu-Ling; Ueng, Kwo-Chang; Hsieh, Yih-Shou; Chiang, Whei-Ling; Yang, Shun-Fa; Chu, Shu-Chen

2012-09-01

Coronary artery disease (CAD) was the second leading cause of death during the last 3 years in Taiwan. Smooth muscle cells, monocytes/macrophages, and endothelial cells produce monocyte chemoattractant protein-1 (MCP-1) within atherosclerotic plaques following binding to the chemokine receptor-2 (CCR-2). Previous studies have well-documented the association between MCP-1 expression and susceptibility to, or clinicopathological features, of CAD. This study investigated the relationships between MCP-1-2518A/G and CCR-2-V64I genetic polymorphisms and CAD in the Taiwanese population. A total of 608 subjects, including 392 non-CAD controls and 216 patients with CAD, were recruited and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to evaluate the effects of these two polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR = 1.629; 95 % CI = 1.003-2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006-2.270), had a higher risk of CAD as compared with AA genotypes. Results also revealed that subjects with at least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD. G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518G could be through effects on atrial fibrillation in CAD patients.

Crevicular and serum levels of monocyte chemoattractant protein-4 and high-sensitivity C-reactive protein in periodontal health and disease.

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Kumari, Minal; Pradeep, A R; Priyanka, N; Kalra, Nitish; Naik, Savitha B

2014-06-01

Chemokines are chemotactic cytokines that are involved in destruction of the periodontal structures. The aim of this study is to determine the presence of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival crevicular fluid (GCF) and serum in periodontal health and disease and to find a correlation between MCP-4 and hsCRP in GCF and serum. 40 subjects (20 males and 20 females) were selected and divided into three groups based on clinical parameters and radiologic parameters: Group 1 (10 healthy); Group 2 (15 gingivitis subjects) and Group 3 (15 chronic periodontitis subjects). The levels of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined by immunoturbidimetry method. The mean GCF and serum concentration of MCP-4 were the highest for group 3 followed by group 2 and least in group 1. Similarly, the mean hsCRP concentrations were highest for group 3 and least in group 1. Moreover, a significant positive correlation was found between serum and GCF MCP-4 and hsCRP levels and periodontal parameters. The levels of MCP-4 and hsCRP increased from healthy to periodontitis. It can be proposed that MCP-4 and hsCRP are the potential biomarkers of inflammation in periodontal health and disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

MCP-1 Levels are Associated with Cardiac Remodeling but not with Resistant Hypertension.

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Ritter, Alessandra Mileni Versuti; Faria, Ana Paula Cabral de; Sabbatini, Andrea; Corrêa, Nathalia Batista; Brunelli, Veridiana; Modolo, Rodrigo; Moreno, Heitor

2017-04-01

Hypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood. This study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects. We enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography. We found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population. Since MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata. A hipertensão arterial é um processo crônico de baixo grau inflamatório, associado com liberação de citocinas e desenvolvimento de lesão em órgãos-alvo. A desregulação dos níveis de proteína quimiotática de monócitos-1 (MCP-1) tem sido associada com elevação da press

Ethylene and 1-MCP regulate major volatile biosynthetic pathways in apple fruit.

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Yang, Xiaotang; Song, Jun; Du, Lina; Forney, Charles; Campbell-Palmer, Leslie; Fillmore, Sherry; Wismer, Paul; Zhang, Zhaoqi

2016-03-01

The effects of ethylene and 1-methylcyclopropene (1-MCP) on apple fruit volatile biosynthesis and gene expression were investigated. Statistical analysis identified 17 genes that changed significantly in response to ethylene and 1-MCP treatments. Genes encoding branched-chain amino acid aminotransferase (BCAT), aromatic amino acid aminotransferase (ArAT) and amino acid decarboxylases (AADC) were up-regulated during ripening and further enhanced by ethylene treatment. Genes related to fatty acid synthesis and metabolism, including acyl-carrier-proteins (ACPs), malonyl-CoA:ACP transacylase (MCAT), acyl-ACP-desaturase (ACPD), lipoxygenase (LOX), hydroperoxide lyase (HPL), alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC2), β-oxidation, acyl-CoA synthetase (ACS), enoyl-CoA hydratase (ECHD), acyl-CoA dehydrogenase (ACAD), and alcohol acyltransferases (AATs) also increased during ripening and in response to ethylene treatment. Allene oxide synthase (AOS), alcohol dehydrogenase 1 (ADH1), 3-ketoacyl-CoA thiolase and branched-chain amino acid aminotransferase 2 (BCAT2) decreased in ethylene-treated fruit. Treatment with 1-MCP and ethylene generally produced opposite effects on related genes, which provides evidence that regulation of these genes is ethylene dependent. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines

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Sulniute, Rima; Palmqvist, Py; Majster, Mirjam; Holm, Cecilia Koskinen; Zwicker, Stephanie; Clark, Reuben; Önell, Sebastian; Johansson, Ingegerd; Lerner, Ulf H.; Lundberg, Pernilla

2015-01-01

Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-κΒ pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in

How to prevent ripening blockage in 1-MCP-treated 'Conference' pears.

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Chiriboga, Maria-Angeles; Schotsmans, Wendy C; Larrigaudière, Christian; Dupille, Eve; Recasens, Inmaculada

2011-08-15

Some European pear varieties treated with 1-methylcyclopropene (1-MCP) often remain 'evergreen', meaning that their ripening process is blocked and does not resume after removal from cold storage. In this work this was confirmed also to be the case in 'Conference' pears. To reverse the blockage of ripening 1-MCP treatments combined with external exogenous ethylene were tested. 1-MCP treatment of 'Conference' pears is very effective in delaying ripening and, more specifically, softening. The same 1-MCP concentration in different experimental years caused a different response. The higher dose of 1-MCP (600 nL L⁻¹) always resulted in irreversible blockage of ripening, whereas the behaviour of fruit receiving a lower dose (300 nL L⁻¹) depended on the year, and this did not depend on maturity at harvest or on storage conditions. Simultaneous exposure to 1-MCP and exogenous ethylene significantly affected fruit ripening, allowing significant softening to occur but at a lower rate compared with control fruit. The application of exogenous ethylene and 1-MCP simultaneously after harvest permitted restoration of the ripening process after storage in 'Conference' pears, extending the possibility of marketing and consumption. Copyright © 2011 Society of Chemical Industry.

Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo.

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Marianne Pons

2011-02-01

Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly population. Debris (termed drusen below the retinal pigment epithelium (RPE have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV. The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1, pro-angiogenic vascular endothelial growth factor (VEGF and anti-angiogenic pigment epithelial derived factor (PEDF in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ, a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice.MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo.We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring angiogenesis might promote drusen accumulation and

Influência do 1-MCP na conservação pós-colheita de rosas cv. Vega Influence of 1-MCP on postharvest conservation of roses cv. Vega

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Júlia De Pietro

2010-10-01

Full Text Available Objetivou-se, neste trabalho, estudar aspectos da fisiologia pós-colheita de rosas cortadas cv. Vega, tratadas com diferentes concentrações de 1-metilcicloropropeno (1-MCP. O experimento foi conduzido em delineamento inteiramente casualizado, em esquema fatorial composto por dois fatores: quatro tratamentos pós-colheita e quatro datas de avaliação (0; 4; 8; 12 dias. As flores foram submetidas aos seguintes tratamentos: 1 Água destilada (controle; 2 1-MCP (100 ppb; 3 1-MCP (250 ppb; 4 1-MCP (500 ppb. Foram realizadas as seguintes avaliações: massa fresca, cor, turgescência, curvatura, taxa respiratória, conteúdo relativo de água, conteúdo de carboidratos solúveis, de redutores e de antocianina. Ao contrário do tratamento controle, todas as concentrações de 1-MCP foram eficientes para retardar a senescência das flores, porém, a concentração de 1-MCP a 500 ppb destacou-se pela melhor manutenção da qualidade, além de prolongar a vida decorativa das hastes até 19 dias.The objective of this work was to study aspects of postharvest physiology of cut roses cv. Vega, treated with different concentrations of 1-metilcloropropene (1-MCP. The experiment was conducted in a complete randomized design composed of two factors: four postharvest treatments and four dates of evaluation (0; 4; 8; 12 days. The following treatments were used: 1 distilled water; 2 1-metilciclopropeno (1-MCP 100 ppb; 3 1-MCP 250 ppb; 4 1-MCP 500 ppb. The following evaluations were made: fresh weight, color, turgor, curvature, respiration rate, relative water content, content of soluble carbohydrates, reducing and anthocyanin. Unlike treatment with distilled water, all concentrations of 1-MCP were effective in delaying the senescence of flowers; however, the concentration of 1-MCP at 500 ppb was highlighted by better maintenance of quality and extended decorate life stem up to 19 days.

Delayed brain ischemia tolerance induced by electroacupuncture pretreatment is mediated via MCP-induced protein 1

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2013-01-01

Background Emerging studies have demonstrated that pretreatment with electroacupuncture (EA) induces significant tolerance to focal cerebral ischemia. The present study seeks to determine the involvement of monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified novel modulator of inflammatory reactions, in the cerebral neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia and to elucidate the mechanisms of EA pretreatment-induced ischemic brain tolerance. Methods Twenty-four hours after the end of the last EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 minutes in male C57BL/6 mice and MCPIP1 knockout mice. Transcription and expression of MCPIP1 gene was monitored by qRT-PCR, Western blot and immunohistochemistry. The neurobehavioral scores, infarction volumes, proinflammatory cytokines and leukocyte infiltration in brain and NF-κB signaling were evaluated after ischemia/reperfusion. Results MCPIP1 protein and mRNA levels significantly increased specifically in mouse brain undergoing EA pretreatment. EA pretreatment significantly attenuated the infarct volume, neurological deficits, upregulation of proinflammatory cytokines and leukocyte infiltration in the brain of wild-type mice after MCAO compared with that of the non-EA group. MCPIP1-deficient mice failed to evoke EA pretreatment-induced tolerance compared with that of the control MCPIP1 knockout group without EA treatment. Furthermore, the activation of NF-κB signaling was significantly reduced in EA-pretreated wild-type mice after MCAO compared to that of the non-EA control group and MCPIP1-deficient mice failed to confer the EA pretreatment-induced inhibition of NF-κB signaling after MCAO. Conclusions Our data demonstrated that MCPIP1 deficiency caused significant lack of EA pretreatment-induced cerebral protective effects after MCAO compared with the control group and that MCPIP1 is

AOPPs Induce MCP-1 Expression by Increasing ROS-Mediated Activation of the NF-κB Pathway in Rat Mesangial Cells: Inhibition by Sesquiterpene Lactones

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Jian-Cheng Wang

2013-12-01

Full Text Available Background: Monocyte chemoattractant protein-1 (MCP-1 plays an important role in extracellular matrix accumulation through macrophage recruitment and activation in the development and progression of diabetic nephropathy. Therefore, this study examined whether advanced oxidation protein products (AOPPs are involved in nuclear factor-κB (NF-κB activation and MCP-1 mRNA and protein expression in mesangial cells (MCs and evaluated the effects of derivatives of sesquiterpene lactones (SLs on AOPP-induced renal damage. Methods: MCP-1 mRNA and protein expression in MCs were determined by quantitative real-time PCR and ELISA, respectively. The level of intracellular reactive oxygen species (ROS was determined by flow cytometry. The protein expression of tubulin, P47, NF-κB p65, phospho-NF-κB p65, IκB, phospho-IκB, IKKß and phospho-IKKß was evaluated by Western blot. Results: AOPPs caused oxidative stress in MCs and activated the NF-κB pathway by inducing IκBa phosphorylation and degradation. Inhibition of ROS by SOD (ROS inhibitor blocked the AOPP-mediated NF-κB pathway. Moreover, the inhibition of AOPP-induced overproduction of MCP-1 mRNA and protein was associated with inhibition of IκBa degradation by SLs. Conclusion: AOPPs induce MCP-1 expression by activating the ROS/NF-κB pathway and can be inhibited by SLs. These findings may provide a novel approach to treat inflammatory and immune renal diseases, including diabetic nephropathy.

MCP-1/CCR-2-double-deficiency severely impairs the migration of hematogenous inflammatory cells following transient cerebral ischemia in mice.

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Schuette-Nuetgen, Katharina; Strecker, Jan-Kolja; Minnerup, Jens; Ringelstein, E Bernd; Schilling, Matthias

2012-02-01

Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR-2 are known to play a major role in inflammatory responses after cerebral ischemia. Mice deficient in either MCP-1 or CCR-2 have been reported to develop smaller infarct sizes and show decreased numbers of infiltrating inflammatory cells. In the present study we used green fluorescent protein (GFP) transgenic mice to investigate the effect of MCP-1/CCR-2-double deficiency on the recruitment of inflammatory cells in a model of both, mild and severe cerebral ischemia. We show that MCP-1/CCR-2-double deficiency virtually entirely abrogates the recruitment of hematogenous macrophages and significantly reduces neutrophil migration to the ischemic brain 4 and 7 days following focal cerebral ischemia. This argues for a predominant role of the MCP-1/CCR-2 axis in chemotaxis of monocytes despite a wide redundancy in the chemokine-receptor-system. Chemokine analysis revealed that even candidates known to be involved in monocyte and neutrophil recruitment like MIP-1α, CXCL-1, C5a, G-CSF and GM-CSF showed a reduced and delayed or even a lack of relevant compensatory response in MCP-1(-/-)/CCR-2(-/-)-mice. Solely, chemokine receptor 5 (CCR-5) increased early in both, but rose above wildtype levels at day 7 in MCP-1(-/-)/CCR-2(-/-)-animals, which might explain the higher number of activated microglial cells compared to control mice. Our study was, however, not powered to investigate infarct volumes. Further studies are needed to clarify whether these mechanisms of inflammatory cell recruitment might be essential for early infarct development and final infarct size and to evaluate potential therapeutic implications. Copyright © 2011 Elsevier Inc. All rights reserved.

The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

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Yuan-kun Xu

Full Text Available BACKGROUND: Osteoarthritis (OA is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1 and receptor chemokine (C-C motif receptor 2 (CCR2 in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001 and the expression of MMP-13 also increased (P < 0.05. MCP-1 stimulation also induced (or enhanced the apoptosis of OA chondrocytes (P < 0.05. Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13 in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA model CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis

Analysis of the temporal expression of chemokines and chemokine receptors during experimental granulomatous inflammation: role and expression of MIP-1α and MCP-1

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Carollo, Maria; Hogaboam, Cory M; Kunkel, Stephen L; Delaney, Stephen; Christie, Mark I; Perretti, Mauro

2001-01-01

Chemokine expression and function was monitored in an experimental model of granulomatous tissue formation after injection of croton oil in complete Freund's adjuvant (CO/CFA) into mouse dorsal air-pouches up to 28 days. In the first week, mast cell degranulation and leukocyte influx (mononuclear cell, MNC, and polymorphonuclear cell, PMN) were associated with CXCR2, KC and macrophage inflammatory protein (MIP)-2 mRNA expression, as determined by TaqMan® reverse transcriptase-polymerase chain reaction. KC (∼400 pg mg protein−1, n=12) and MIP-2 (∼800 pg mg protein−1, n=12) proteins peaked at day 7, together with myeloperoxidase (MPO) activity. Highest MIP-1α (>1 ng mg protein−1, n=12) levels were measured at day 3. After day 7, a gradual increase in CCR2 and CCR5 mRNA, monocyte chemoattractant protein (MCP)-1 mRNA and protein expression was measured. MCP-1 protein peaked at day 21 (∼150 pg mg protein−1, n=12) and was predominantly expressed by mast cells. A gradual increase in N-acetyl-β-D-glucosaminidase (NAG) activity (maximal at 28 days) was also measured. An antiserum against MIP-1α did not modify the inflammatory response measured at day 7 (except for a 50% reduction in MIP-1α levels), but provoked a significant increase in MPO, NAG and MCP-1 levels as measured at day 21 (n=6, Pvalues (n=8, P<0.05). In conclusion, we have shown that CO/CFA initiates a complex inflammatory reaction in which initial expression of MIP-1α serves a protective role whereas delayed expression of MCP-1 seems to have a genuine pro-inflammatory role. PMID:11704636

Vascular endothelial growth factor (VEGF and monocyte chemoattractant protein (MCP-1 levels unaltered in symptomatic atherosclerotic carotid plaque patients from North India

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Dheeraj eKhurana

2013-04-01

Full Text Available We aimed to identify the role of vascular endothelial growth factor(VEGF and monocyte chemoattractant protein(MCP-1 as a serum biomarker of symptomatic carotid atherosclerotic plaque in North Indian population. Individuals with symptomatic carotid atherosclerotic plaque have high risk of ischemic stroke. Previous studies from western countries have shown an association between VEGF and MCP-1 levels and the incidence of ischemic stroke. In this study, venous blood from 110 human subjects was collected, 57 blood samples of which were obtained from patients with carotid plaques, 38 neurological controls without carotid plaques and another 15 healthy controls who had no history of serious illness. Serum VEGF and MCP-1 levels were measured using commercially available enzyme-linked immunosorbent assay(ELISA. We also correlated the data clinically and carried out risk factor analysis based on the detailed questionnaire obtained from each patient. For risk factor analysis, a total of 70 symptomatic carotid plaque cases and equal number of age and sex matched healthy controls were analyzed. We found that serum VEGF levels in carotid plaque patients did not show any significant change when compared to either of the controls. Similarly, there was no significant upregulation of monocyte chemoattractant protein-1 in the serum of these patients. The risk factor analysis revealed that hypertension, diabetes, and physical inactivity were the main correlates of carotid atherosclerosis(p<0.05. Prevalence of patients was higher residing in urban areas as compared to rural region. We also found that patients coming from mountaineer region were relatively less vulnerable to cerebral atherosclerosis as compared to the ones residing at plain region. We conclude that the pathogenesis of carotid plaques may progress independent of these inflammatory molecules. In parallel, risk factor analysis indicates hypertension, diabetes and sedentary lifestyle as the most

Nuclear NF-κB p65 in peripheral blood mononuclear cells correlates with urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.

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Bin Yi

Full Text Available AIMS: To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. METHODS: According to their urinary albumin-to-creatinine ratio (uACR, 107 patients with type 2 diabetes (eGFR >60 ml/min were divided into normal albuminuria group (DN0 group, 38 cases, microalbuminuria group (DN1 group, 38 cases, and macroalbuminuria group (DN2 group, 31 cases, compared with matched healthy normal control group (NC group, 30 cases. Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS: Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION: Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

Ação do 1-metilciclopropeno (1-MCP na vida de prateleira da banana 'maçã' Action of 1-methylcyclopropene (1-MCP on shelf life of 'apple' banana

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Ana Carla Marques Pinheiro

2005-04-01

Full Text Available Objetivou-se avaliar o efeito do 1-metilciclopropeno (1-MCP, em diferentes concentrações, sobre a vida pós-colheita e sob as variáveis associadas aos atributos de qualidade de banana 'Maçã'. Frutos verde-maturos foram submetidos a cinco concentrações de 1-MCP (0; 50; 100; 150 e 200 etaL.L-1, por 12 horas, e foram analisados durante o amadurecimento sob condição ambiente (20±1ºC e 80±5% UR. O tratamento com 50 etaL.L-1 de 1-MCP atrasou o início do amadurecimento das bananas em aproximadamente 8 dias, baseando-se nas primeiras mudanças de coloração da casca, enquanto os tratamentos 100; 150 e 200 etaL.L-1 atrasaram-no em aproximadamente 10 dias. Observou-se, durante o amadurecimento, o amaciamento dos frutos, associado à conversão de amido em açúcares e ao aumento na solubilização péctica e na atividade da pectinametilesterase (PME e poligalacturonase (PG. A aplicação de 50 etaL.L-1de 1-MCP é a mais adequada por promover a extensão da vida de prateleira de bananas 'Maçã', preservando sua qualidade com base nas análises de açúcares solúveis totais, pectinas total e solúvel, firmeza e aparência externa ao final do armazenamento.The objective of this work was to evaluate the influence of the 1-MCP, at different concentrations, on quality and shelf life of 'Apple' banana. Green mature fruits were submitted to five concentrations of 1-MCP (0, 50, 100, 150 and 200 etaL.L-1, for 12 hours and analyzed during the ripening at room temperature (20ºC ± 1 and 80% ± 5 RH . The 1-MCP at 50 etaL.L-1 delayed, in 8 days, the begining of the ripening, based in the first changes of peel color, whereas 100, 150 and 200 etaL.L-1 treatments delayed the begining of the ripening in 10 days, in comparison to the control. The softening of the fruits, associated to the conversion of starch in sugar and the increasing in the pectic solubilization and activity of pectinmethylsterase and polygalacturonase, was observed during the ripening

Study of the effects of 1-MCP to blueberry under cold storage

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Tao, Shenchen; Chu, Huailiang; Chen, Xiaomin; Yuan, Huwei; Qiu, Lingling; Zhao, Liang; Yan, Daoliang; Zheng, Bingsong

2017-04-01

Blueberry is one of the thinnest exocarp fruits in the world, which is difficult to keep fresh due to the special structure of its skin. 1-Methlcyclopropene (1-MCP) is able to combine with ethylene(ETH) receptor. In this study we investigated the effect of 1-MCP on rotting rate, weight loss ratio, soluble sugar content, titratable acid content, antioxidant enzyme activities and malondialdehyde (MDA) content in blueberry (Vaccinium corymbosun ‘O Neal’ and ‘North Road’) under cold storage. 1-MCP reduced the rotting rate, weight loss ratio and MDA content, while keeping high-leveled stability in antioxidant enzyme activities, soluble sugar content and titratable acid content. These results showed the role of 1-MCP in alleviating the negative effects of blueberry and suggested that 1-MCP could be used as a preservative for keeping thin exocarp fruit in fresh.

The host response to the probiotic Escherichia coli strain Nissle 1917: Specific up-regulation of the proinflammatory chemokine MCP-1

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Ukena Sya N

2005-12-01

Full Text Available Abstract Background The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells. Methods Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA to detect secretion of corresponding proteins. Results Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1, macrophage inflammatory protein-2 alpha (MIP-2α and macrophage inflammatory protein-2 beta (MIP-2β was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2α mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue. Conclusion Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.

Associations Between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes

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S.G. Mansour

2017-07-01

Discussion: Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.

Pós colheita de bananas-maçã submetidas ao 1-MCP e armazenadas á temperatura ambiente Postharvest of 'apple' banana submetted to 1-MCP and storage in room temperature

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Ana Carla Marque Pinheiro

2006-04-01

Full Text Available Bananas da cultivar Maçã foram adquiridas no estádio dois de coloração da casca (verde maturos e submetidas à ação de 1-MCP. O 1-MCP foi aplicado por 12 horas nas seguintes concentrações: 0 (controle, 50, 100, 150, 200 hL.L-1. Após aplicação, os frutos foram armazenados à temperatura ambiente (temperatura média 20ºC ± 1 e umidade relativa 80% ± 5 e avaliados à medida que atingiam os graus 3, 5 e 7 de coloração da casca. O tratamento com 1-MCP atrasou o início do amadurecimento de bananas-maçã armazenadas sob temperatura ambiente, baseado nas primeiras mudanças de coloração da casca. A aplicação de 1-MCP em bananas-maçã, ditou maiores valores de perda de massa e relação polpa/casca (nos graus 5 e 7 de coloração da casca. O 1-MCP, nas doses 100, 150 e 200 hL.L-1 de 1-MCP promoveu desverdecimento desuniforme e tonalidade avermelhada na casca. O tratamento 50 hL.L-1 de 1-MCP é o mais adequado, por promover a extensão da vida pós-colheita de bananas-maçã da cultivar armazenadas sob temperatura ambiente sem afetar a coloração da casca dos frutos, apresentando qualidade, baseando-se na cor da casca, firmeza, acidez titulável, pH e sólidos solúveis, semelhante ao controle.Mature green 'Apple' bananas were submitted to five concentrations of 1-MCP (0, 50, 100, 150 and 200 hL.L-1 for 12 hours. After treatment, the fruits were stored at room temperature (20ºC ± 1 and 80% ± 5 RH and analyzed at 3,5 and 7 color degree of peel. The treatment with 1-MCP delayed the start of the ripening based in the first changes of peel color. The treatment of 'Apple' bananas with 1-MCP promoted higher values of mass loss and pulp/peel ratio (5 and 7 degrees of color peel. The fruits treated with 100, 150 and 200 nL.L-1 of 1-MCP showed heterogeneous degreening and development of red color on the peel. 1-MCP at 50 nL.L-1 was the most appropriated treatment for promoting the extension of postharvest life of 'Apple' bananas stored

VIDA COMERCIAL DE PITAHAYA AMARILLA TRATADA CON 1-MCP

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LILIANA SERNA-COCK

Full Text Available 1-metilciclopropeno (1-MCP, un inhibidor del etileno, ha sido utilizado para extender la vida comercial de diferentes frutas. El objetivo de este trabajo fue evaluar el efecto de la aplicación de soluciones acuosas de 10, 100 y 200 gL-1 de 1-MCP, con tiempos de exposición de 1, 5 y 10 minutos, sobre la vida comercial de pitahaya amarilla en estado de madurez 4. Durante 15 días de almacenamiento (25 ± 2°C y 75% de humedad relativa, se evaluaron cambios físicos como la pérdida de peso y la aparición de pardeamiento; y se midieron cambios químicos como sólidos solubles, pH, acidez e índice de madurez. Se presentaron diferencias significativas entre los tratamientos. Los resultados demostraron que aplicaciones de 200 gL-1 de 1-MCP durante 10 minutos prolongó por tres días, la vida comercial de la pitahaya amarilla, y redujo cambios en los sólidos solubles y la acidez

Effect of 1-methylcyclopropene (1- MCP) treatment on antioxidant ...

African Journals Online (AJOL)

ajl2

2013-02-13

Feb 13, 2013 ... of active oxygen-related metabolism of post-harvest Japanese apricot. The results ... a high content of vitamin C (ascorbic acid) and retarding the decrease ..... components analysis of the nfluence of 1-MCP and salicylic acid.

Atraso do amadurecimento de banana 'Maçã' pelo 1-MCP, aplicado previamente à refrigeração Ripening delay of 'Apple' banana submitted to 1-MCP, prevoiously applied to refrigeration

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Gustavo Costa Almeida

2006-08-01

Full Text Available O objetivo deste trabalho foi avaliar o efeito de diferentes períodos de exposição da banana 'Maçã' a 50 ppb de 1-MCP (0; 3; 6; 9; 12 e 24 horas sobre sua vida pós-colheita e qualidade. Após exposição ao 1-MCP, os frutos verde-maturos foram armazenados por 30 dias em câmaras com temperatura de 13ºC ± 0,5 e umidade relativa de 95%. Em seguida, as bananas foram armazenadas à temperatura de 20ºC ± 1, até amarelecimento completo da casca. A exposição de banana 'Maçã' a 50 ppb de 1-MCP, por 9 horas, retardou em 7 dias o seu amadurecimento, em comparação a frutos não expostos ao 1-MCP, após 30 dias de armazenamento refrigerado (13ºC, sem prejuízos à sua aparência e composição química. A exposição de banana 'Maçã' a 50 ppb de 1-MCP, por 3 e 6 horas, não estendeu sua vida pós-colheita, tampouco alterou sua composição química. Embora a exposição de banana 'Maçã' a 50 ppb de 1-MCP, por 12 e 24 horas, tenha retardado o seu amadurecimento, promoveu alterações indesejáveis na casca do fruto. Logo, a aplicação de 50 ppb de 1-MCP, por 9 horas, antes da refrigeração, constitui-se numa alternativa viável para prolongar o período de comercialização da banana.The aim of this work was to evaluate 'Apple' banana different periods exposure effect to 50 ppb of 1-MCP (0, 3, 6, 9 and 24 hours on its postharvest life and quality. Mature-green fruits were stored for 30 days in chambers at 13ºC + 0,5 and relative humidity 95%, after exposure to 1-MCP. Then, the bananas were stored at 20ºC + 1 until peel complete yellowing. 'Apple' banana to 50 ppb of 1-MCP exposure during 9 hours delayed in seven days the fruit ripening, comparing to fruit control, after 30 days of cool storage (13ºC, without changing its appearance and chemical composition. The exposure of 'Apple' banana to 50 ppb of 1-MCP for 3 and 6 hours did not extend its postharvest life; neither changed its chemical composition. Although the exposure of

Rhizoma coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFB-Dependent Pathway

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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.

Expression of EMAP-II in the rat dental follicle and its potential role in tooth eruption

Science.gov (United States)

Liu, Dawen; Wise, Gary E.

2008-01-01

Endothelial monocyte-activating polypeptide II (EMAP-II) is an inflammatory cytokine with chemotactic activity. Because the dental follicle (DF) recruits mononuclear cells (osteoclast precursors) to promote the osteoclastogenesis needed for tooth eruption, it was the aim of this study to determine if EMAP-II may contribute to this recruitment. Using a DNA microarray, EMAP-II was found to be highly expressed in vivo in the DFs of day 1 to day 11 postnatal rats, with its expression elevated at days 1 and 3. Using a siRNA to knock down EMAP-II expression also resulted in a reduction in expression of CSF-1 and MCP-1 in the DF cells. Addition of EMAP-II protein to the DF cells partially restored the expression of CSF-1 and MCP-1. In chemotaxis assays using either conditioned medium of the DF cells with anti-EMAP-II antibody added or conditioned medium of DF cells with EMAP-II knocked down by siRNA, migration indexes of bone marrow mononuclear cells were significantly reduced. These results suggest that EMAP-II is another chemotactic molecule in the dental follicle involved in recruitment of mononuclear cells, and that EMAP-II may exert its chemotactic function directly by recruiting mononuclear cells and indirectly by enhancing the expression of other chemotactic molecules (CSF-1 and MCP-1). PMID:18705801

RETARDAMENTO DA MATURAÇÃO DE MAÇÃS 'FUJI' PELO TRATAMENTO COM 1-MCP E MANEJO DA TEMPERATURA DELAYING 'FUJI' APPLE RIPENING BY 1-MCP TREATMENT AND MANAGEMENT OF STORAGE TEMPERATURE

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LUIZ CARLOS ARGENTA

2001-08-01

Full Text Available Maçãs cv. Fuji foram tratadas com 42 mimol·m-3 de 1-metilciclopropeno (1-MCP por 24 h a 20°C, um dia após a colheita, e então armazenadas a 0; 10 ou 20ºC por 70 dias. Tratamento com 1-MCP efetivamente retardou a maturação de maçãs 'Fuji'. 1-MCP reduziu a taxa respiratória dos frutos mantidos a 10 e 20ºC e inibiu a produção de etileno dos frutos mantidos nas três temperaturas de armazenagem. Frutos tratados com 1-MCP e armazenados a 20ºC exibiram taxas respiratórias similares ou inferiores àquelas de frutos-controle armazenados a 10ºC. Quando armazenados a 10 ou 20ºC, frutos tratados com 1-MCP preservaram mais a firmeza da polpa e a acidez titulável e exibiram menor amarelecimento da epiderme que frutos-controle. Entretanto, não houve benefícios significativos do tratamento 1-MCP sobre a conservação da qualidade dos frutos armazenados a 0ºC no período de 70 dias após a colheita. Os resultados indicam que o tratamento com 1-MCP pode ser uma estratégia para o aumento da conservação de maçãs cv. Fuji durante o transporte e a distribuição sob 10 ou 20ºC. O prolongamento da armazenagem a 20ºC por período superior a 40 dias pode ser limitado pelo murchamento dos frutos e desenvolvimento de podridões.'Fuji' apples were treated with 42 mumol·m-3 of 1-methylcyclopropene (1-MCP for 24 h at 20°C then stored at 0, 10 or 20 ºC for 70 days. MCP treatment reduced respiration on fruit held at 10 and 20 ºC and inhibited ethylene production regardless of storage temperature. Treated fruits held at 20ºC presented respiration rate similar to those of untreated fruits held at 10ºC. For fruit held at 10 or 20ºC, MCP treatment inhibited softening, loss of acidity and color changes on fruit surface. However, there was no considerable benefit of 1-MCP treatment on maintenance of fruit quality during short-term (70 days and storage at 0ºC. Results indicated that 1-MCP is an effective mean to delay ripening and to retain

1-MCP pretreatment prevents bud and flower abscission in Dendrobium orchids

NARCIS (Netherlands)

Uthaichay, N.; Ketsa, S.; Doorn, van W.G.

2007-01-01

Dendrobium orchid inflorescences were treated for 4 h at 25 °C with or without 100¿500 nl/l 1-MCP and were then placed in water at 25 °C to follow abscission. In controls, depending on the experiment, 20¿80% of the floral buds and 0¿20% of the open flowers abscised within 1 week. The 1-MCP

Aplicação de 1-MCP em caqui 'quioto' armazenado sob refrigeração e atmosfera controlada Effect of 1-MCP applied at different times during cold and Ca storage

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Auri Brackmann

2003-04-01

Full Text Available O objetivo deste trabalho foi de avaliar o efeito do 1-MCP aplicado em diferentes épocas durante o armazenamento refrigerado (AR e em atmosfera controlada (AC sobre a qualidade do caqui cv. Quioto. O delineamento experimental utilizado foi o inteiramente casualizado, com quatro repetições de 30 frutos, e os tratamentos foram os seguintes: armazenamento refrigerado (AR; armazenamento refrigerado(AR + 1-MCP (1000ppb no início do armazenamento; armazenamento refrigerado(AR +1-MCP (1000ppb no final do armazenamento; armazenamento em atmosfera controlada (AC com 1kPa de O2 e AC 5kPa de CO2 e AC com 1kPa de O2 e 5kPa de CO2 + 1-MCP no fim do armazenamento, após 2 meses de armazenamento a -0,5ºC mais 5 dias de exposição dos frutos a 10ºC e 3 dias a 20ºC. No armazenamento refrigerado, o 1-MCP, aplicado tanto no início do armazenamento como no final, proporcionou maior firmeza de polpa. Para os parâmetros: sólidos solúveis totais, podridão e escurecimento da película, não houve diferença estatística entre os tratamentos. Conclui-se que a aplicação de 1-MCP, tanto no início como no final do armazenamento mantém elevada a firmeza de polpa.The objective of this work was to evaluate the effect of 1-MCP applied at different period during the cold storage (CS and in controlled atmosphere (CA on the quality of 'Quioto'. Persimmon. The experimental design was completely randomized with four replications of 30 fruits and the tested treatments were: cold storage (CS, cold storage + 1-MCP (1000ppb in the beginning of the storage, cold storage + 1-MCP (1000ppb in the end of the storage period; storage in controlled atmosphere (CA with 1kPa of O2 and 5kPa of CO2 and 1kPa of O2 and 5kPa of CO2 + 1-MCP in the end of the storage, after 2 months of storage at -0.5ºC, plus 5 days at 10ºC and 3 days at 20ºC. In the cooled storage, the 1-MCP, applied as in the beginning of the storage as in the end of the storage, provided greater pulp firmness

Direct and indirect radioiodination of protein: comparative study of chemotactic peptide labeling

International Nuclear Information System (INIS)

Lavinas, Tatiana

2004-01-01

The development of simple methods for protein radioiodination have stimulated the use of radioiodinated peptides in vivo. There are two basic methods for labeling proteins with radioiodine: direct labeling, reaction of an electrophilic radioiodine with functional activated groups on protein, like the phenol ring in the tyrosine residue, and the conjugation of a previously radioiodinated molecule to the protein, referred as indirect method. The great problem related to the direct radioiodination of proteins is the in vivo dehalogenation. This problem can be minimized if a non-phenolic prosthetic group is used in the indirect radioiodination of the peptide. The ATE prosthetic group, N-succinimidyl 3-(tri-n-butylstannyl) benzoate, when radioiodinated by electrophilic iododestannilation produces N-succinimidyl 3-[ 123 l/ 131 l] iodine benzoate (SIB) that is subsequently conjugated to the protein by the acylation of the lysine group. There are many radiopharmaceuticals employed in scintigraphic images of infection and inflammation used with some limitations. These limitations stimulated the improvement of a new class of radiopharmaceuticals, the receptor-specific related labeled peptides, as the mediators of the inflammatory response, that presents high affinity by receptors expressed in the inflammation process, and fast clearance from blood and non-target tissues. One of these molecules is the synthetic chemotactic peptide fNleLFNIeYK that presents potent chemotaxis for leukocytes, with high affinity by the receptors presented in polymorphonuclear leukocytes and mononuclear phagocytes. The objective of this work included the synthesis of ATE prosthetic group and comparative radioiodination of the chemotactic peptide fNleLFNIeYK by direct and indirect methods, with radiochemical purity determination and evaluation of in vivo and in vitro stability of the compounds. This work presented an original contribution in the comparative biological distribution studies of the

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

Correlation of serum MCP-1 and VE-cadherin levels with neural function and carotid atherosclerosis in patients with acute cerebral infarction

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Yan-Bing Xi

2017-05-01

Full Text Available Objective: To study the correlation of serum monocyte chemoattractant protein-1 (MCP-1 and vascular endothelial cadherin (VE-cadherin levels with neural function and carotid atherosclerosis in patients with acute cerebral infarction. Methods: A total of 78 patients who were diagnosed with acute cerebral infarction in our hospital between May 2013 and August 2016 were selected as pathological group, and 80 healthy volunteers who received physical examination in our hospital during the same period were selected as control group. Serum was collected to determine the levels of MCP-1, VE-cadherin, nerve injury molecules, inflammatory mediators, proteases and their hydrolysate. Results: Serum MCP-1, VE-cadherin, NGB, NSE, S100β, HMGB-1, sCD40L, YKL-40, visfatin, CatK, MMP9 and ICTP levels of pathological group were significantly higher than those of control group; serum MCP-1 and VE-cadherin levels of pathological group were positively correlated with NGB, NSE, S100β, HMGB-1, sCD40L, YKL-40, visfatin, CatK, MMP9 and ICTP levels. Conclusion: Serum MCP-1 and VE-cadherin levels abnormally increase in patients with acute cerebral infarction, and are closely related to the nerve injury and atherosclerosis process.

EFECTO DEL 1-METIL-CICLOPROPENO (1-MCP EN LA MADURACIÓN DE BANANO

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Kattia Chang-Yuen

2005-01-01

Full Text Available Se evaluó la eficacia del 1-metil-ciclopropeno (1-MCP en la maduración del banano (Musa sp Cavendish, aplicado después del empaque en fruta para el mercado de EE.UU. y Europa. Se utilizó fruta de 3 diferentes compañías bananeras; la fruta fue expuesta a 0, 20 y 30 nl l-1 de 1-MCP, por 24 h. Posteriormente, fue sometida a simulación de transporte, según el mercado de destino (7 días EE.UU. y 15 días Europa. Finalizada la simulación se indujo el proceso de maduración con etileno. Las evaluaciones se realizaron cada 2 días, e incluyeron análisis de calidad externa (enfermedades poscosecha y desarrollo de color externo de la cáscara y de calidad interna (oBrix, firmeza, porcentaje de acidez titulable y tasa de produc ción de CO2. Una aplicación de 30 nl l-1 de 1-MCP, generó una ganancia de más de 4 días de vida de anaquel por encima de la fruta control.La apariencia externa y la calidad interna de la fruta no se vio afectada de forma negativa por la exposición al 1-MCP, aunque se recomienda realizar pruebas sensoriales con consumidores en los mercados de destino.

Activation of farnesoid X receptor downregulates monocyte chemoattractant protein-1 in murine macrophage

Energy Technology Data Exchange (ETDEWEB)

Li, Liangpeng; Zhang, Qian; Peng, Jiahe; Jiang, Chanjui; Zhang, Yan; Shen, Lili; Dong, Jinyu; Wang, Yongchao; Jiang, Yu, E-mail: yujiang0207@163.com

2015-11-27

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, which plays important roles in bile acids/lipid homeostasis and inflammation. Monocyte chemoattractant protein-1 (MCP-1) contributes to macrophage infiltration into body tissues during inflammation. Here we investigated whether FXR can regulate MCP-1 expression in murine macrophage. FXR activation down regulate MCP-1 mRNA and protein levels in ANA-1 and Raw264.7 cells. Luciferase reporter assay, Gel shift and Chromatin immunoprecipitation assays have revealed that the activated FXR bind to the FXR element located in −738 bp ∼  −723 bp in MCP-1 promoter. These results suggested that FXR may serve as a novel target for regulating MCP-1 levels for the inflammation related diseases therapies. - Highlights: • FXR is expressed in murine macrophage cell line. • FXR down regulates MCP-1 expression. • FXR binds to the DR4 in MCP-1 promoter.

Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

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Kazuko Ino

Full Text Available Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP(+CD45(- cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4. Because the vast majority of EGFP(+CD45(- cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs. EGFP(+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1 and angiotensin II (Ang II increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2 and Ang II type 1 receptor (AT1R, were expressed on Ly6C(high monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+F4/80(+CCR2(+ monocytic cells and EGFP(+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+ PaSCs in injured mice. We propose that CCR2(+ monocytes migrate into the pancreas possibly via the

Conservação da qualidade de caqui 'Fuyu' em ambiente refrigerado pela combinação de 1-MCP e atmosfera modificada Quality maintenance of 'Fuyu' persimmon in cold storage by combining 1-MCP and modified atmosphere

Directory of Open Access Journals (Sweden)

Luiz Carlos Argenta

2009-06-01

Full Text Available O presente estudo analisou os efeitos do inibidor da ação do etileno 1-MCP (1-metilciclopropeno, da AM (atmosfera modificada e do oxidante de etileno KMnO4 (permanganato de potássio sobre a qualidade de caqui 'Fuyu' após a armazenagem refrigerada. Os fatores 1-MCP, AM e KMnO4 foram combinados de quatro maneiras, correspondendo aos seguintes tratamentos: T1 Controle + AM + KMnO4;T2 1-MCP + AM + KMnO4; T3 1-MCP + AM, e T4 1-MCP + AA (AA=atmosfera do ar. Frutos maduro-firmes com coloração da casca predominantemente amarela foram colhidos em sete pomares comerciais no nordeste do Estado do Rio Grande do Sul. Parte dos frutos foi exposta a 0.3 µL L-1 de 1-MCP por 12 h em 24 h após a colheita. A seguir, os frutos foram armazenados sob AA ou sob AM induzida por bolsas de polietileno (0,04 mm de espessura, por 20; 40; 60 ou 80 dias a -0,1±0,8ºC. Dois sachês contendo 8,5 g de Alumina-KMnO4foram adicionados em cada uma das bolsas de polietileno dos tratamentos um e dois, antes de elas serem vedadas. Os frutos de cada período de armazenagem refrigerada foram analisados após 0; 3; 6 ou 9 dias de prateleira sob AA a 22±1ºC. O tratamento 1-MCP retardou o amolecimento da polpa, mas não afetou consistentemente o desenvolvimento de 'estrias' e manchas pretas na superfície dos frutos armazenados sob AM contendo KMnO4. A incidência de 'estrias' e manchas pretas em frutos tratados com 1-MCP e armazenados sob AM foi significativamente menor que a de frutos tratados com 1-MCP e armazenados sob AA. Houve efeitos aditivos do 1-MCP e AM na conservação da firmeza e na redução de danos por frio manifestados pela formação de textura gel-firme e manchas translúcidas na casca. O uso de KMnO4 não aumentou a conservação da qualidade dos frutos quando tratados com 1-MCP e armazenados sob AM. O desenvolvimento dos distúrbios da epiderme dependeu do pomar e de períodos de armazenagem e prateleira. No entanto, os benefícios da combinação de 1-MCP e

The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder

Science.gov (United States)

Dalgard, C; Eidelman, O; Jozwik, C; Olsen, C H; Srivastava, M; Biswas, R; Eudy, Y; Rothwell, S W; Mueller, G P; Yuan, P; Drevets, W C; Manji, H K; Vythlingam, M; Charney, D S; Neumeister, A; Ursano, R J; Jacobowitz, D M; Pollard, H B; Bonne, O

2017-01-01

Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h. The PTSD and healthy control patients are from the NIMH Chronic PTSD and healthy control cohort, initially described by Bonne et al. (2011), in which the PTSD patients have relatively low comorbidity for major depressive disorder (MDD), drug or alcohol use. We find that in plasma, but not CSF, the bivariate MCP4 (CCL13)/ MCP1(CCL2) ratio is ca. twofold elevated in PTSD patients compared with healthy controls. The MCP-4/MCP-1 ratio is invariant over circadian time, and is independent of gender, body mass index or the age at which the trauma was suffered. By contrast, MIP-1β is a candidate biomarker for PTSD only in females, whereas TARC is a candidate biomarker for PTSD only in males. It remains to be discovered whether these disease-specific differences in circadian expression for these specific immune signaling molecules are biomarkers, surrogates, or drivers for PTSD, or whether any of these analytes could contribute to therapy. PMID:28170001

Neogambogic acid prevents silica-induced fibrosis via inhibition of high-mobility group box 1 and MCP-1-induced protein 1

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wei [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Zhang, Mei, E-mail: meizhang1717@163.com [Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Wang, Zhongjiang [Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Cheng, Yusi; Liu, Haijun [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Zhou, Zewei [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Han, Bing [Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Chen, Baoan [Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Yao, Honghong, E-mail: yaohh@seu.edu.cn [Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Chao, Jie, E-mail: chaojie@seu.edu.cn [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China)

2016-10-15

Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO{sub 2}); early stages are characterized by alveolar inflammation, and later stages are characterized by progressive lung fibrosis. Mounting evidence indicates that high-mobility group box 1 (HMGB1) is involved in pulmonary fibrosis. Whether neogambogic acid (NGA) inhibits macrophage and fibroblast activation induced by SiO{sub 2} by targeting HMGB1 remains unclear. Methods and results: Experiments using cultured mouse macrophages (RAW264.7 cells) demonstrated that SiO{sub 2} treatment induces the expression of HMGB1 in a time- and dose-dependent manner via mitogen-activated protein kinases (MAPKs) and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; in turn, this expression causes macrophage apoptosis and fibroblast activation. Pretreating macrophages with NGA inhibited the HMGB1 expression induced by SiO{sub 2} and attenuated both macrophage apoptosis and fibroblast activation. Moreover, NGA directly inhibited MCP-1-induced protein 1 (MCPIP1) expression, as well as markers of fibroblast activation and migration induced by SiO{sub 2}. Furthermore, the effects of NGA on macrophages and fibroblasts were confirmed in vivo by exposing mice to SiO{sub 2}. Conclusion: NGA can prevent SiO{sub 2}-induced macrophage activation and apoptosis via HMGB1 inhibition and SiO{sub 2}-induced fibrosis via the MCPIP1 pathway. Targeting HMGB1 and MCPIP1 with NGA could provide insights into the potential development of a therapeutic approach for alleviating the inflammation and fibrosis induced by SiO{sub 2}. - Highlights: • The SiO{sub 2} induced HMGB1 in alveolar macrophage and MCPIP1 in fibroblast. • NGA rescued the SiO{sub 2}-induced apoptosis of alveolar macrophages via HMGB1 signaling. • NGA inhibited the fibroblast activation induced by SiO{sub 2} via MCPIP1 signaling. • NGA might represent a potential therapeutic approach for silicosis.

Quantitative analysis of the secretion of the MCP family of chemokines by muscle cells

DEFF Research Database (Denmark)

Henningsen, Jeanette; Pedersen, Bente Klarlund; Kratchmarova, Irina

2011-01-01

by Amino acids in Cell culture (SILAC) method for quantitative analysis resulted in the identification and generation of quantitative profiles of 59 growth factors and cytokines, including 9 classical chemokines. The members of the CC chemokine family of proteins such as monocyte chemotactic proteins 1, 2...

Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

Directory of Open Access Journals (Sweden)

Charo Israel F

2004-09-01

Full Text Available Abstract Background Asthma is characterized by type 2 T-helper cell (Th2 inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2 and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. Methods To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. Results We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. Conclusion We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.

N-caffeoyltryptomine, a potent anti-inflammatory phenolic amide, suppressed MCP-1 expression in LPS-stimulated THP-1 cells and rats fed with a high fat diet

Science.gov (United States)

Monocyte chemoattractant protein-1 (MCP-1) is a well-known chemokine critically involved in the pathophysiological progression of cardiovascular diseases such as arthrosclerosis. N-caffeoyltryptamine is a phenolic amide with strong anti-inflammatory effects. Therefore, in this paper, the potential e...

Quality management of cut carnation 'Tempo' with 1- MCP

African Journals Online (AJOL)

STORAGESEVER

2009-10-19

Oct 19, 2009 ... carnation 'Tempo' which is an ethylene-sensitive flower, were evaluated. The effects of 1-MCP .... rolling of the petals. Water uptake rate (ml g-1 .... The studies of Chamani (2006) on Rosa 'First red' cut flowers revealed that ...

Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

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Salacz ME

2016-04-01

Full Text Available Michael E Salacz,1,2 Richard E Kast,3 Najmaldin Saki,4 Ansgar Brüning,5 Georg Karpel-Massler,6 Marc-Eric Halatsch6 1Department of Internal Medicine, 2Department of Neurosurgery, University of Kansas, Kansas City, KS, USA; 3IIAIGC Study Center, Burlington, VT, USA; 4Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Molecular Biology Laboratory, University Hospital Munich, Munich, Germany; 6Department of Neurosurgery, University of Ulm, Ulm, Germany Abstract: To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs (monocyte, macrophage, microglia, dendritic cells that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low

Circulating MCP-1 level and вˆј2518 gene polymorphism as a ...

African Journals Online (AJOL)

Azza M. Hassan

that plays an important role in the recruitment of monocytes/macrophages into renal tubulointer- stitium. A biallelic A/G polymorphism at position 2518 in the MCP-1 gene was found ..... minurea, but also with UAE in their type 2 diabetic patients. This is explained by the pivotal role played by increased MCP-. 1 production due ...

A mechanistic modelling approach to understand 1-MCP inhibition of ethylene action and quality changes during ripening of apples.

Science.gov (United States)

Gwanpua, Sunny George; Verlinden, Bert E; Hertog, Maarten Latm; Nicolai, Bart M; Geeraerd, Annemie H

2017-08-01

1-Methylcyclopropene (1-MCP) inhibits ripening in climacteric fruit by blocking ethylene receptors, preventing ethylene from binding and eliciting its action. The objective of the current study was to use mathematical models to describe 1-MCP inhibition of apple fruit ripening, and to provide a tool for predicting ethylene production, and two important quality indicators of apple fruit, firmness and background colour. A model consisting of coupled differential equations describing 1-MCP inhibition of apple ripening was developed. Data on ethylene production, expression of ethylene receptors, firmness, and background colour during ripening of untreated and 1-MCP treated apples were used to calibrate the model. An overall adjusted R 2 of 95% was obtained. The impact of time from harvest to treatment, and harvest maturity on 1-MCP efficacy was modelled. Different hypotheses on the partial response of 'Jonagold' apple to 1-MCP treatment were tested using the model. The model was validated using an independent dataset. Low 1-MCP blocking efficacy was shown to be the most likely cause of partial response for delayed 1-MCP treatment, and 1-MCP treatment of late-picked apples. Time from harvest to treatment was a more important factor than maturity for 1-MCP efficacy in 'Jonagold' apples. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection

DEFF Research Database (Denmark)

Relster, Mette Marie; Holm, Anette; Pedersen, Court

2017-01-01

), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI....... Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable...

Fish-oil-derived n-3 PUFAs reduce inflammatory and chemotactic adipokine-mediated cross-talk between co-cultured murine splenic CD8+ T cells and adipocytes.

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Monk, Jennifer M; Liddle, Danyelle M; De Boer, Anna A; Brown, Morgan J; Power, Krista A; Ma, David Wl; Robinson, Lindsay E

2015-04-01

Obese adipose tissue (AT) inflammation is characterized by dysregulated adipokine production and immune cell accumulation. Cluster of differentiation (CD) 8+ T cell AT infiltration represents a critical step that precedes macrophage infiltration. n-3 (ω-3) Polyunsaturated fatty acids (PUFAs) exert anti-inflammatory effects in obese AT, thereby disrupting AT inflammatory paracrine signaling. We assessed the effect of n-3 PUFAs on paracrine interactions between adipocytes and primary CD8+ T cells co-cultured at the cellular ratio observed in obese AT. C57BL/6 mice were fed either a 3% menhaden fish-oil + 7% safflower oil (FO) diet (wt:wt) or an isocaloric 10% safflower oil (wt:wt) control (CON) for 3 wk, and splenic CD8+ T cells were isolated by positive selection (via magnetic microbeads) and co-cultured with 3T3-L1 adipocytes. Co-cultures were unstimulated (cells alone), T cell receptor stimulated, or lipopolysaccharide (LPS) stimulated for 24 h. In LPS-stimulated co-cultures, FO reduced secreted protein concentrations of interleukin (IL)-6 (-42.6%), tumor necrosis factor α (-67%), macrophage inflammatory protein (MIP) 1α (-52%), MIP-1β (-62%), monocyte chemotactic protein (MCP) 1 (-23%), and MCP-3 (-19%) vs. CON, which coincided with a 74% reduction in macrophage chemotaxis toward secreted chemotaxins in LPS-stimulated FO-enriched co-culture-conditioned media. FO increased mRNA expression of the inflammatory signaling negative regulators monocyte chemoattractant 1-induced protein (Mcpip; +9.3-fold) and suppressor of cytokine signaling 3 (Socs3; +1.7-fold), whereas FO reduced activation of inflammatory transcription factors nuclear transcription factor κB (NF-κB) p65 and signal transducer and activator of transcription 3 (STAT3) by 27% and 33%, respectively. Finally, mRNA expression of the inflammasome components Caspase1 (-36.4%), Nod-like receptor family pyrin domain containing 3 (Nlrp3; -99%), and Il1b (-68.8%) were decreased by FO compared with CON (P �

L-Cysteine supplementation increases adiponectin synthesis and secretion, and GLUT4 and glucose utilization by upregulating disulfide bond A-like protein expression mediated by MCP-1 inhibition in 3T3-L1 adipocytes exposed to high glucose.

Science.gov (United States)

Achari, Arunkumar Elumalai; Jain, Sushil K

2016-03-01

Adiponectin is an anti-diabetic and anti-atherogenic adipokine; its plasma levels are decreased in obesity, insulin resistance, and type 2 diabetes. An adiponectin-interacting protein named disulfide bond A-like protein (DsbA-L) plays an important role in the assembly of adiponectin. This study examined the hypothesis that L-cysteine (LC) regulates glucose homeostasis through the DsbA-L upregulation and synthesis and secretion of adiponectin in diabetes. 3T3L1 adipocytes were treated with LC (250 and 500 µM, 2 h) and high glucose (HG, 25 mM, 20 h). Results showed that LC supplementation significantly (p L, adiponectin, and GLUT-4 protein expression and glucose utilization in HG-treated adipocytes. LC supplementation significantly (p L expression and adiponectin levels in 3T3-L1 cells. Treatment with LC prevented the decrease in DsbA-L, adiponectin, and GLUT-4 expression in 3T3L1 adipocyte cells exposed to MCP-1. Thus, this study demonstrates that DsbA-L and adiponectin upregulation mediates the beneficial effects of LC on glucose utilization by inhibiting MCP-1 secretion in adipocytes and provides a novel mechanism by which LC supplementation can improve insulin sensitivity in diabetes.

CHANGES IN MECHANICAL PROPERTIES OF MINIMALLY-PROCESSED YELLOW PITAHAYA TREATED WITH 1-MCP

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LILIANA SERNA COCK

2012-01-01

Full Text Available Se evaluaron las propiedades mecánicas de esfuerzo del límite de fluencia (sL, modulo de deformación (Ed, esfuerzo de ruptura (sF, y deformación de Hencky en la ruptura (eHF de muestras de pitahaya amarilla mínimamente procesada y tratadas con 200 μgL-1 de 1-MCP durante el almacenamiento a 10±1 °C y 85% de humedad relativa. Las muestras fueron sometidas a pruebas de compresión uniaxial hasta la ruptura. Los resultados mostraron que las muestras tratadas con 1-MCP presentaron los mayores valores del esfuerzo del límite de fluencia, modulo de elasticidad y esfuerzo de ruptura. Esto indica que la aplicación del 1-MCP proporciona mayor firmeza a la fruta y puede representar una alternativa para disminuir cambios indeseables de textura durante el almacenamiento.

'Diffuse skin browning' in 1-MCP-treated apples: etiology and systems of control.

Science.gov (United States)

Larrigaudière, Christian; Vilaplana, Rosa; Recasens, Inmaculada; Soria, Yolanda; Dupille, Eve

2010-11-01

'Diffuse skin browning' (DSB) is a physiological disorder that affects Golden Delicious apples treated with 1-methylcyclopropene (1-MCP). Although a very high incidence is found, very little is known about the etiology of this disorder. This study aims to provide an understanding of the causes of this disorder and prevent it. A very high incidence of DSB was found in 1-MCP-treated apples independent of the location of the orchard. Similar to superficial scald, harvest maturity determines the DSB incidence, with the more mature fruit being less sensitive. The 1-MCP dose (156 nL L(-1) or 625 nL L(-1)) and the temperature at which the 1-MCP treatment was applied (0.5 or 20 °C) did not affect the incidence of DSB. Diphenylamine (DPA) treatment did not prevent DSB, contrary to superficial scald. Additionally, controlled atmosphere storage only partially reduced the incidence of DSB, whereas progressive cooling strategies completely inhibited DSB occurrence. A direct correlation was found between the sensitivity of the Golden Delicious clone to russeting and its sensitivity to develop DSB during storage. Our results indicated that DSB and superficial scald are two different disorders involving different oxidative processes. DSB can be prevented by progressive cooling and selection of russeting-resistant clones. 2010 Society of Chemical Industry

Studies of MCP properties

International Nuclear Information System (INIS)

Lehmann, A; Britting, A; Eyrich, W; Uhlig, F

2009-01-01

Cherenkov detectors of the DIRC type will be used for the particle identification of the PANDA experiment at FAIR. Because of their advantageous properties inside a magnetic field micro-channel plate (MCP) photomultipliers (PMT) are very attractive photon sensors for the two PANDA DIRCs. Various types of MCP-PMTs were investigated. Their gains and their time resolutions were measured as a function of the magnitude and the direction of a magnetic field. It was found that with a pore size of ≤ 10 μm efficient single photon detection is possible even at 2 Tesla if the field direction is close to parallel to the PMT axis. The gain of most of the studied MCP-PMTs remains stable up to a photon density of roughly 1 MHz/cm 2 , while the new Hamamatsu R10754-00-L4 can stand rates of about 10 MHz/cm 2 before the gain starts decreasing. The time resolution of all investigated MCP-PMTs was better than 50 ps (σ). The response of the multi-anode MCP-PMTs was scanned as a function of the position of the photo cathode plane in particular to measure the crosstalk among adjacent pixels. Most of the sensors show a satisfactory behavior.

The Effect of Post-Resistance Exercise Amino Acids on Plasma MCP-1 and CCR2 Expression

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Adam J. Wells

2016-07-01

Full Text Available The recruitment and infiltration of classical monocytes into damaged muscle is critical for optimal tissue remodeling. This study examined the effects of an amino acid supplement on classical monocyte recruitment following an acute bout of lower body resistance exercise. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm ingested supplement (SUPP or placebo (PL immediately post-exercise in a randomized, cross-over design. Blood samples were obtained at baseline (BL, immediately (IP, 30-min (30P, 1-h (1H, 2-h (2H, and 5-h (5H post-exercise to assess plasma concentrations of monocyte chemoattractant protein 1 (MCP-1, myoglobin, cortisol and insulin concentrations; and expressions of C-C chemokine receptor-2 (CCR2, and macrophage-1 antigen (CD11b on classical monocytes. Magnitude-based inferences were used to provide inferences on the true effects of SUPP compared to PL. Changes in myoglobin, cortisol, and insulin concentrations were similar between treatments. Compared to PL, plasma MCP-1 was “very likely greater” (98.1% likelihood effect in SUPP at 2H. CCR2 expression was “likely greater” at IP (84.9% likelihood effect, “likely greater” at 1H (87.7% likelihood effect, “very likely greater” at 2H (97.0% likelihood effect, and “likely greater” at 5H (90.1% likelihood effect in SUPP, compared to PL. Ingestion of SUPP did not influence CD11b expression. Ingestion of an amino acid supplement immediately post-exercise appears to help maintain plasma MCP-1 concentrations and augment CCR2 expression in resistance trained men.

Correlation of MCP-4 and high-sensitivity C-reactive protein as a marker of inflammation in obesity and chronic periodontitis.

Science.gov (United States)

Pradeep, A R; Kumari, Minal; Kalra, Nitish; Priyanka, N

2013-03-01

Obesity is increasing in prevalence worldwide and has emerged as a strong risk factor for periodontal disease. Conversely, the remote effects of periodontal disease on various systemic diseases have been proposed. The aim of this study is to determine the presence of MCP-4 and high sensitivity C reactive protein (hsCRP) levels in gingival crevicular fluid (GCF) and serum in obese and non-obese subjects with chronic periodontitis and to find a correlation between MCP-4 and hsCRP in GCF and serum. Forty subjects (20 males and 20 females) were selected and divided into four groups (10 subjects in each group), based on clinical parameters: group NOH (non-obese healthy), group OH (obese healthy), Group NOCP (non-obese with chronic periodontitis) and group OCP (obese with chronic periodontitis). The levels of serum and GCF MCP-4 were determined by ELISA and hsCRP levels were determined by immunoturbidimetry method. The mean GCF and serum concentration of MCP-4 was highest for group OCP followed by group NOCP, group OH (in GCF); group OH, group NOCP(in serum) and least in group NOH. The mean hsCRP concentration was highest for group OCP followed by group OH, group NOCP and group NOH. A significant positive correlation was found between serum and GCF MCP-4 and hsCRP levels. GCF MCP-4 concentrations increased in periodontal disease compared to health and correlated positively with the severity of disease indicating it as a novel marker of periodontal disease. The serum concentration of MCP-4 was found to be more in obese group as compared to nonobese group indicating it as a marker of obesity. Furthermore, based on the positive correlation of MCP-4 and hsCRP found in this study, it can be proposed that MCP-4 and hsCRP may be the markers linking chronic inflammation in obesity and periodontal disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Monocyte chemotactic protein-4 (MCP-4/CCL-13) and CC ...

African Journals Online (AJOL)

EL-HAKIM

chronic inflammation and local tissue eosinophilia. Atopic asthma is characterized by a 50-fold increase in the number of eosinophils relative to neutrophils in the bronchial mucosa. This is the result of the cumulative and sequential effects of variable increases in selective eosinophil versus neutrophil migration occurring at ...

Shewanella oneidensis MR-1 chemotaxis proteins and electron-transport chain components essential for congregation near insoluble electron acceptors.

Science.gov (United States)

Harris, H Wayne; El-Naggar, Mohamed Y; Nealson, Kenneth H

2012-12-01

Shewanella oneidensis MR-1 cells utilize a behaviour response called electrokinesis to increase their speed in the vicinity of IEAs (insoluble electron acceptors), including manganese oxides, iron oxides and poised electrodes [Harris, El-Naggar, Bretschger, Ward, Romine, Obraztsova and Nealson (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 326-331]. However, it is not currently understood how bacteria remain in the vicinity of the IEA and accumulate both on the surface and in the surrounding medium. In the present paper, we provide results indicating that cells that have contacted the IEAs swim faster than those that have not recently made contact. In addition, fast-swimming cells exhibit an enhancement of swimming reversals leading to rapid non-random accumulation of cells on, and adjacent to, mineral particles. We call the observed accumulation near IEAs 'congregation'. Congregation is eliminated by the loss of a critical gene involved with EET (extracellular electron transport) (cymA, SO_4591) and is altered or eliminated in several deletion mutants of homologues of genes that are involved with chemotaxis or energy taxis in Escherichia coli. These genes include chemotactic signal transduction protein (cheA-3, SO_3207), methyl-accepting chemotaxis proteins with the Cache domain (mcp_cache, SO_2240) or the PAS (Per/Arnt/Sim) domain (mcp_pas, SO_1385). In the present paper, we report studies of S. oneidensis MR-1 that lend some insight into how microbes in this group can 'sense' the presence of a solid substrate such as a mineral surface, and maintain themselves in the vicinity of the mineral (i.e. via congregation), which may ultimately lead to attachment and biofilm formation.

Effects of Triptergium Glycosides on Expressions of MCP- 1 and ...

African Journals Online (AJOL)

the pathogenesis of diabetic nephropathy (DN), which is one of the chronic ..... the release of lysosomal enzymes and TGF, increase the ... important roles in the pathogenesis of this disease. Thus, MCP-1 and CTGF are potential targets for ...

Quality management of cut carnation 'Tempo' with 1- MCP | Abadi ...

African Journals Online (AJOL)

Quality management of cut carnation 'Tempo' with 1- MCP. ... African Journal of Biotechnology ... time durations (3, 6 and 9 h) on the vaselife, water uptake, loss of fresh weight and chlorophyll index of cut carnation 'Tempo' which is an ...

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.

Antifungal activity of 1-methylcyclopropene (1-MCP) against anthracnose (Colletotrichum gloeosporioides) in postharvest mango fruit and its possible mechanisms of action.

Science.gov (United States)

Xu, Xiangbin; Lei, Huanhuan; Ma, Xiuyan; Lai, Tongfei; Song, Hongmiao; Shi, Xuequn; Li, Jiangkuo

2017-01-16

Anthracnose caused by Colletotrichum gloeosporioides is one of the most important postharvest diseases in mango fruit, often causing huge economic losses. In this study, the effect of 1-methylcyclopropene (1-MCP) against anthracnose in postharvest mango fruit and the mechanisms involved were investigated. 1-MCP induced reactive oxygen species (ROS) generation, damaged the mitochondria and destroyed the integrity of plasma membrane of spores of C. gloeosporioides, significantly suppressing spore germination and mycelial growth of C. gloeosporioides. 1-MCP also decreased the decay incidence and lesion expansion of mango fruit caused by C. gloeosporioides. For the first time this study demonstrated that 1-MCP suppressed anthracnose of postharvest mango fruit by directly inhibiting spore germination and mycelial growth of C. gloeosporioides, thus providing a promising strategy for disease control. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimal methylation noise for best chemotactic performance of E. coli

Science.gov (United States)

Dev, Subrata; Chatterjee, Sakuntala

2018-03-01

In response to a concentration gradient of chemoattractant, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high chemoattractant concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequences on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell in a significant way. We model the intracellular reaction network in terms of coupled time evolution of three stochastic variables—kinase activity, methylation level, and CheY-P protein level—and study the effect of methylation noise on the chemotactic performance of the cell. In presence of a spatially varying nutrient concentration profile, a good chemotactic performance allows the cell to climb up the concentration gradient quickly and localize in the nutrient-rich regions in the long time limit. Our simulations show that the best performance is obtained at an optimal noise strength. While it is expected that chemotaxis will be weaker for very large noise, it is counterintuitive that the performance worsens even when noise level falls below a certain value. We explain this striking result by detailed analysis of CheY-P protein level statistics for different noise strengths. We show that when the CheY-P level falls below a certain (noise-dependent) threshold the cell tends to move down the concentration gradient of the nutrient, which has a detrimental effect on its chemotactic response. This threshold value decreases as noise is increased, and this effect is responsible for noise-induced enhancement of chemotactic performance. In a harsh chemical environment, when the nutrient degrades with time, the amount of nutrient intercepted by the cell trajectory is an effective performance criterion. In this case also, depending on the nutrient lifetime, we find an optimum noise strength when the performance is at its best.

Single ion counting with a MCP (microchannel plate) detector

Energy Technology Data Exchange (ETDEWEB)

Tawara, Hiroko; Sasaki, Shinichi; Miyajima, Mitsuhiro [National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan); Shibamura, Eido

1996-07-01

In this study, a single-ion-counting method using alpha-particle-impact ionization of Ar atoms is demonstrated and the preliminary {epsilon}{sub mcp} for Ar ions with incident energies of 3 to 4.7 keV is determined. The single-ion counting by the MCP is aimed to be performed under experimental conditions as follows: (1) A signal from the MCP is reasonably identified as incidence of single Ar-ion. (2) The counting rate of Ar ions is less than 1 s{sup -1}. (3) The incident Ar ions are not focused on a small part of an active area of the MCP, namely, {epsilon}{sub mcp} is determined with respect to the whole active area of the MCP. So far, any absolute detection efficiency has not been reported under these conditions. (J.P.N.)

The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

Directory of Open Access Journals (Sweden)

Hai-Shu Lin

2013-11-01

Full Text Available MS-275 (entinostat and SAHA (vorinostat, two histone deacetylase (HDAC inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA. To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α  MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1, an endogenous suppressor of p38α  in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation of p38α  was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2, monocyte chemotactic protein-2 (MCP-2 and macrophage migration inhibitory factor (MIF in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors.

Plasma Monocyte Chemoattractant Protein-1 Level as a Predictor of the Severity of Community-Acquired Pneumonia

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Kok-Khun Yong

2016-01-01

Full Text Available Monocyte chemoattractant protein (MCP-1 increases in the serum of immunocompetent patients with community-acquired pneumonia (CAP. However, the correlation between the circulating level of MCP-1 and severity of CAP remains unclear. This study investigated differential changes in the plasma MCP-1 levels of patients with CAP before and after an antibiotic treatment and further analyzes the association between the CAP severity and MCP-1 levels. We measured the plasma MCP-1 levels of 137 patients with CAP and 74 healthy controls by using a commercial enzyme-linked immunosorbent assay. Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II; confusion, urea level, respiratory rate, blood pressure, and age of >64 years (CURB-65; and pneumonia severity index (PSI scores were determined for assessing the CAP severity in these patients. The antibiotic treatment reduced the number of white blood cells (WBCs and neutrophils as well as the level of C-reactive protein (CRP and MCP-1. The plasma MCP-1 level, but not the CRP level or WBC count, correlated with the CAP severity according to the PSI (r = 0.509, p < 0.001, CURB-65 (r = 0.468, p < 0.001, and APACHE II (r = 0.360, p < 0.001 scores. We concluded that MCP-1 levels act in the development of CAP and are involved in the severity of CAP.

Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

International Nuclear Information System (INIS)

Takahashi, Nobuhiko; Yoshizaki, Takayuki; Hiranaka, Natsumi; Suzuki, Takeshi; Yui, Tomoo; Akanuma, Masayasu; Oka, Kazuya; Kanazawa, Kaoru; Yoshida, Mika; Naito, Sumiyoshi; Fujiya, Mikihiro; Kohgo, Yutaka; Ieko, Masahiro

2011-01-01

Highlights: ► Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. ► Adipose lipin-1 expression is reduced in obesity. ► Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. ► Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytes by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-κB activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.

Suppression of lipin-1 expression increases monocyte chemoattractant protein-1 expression in 3T3-L1 adipocytes

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Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Yoshizaki, Takayuki [Innovation Center, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065 (Japan); Hiranaka, Natsumi; Suzuki, Takeshi [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yui, Tomoo; Akanuma, Masayasu; Oka, Kazuya [Department of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Kanazawa, Kaoru [Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yoshida, Mika; Naito, Sumiyoshi [Department of Clinical Laboratory, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Fujiya, Mikihiro; Kohgo, Yutaka [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Ieko, Masahiro [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan)

2011-11-11

Highlights: Black-Right-Pointing-Pointer Lipin-1 affects lipid metabolism, adipocyte differentiation, and transcription. Black-Right-Pointing-Pointer Adipose lipin-1 expression is reduced in obesity. Black-Right-Pointing-Pointer Lipin-1 depletion using siRNA in 3T3-L1 adipocytes increased MCP-1 expression. Black-Right-Pointing-Pointer Lipin-1 is involved in adipose inflammation. -- Abstract: Lipin-1 plays a crucial role in the regulation of lipid metabolism and cell differentiation in adipocytes. Expression of adipose lipin-1 is reduced in obesity, and metabolic syndrome. However, the significance of this reduction remains unclear. This study investigated if and how reduced lipin-1 expression affected metabolism. We assessed mRNA expression levels of various genes related to adipocyte metabolism in lipin-1-depleted 3T3-L1 adipocytes by introducing its specific small interfering RNA. In lipin-1-depleted adipocytes, mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1) were significantly increased, although the other genes tested were not altered. The conditioned media from the cells promoted monocyte chemotaxis. The increase in MCP-1 expression was prevented by treatment with quinazoline or salicylate, inhibitors of nuclear factor-{kappa}B activation. Because MCP-1 is related to adipose inflammation and systemic insulin resistance, these results suggest that a reduction in adipose lipin-1 in obesity may exacerbate adipose inflammation and metabolism.

EFECTO DEL 1-METILCICLOPROPENO (1-MCP Y TRATAMIENTO HIDROTÉRMICO SOBRE LA FISIOLOGÍA Y CALIDAD DEL MANGO 'KEITT'

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J. A. Osuna-García

2007-01-01

Full Text Available El objetivo del presente trabajo fue evaluar el efecto del 1-MCP (0 y 300 nl·litro-1 y diferentes niveles de tratamiento hidrotérmico (0, 52 °C por 5 min y 46 °C por 110 min sobre la fisiología y calidad de mango 'Keitt'. Se analizó velocidad de respiración, pérdida de peso, firmeza, color de pulpa, sólidos solubles totales y porcentaje de frutos enfermos. Se encontró que la efectividad del 1-MCP varió acorde al nivel de tratamiento hidrotérmico. En frutos sin hidrotérmico el 1-MCP disminuyó velocidad de respiración, no influyó en la pérdida de peso, mantuvo cuatro veces más la firmeza y retrasó el cambio de color de pulpa y el aumento de los sólidos solubles. Sin embargo, bajo tratamiento hidrotérmico por 5 min el 1-MCP incrementó velocidad de respiración, no influyó en la pérdida de peso, mantuvo dos veces más la firmeza de pulpa, retrasó el desarrollo del color de pulpa y mantuvo sin cambios los sólidos solubles. La efectividad del 1-MCP sobre firmeza y pérdida de peso fue significativamente afectada por el tratamiento hidrotérmico de 110 min, y no tuvo ningún efecto sobre el control de enfermedades, sin embargo, el tratamiento con agua caliente por 5 min redujo en más de 50 % la presencia de frutos enfermos. El 1-MCP en combinación con el tratamiento hidrotérmico de 5 min alargó en cinco días la vida de anaquel de los frutos y podría ser una alternativa viable en mercados que no requieren tratamiento hidrotérmico cuarentenario para el control de mosca de la fruta.

Resposta da aplicação do 1-MCP em frutos de mamoeiro 'Golden' em diferentes estádios de maturação Responses of 1-MCP applications in 'Golden' papaya fruits on differents maturation stages

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Maximiliano Silva de Souza

2009-09-01

Full Text Available O estudo de fatores que influenciam no processo de amadurecimento é fundamental para o planejamento do processo de comercialização, principalmente em frutos com padrão de respiração climatérico e perecível, como é o caso do mamão. Nesse trabalho, avaliou-se o efeito da aplicação do 1-MCP (1-metilciclopropeno sobre o amadurecimento de frutos de mamoeiro nos estádios 0; 1 e 2 de maturação. O 1-MCP diminui a produção de etileno (≈79% e a taxa respiratória (≈45%, principalmente em frutos no estádio 0 de maturação. O uso deste inibidor da ação do etileno retardou a perda de coloração verde da casca dos frutos, principalmente em frutos nos estádios 0 e 1 de maturação. Houve redução na perda de firmeza do fruto e do mesocarpo nos estádios 1 e 2. Entretanto, em frutos no estádio 0 de maturação, a firmeza do mesocarpo manteve-se alta, o que pode comprometer a aceitação destes frutos pelo consumidor. O teor de sólidos solúveis não foi influenciado pela aplicação do 1-MCP. O efeito do 1-MCP na redução da atividade das enzimas PME e PG foi maior em frutos nos estádios 0 e 1 de maturação em comparação a frutos no estádio 2 de maturação. A atividade da PME demonstrou crescente aumento ao longo do período de armazenamento, porém a atividade da PG permaneceu baixa ao longo dos cinco primeiros dias, com aumento posterior. Os resultados mostraram que a PME exerce influência significativa na perda de firmeza da polpa nos primeiros dias, com atuação posterior da PG. O 1-MCP mostrou-se eficiente em retardar o processo de amadurecimento de frutos de mamoeiro, tornando-se mais eficiente quando associado a estádios de maturação iniciais.The study of factors that influence the process of ripening is critical for planning the marketing process, mainly in standard breathing climacteric and perishing fruits, as it is the case of papaya. In this work it was evaluated the effect of the application of 1-MCP (1

Conservação pós-colheita de melão Charentais tratado com 1-MCP e armazenado sob refrigeração e atmosfera modificada Postharvest conservation of charentais melons treated with 1-MCP and stored under refrigeration and modified atmosphere

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Pahlevi A de Souza

2008-12-01

Full Text Available Objetivando avaliar a vida útil pós-colheita de melão tipo Charentais (Cucumis melo L. sob refrigeração, tratados com 1-MCP e associado ou não a atmosfera modificada (AM, foram conduzidos dois experimentos em laboratório da Embrapa Agroindústria Tropical, Fortaleza-CE. Os frutos foram provenientes da Agroindústria Nolem Comercial Importadora e Exportadora Ltda, localizada no Agropólo Mossoró Açu-RN. Os frutos foram tratados com 300 e 600 ppb de 1-MCP, em seguida, metade desses frutos foram embalados em filmes plásticos, mantendo-se frutos embalados sem aplicação de 1-MCP nas mesmas condições de armazenamento dos demais. Os melões foram armazenados por 21 dias sendo 14 dias (9±1ºC e 87±5% UR + 7 dias (22±2ºC e 70±5% UR. Em função da aparência externa, a vida útil pós-colheita dos frutos armazenados sob atmosfera modificada, com ou sem tratamento inicial de 1-MCP foi de 21 dias, enquanto que dos frutos tratados inicialmente apenas com 1-MCP foi de 19 dias. A aplicação do 1-MCP proporcionou redução na atividade respiratória e na produção de etileno, e maior retenção da firmeza da polpa, menor perda de massa e melhor aparência externa quando associado a atmosfera modificada. A atmosfera modificada, isoladamente, foi eficiente em reduzir a perda de massa e manter melhor aparência externa.Aiming to evaluate the postharvest shelf life of Charentais melon (Cucumis melo L. stored under refrigeration, the fruits were treated with 1-MCP, associated or not with modified atmosphere (MAP. Two experiments were carried out at the laboratory of Embrapa Agroindústria Tropical in Fortaleza, Brazil, analyzing the chemical and physic quality characteristics. The fruits were obtained at the Agroindústria Nolem Comercial Importadora e Exportadora Ltda, located in Mossoró Açu, Brazil. The fruits were treated with 300 and 600 nL L-1 of 1-MCP, half of those were wrapped in plastic films, which were wrapped without the use of 1

Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans.

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David Patsouris

Full Text Available Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D. However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.

EFECTO DEL EMPAQUE Y DEL 1-MCP SOBRE CARACTERÍSTICAS FÍSICAS, QUÍMICAS Y FISIOLÓGICAS DE PITAHAYA AMARILLA EFEITO DA EMBALAGEM E DO 1-MCP SOB AS PROPRIEDADES QUÍMICAS, FÍSICAS E FISIOLÓGICAS DA PITAHAYA AMARELA EFFECT OF PACKAGING AND 1-MCP ON PHYSICAL, CHEMICAL AND PHYSIOLOGICAL CHARACTERISTICS OF PITAHAYA YELLOW

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LILIANA SERNA C

2011-12-01

Full Text Available En pitahaya amarilla entera con grado de madurez 3, se evaluó el efecto del empaque (canastillas plásticas y cajas de cartón tipo exportación y la aplicación de soluciones acuosas de 1-Metilciclopropeno (200 y 400 µgL-1, sobre la pérdida de peso, firmeza, color, sólidos solubles, acidez titulable, tasa respiratoria y tiempo de vida comercial. Se encontró que en los dos empaques, la aplicación de soluciones acuosas de 200 y 400 µgL-1 de 1-Metilciclopropeno (1-MCP disminuyó los cambios en acidez, tasa respiratoria y color, sin embargo, aumentó la pérdida de peso durante el almacenamiento. El tipo de empaque afectó significativamente la pérdida de peso, los sólidos solubles y el color. La aplicación de 200 µgL-1 de 1-MCP generó menor variación en la luminosidad y en la coloración verde-amarilla en la fruta. Concentraciones de 200 y 400 µgL-1 de 1-MCP y el empaque en canastillas plásticas para mercado local permitieron prolongar el tiempo de vida comercial de la pitahaya amarilla 3 días. Los resultados de este estudio confirman además que la pitahaya amarilla es una fruta climatérica.Na pitahaya amarela inteira com grau tres de madures, foi avallado os efeitos da embalagem (cestos de plástico e caixas de papelão tipo exportação e a aplicação de soluções aquosas de 1-metilciclopropeno (200 e 400 µgL-1 sobre a perda de peso, firmeza, cor, teor de sólidos solúveis totais, acidez, taxa de respiração e tempo de vida comercial. Foi observado que nas duas embalagens, a aplicação de soluções aquosas de 200 e 400 µgL-1 de 1-Metilciclopropeno (1-MCP reduziu as variações na acidez, taxa de respiração e cor, no entanto, aumentou a perda de peso durante o armazenamento. 0 tipo da embalagem afetou significativamente a perda de peso, o teor de sólidos solúveis totais, e acor. A aplicação de 200 µgL-1 de 1-MCP gerou menor variação na luminosidade e na cor verde-amarela no fruto. Concentrações de 200 e 400

Effects of Roux-en-Y Gastric Bypass on Fasting and Postprandial Levels of the Inflammatory Markers YKL-40 and MCP-1 in Patients with Type 2 Diabetes and Glucose Tolerant Subjects

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Thomsen, Stine Brinkløv; Rathcke, Camilla Noelle; Jørgensen, Nils Bruun

2013-01-01

Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states......, following Roux-en-Y gastric bypass (RYGB) in subjects with type 2 diabetes (T2D) and normal glucose tolerance (NGT). Methods. Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year) RYGB. Results....... Fasting state MCP-1 levels decreased after RYGB in both groups (P values...

Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent

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Majkova, Zuzana; Smart, Eric; Toborek, Michal; Hennig, Bernhard

2009-01-01

Atherosclerosis, the primary cause of heart disease and stroke is initiated in the vascular endothelium, and risk factors for its development include environmental exposure to persistent organic pollutants. Caveolae are membrane microdomains involved in regulation of many signaling pathways, and in particular in endothelial cells. We tested the hypothesis that intact caveolae are required for coplanar PCB77-induced up-regulation of monocyte chemoattractant protein-1 (MCP-1), an endothelium-derived chemokine that attracts monocytes into sub-endothelial space in early stages of the atherosclerosis development. Atherosclerosis-prone LDL-R -/- mice (control) or caveolin-1 -/- /LDL-R -/- mice were treated with PCB77. PCB77 induced aortic mRNA expression and plasma protein levels of MCP-1 in control, but not caveolin-1 -/- /LDL-R -/- mice. To study the mechanism of this effect, primary endothelial cells were used. PCB77 increased MCP-1 levels in endothelial cells in a time- and concentration-dependent manner. This effect was abolished by caveolin-1 silencing using siRNA. Also, MCP-1 up-regulation by PCB77 was prevented by inhibiting p38 and c-Jun N-terminal kinase (JNK), but not ERK1/2, suggesting regulatory functions via p38 and JNK MAPK pathways. Finally, pre-treatment of endothelial cells with the aryl hydrocarbon receptor (AhR) inhibitor α-naphthoflavone (α-NF) partially blocked MCP-1 up-regulation. Thus, our data demonstrate that coplanar PCB77 can induce MCP-1 expression by endothelial cells and that this effect is mediated by AhR, as well as p 38 and JNK MAPK pathways. Intact caveolae are required for these processes both in vivo and in vitro. This further supports a key role for caveolae in vascular inflammation induced by persistent organic pollutants.

Abnormal monocyte recruitment and collateral artery formation in monocyte chemoattractant protein-1 deficient mice

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Voskuil, Michiel; Hoefer, Imo E.; van Royen, Niels; Hua, Jing; de Graaf, Stijn; Bode, Christoph; Buschmann, Ivo R.; Piek, Jan J.

2004-01-01

Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of collateral artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of collateral

Reconstitution of a physical complex between the N-formyl chemotactic peptide receptor and G protein. Inhibition by pertussis toxin-catalyzed ADP ribosylation.

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Bommakanti, R K; Bokoch, G M; Tolley, J O; Schreiber, R E; Siemsen, D W; Klotz, K N; Jesaitis, A J

1992-04-15

Photoaffinity-labeled N-formyl chemotactic peptide receptors from human neutrophils solubilized in octyl glucoside exhibit two forms upon sucrose density gradient sedimentation, with apparent sedimentation coefficients of approximately 4 and 7 S. The 7 S form can be converted to the 4 S form by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) with an EC50 of approximately 20 nM, suggesting that the 7 S form may represent a physical complex of the receptor with endogenous G protein (Jesaitis, A. J., Tolley, J. O., Bokoch, G. M., and Allen, R. A. (1989) J. Cell Biol. 109, 2783-2790). To probe the nature of the 7 S form, we reconstituted the 7 S form from the 4 S form by adding purified G protein. The 4 S form, obtained by solubilizing GTP gamma S-treated neutrophil plasma membranes, was incubated with purified (greater than 95%) Gi protein from bovine brain (containing both Gi alpha 1 and Gi alpha 2) or with neutrophil G protein (Gn), and formation of the 7 S complex was analyzed on sucrose density gradients. The EC50 of 7 S complex formation induced by the two G proteins was 70 +/- 25 and 170 +/- 40 nM for Gn and Gi, respectively. No complexation was measurable when bovine transducin (Gt) was used up to 30 times the EC50 for Gn. The EC50 for Gi was the same for receptors, obtained from formyl peptide-stimulated or unstimulated cells. The addition of 10 microM GTP gamma S to the reconstituted 7 S complex caused a complete revision of the receptor to the 4 S form, and anti-Gi peptide antisera immunosedimented the 7 S form. ADP-ribosylation of Gi prevented formation of the 7 S form even at 20 times the concentration of unribosylated Gi normally used to attain 50% conversion to the 7 S form. These observations suggest that the 7 S species is a physical complex containing N-formyl chemotactic peptide receptor and G protein.

Platelet-derived growth factor (PDGF-BB-mediated induction of monocyte chemoattractant protein 1 in human astrocytes: implications for HIV-associated neuroinflammation

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Bethel-Brown Crystal

2012-12-01

Full Text Available Abstract Chemokine (C-C motif ligand 2, also known as monocyte chemoattractant protein 1 (MCP-1 is an important factor for the pathogenesis of HIV-associated neurocognitive disorders (HAND. The mechanisms of MCP-1-mediated neuropathogenesis, in part, revolve around its neuroinflammatory role and the recruitment of monocytes into the central nervous system (CNS via the disrupted blood-brain barrier (BBB. We have previously demonstrated that HIV-1/HIV-1 Tat upregulate platelet-derived growth factor (PDGF-BB, a known cerebrovascular permeant; subsequently, the present study was aimed at exploring the regulation of MCP-1 by PDGF-BB in astrocytes with implications in HAND. Specifically, the data herein demonstrate that exposure of human astrocytes to HIV-1 LAI elevated PDGF-B and MCP-1 levels. Furthermore, treating astrocytes with the human recombinant PDGF-BB protein significantly increased the production and release of MCP-1 at both the RNA and protein levels. MCP-1 induction was regulated by activation of extracellular-signal-regulated kinase (ERK1/2, c-Jun N-terminal kinase (JNK and p38 mitogen-activated protein (MAP kinases and phosphatidylinositol 3-kinase (PI3K/Akt pathways and the downstream transcription factor, nuclear factor κB (NFκB. Chromatin immunoprecipitation (ChIP assays demonstrated increased binding of NFκB to the human MCP-1 promoter following PDGF-BB exposure. Conditioned media from PDGF-BB-treated astrocytes increased monocyte transmigration through human brain microvascular endothelial cells (HBMECs, an effect that was blocked by STI-571, a tyrosine kinase inhibitor (PDGF receptor (PDGF-R blocker. PDGF-BB-mediated release of MCP-1 was critical for increased permeability in an in vitro BBB model as evidenced by blocking antibody assays. Since MCP-1 is linked to disease severity, understanding its modulation by PDGF-BB could aid in understanding the proinflammatory responses in HAND. These results suggest that astrocyte

Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

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Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

2015-11-15

Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Qualidade de caqui 'Rama forte' após armazenamento refrigerado, influenciada pelos tratamentos 1-MCP e/ou CO2

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João Peterson Pereira Gardin

2012-12-01

Full Text Available Avaliaram-se os efeitos dos tratamentos com CO2 e 1-MCP (1-metilciclopropeno sobre a adstringência (índice de tanino, firmeza da polpa e distúrbios da epiderme em caqui 'Rama Forte'. Frutos foram tratados com 1-MCP por 24 h, logo após a colheita e/ou com alto CO2 (70% por 24 ou 48 h, um dia após a colheita ou após o armazenamento refrigerado (AR. Os caquis foram armazenados sob atmosfera modificada a 0 ºC, por 45 dias, e a seguir mantidos a 23 ºC, por 9 dias. Frutos-controle (não tratados com 1-MCP nem com CO2 amoleceram em três dias e perderam aproximadamente 50% da adstringência em 6 dias após o AR. A exposição ao CO2 acelerou a redução da adstringência. Esse efeito do CO2 foi menor em frutos tratados com 1-MCP, especialmente quando o CO2 foi aplicado após o AR, por apenas 24 h. O tratamento com 1-MCP inibiu o amolecimento e a redução da adstringência, especialmente nos frutos não tratados com CO2. O amolecimento de frutos tratados com 1-MCP foi maior quando a exposição ao CO2 ocorreu antes do AR. A combinação dos tratamentos com 1-MCP e alto CO2 reduziu a incidência de podridões e manchas translúcidas, mas não alterou o desenvolvimento de pintas pretas ('estrias'. Os resultados indicam que é possível induzir perda da adstringência sem excessiva perda da firmeza da polpa de caquis 'Rama Forte' após o AR pela associação dos tratamentos com 1-MCP logo após a colheita e alto CO2 após o AR.

Qualidade pós-colheita de quivi 'Hayward' tratado com 1-MCP e armazenado sob diferentes atmosferas

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Marcelo José Vieira

2012-06-01

Full Text Available Este trabalho teve por objetivo avaliar o efeito do 1-MCP sobre o amadurecimento e a qualidade pós-colheita de quivi 'Hayward' armazenado sob diferentes atmosferas. Foram conduzidos dois experimentos, com frutos colhidos em pomar comercial localizado em Fraiburgo-SC. No experimento 1, os frutos foram tratados com três doses de 1-MCP (0,0; 0,5 ou 1,0 µL L-1 e armazenados sob atmosfera controlada (AC, contendo 2,0kPa de O2 + 4,5kPa de CO2, a 0ºC ± 0,5ºC, 92 ± 3% UR, e com <40 ηL L-1 de etileno no ambiente, durante 90 e 120 dias, mais sete dias de vida de prateleira a 23ºC. No experimento 2, os frutos foram tratados com 0,0 ou 0,7 µL L-1 de 1-MCP e armazenados sob atmosfera ambiente (AA, contendo 21 kPa de O2 + 0,03 kPa de CO2, a 0 ± 0,5ºC, 90 ± 3% UR, e com 200 a 250 ηL L-1 de etileno no ambiente, durante 30, 60, 90 e 120 dias, mais um e sete dias de vida de prateleira a 23ºC ou AC (contendo 2,0 kPa de O2 + 4,5 kPa de CO2, a 0ºC ± 0,5ºC, 92 ± 3% UR, e com <40 ηL L-1 de etileno no ambiente, durante 60, 90, 120 e 150 dias, mais um e sete dias de vida de prateleira a 23ºC. Os benefícios do tratamento com 1-MCP sobre a conservação da qualidade foram observados tanto para frutos armazenados sob AA quanto sob AC. No experimento 1, não houve diferença entre as doses de 1-MCP de 0,5 e 1,0 µL L-1 sobre o controle do amadurecimento e manutenção da qualidade dos frutos armazenados em AC. No experimento 2, o tratamento com 1-MCP retardou o aumento na taxa de produção de etileno após remoção de câmara fria. A redução da taxa de produção de etileno nos frutos tratados com 1-MCP foi associada ao aumento na conservação da firmeza da polpa sob AC e AA, e redução na incidência de pericarpo translúcido sob AA. O potencial de armazenamento foi aumentado pelo tratamento com 1-MCP em aproximadamente 60 e 30 dias, nos frutos armazenados sob AA e AC, respectivamente.

Influence of 1-MCP treatments on eating quality and consumer preferences of ‘Qinmei’ kiwifruit during shelf life

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Consumers and growers in China sometime complain that Kiwifruits treated with an ethylene action inhibitor 1-MCP are difficult to ripen and show poor eating quality. This study addresses the quality parameters affecting consumer preferences and reevaluates the necessity of 1-MCP application for stor...

Effect of DPA and 1-MCP on chemical compounds related to superficial scald of Granny Smith apples

Energy Technology Data Exchange (ETDEWEB)

Moggia, C.; Moya-Leon, M. A.; Pereira, M.; Yuri, J. A.; Lobos, G. A.

2010-07-01

Research was carried out to study the mode of action of diphenylamine (DPA) and 1-methylcyclopropene (1-MCP), on control of superficial scald of Granny Smith apples (Malus domestica Borkh.), and its relation with chemical compounds. Fruit was harvested from a commercial orchard in Chile, 182 and 189 days after full bloom and received the following treatments: DPA (2,000 ppm); 1-MCP (1.2 ppm) and control (no treatment). All fruit was stored for 4 or 6 months at 0 degree centigrade. A completely randomized factorial design was used (2 harvest dates by 3 post harvest treatments). Monthly measurements were made on maturity indices, ethylene production rate (EPR), scald related compounds [a-farnesene (AF), conjugated trienes (CT), total anti-oxidants (AO)], and cell membrane stability. Following 4 and 6 months of storage, plus 7 days at 20 degree centigrade, scald was evaluated. After 6 months, DPA-treated fruit, from both harvests, showed similar firmness, EPR and AO, compared to the control. However, AF and CT were lower, and cell membrane stability higher. Conversely, 1-MCP-treated fruit showed a noticeable EPR suppression and AF inhibition, along with higher firmness, lower CT and AO, compared to the control and DPA. Furthermore, cell membrane stability was superior to that of the control and similar to that of the DPA. Treated fruit (DPA and 1-MCP) showed an important reduction in scald compared to the control. The effect of 1-MCP on the investigated compounds and the reduction in scald, confirms that ethylene plays a major role on its development. (Author) 50 refs.

Relative contributions of decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 in the protection of melanocytes from homologous complement

NARCIS (Netherlands)

Venneker, G. T.; Vodegel, R. M.; Okada, N.; Westerhof, W.; Bos, J. D.; Asghar, S. S.

1998-01-01

Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed

IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay

DEFF Research Database (Denmark)

Ruhwald, Morten; Bjerregaard-Andersen, Morten; Rabna, Paulo

2009-01-01

and mitogen in the Quantiferon In Tube test tubes. Levels of biomarkers were measured using Luminex and ELISA (IFN-gamma). RESULTS: We found all five new biomarkers were expressed in significantly higher concentrations compared to IFN-gamma. IP-10 and MCP-3 levels in the un-stimulated samples were higher...

A case-control association study between Obsessive-Compulsive Disorder (OCD and the MCP-1 -2518G/A polymorphism in a Chinese sample Estudo de associação de casos-controle entre Transtorno Obsessivo-Compulsivo (TOC e polimorfismo MCP-1 -2518G/A em uma coorte chinesa

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Xinhua Zhang

2012-12-01

Full Text Available OBJECTIVE: To investigate the association between Obsessive-Compulsive Disorder (OCD and a functional polymorphism of MCP-1 in the Chinese Han population. METHOD: We genotyped and performed a case-control association analysis of the MCP-1 -2518G/A polymorphism in 200 OCD patients and 294 healthy control subjects. RESULTS: There was no significant difference in MCP-1 -2518G/A genotypic and allelic frequencies between OCD cases and controls (x² = 1.123, df = 2, P = 0.57 by genotype; x² = 0.802, df = 1, P = 0.37 by allele. CONCLUSIONS: Our results indicated that MCP-1 -2518G/A may not play a major role in the genetic predisposition of the Chinese Han population to OCD. However, further studies using a larger number of subjects are required to obtain a clear conclusion.OBJETIVO: Investigar a relação entre Transtorno Obsessivo-Compusilvo (TOC e um polimorfismo funcional de MCP-1 na população chinesa de etnia Han. MÉTODOS: Determinamos os genótipos e realizamos uma análise de associações de casos-controle de polimorfismo MCP-1 -2518G/A em 200 indivíduos com TOC e 294 indivíduos saudáveis (controle. RESULTADOS: Não houve diferença significativa no genótipo MCP-1 -2518G/A e nas frequências alélicas entre casos de TOC e controles (x² = 1,123, df = 2, P = 0,57 por genotipo; x² = 0,802, df = 1, P = 0,37 por alelo. CONCLUSÕES: Nossos resultados indicaram que MCP-1 -2518G/A pode não ter grande participação na predisposição genética da etnia Han no que diz respeito ao TOC. Contudo, novos estudos com um maior número de indivíduos são necessários para uma conclusão mais clara.

TOF-SIMA analysis of coating on MCP

International Nuclear Information System (INIS)

Luo Chunping; Liang Handong; Sun Dongxu

2007-01-01

Microchannel plate (MCP) is a sophisticated electronic optical device. It has advantages of high gain, small size, and low using voltage as a detector. The electronic transmission film on the MCP input plane could effectively avoid the positive ion feedback, and protect the photocathode, eliminate flicker noise, and prolong the lifespan of the device. In conclusion, the different films of the input plane can affect the performance of the MCP. Therefore, there is practical value to study surface coating composition of MCP for understanding the relationship between composition and performance and developing high-powered MCP. In the experiment, TOF-SIMS is used to study the surface coating composition of MCP. The results show that there are some main metal elements such as Si, K, Cr, Ni, Rh, Cs and Pb in the surface of the MCP. (authors)

Postharvest quality of ‘Galaxy’ apples submitted to the treatment with 1-MCP and different cooling times between harvest and cold storage

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Crizane Hackbarth

Full Text Available ABSTRACT: In this research it was evaluated if the use of 1-methylcyclopropene (1-MCP, associated to different cooling times between the harvest and storage, replaces the pre-cooling in ‘Galaxy’ apples. Treatments were arranged in a factorial scheme, combining the following factors: application of 1-MCP (with or without and different times between harvest and cooling (24 hours, 96 hours, 144 hours and 192 hours in 2013; and 24 hours, 48 hours, 144 hours and 240 hours in 2014. After four months of cold storage (1.0±0.2°C/92±5% RH - Relative Humidity were evaluated: flesh firmness, texture, titratable acidity (TA, soluble solids (SS and skin color. Apples treated with 1-MCP showed greater flesh firmness, texture and SS, in both years, and more TA and lower incidence of mealy flesh compared to apples not treated with 1-MCP in 2013. The 1-MCP was effective in maintaining the fruit quality, even with the cooling delay of up to 240 hours. Cooling delay of 192 hours and 240 hours in ‘Galaxy’ apples not treated with 1-MCP should be avoided because it reduces the quality of fruits.

Changes in quality and biochemical parameters in 'Idared' apples during prolonged shelf life and 1-MCP treatment.

Science.gov (United States)

Bizjak, Jan; Slatnar, Ana; Stampar, Franci; Veberic, Robert

2012-12-01

In this study, changes in quality and various biochemical parameters of 'Idared' apples during prolonged shelf life period after ultra-low oxygen (ULO) storage were investigated. Additionally, the impact of the postharvest application of 1-methylcyclopropene (1-MCP) on different parameters was evaluated. After the harvest, apples were stored in the ULO storage for 6 months and then exposed to room temperature. Fruit firmness, peel color, and changes in sugars, organic acids and phenolics were monitored during the 3 weeks of shelf life. Malic acid, sugars and firmness decreased at room temperature. However, the color of the apples remained unchanged. The level of citric and ascorbic acid remained constant. Levels of phenolics in the peel increased significantly, whereas remained constant in the pulp of apples. 1-MCP treatment resulted in higher amounts of fructose and glucose, malic acid and greater firmness of apples. However, 1-MCP did not influence the phenolic content, ascorbic acid or color. The results obtained indicate that the content of different health-promoting compounds of apples does not change dramatically at room temperature. At the same time these results suggest that 1-MCP could be useful for maintaining certain quality and biochemical parameters and might extend the shelf life of apples.

Monocyte chemoattractant protein 1, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in exudative age-related macular degeneration.

Science.gov (United States)

Jonas, Jost B; Tao, Yong; Neumaier, Michael; Findeisen, Peter

2010-10-01

To examine intraocular concentrations of monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and vascular endothelial growth factor (VEGF) in eyes with exudative age-related macular degeneration (AMD). The investigation included a study group of 28 patients (28 eyes) with exudative AMD and a control group of 25 patients (25 eyes) with cataract. The concentrations of MCP-1, sICAM-1, sVCAM-1, and VEGF in aqueous humor samples obtained during surgery were measured using a solid-phase chemiluminescence immunoassay. The study group as compared with the control group had higher aqueous concentrations of sICAM-1 (mean [SD], 844 [2073] vs 246 [206] pg/mL, respectively; P < .001), sVCAM-1 (mean [SD], 7978 [7120] vs 2999 [1426] pg/mL, respectively; P < .001), and MCP-1 (mean [SD], 587 [338] vs 435 [221] pg/mL, respectively; P = .07). The concentration of VEGF did not vary significantly between the groups (P = .76). The MCP-1 concentration was significantly associated with macular thickness (r = 0.40; P = .004). It decreased significantly with the type of subfoveal neovascular membrane (classic membrane type, occult membrane, retinal pigment epithelium detachment) (P = .009). The concentrations of sICAM-1, sVCAM-1, and VEGF were not significantly associated with membrane type and macular thickness (P ≥ .18). Concentrations of MCP-1, sICAM-1, and sVCAM-1 are significantly associated with exudative AMD, even in the presence of normal VEGF concentrations. Intraocular MCP-1 concentrations are correlated with the subfoveal neovascular membrane type and the amount of macular edema. One may infer that MCP-1, sICAM-1, and sVCAM-1 could potentially be additional target molecules in therapy for exudative AMD.

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

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Malathesha Ganachari

2010-01-01

Full Text Available We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

Science.gov (United States)

Ganachari, Malathesha; Ruiz-Morales, Jorge A; Gomez de la Torre Pretell, Juan C; Dinh, Jeffrey; Granados, Julio; Flores-Villanueva, Pedro O

2010-01-25

We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

Efficiency enhancements for MCP-based beta autoradiography imaging

CERN Document Server

Lees, J E

2002-01-01

We describe three approaches to increase the beta detection efficiency of microchannel plate detectors for biological beta autoradiography:(a)reversing the microchannel plate (MCP) bias polarity, changing the conventional high negative voltage on the input MCP to a grounded input, (b) a reduction in MCP pore size from 12.5 to 6 mu m, (c) using a CsI coating as an efficient secondary electron emitter. We also present our first measurements of double-tracer ( sup 3 H and sup 1 sup 4 C) imaging using pulse height analysis to distinguish between isotopes.

Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.

Science.gov (United States)

Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T

2016-01-01

Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.

Aumento da expressão do MCP-1 coroidal e escleral em modelo experimental de hipercolesterolemia

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Rogil José de Almeida Torres

2012-02-01

Full Text Available OBJETIVO: O objetivo deste trabalho é demonstrar experimentalmente que a dieta rica em colesterol provoca aumento da expressão da MCP-1 na coroide e esclera. MÉTODO: Coelhos New Zealand foram organizados em dois grupos: GN (grupo dieta normal, composto por 8 coelhos (8 olhos, recebeu ração padrão para coelhos, durante 4 semanas; GH (grupo hipercolesterolêmico, composto por 13 coelhos (13 olhos, recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 8ª semana para o GH e 4ª semana para o GN foi realizada a eutanásia dos animais e os olhos foram submetidos à análise imuno-histoquímica com o anticorpo anti-MCP-1. RESULTADOS: A dieta provocou significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001. Houve significativo aumento da expressão da MCP-1 na coroide e esclera dos animais do GH em relação ao GN (p<0,001. CONCLUSÃO: Este estudo demonstrou que a dieta hipercolesterolêmica em coelhos induz ao aumento da expressão do MCP-1 na coroide e esclera.

Generation and partial characterization of an eosinophil chemotactic cytokine produced by sensitized equine mononuclear cells stimulated with Strongylus vulgaris antigen.

Science.gov (United States)

Dennis, V A; Klei, T R; Chapman, M R

1993-07-01

Supernatants generated by stimulation of peripheral blood mononuclear cells (PBMC) from Strongylus vulgaris sensitized or immunized ponies were assayed in vitro for eosinophil chemotactic activity (ECA) using the filter system in blind well chambers. The supernatants from these cultures were chemotactic for eosinophils, but not for neutrophils. Supernates from cultures of unsensitized PBMC stimulated with S. vulgaris antigen were not chemotactic for eosinophils. ECA was first detected in culture supernatants after 1.5 h of incubation and was dependent on both antigen and PBMC concentrations, but independent of serum concentrations. Both female and male S. vulgaris worm antigens stimulated ECA production from sensitized PBMC. ECA was not induced by in vitro stimulation of sensitized S. vulgaris PBMC by female Strongylus edentatus worm antigen. Partial characterization of the eosinophil chemotactic cytokine showed it to be nondialyzable, greater than 8000 molecular weight (MW), and sensitive to heating (56 and 95 degrees C), trypsin, and sodium metaperiodate treatments, suggesting that the cytokine is a protein containing some essential carbohydrate moieties. The cytokine described in this paper could partially contribute to the in vivo blood and tissue eosinophilia in experimental S. vulgaris infection.

Diclofenac, a selective COX-2 inhibitor, inhibits DMH-induced colon tumorigenesis through suppression of MCP-1, MIP-1α and VEGF.

Science.gov (United States)

Kaur, Jasmeet; Sanyal, S N

2011-09-01

Angiogenesis is a physiological process involving growth of new blood vessels from pre-existing ones; however, it also plays a critical role in tumor progression. It favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore targeting angiogenesis will be profitable as a mechanism to inhibit tumor's lifeline. Further, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF)-master switch in angiogenesis and other molecules in the neoplastic and pro-inflammatory milieu. We studied the role of two important chemokines [monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-lα] alongwith VEGF and matrix metalloproteinases (MMPs) in non-steroidal anti-inflammatory drugs (NSAIDs)-induced chemopreventive effect in experimental colon cancer in rat. 1,2-Dimethylhydrazine (DMH, 30 mg/kg body weight, subcutaneously (s.c.) once-a-week) for 18 wk was used as pro-carcinogen and diclofenac (8 mg/kg body weight, orally daily) as the preferential cyclooxygenase-2 (COX-2) inhibitor. Expression of COX-2 and VEGF was found to be significantly elevated in the DMH-treated group as compared to the control, which was lowered notably by Diclofenac co-administration with DMH. Gelatin zymography showed prominent MMP-9 activity in the DMH-treated rats, while the activity was nearly absent in all the other groups. Expression of MCP-1 was found to be markedly increased whereas MIP-1α expression was found to be decreased in colonic mucosa from DMH-treated rats, which was reversed in the DMH + Diclofenac group. Our results indicate potential role of chemokines alongwith VEGF in angiogenesis in DMH-induced cancer and its chemoprevention with diclofenac. Copyright ©2011 Wiley-Liss, Inc.

EFECTO DEL 1-METILCICLOPROPENO (1-MCP SOBRE LA FISIOLOGÍA Y CALIDAD DE FRUTOS DE JACA (Artocarpus heterophyllus Lam.

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M. Mata-Montes de Oca

2007-01-01

Full Text Available Debido a sus características de color y sabor de pulpa, la demanda de fruta de jaca se ha incrementado considerablemente. La mayoría de la producción de Nayarit es exportada a los Estados Unidos de Norteamérica. Sin embargo, debido a su corta vida de anaquel y susceptibilidad al daño por frío la fruta es exportada vía aérea con altos costos de flete. Se reporta que el 1-Metilciclopropeno (1-MCP retarda el proceso de madurez, alarga la vida de anaquel y mantiene la calidad de varios frutales, así que el objetivo de este estudio fue evaluar el efecto del 1-MCP sobre la fisiología y calidad del fruto de jaca almacenado a 20 ºC. Las frutas fueron cosechadas en madurez fisiológica, lavadas y tratadas con 1-MCP a 100 y 300 nl·litro-1 en cámaras selladas por 12 h a 20 ± 1 ºC; 85 ± 5 % de HR manteniendo un testigo sin tratar. Las variables evaluadas fueron: velocidad de respiración y de producción de etileno, sólidos solubles totales, acidez titulable, firmeza de la pulpa y de la fruta entera, color en la pulpa y pérdida de peso. El 1-MCP no afectó la mayoría de las variables de calidad pero retrasó significativamente la velocidad de respiración y la producción de etileno así como el ablandamiento de la pulpa, lo que permitió prolongar la vida de anaquel hasta por ocho y 12 días a 100 y 300 nl·litro-1, respectivamente.

Effects of Roux-en-Y Gastric Bypass on Fasting and Postprandial Levels of the Inflammatory Markers YKL-40 and MCP-1 in Patients with Type 2 Diabetes and Glucose Tolerant Subjects

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Stine Brinkløv Thomsen

2013-01-01

Full Text Available Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1 are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states, following Roux-en-Y gastric bypass (RYGB in subjects with type 2 diabetes (T2D and normal glucose tolerance (NGT. Methods. Ten obese patients with T2D and 10 subjects with NGT were examined in the fasting state and after a standard meal prior to and after (1 week, 3 months, and 1 year RYGB. Results. Fasting state MCP-1 levels decreased after RYGB in both groups (P values < 0.0001 whereas fasting YKL-40 levels were unchanged (P values ≥ 0.120. Postprandial MCP-1 levels showed a tendency towards a decrease on most study days; however, the changes were only significant at 1 week (P=0.001 and 1 yr (P<0.0001 in the T2D group and at 3 mo after RYGB in the NGT group (P=0.009. YKL-40 levels showed a slight, postprandial suppression on all study days in the T2D group (all P values ≤ 0.021. Conclusions. Fasting MCP-1 levels, but not YKL-40 levels, decrease after RYGB in subjects with T2D and NGT. Postprandial changes of inflammatory markers are discrete and inconsistent.

Relationship between genetic polymorphisms in MCP-1, CCR-2, and non-small-cell lung cancer in the Han nationality of Northern China.

Science.gov (United States)

Yang, L; Wang, J; Li, F-G; Han, M; Chang, X-J; Wang, Z-T

2015-04-22

Lung cancer is a common malignant tumor worldwide and is now the leading cause of cancer-related deaths. Monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) are important chemokines. We examined the polymorphisms of 338 unrelated patients with non-small cell lung carcinoma (NSCLC) and 200 unrelated healthy controls of Han nationality in Northern China using polymerase chain reaction-restriction fragment length polymorphism. We found a significant increase in the frequency of the MCP-1 AA genotype [0.293 vs 0.195, odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.60] and a significant decrease in the frequency of the GG genotype (0.290 vs 0.41, OR = 0.64, 95%CI = 0.47-0.87) in NSCLC patients compared to controls. The frequencies of AA-ww (0.151 vs 0.090, P = 0.041, OR = 1.80, 95%CI = 1.33-2.43) and AA-wm (0.136 vs 0.080, P = 0.049, OR = 1.81, 95%CI = 1.01-3.27) were higher in lung cancer patients than in healthy controls; the frequency of GG-wm (0.121 vs 0.190, P = 0.030, OR = 0.60, 95%CI = 0.38-0.95) was lower in lung cancer patients than in healthy controls. Based on these results, the polymorphism in MCP-1 may be correlated with the development of NSCLC in the Han nationality of Northern China. However, the polymorphism in CCR-2 is not involved in NSCLC.

TRPV1 and the MCP-1/CCR2 Axis Modulate Post-UTI Chronic Pain.

Science.gov (United States)

Rosen, John M; Yaggie, Ryan E; Woida, Patrick J; Miller, Richard J; Schaeffer, Anthony J; Klumpp, David J

2018-05-08

The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.

MCP-1, ICAM-1 and VCAM-1 are present in early aneurysmal dilatation in experimental rats

International Nuclear Information System (INIS)

Jun Fan; Hao-Tong; Jing Di; Fang Liu; Hai-Hua Zhao; Shu-Ling Bai; Xiang Li; Linlin Zhong

2010-01-01

Recent studies have suggested that inflammation actively participates in ascending aortic aneurysm formation. The aim of the present study was to evaluate the expression changes of adhesion molecules and MMPs in an experimental model of ascending aortic aneurysm induced by ascending aorta banding in Wistar rats. Twelve rats developed aortic dilation after ascending aorta banding treatment, while nine normal animals underwent surgery without banding were used as controls. Light microscope and scanning electron microscope showed that the wall of the ascending aorta became disorganized as well as infiltration by inflammatory cells in aneurysmal rats. By using immunohistochemical techniques, a significant increase in the immunostaining of MCP-1 was observed in the aneurysmal wall as compared to the normal aortic wall. Under similar experimental conditions, we also found that the immunostaining of ICAM-1 and VCAM-1 was markedly increased in the aneurysmal wall. In addition, gelatin zymo graphic analysis showed that the expression and activities of MMP-2 and MMP-9 were remarkably enhanced in the ascending aorta of ascending aortic aneurysmal rats as compared to normal rats. These results demonstrate that MCP-1, ICAM-1 and VCAM-1 are involved in the pathogenesis of ascending aortic aneurysm and an increase in the immunostaining and activity of MMP-2 and MMP-9 may promote the progression of ascending aortic aneurysm. (authors)

Controlled atmosphere pO2 alters ripening dynamics of 1-MCP treated ‘d’Anjou’ pear (Pyrus communis L.) fruit

Science.gov (United States)

Ripening and development of physiological disorders and decay were assessed in ‘d’Anjou’ pear fruit following 1-methylcyclopropene (1-MCP) treatment and cold storage in air or controlled atmosphere (CA). Fruit were exposed after harvest to 0 or 12.6 µmol•L-1 1-MCP and then stored at 0.5 oC in air o...

Ethylene and 1-MCP affect the postharvest behavior of yellow pitahaya fruits (Selenicereus megalanthus Haw.

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Yuli Alexandra Deaquiz

2014-04-01

Full Text Available The pitahaya or dragon fruit is one of the most representative exotic fruits that Colombia has, with an important, growing international market, but the cultivation and postharvest of this fruit lack sufficient technological support to be more competitive. Therefore, alternatives that provide good-quality products that meet market requirements are very important. Therefore, the objective of this research was to determine the effect of a ripening retardant and ethylene application on the conservation and quality of pitahaya fruits and the possible changes during ripening associated with ethylene, for which a completely randomized design with three treatments was used, corresponding to the application of ethylene (ethephon, 3 mL L-1, 1-methylcyclopropene (1-MCP, 600 mg L-1 and a control, with four replications, for a total of 12 experimental units. The fruits were stored at 18°C with 75% relative humidity. The 1-MCP application significantly decreased the loss of firmness, total soluble solids, loss of fresh mass and respiratory rate. Fruits from the control and ethylene treatment tended toward a climateric respiratory behavior. The total carotenoid content of the fruits was significantly higher in the ethylene application and the control treatment, which was consistent with the color change of the fruits. It can be concluded that the 1-MCP application reduced the ethylene action, slowing the ripening of the dragon fruits.

Ion Feedback Suppression Using Inclined MCP Holes in a Single-MCP+Micromegas+Pads Detector

International Nuclear Information System (INIS)

Va'vra, J.; Sumiyoshi, T.

2005-01-01

We show that the ion backflow to photocathode can be completely suppressed if one uses inclined MCP holes in a presence of magnetic field. The inclined hole angles are chosen to be aligned with the Lorentz electron angle allowing the electron transmission and amplification, while positive ions, traveling along a different angle, are caught on the MCP hole walls. The detector under investigation is a new gaseous detector structure based on a tandem of two parts, a single MCP (Microchannel) plate, a Micromegas with pad readout. We are aiming to develop a gaseous photon detector with the Bialkali photocathode, however, one could use some ideas in the paper for other types of detectors

Ion feedback suppression using inclined MCP holes in a 'single-MCP+micromegas+pads' detector

International Nuclear Information System (INIS)

Va'vra, J.; Sumiyoshi, T.

2005-01-01

We show that the ion backflow to photocathode can be completely suppressed if one uses inclined MCP holes in the presence of a magnetic field. The inclined hole angles are chosen to be aligned with the Lorentz electron angle allowing the electron transmission and amplification, while positive ions, traveling along a different angle, are caught on the MCP hole walls. The detector under investigation is a new gaseous detector structure based on a tandem of two parts, a single MCP (microchannel plate), a micromegas with pad readout. We are aiming to develop a gaseous photon detector with the Bialkali photocathode, however, one could use some ideas in the paper for other types of detectors

Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

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Blankenberg, F.G. [Div. of Pediatric Radiology, Stanford, CA (United States); Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A. [Division of Cardiovascular Medicine, Department of Medicine, Stanford, California (United States); Tait, J.F. [Dept. of Laboratory Medicine, Univ. of Washington, Seattle (United States); Post, A.M.; Strauss, H.W. [Div. of Nuclear Medicine, Stanford Univ., CA (United States)

2001-12-01

Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

International Nuclear Information System (INIS)

Blankenberg, F.G.; Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A.; Tait, J.F.; Post, A.M.; Strauss, H.W.

2001-01-01

Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

Concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal

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Juliano Magalhães Guedes

2015-08-01

Full Text Available O objetivo desta revisão sistemática foi verificar a relação das concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal. As bases de dados investigadas PUBMED, SciELO, LILACS e Periódico Capes foram consultadas retrospectivamente para os últimos seis anos (2009 a 2014 utilizando combinações de palavras chaves como inflamação, IL-6, TNF-α, MCP-1 combinadas com crianças e escolares. Foram analisados 21 artigos. Foi encontrado associação entre sobrepeso/obesidade com IL-6, TNF-α e MCP-1 em 73,3% (11/15, 80% (12/15 e 60% (3/5 dos estudos que analisaram tais marcadores, respectivamente. Crianças com excesso de massa corporal possuem concentrações elevadas de IL-6, TNF-α e MCP-1 resultando em inflamação sistêmica crônica e aumentando o risco de desenvolvimento de outras doenças cardiovasculares. 

Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

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Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

2008-06-01

Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

Manejo da podridão de melão pelo controle do amadurecimento através do 1-mcp, sob duas condições de armazenamento Melon rot management by ripening control whith 1-MCP treatment under two storage conditions

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Daniel Terao

2009-06-01

Full Text Available Objetivou-se neste trabalho avaliar o efeito de 1-MCP (300 nL.L¹ nas alterações fisiológicas que ocorrem durante o amadurecimento do melão, tipo Orange cv. Orange Flesh e sua influência no controle da podridão causada por Fusarium pallidoroseum, em dois ambientes de armazenamento, sem refrigeração (29 ± 1 ºC e umidade relativa de 65 ± 2 % e refrigerado (10 ± 2 ºC e umidade relativa 90 ± 3 % durante 15 dias e nove dias adicionais em condição ambiente. Avaliouse a atividade respiratória, produção de etileno, perda de matéria fresca, cor da casca e da polpa, firmeza da polpa, pH, acidez total titulável, sólidos solúveis totais, açúcares solúveis totais e severidade da doença. O delineamento foi inteiramente casualizado em arranjo fatorial com quatro repetições/tratamento. Frutos tratados com 1-MCP, armazenados em ambiente sem refrigeração, mantiveram firmeza da polpa praticamente inalterada até o 15º dia e quando em refrigeração mantiveram-se inalterados até o final da avaliação aos 24 dias após a colheita, retardando também a abscisão do pedúnculo, uma variável indicativa de maturação. O tratamento com 1-MCP retardou o amadurecimento de frutos controlando a podridão de F. pallidoroseum. Este tratamento também reduziu a respiração, produção, etileno, perda de peso, não influenciando significativamente as variáveis de qualidade do fruto: coloração da casca e polpa dos frutos, teor de sólidos solúveis totais e açúcares solúveis totais durante o período de armazenamento, bem como pH e acidez total titulável nas diferentes condições de armazenamento estudadas. A refrigeração interagiu positivamente com o 1-MCP, aumentando o tempo de conservação e sanidade do melão.The objective of this experiment was to evaluate the effect of 1-replicates. Fruit treated with 1-MCP stored at room temperature MCP (at 300 nL.L-1on de physiological changes occurring during kept the pulp firmness until 15

Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1

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Simmons Zachary

2009-02-01

Full Text Available Abstract Background Polymorphisms in the MHC class 1-like gene known as HFE have been proposed as genetic modifiers of neurodegenerative diseases that include neuroinflammation as part of the disease process. Variants of HFE are relatively common in the general population and are most commonly associated with iron overload, but can promote subclinical cellular iron loading even in the absence of clinically identified disease. The effects of the variants as well as the resulting cellular iron dyshomeostasis potentially impact a number of disease-associated pathways. We tested the hypothesis that the two most common HFE variants, H63D and C282Y, would affect cellular secretion of cytokines and trophic factors. Methods We screened a panel of cytokines and trophic factors using a multiplexed immunoassay in human neuroblastoma SH-SY5Y cells expressing different variants of HFE. The influence of cellular iron secretion on the potent chemokine monocyte chemoattractant protein-1 (MCP-1 was assessed using ferric ammonium citrate and the iron chelator, desferroxamine. Additionally, an antioxidant, Trolox, and an anti-inflammatory, minocycline, were tested for their effects on MCP-1 secretion in the presence of HFE variants. Results Expression of the HFE variants altered the labile iron pool in SH-SY5Y cells. Of the panel of cytokines and trophic factors analyzed, only the release of MCP-1 was affected by the HFE variants. We further examined the relationship between iron and MCP-1 and found MCP-1 secretion tightly associated with intracellular iron status. A potential direct effect of HFE is considered because, despite having similar levels of intracellular iron, the association between HFE genotype and MCP-1 expression was different for the H63D and C282Y HFE variants. Moreover, HFE genotype was a factor in the effect of minocycline, a multifaceted antibiotic used in treating a number of neurologic conditions associated with inflammation, on MCP-1

Atherogenic ω-6 Lipids Modulate PPAR- EGR-1 Crosstalk in Vascular Cells

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Jia Fei

2011-01-01

Full Text Available Atherogenic ω-6 lipids are physiological ligands of peroxisome proliferator-activated receptors (PPARs and elicit pro- and antiatherogenic responses in vascular cells. The objective of this study was to investigate if ω-6 lipids modulated the early growth response-1 (Egr-1/PPAR crosstalk thereby altering vascular function. Rat aortic smooth muscle cells (RASMCs were exposed to ω-6 lipids, linoleic acid (LA, or its oxidized form, 13-HPODE (OxLA in the presence or absence of a PPARα antagonist (MK886 or PPARγ antagonist (GW9662 or PPAR-specific siRNA. Our results demonstrate that ω-6 lipids, induced Egr-1 and monocyte chemotactic protein-1 (MCP-1 mRNA and protein levels at the acute phase (1–4 hrs when PPARα was downregulated and at subacute phase (4–12 hrs by modulating PPARγ, thus resulting in altered monocyte adhesion to RASMCs. We provide novel insights into the mechanism of action of ω-6 lipids on Egr-1/PPAR interactions in vascular cells and their potential in altering vascular function.

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis

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Supanat Worawichawong

2016-12-01

Full Text Available Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1 and protective cytokines such as epidermal growth factor (EGF likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN. Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58. By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85, but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

Chondroitin Sulfate Inhibits Monocyte Chemoattractant Protein-1 Release From 3T3-L1 Adipocytes: A New Treatment Opportunity for Obesity-Related Inflammation?

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Thomas V Stabler

2017-08-01

Full Text Available Monocyte chemoattractant protein-1 (MCP-1 overproduction from inflamed adipose tissue is a major contributor to obesity-related metabolic syndromes. 3T3-L1 embryonic fibroblasts were cultured and differentiated into adipocytes using an established protocol. Adipocytes were treated with lipopolysaccharide (LPS to induce inflammation and thus MCP-1 release. At the same time, varying concentrations of chondroitin sulfate (CS were added in a physiologically relevant range (10-200 µg/mL to determine its impact on MCP-1 release. Chondroitin sulfate, a natural glycosaminoglycan of connective tissue including the cartilage extracellular matrix, was chosen on the basis of our previous studies demonstrating its anti-inflammatory effect on macrophages. Because the main action of MCP-1 is to induce monocyte migration, cultured THP-1 monocytes were used to test whether CS at the highest physiologically relevant concentration could inhibit cell migration induced by human recombinant MCP-1. Chondroitin sulfate (100-200 µg/mL inhibited MCP-1 release from inflamed adipocytes in a dose-dependent manner ( P  < .01, 95% confidence interval [CI]: −5.89 to −3.858 at 100 µg/mL and P  < .001, 95% CI: −6.028 to −3.996 at 200 µg/mL but had no effect on MCP-1–driven chemotaxis of THP-1 monocytes. In summary, CS could be expected to reduce macrophage infiltration into adipose tissue by reduction in adipocyte expression and release of MCP-1 and as such might reduce adipose tissue inflammation in response to pro-inflammatory stimuli such as LPS, now increasingly recognized to be relevant in vivo.

Comparison of the Effect of 1-MCP and Low-Pressure Air on Shelflife of Strawberry Fruit (Fragaria ananassa cv. Camarossa

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B. Modares

2013-10-01

Full Text Available Strawberry (Fragaria×ananassa has tasteful, fragrant and nutritious fruits. But, because of delicate texture and high metabolic activities of the fruits at maturity, are very sensitive and easily decayed, and thus have short shelflife. Ethylene is one of the main causes of postharvest fruit losses, which could reduce the shelflife of strawberry. Therefore, an experiment was carried out to examine the effect of 1 µL/L 1-MCP treatment and low-pressure air pretreatment at 0.2 atm in 2 hours on apparent and physicochemical characteristics of strawberry fruit, cultivar Camarossa, during storage in cold store. The study was performed as split plots in time, based on complete randomized design with 3 replications. The results showed that the highest marketability (90%, fruit firmness (7.95 N, titrable organic acids (1.15 g/100 cc, vitamin C (78.13 mg/100 cc and total soluble solids (10.48 % and the lowest amount of apparent decay (13.3 %, acidity (3.63 and taste index (9.04 were obtained in 1-MCP and low-pressure air treatments, which shows the effect of treatments on reducing the rate of biochemical variations in fruit texture. Correlation coefficients between all treatments were significant (P≤0.01. Meanwhile, the positive effect of 1-MCP on appearance and studied physicochemical characteristics was more than low-pressure air pretreatment. Even, the combination of these two treatments had no significant difference with 1-MCp treatment alone. In general, this observation depicts the more positive and significant effect of 1-MCP treatment in delaying the maturity and improving the qualitative traits of strawberry fruits after being stored in cold storage.

Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

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Gomez-Lopez Nardhy

2013-01-01

Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

Plasma leptin concentrations are greater in type II diabetic patients and stimulate monocyte chemotactic peptide-1 synthesis via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway

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Jin Joo Cha

2012-09-01

Conclusions: Overall, these findings suggest that activation of leptin synthesis may promote MCP-1 activation in a diabetic environment via the MAPK pathway in VSMCs and that it possibly contributes to the acceleration of atherosclerosis.

Strontium-Substituted Bioceramics Particles: A New Way to Modulate MCP-1 and Gro-α Production by Human Primary Osteoblastic Cells

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Julien Braux

2016-12-01

Full Text Available Background: To avoid morbidity and limited availability associated with autografts, synthetic calcium phosphate (CaP ceramics were extensively developed and used as bone filling materials. Controlling their induced-inflammatory response nevertheless remained a major concern. Strontium-containing CaP ceramics were recently demonstrated for impacting cytokines’ secretion pattern of human primary monocytes. The present study focuses on the ability of strontium-containing CaP to control the human primary bone cell production of two major inflammatory and pro-osteoclastogenic mediators, namely MCP-1 and Gro-α, in response to ceramics particles. Methods: This in vitro study was performed using human primary osteoblasts in which their response to ceramics was evaluated by PCR arrays, antibody arrays were used for screening and real-time PCR and ELISA for more focused analyses. Results: Study of mRNA and protein expression highlights that human primary bone cells are able to produce these inflammatory mediators and reveal that the adjunction of CaP in the culture medium leads to their enhanced production. Importantly, the current work determines the down-regulating effect of strontium-substituted CaP on MCP-1 and Gro-α production. Conclusion: Our findings point out a new capability of strontium to modulate human primary bone cells’ communication with the immune system.

Storage of strawberries (Fragaria ananassa L. cv. ‘Oso Grande’, subjected to 1-MCP - doi: 10.4025/actascitechnol.v34i3.8790

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Polyanna Alves Silva

2012-05-01

Full Text Available This study aimed to investigate the influence of 1 - methylcyclopropene (1-MCP on the substances involved in the softening of strawberry, cultivar Oso Grande, stored at room temperature, from the municipality of Itutinga, State of Minas Gerais. The parameters evaluated were: firmness, total pectin, percentage of solubilization, activities of the enzymes pectinmethylesterase (PME (EC 3.1.1.11 and polygalacturonase (PG (EC 3.2.1.15. It was concluded that 1-MCP delayed the softening of the fruits, since the fruits that were treated with 1-MCP after storage, have shown greater firmness, lower activities of PG and PME, and lower contents of total pectin, soluble pectin and percentage of solubilization. 

The chemotactic activity of sputum from patients with bronchiectasis.

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Mikami, M; Llewellyn-Jones, C G; Bayley, D; Hill, S L; Stockley, R A

1998-03-01

Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to be an important component of continuing inflammation and progression of chronic destructive lung diseases. Although chemoattractants are required for the PMN to migrate, the nature of the chemoattractants in the airways has not yet been clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4 receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19 patients with bronchiectasis were studied. In preliminary studies the chemotactic responses to IL-8 and LTB4 were found to be additive, and we were able to remove their contribution independently with the appropriate antibody and antagonist. The chemotactic activity of the secretions was related to the macroscopic appearance (mucoid, mucopurulent, and purulent), and this appeared to be related to an increase in IL-8 contribution. Chemotactic activity was reduced by antibiotic therapy and again that seemed to relate to a reduction in the IL-8 contribution. The contributions of LTB4 were similar among the three types of sputum in varying clinical states. These data suggest that LTB4 and IL-8 are important chemotactic factors in lung secretions from such patients, although IL-8 appears to play a more important role during acute exacerbations. These results may be useful in determining therapeutic strategies for chronic destructive lung diseases in the future.

Evidence for a novel chemotactic C1q domain-containing factor in the leech nerve cord.

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Tahtouh, Muriel; Croq, Françoise; Vizioli, Jacopo; Sautiere, Pierre-Eric; Van Camp, Christelle; Salzet, Michel; Daha, Mohamed R; Pestel, Joël; Lefebvre, Christophe

2009-02-01

In vertebrates, central nervous system (CNS) protection is dependent on many immune cells including microglial cells. Indeed, activated microglial cells are involved in neuroinflammation mechanisms by interacting with numerous immune factors. Unlike vertebrates, some lophotrochozoan invertebrates can fully repair their CNS following injury. In the medicinal leech Hirudo medicinalis, the recruitment of microglial cells at the lesion site is essential for sprouting of injured axons. Interestingly, a new molecule homologous to vertebrate C1q was characterized in leech, named HmC1q (for H. medicinalis) and detected in neurons and glial cells. In chemotaxis assays, leech microglial cells were demonstrated to respond to human C1q. The chemotactic activity was reduced when microglia was preincubated with signaling pathway inhibitors (Pertussis Toxin or wortmannin) or anti-human gC1qR antibody suggesting the involvement of gC1qR in C1q-mediated migration in leech. Assays using cells preincubated with NO chelator (cPTIO) showed that C1q-mediated migration was associated to NO production. Of interest, by using anti-HmC1q antibodies, HmC1q released in the culture medium was shown to exhibit a similar chemotactic effect on microglial cells as human C1q. In summary, we have identified, for the first time, a molecule homologous to mammalian C1q in leech CNS. Its chemoattractant activity on microglia highlights a new investigation field leading to better understand leech CNS repair mechanisms.

Anti-Inflammatory Effect of Myristicin on RAW 264.7 Macrophages Stimulated with Polyinosinic-Polycytidylic Acid

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Wansu Park

2011-08-01

Full Text Available Myristicin (1-allyl-5-methoxy-3,4-methylenedioxybenzene is an active aromatic compound found in nutmeg (the seed of Myristica fragrans, carrot, basil, cinnamon, and parsley. Myristicin has been known to have anti-cholinergic, antibacterial, and hepatoprotective effects, however, the effects of myristicin on virus-stimulated macrophages are not fully reported. In this study, the anti-inflammatory effect of myristicin on double-stranded RNA (dsRNA-stimulated macrophages was examined. Myristicin did not reduce the cell viability of RAW 264.7 mouse macrophages at concentrations of up to 50 µM. Myristicin significantly inhibited the production of calcium, nitric oxide (NO, interleukin (IL-6, IL-10, interferon inducible protein-10, monocyte chemotactic protein (MCP-1, MCP-3, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein (MIP-1α, MIP-1β, and leukemia inhibitory factor in dsRNA [polyinosinic-polycytidylic acid]-induced RAW 264.7 cells (P < 0.05. In conclusion, myristicin has anti-inflammatory properties related with its inhibition of NO, cytokines, chemokines, and growth factors in dsRNA-stimulated macrophages via the calcium pathway.

Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.

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Ye, Baixin; Xiong, Xiaoxing; Deng, Xu; Gu, Lijuan; Wang, Qiongyu; Zeng, Zhi; Gao, Xiang; Gao, Qingping; Wang, Yueying

2017-12-01

Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.

Dynamics of the Chemotactic Boycott Effect

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Cisneros, Luis; Wolgemuth, Charles; Tuval, Idan

2005-03-01

Aerobic bacteria often live in thin fluid layers on irregular surfaces, near solid-air-water contact lines where the interplay between fluid interface geometry, nutrient transport, and chemotaxis is central to the micro-ecology. To elucidate these processes, we use the simplified geometry of a sessile drop and provide direct experimental evidence for the ``chemotactic Boycott effect" in suspensions of B. subtilis: upward oxygentaxis toward the drop surface leads to accumulation of cells in a thin layer, which flows down to the contact line and produces there a persistent vortex which traps cells near the meniscus. These phenomena are explained quantitatively with a mathematical model consisting of coupled oxygen diffusion and consumption, chemotaxis, and viscous fluid dynamics; they are shown to be associated with a singularity in the chemotactic dynamics at the contact line.

Spatially and Temporally Regulated NRF2 Gene Therapy Using Mcp-1 Promoter in Retinal Ganglion Cell Injury

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Kosuke Fujita

2017-06-01

Full Text Available Retinal ganglion cell degeneration triggered by axonal injury is believed to underlie many ocular diseases, including glaucoma and optic neuritis. In these diseases, retinal ganglion cells are affected unevenly, both spatially and temporally, such that healthy and unhealthy cells coexist in different patterns at different time points. Herein, we describe a temporally and spatially regulated adeno-associated virus gene therapy aiming to reduce undesired off-target effects on healthy retinal neurons. The Mcp-1 promoter previously shown to be activated in stressed retinal ganglion cells following murine optic nerve injury was combined with the neuroprotective intracellular transcription factor Nrf2. In this model, Mcp-1 promoter-driven NRF2 expression targeting only stressed retinal ganglion cells showed efficacy equivalent to non-selective cytomegalovirus promoter-driven therapy for preventing cell death. However, cytomegalovirus promoter-mediated NRF2 transcription induced cellular stress responses and death of Brn3A-positive uninjured retinal ganglion cells. Such undesired effects were reduced substantially by adopting the Mcp-1 promoter. Combining a stress-responsive promoter and intracellular therapeutic gene is a versatile approach for specifically targeting cells at risk of degeneration. This strategy may be applicable to numerous chronic ocular and non-ocular conditions.

Local Production of Chemokines during Experimental Vaginal Candidiasis

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Saavedra, Michael; Taylor, Brad; Lukacs, Nicholas; Fidel, Paul L.

1999-01-01

Recurrent vulvovaginal candidiasis, caused by Candida albicans, is a significant problem in women of childbearing age. Although cell-mediated immunity (CMI) due to T cells and cytokines is the predominant host defense mechanism against C. albicans at mucosal tissue sites, host defense mechanisms against C. albicans at the vaginal mucosa are poorly understood. Based on an estrogen-dependent murine model of vaginal candidiasis, our data suggest that systemic CMI is ineffective against C. albicans vaginal infections. Thus, we have postulated that local immune mechanisms are critical for protection against infection. In the present study, the kinetic production of chemokines normally associated with the chemotaxis of T cells, macrophages (RANTES, MIP-1α, MCP-1), and polymorphonuclear neutrophils (MIP-2) was examined following intravaginal inoculation of C. albicans in estrogen-treated or untreated mice. Results showed significant increases in MCP-1 protein and mRNA in vaginal tissue of infected mice as early as 2 and 4 days postinoculation, respectively, that continued through a 21-day observation period, irrespective of estrogen status. No significant changes were observed with RANTES, MIP-1α, or MIP-2, although relatively high constitutive levels of RANTES mRNA and MIP-2 protein were observed. Furthermore, intravaginal immunoneutralization of MCP-1 with anti-MCP-1 antibodies resulted in a significant increase in vaginal fungal burden early during infection, suggesting that MCP-1 plays some role in reducing the fungal burden during vaginal infection. However, the lack of changes in leukocyte profiles in vaginal lavage fluids collected from infected versus uninfected mice suggests that MCP-1 functions to control vaginal C. albicans titers in a manner independent of cellular chemotactic activity. PMID:10531235

Lifetime of MCP-PMTs and other performance features

Science.gov (United States)

Lehmann, A.; Böhm, M.; Eyrich, W.; Miehling, D.; Pfaffinger, M.; Stelter, S.; Uhlig, F.; Ali, A.; Belias, A.; Dzhygadlo, R.; Gerhardt, A.; Götzen, K.; Kalicy, G.; Krebs, M.; Lehmann, D.; Nerling, F.; Patsyuk, M.; Peters, K.; Schepers, G.; Schmitt, L.; Schwarz, C.; Schwiening, J.; Traxler, M.; Düren, M.; Etzelmüller, E.; Föhl, K.; Hayrapetyan, A.; Kreutzfeld, K.; Merle, O.; Rieke, J.; Schmidt, M.; Wasem, T.; Achenbach, P.; Cardinali, M.; Hoek, M.; Lauth, W.; Schlimme, S.; Sfienti, C.; Thiel, M.

2018-02-01

The bar PANDA experiment at FAIR will use DIRC detectors for the separation of hadrons. The compactness of the bar PANDA detector requires the image planes of these detectors to be placed inside the magnetic field of the solenoid. Due to this and other boundary conditions MCP-PMTs were identified as the only suitable photon sensors. Until recently the major obstacle for an application of MCP-PMTs in high rate experiments like bar PANDA were serious aging problems which led to damage at the photo-cathode and a fast declining quantum efficiency as the integrated anode charge (IAC) increased. With new countermeasures against the aging, in particular due to the application of an atomic layer deposition (ALD) technique to coat the MCP pores, the lifetime of MCP-PMTs has meanwhile increased by a factor >50 which is fully sufficient for bar PANDA. The recent results of our long-term lifetime measurements are discussed. New 2-inch MCP-PMT prototypes from Hamamatsu show an encouraging behavior. However, the currently best performing MCP-PMT is a 2-inch PHOTONIS tube with two ALD-layers which reaches an IAC of >16 C/cm2 without any visible sign of aging. In the second part of these proceedings a new data acquisition system of the PADIWA/TRB type is presented which allows a quasi-parallel measurement of many MCP-PMT performance parameters. Especially unwanted effects like dark-count rate, crosstalk, ion after-pulsing, and recoil electrons can be studied in more detail than ever before. Exemplary results for these parameters are shown. The discussed DAQ system will be used for the comprehensive data quality checks of the MCP-PMTs being built into the DIRCs.

Novel biochemical markers of psychosocial stress in women.

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Marie Asberg

Full Text Available BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma, tumor necrosis factor-alpha (TNF-alpha, monocyte chemotactic protein-1 (MCP-1, epidermal growth factor (EGF, vascular endothelial growth factor (VEGF, thyroid stimulating hormone (TSH, total tri-iodothyronine (TT3, total thyroxine (TT4, prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation

Energy Technology Data Exchange (ETDEWEB)

Morooka, Nobukatsu, E-mail: amorooka@gunma-u.ac.jp [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Ueguri, Kei [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Yee, Karen Kar Lye [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan); Human Resources Cultivation Center, Gunma University, 1-5-1 Tenjin-cho, Kiryushi, Gunma, 376-8515 (Japan); Yanase, Toshihiko [Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, 814-0180 (Japan); Sato, Takashi [Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512 (Japan)

2016-09-02

Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

Androgen-androgen receptor system improves chronic inflammatory conditions by suppressing monocyte chemoattractant protein-1 gene expression in adipocytes via transcriptional regulation

International Nuclear Information System (INIS)

Morooka, Nobukatsu; Ueguri, Kei; Yee, Karen Kar Lye; Yanase, Toshihiko; Sato, Takashi

2016-01-01

Age-related decreases in sex hormones are closely related to chronic inflammation in obesity and metabolic diseases. Particularly, the molecular basis of androgen activity in regulating inflammation and controlling metabolism remains largely unknown. Obese adipocytes secrete monocyte chemoattractant protein-1 (MCP-1), a key chemokine that promotes the infiltration of monocytes/macrophages into adipose tissue, thereby leading to metabolic disorders. Here, we studied the role of androgen-androgen receptor (AR) action in regulating MCP-1 expression in adipose tissue. We observed the induction of Mcp-1 expression in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. Additionally, Mcp-1 expression was upregulated by culturing in conditioned medium derived from inflammatory macrophages (M1-Mφ) containing tumor necrosis factor-alpha (TNF-α). We found that sex hormones downregulated TNF-α-induced Mcp-1 and interleukin (Il)-6 expression in 3T3-L1 adipocytes. Furthermore, luciferase-reporter analysis indicated that MCP-1 promoter activity was predominantly suppressed by dihydrotestosterone (DHT)-AR interactions through functional canonical nuclear factor-kappa B (NF-κB) sites, whereas non-canonical NF-κB site containing important flanking sequences exhibited minor contributions to DHT-AR transcriptional repression. These findings suggested that androgen-AR suppressed obesity-induced chronic inflammation in adipose tissue. - Highlights: • DHT, non-aromatizable androgen suppresses Mcp-1 expression in adipocytes. • Mcp-1 transcription was negatively regulated by DHT-AR action. • DHT-AR selectively regulates Mcp-1 transcription through distinct NF-κB sites.

Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis.

Science.gov (United States)

Pan, Y W; Zhou, Z G; Wang, M; Dong, J Q; Du, K P; Li, S; Liu, Y L; Lv, P J; Gao, J B

2016-11-03

Early detection and treatment is critically important for lung cancer patients. Inflammatory mediators such as IL-6, IL-10, and MCP-1 participate in lung cancer regulation. CEA, CA125, and ProGRP are commonly used serum tumor markers for lung cancer. In this study, we assessed the sensitivity and specificity of CEA, CA125, and ProGRP when used in combination with IL-6, IL-10, and MCP in lung cancer diagnosis. Serum from three different groups (healthy controls, individuals with high risk for lung cancer, and lung cancer patients) was collected. Electrochemiluminescence was used to detect expressions of CEA, CA125, and ProGRP; ELISA was used to examine serum levels of IL-6, IL-10, and MCP-1. Specificity and sensitivity of single as well as combination markers in lung cancer diagnosis were determined. Results indicated that CEA, CA125, ProGRP, and MCP-1 were significantly up-regulated in lung cancer patients as compared to those in controls and high risk individuals. Higher IL-6 and IL-10 levels were observed in both lung cancer patients and high-risk individuals as compared to those in controls. Highest sensitivity (95.2%) in cancer diagnosis was achieved when all six markers were used. This was followed by a combination of IL-6, IL-10, CEA, CA125, and ProGRP (92.6%). The most sensitive (88.6%). Four-marker combination was composed of IL-6, CEA, CA125, and ProGRP. As the combined usage of CEA, CA125, ProGRP, IL-6, IL-10, and MCP-1 significantly improved sensitivity of lung cancer detection; this biomarker arrangement may be beneficial for early diagnosis, treatment, and prognosis of lung cancer.

Single electron counting using a dual MCP assembly

International Nuclear Information System (INIS)

Yang, Yuzhen; Liu, Shulin; Zhao, Tianchi; Yan, Baojun; Wang, Peiliang; Yu, Yang; Lei, Xiangcui; Yang, Luping; Wen, Kaile; Qi, Ming

2016-01-01

The gain, pulse height resolution and peak-to-valley ratio of single electrons detected by using a Chevron configured Microchannel Plate (MCP) assembly are studied. The two MCPs are separated by a 280 µm gap and are biased by four electrodes. The purpose of the study is to determine the optimum bias voltage arrangements for single electron counting. By comparing the results of various bias voltage combinations, we conclude that good performance for the electron counting can be achieved by operating the MCP assembly in saturation mode. In addition, by applying a small reverse bias voltage across the gap while adjusting the bias voltages of the MCPs, optimum performance of electron counting can be obtained. - Highlights: • Dual MCPs assembly with four electrodes using different voltage combinations has been investigated for single electron counting. • Both the MCP voltages and the gap voltage can affect the gain, pulse height resolution and P/V ratio. • A high gain of the first stage MCP, a saturation mode of the second stage MCP and an appropriately reverse gap voltage can improve the resolution greatly. • The optimum voltage arrangements is significant for the design of MCP detectors in single electron counting applications.

The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice

Energy Technology Data Exchange (ETDEWEB)

Choi, Jeong A. [Neural Injury Research Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Chung, Yoo-Ri [Department of Ophthalmology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Byun, Hyae-Ran [Neural Injury Research Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Park, Hwangseo [Department of Bioscience and Biotechnology, Sejong University, Seoul (Korea, Republic of); Koh, Jae-Young, E-mail: jkko@amc.seoul.kr [Neural Injury Research Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yoon, Young Hee, E-mail: yhyoon@amc.seoul.kr [Department of Ophthalmology, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2017-01-15

Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) or modified low-density lipoprotein (mLDL). The diameter of retinal vessels and the number of pericytes were severely reduced, and the levels of MCP1 and PKC were increased in STZ-induced diabetic mice. Administration of riluzole reversed all of these changes. Furthermore, the increased expression of MCP1 in AGE- or mLDL-treated cultured retinal pericytes was inhibited by treatment with riluzole or the PKC inhibitor GF109203X. In silico modeling showed that riluzole fits well within the catalytic pocket of PKC. Taken together, our results demonstrate that riluzole attenuates both MCP1 induction and pericyte loss in diabetic retinopathy, likely through its direct inhibitory effect on PKC. - Highlights: • The effects of riluzole were examined in streptozotocin-induced diabetic mice. • The diameter of retinal vessels and the number of pericytes were severely reduced. • The levels of MCP1 and PKC were increased, while riluzole reversed all changes. • Riluzole attenuated the level of MCP1 in AGE- or mLDL-treated retinal pericytes. • Riluzole attenuated both MCP1 induction and pericyte loss in diabetic retinopathy.

The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice

International Nuclear Information System (INIS)

Choi, Jeong A.; Chung, Yoo-Ri; Byun, Hyae-Ran; Park, Hwangseo; Koh, Jae-Young; Yoon, Young Hee

2017-01-01

Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) or modified low-density lipoprotein (mLDL). The diameter of retinal vessels and the number of pericytes were severely reduced, and the levels of MCP1 and PKC were increased in STZ-induced diabetic mice. Administration of riluzole reversed all of these changes. Furthermore, the increased expression of MCP1 in AGE- or mLDL-treated cultured retinal pericytes was inhibited by treatment with riluzole or the PKC inhibitor GF109203X. In silico modeling showed that riluzole fits well within the catalytic pocket of PKC. Taken together, our results demonstrate that riluzole attenuates both MCP1 induction and pericyte loss in diabetic retinopathy, likely through its direct inhibitory effect on PKC. - Highlights: • The effects of riluzole were examined in streptozotocin-induced diabetic mice. • The diameter of retinal vessels and the number of pericytes were severely reduced. • The levels of MCP1 and PKC were increased, while riluzole reversed all changes. • Riluzole attenuated the level of MCP1 in AGE- or mLDL-treated retinal pericytes. • Riluzole attenuated both MCP1 induction and pericyte loss in diabetic retinopathy.

Prolongamento da vida pós-colheita de bananas-maçã submetidas ao 1-metilciclopropeno (1-MCP - qualidade sensorial e física Extension of postharvest life of 'Apple1 banana subjected to1-methylcyclopropene (1-MCP - sensory and physical quality

Directory of Open Access Journals (Sweden)

Ana Carla Marques Pinheiro

2010-03-01

Full Text Available Objetivou-se avaliar o efeito do 1-metilciclopropeno (1-MCP sobre a qualidade e extensão da vida pós-colheita de bananas-maçã. Frutas no grau 2 de coloração da casca foram tratadas com 50 nL.L-1 de 1-MCP durante 0 (controle, 6, 9, 12 e 24 horas. Posteriormente, foram armazenadas sob condição ambiente: 22± 2 ºC 85± 5% UR. Avaliaram-se as características sensoriais: aparência dos frutos no grau 4 (frutos mais verdes que amarelos e grau 7 (frutos amarelos com pontuações marrons de coloração da casca; descasque, aroma, sabor, firmeza da polpa e aspecto global nos frutos no grau 7, utilizando-se um teste de aceitabilidade através de escala hedônica de 9 pontos; e ainda a intenção de compra nos frutos nos graus 4 e 7, através de escala de 5 pontos. Avaliou-se também, visualmente, a extensão da vida pós-colheita, e, instrumentalmente, a coloração da casca e firmeza da polpa. Conclui-se que a aplicação de 50 nL.L-1 por um período de 12 horas é a mais adequada, pois promove extensão na vida pós-colheita de bananas-maçã, armazenadas em temperatura ambiente, em aproximadamente 11 dias, sem alterar a qualidade sensorial, a intenção de compra, coloração da casca e firmeza dos frutos quando maduros, comparados ao controle.The objective of this work was to evaluate the effect of 1-methylcyclopropene (1-MCP on the quality and extension of postharvest life of 'Apple1 banana. The fruit, at degree 2 of peel color was treated with 50 nL.L-1 of 1-MCP for 0 (control, 6, 9, 12 and 24 hours. Next, It was stored at room temperature: 22± 2 ºC 85± 5 per cent RH. The following sensory characteristics were evaluated: appearance of the fruit at degree 4 (greener than yellow and degree 7 (yellow with brown spots of peel color; peeling, aroma, flavor, firmness of pulp and global aspect of the fruit at degree 7, using a test of acceptability using the 9-point hedonic scale and also the intention of buying the fruit at degrees 4 and 7

Comparisons of the Postprandial Inflammatory and Endotoxaemic Responses to Mixed Meals in Young and Older Individuals: A Randomised Trial

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Amber M. Milan

2017-04-01

Full Text Available Postprandial inflammation and endotoxaemia are determinants of cardiovascular and metabolic disease risk which are amplified by high fat meals. We aimed to examine the determinants of postprandial inflammation and endotoxaemia in older and younger adults following a high fat mixed meal. In a randomised cross-over trial, healthy participants aged 20–25 and 60–75 years (n = 15/group consumed a high-fat breakfast and a low-fat breakfast. Plasma taken at baseline and post-meal for 5 h was analysed for circulating endotoxin, cytokines (monocyte chemotactic protein-1 (MCP-1, interleukin (IL-1β, IL-6, and tumour necrosis factor-alpha (TNF-α, lipopolysaccharide binding protein (LBP, and inflammatory gene expression in peripheral blood mononuclear cells (PBMC. Older subjects had lower baseline PBMC expression of Glutathione peroxidase 1 (GPX-1 but greater insulin-like growth factor-binding protein 3 (IGFBP3 and circulating MCP-1 compared to younger subjects. After either meal, there were no age differences in plasma, chylomicron endotoxin, or plasma LBP concentrations, nor in inflammatory cytokine gene and protein expression (MCP-1, IL-1β, and TNF-α. Unlike younger participants, the older group had decreased superoxide dismutase (SOD-2 expression after the meals. After a high-fat meal, older adults have no increased inflammatory or endotoxin response, but an altered oxidative stress gene response compared with younger adults. Healthy older adults, without apparent metabolic dysfunction, have a comparable postprandial inflammatory and endotoxaemia response to younger adults.

Development of MCP transient operation strategy for the SMART-P

International Nuclear Information System (INIS)

Yoo, S. E.; Choi, B. S.; Kang, H. O.; Yoon, J. H.; Ji, S. K.

2003-01-01

SMART-P MCP(Main Coolant Pump) transient operation strategies are developed. A Modular Modeling System (MMS) computer code is used for the evaluation of the developed operation strategies. In the SMART-P, normal operating modes are classified into MCP high speed(3600 rpm) mode and MCP low speed mode. Also, natural circulation mode is defined as a performance test case. MCP operation transients occur when changing modes from one to another, and system parameters(core power, system pressure, temperature) are having transients. These transients affect on system performance and, in some cases, limit system operation. In this study, MCP operation strategies are developed and obtained acceptable results

Enhanced neutrophil chemotactic activity after bronchial challenge in subjects with grain dust-induced asthma.

Science.gov (United States)

Park, H S; Jung, K S

1998-03-01

There have been few reports suggesting involvement of neutrophils in induction of bronchoconstriction after inhalation of grain dust. To understand the role of neutrophils in pathogenesis of grain dust-induced asthma. We observed serum neutrophil chemotactic activity during grain dust-bronchoprovocation tests in six asthmatic subjects with positive bronchial challenges (group I). They were compared with those of six symptomatic subjects from the same workplace with negative bronchial challenges (group II). After grain dust inhalation, serum neutrophil chemotactic activity significantly increased at 30 minutes (P = .028), and then decreased to baseline level at 240 minutes (P = .028) in five subjects of group I having isolated early asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for up to 240 minutes in one asthmatic subject having both early and late asthmatic responses. There was, however, no significant change in serum neutrophil chemotactic activity during bronchial challenges in subjects of group II. Pre-incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the neutrophil chemotactic activity results of group I subjects. These results suggest that enhanced neutrophil chemotactic activity distinct from IL-8 may contribute to significant bronchoconstriction induced by grain dust.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

Science.gov (United States)

Na, Yong-Jin; Lee, Dong-Hyung; Kim, Seung-Chul; Joo, Jong-Kil; Wang, Ji-Won; Jin, Jun-O; Kwak, Jong-Young; Lee, Kyu-Sup

2011-06-01

Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

Energy Technology Data Exchange (ETDEWEB)

Gallin, J I

1974-01-01

The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

Urease plays an important role in the chemotactic motility of Helicobacter pylori in a viscous environment.

Science.gov (United States)

Nakamura, H; Yoshiyama, H; Takeuchi, H; Mizote, T; Okita, K; Nakazawa, T

1998-10-01

Helicobacter pylori exhibits chemotactic responses to urea, flurofamide, acetohydroxamic acid, and sodium bicarbonate. In buffer, the chemotactic activities of a urease-positive strain were higher than those of the isogenic urease-negative strain. Moreover, the chemotactic activities of the urease-positive strain were increased in a viscous solution containing 3% polyvinylpyrrolidone, whereas those of the urease-negative mutant were not. These results are in accordance with the fact that the mutant strain did not show swarming in motility agar regardless of having flagella. Incubation of the wild-type strain with flurofamide resulted in partial inhibition of the chemotactic activities in the viscous solution. In addition, incubation with acetohydroxamic acid, a low-molecular-weight, diffusible urease inhibitor, resulted in complete loss of chemotactic activity in the viscous solution. The inhibition of the chemotactic activity by urease inhibitors paralleled the inhibition of urease. The chemotactic activity of H. pylori was also inhibited by the proton carrier carbonyl cyanide m-chlorophenylhydrazone, showing that H. pylori utilizes proton motive force for motility. These results indicate that cytoplasmic urease plays an important role in the chemotactic motility of H. pylori under a condition that mimics the ecological niche of the bacterium, the gastric mucous layer.

Characterization of a proteolytically stable multifunctional host defense peptidomimetic

DEFF Research Database (Denmark)

Jahnsen, Rasmus D; Haney, Evan F; Franzyk, Henrik

2013-01-01

The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory...... concentration (MIC). Moreover, it was demonstrated that HDM-4 was distributed widely in the bacterial cell at lethal concentrations, and that it could bind to DNA. It was confirmed that the multimodal action of HDM-4 resulted in it being less likely to lead to resistance development as compared to single......-target antibiotics. HDM-4 exhibited multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4 modulated the immune response by inducing the release of the chemoattractants interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from human peripheral blood mononuclear cells. In addition...

Effects of postharvest application of 1-MCP and postcutting dip treatment on the quality and nutritional properties of fresh-cut kiwifruit.

Science.gov (United States)

Antunes, Maria D C; Dandlen, Susana; Cavaco, Ana M; Miguel, Graça

2010-05-26

Consumption of minimally processed fruit and vegetables has increased significantly in the past few years due to the consumers' life style. The aim of this study was to evaluate the effect of treatment with ascorbic acid or calcium chloride on the quality parameters of fresh-cut kiwifruit prepared from fruit previously stored for 3 months, either treated or not treated with 1-methylcyclopropene (1-MCP) before storage. Harvested fruit were treated with 1 microL L(-1) 1-MCP for 20 h at room temperature ( approximately 20 degrees C) (MCP) or had no treatment (C) and were then stored at 0 degrees C. After 3 months, fruit were removed from storage, peeled, and cut longitudinally in quarters, dipped in 2% ascorbic acid (Asc), 2% calcium chloride (Ca), or just water (cont), and kept at 2 degrees C for 8 days. Measurements of firmness, soluble solids content (SSC) ( degrees Brix), color (CIE L*, a*, b*), electrolyte leakage, sugars, organic acids, total phenolics, and antioxidant activity (DPPH and ABTS) were performed at 0, 4, and 8 days. A taste panel was performed on the seventh shelf life day. It was shown that whole MCP-treated kiwifruit kept better than the control through the 3 months storage, this effect being lost through the fresh-cut shelf life period. Furthermore, the postcut dip on 2% CaCl(2) was effective on delaying softening and browning of fresh-cut kiwifruit, which were also the fruit preferred by panelists. Both ascorbic acid and CaCl(2) were effective on preserving or improving nutritional properties (phenolics, ascorbic acid, DPPH, and ABTS) mainly in the first 4 days of shelf life. The CaCl(2) had a further beneficial effect until 8 shelf life days. It is suggested that CaCl(2) is better in keeping overall quality through 8 days of shelf life at 2 degrees C in fresh-cut kiwifruit followed by Asc, and 1-MCP has negligible effect in the conditions of this experiment.

Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for a neuroinflammatory model of chronic alcoholism.

Science.gov (United States)

Umhau, John C; Schwandt, Melanie; Solomon, Matthew G; Yuan, Peixiong; Nugent, Allison; Zarate, Carlos A; Drevets, Wayne C; Hall, Samuel D; George, David T; Heilig, Markus

2014-05-01

Liver inflammation in alcoholism has been hypothesized to influence the development of a neuroinflammatory process in the brain characterized by neurodegeneration and altered cognitive function. Monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted in the alcoholic brain at autopsy and may have a role in this process. We studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1β and tumor necrosis factor-α in 13 healthy volunteers and 28 alcoholics during weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as markers of alcohol-related liver inflammation. Compared to healthy volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4 and day 25 (p alcohol-induced liver inflammation, as defined by peripheral concentrations of GGT and AST/GOT. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Effect of Serum and Oxygen Concentration on Gene Expression and Secretion of Paracrine Factors by Mesenchymal Stem Cells

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Patrick Page

2014-01-01

Full Text Available Mesenchymal stem cells (MSC secrete paracrine factors that may exert a protective effect on the heart after coronary artery occlusion. This study was done to determine the effect of hypoxia and serum levels on the mRNA expression and secretion of paracrine factors. Mouse bone marrow MSC were cultured with 5% or 20% serum and in either normoxic (21% O2 or hypoxic (1% O2 conditions. Expression of mRNA for vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, macrophage inflammatory protein-1α (MIP-1α, MIP-1β, and matrix metalloproteinase-2 (MMP-2 was determined by RT-qPCR. Secretion into the culture media was determined by ELISA. Hypoxia caused a reduction in gene expression for MCP-1 and an increase for VEGF (5% serum, MIP-1α, MIP-1β, and MMP-2. Serum reduction lowered gene expression for VEGF (normoxia, MCP-1 (hypoxia, MIP-1α (hypoxia, MIP-1β (hypoxia, and MMP-2 (hypoxia and increased gene expression for MMP-2 (normoxia. The level of secretion of these factors into the media generally paralleled gene expression with some exceptions. These data demonstrate that serum and oxygen levels have a significant effect on the gene expression and secretion of paracrine factors by MSC which will affect how MSC interact in vivo during myocardial ischemia.

Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

International Nuclear Information System (INIS)

Sáenz-López, Pablo; Carretero, Rafael; Cózar, José Manuel; Romero, José Maria; Canton, Julia; Vilchez, José Ramón; Tallada, Miguel; Garrido, Federico; Ruiz-Cabello, Francisco

2008-01-01

Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development

Transport of Chemotactic Bacteria in Porous Media with Structured Heterogeneity

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Ford, R. M.; Wang, M.; Liu, J.; Long, T.

2008-12-01

Chemical contaminants that become trapped in low permeability zones (e.g. clay lenses) are difficult to remediate using conventional pump-and-treat approaches. Chemotactic bacteria that are transported by groundwater through more permeable regions may migrate toward these less permeable zones in response to chemical gradients created by contaminant diffusion from the low permeability source, thereby enhancing the remediation process by directing bacteria to the contaminants they degrade. What effect does the heterogeneity associated with coarse- and fine-grained layers that are characteristic of natural groundwater environments have on the transport of microorganisms and their chemotactic response? To address this question experiments were conducted over a range of scales from a single capillary tube to a laboratory- scale column in both static and flowing systems with and without chemoattractant gradients. In static capillary assays, motile bacteria accumulated at the interface between an aqueous solution and a suspension of agarose particulates. In microfluidic devices with an array of staggered cylinders, chemotactic bacteria migrated transverse to flow in response to a chemoattractant gradient. In sand columns packed with a coarse-grained core and surrounded by a fine-grained annulus, chemotactic bacteria migrated preferentially toward a chemoattractant source along the centerline. Mathematical models and computer simulations were developed to analyze the experimental observations in terms of transport parameters from the advection- disperson-sorption equation.

Lipopolysaccharide regulated protein expression is only partly impaired in monocytes from patients with type I diabetes

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Abke Sabine

2006-03-01

Full Text Available Abstract Background Monocytes play an important role in innate immunity and atherosclerosis. A disturbed secretion of cytokines in lipopolysaccharide (LPS activated monocytes from type 1 diabetes (T1D patients has been described and may contribute to the impaired inflammatory response in these individuals. In the present study the influence of LPS on five different proteins with a function in immunity and atherosclerosis was analyzed in monocytes from controls and T1D patients. Methods Monocytes were isolated from controls and T1D patients and the LPS-stimulated increase of IL-6, CXCL8, monocyte chemotactic protein 1 (CCL2, MCP-1 and superoxide dismutase (SOD 2, as well as the LPS-mediated decrease of apolipoprotein E (Apo E in primary human monocytes from controls and T1D patients was determined. Results CCL2 and IL-6 secretion in response to LPS was found significantly reduced in monocytes from T1D patients when compared to controls whereas basal CCL2 release was similar in control and T1D cells. In contrast, CXCL8 and apolipoprotein E secretion and SOD 2 expression upon LPS stimulation is similar from T1D and control monocytes. Conclusion These data indicate that LPS-mediated protein expression is only partly disturbed in monocytes from T1D patients. Reduced secretion of IL-6 and CCL2 in activated monocytes of these patients may contribute to an impaired inflammatory response and vascular disease.

Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-α Stimulated Human Umbilical Vein Endothelial Cells

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Chaur-Jong Hu

2009-01-01

Full Text Available Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1 is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8, a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1 in human umbilical vein endothelial cells (HUVECs. Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis.

Monocyte chemoattractant protein-1 promoter -2518 polymorphism and susceptibility to vasculitis, rheumatoid arthritis, and multiple sclerosis: A meta-analysis.

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Lee, Y H; Bae, S-C

2016-03-20

The purpose of this study was to examine whether the monocyte chemoattractant protein-1 (MCP-1) promoter -2518 A/G polymorphism (rs1024611) is associated with susceptibility to vasculitis, rheumatoid arthritis (RA), or multiple sclerosis (MS). A meta-analysis was conducted on the association between the MCP-1 -2518 A/G polymorphism and vasculitis, RA, and MS. Fourteen studies from 13 articles, including six on vasculitis, five on RA, and three on MS, consisting of 3,038 patients and 3,545 controls were available for the meta-analysis. The meta-analysis revealed no association between the MCP-1 -2518 G allele and vasculitis (odds ratio [OR] = 0.990, 95% confidence interval [CI] = 0.749-1.309, p = 0.943). Stratification by ethnicity indicated no association between the G allele of the MCP-1 -2518 A/G polymorphism and vasculitis in Asians and Caucasians. Meta-analysis by vasculitis type revealed an association between the GG+GA genotype of the MCP-1 -2518 A/G polymorphism and Behçet's disease (BD; OR = 1.349, 95% CI = 1.013-1.796, p = 0.040). However, sensitivity analysis showed that the association was not statistically significant after removing a study that was conducted in China (OR = 1.030, 95% CI = 0.667-1.590, p = 0.895), which indicated that the association was not statistically robust. The meta-analysis revealed no association between the MCP-1 -2518 G allele and RA (OR = 0.986, 95% CI = 0.890-1.093, p = 0.793) or MS (OR = 1.281, 95% CI = 0.802-2.046, p = 0.301). Our meta-analysis demonstrates that the MCP-1 -2518 A/G polymorphism is not associated with susceptibility to vasculitis, RA, or MS.

Riboflavin Reduces Pro-Inflammatory Activation of Adipocyte-Macrophage Co-culture. Potential Application of Vitamin B2 Enrichment for Attenuation of Insulin Resistance and Metabolic Syndrome Development.

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Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

2016-12-15

Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related inflammation, which is the main cause of insulin resistance, diabetes mellitus 2 or arteriosclerosis. We determined whether pretreatment with a low dose of riboflavin (10.4-1000 nM) affected the pro-inflammatory activity of adipocyte-macrophage co-culture (3T3 L1-RAW 264.7) following lipopolysaccharide stimulation (LPS; 100 ng/mL) which mimics obesity-related inflammation. The apoptosis of adipocytes and macrophages as well as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1beta (IL-1β), monocyte chemotactic protein 1 (MCP-1), high-mobility group box 1 (HMGB1), transforming growth factor-beta 1 (TGFβ), interleukin 10 (IL-10), inducible nitric oxide synthase (iNOS), nitric oxide (NO), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1) expression and release, macrophage migration and adipokines (adiponectin and leptin) were determined. Our results indicated an efficient reduction in pro-inflammatory factors (TNFα, IL-6, MCP-1, HMGB1) upon culture with riboflavin supplementation (500-1000 nM), accompanied by elevation in anti-inflammatory adiponectin and IL-10. Moreover, macrophage migration was reduced by the attenuation of chemotactic MCP-1 release and degradation of the extracellular matrix by MMP-9. In conclusion, riboflavin effectively inhibits the pro-inflammatory activity of adipocyte and macrophage co-cultures, and therefore we can assume that its supplementation may reduce the likelihood of conditions associated with the mild inflammation linked to obesity.

Riboflavin Reduces Pro-Inflammatory Activation of Adipocyte-Macrophage Co-culture. Potential Application of Vitamin B2 Enrichment for Attenuation of Insulin Resistance and Metabolic Syndrome Development

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Agnieszka Irena Mazur-Bialy

2016-12-01

Full Text Available Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related inflammation, which is the main cause of insulin resistance, diabetes mellitus 2 or arteriosclerosis. We determined whether pretreatment with a low dose of riboflavin (10.4–1000 nM affected the pro-inflammatory activity of adipocyte-macrophage co-culture (3T3 L1-RAW 264.7 following lipopolysaccharide stimulation (LPS; 100 ng/mL which mimics obesity-related inflammation. The apoptosis of adipocytes and macrophages as well as tumor necrosis factor-alpha (TNF-α, interleukin 6 (IL-6, interleukin 1beta (IL-1β, monocyte chemotactic protein 1 (MCP-1, high-mobility group box 1 (HMGB1, transforming growth factor–beta 1 (TGFβ, interleukin 10 (IL-10, inducible nitric oxide synthase (iNOS, nitric oxide (NO, matrix metalloproteinase 9 (MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1 expression and release, macrophage migration and adipokines (adiponectin and leptin were determined. Our results indicated an efficient reduction in pro-inflammatory factors (TNFα, IL-6, MCP-1, HMGB1 upon culture with riboflavin supplementation (500–1000 nM, accompanied by elevation in anti-inflammatory adiponectin and IL-10. Moreover, macrophage migration was reduced by the attenuation of chemotactic MCP-1 release and degradation of the extracellular matrix by MMP-9. In conclusion, riboflavin effectively inhibits the pro-inflammatory activity of adipocyte and macrophage co-cultures, and therefore we can assume that its supplementation may reduce the likelihood of conditions associated with the mild inflammation linked to obesity.

Human chorionic gonadotropin triggers angiogenesis via the modulation of endometrial stromal cell responsiveness to interleukin 1: a new possible mechanism underlying embryo implantation.

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Bourdiec, Amélie; Shao, Rong; Rao, C V; Akoum, Ali

2012-09-01

Deep functional changes occurring within the endometrium during implantation are orchestrated by embryonic and maternal signals. Human chorionic gonadotropin (hCG), a major embryonic signal, plays a critical role in the initiation and maintenance of pregnancy. Interleukin (IL) 1, one of the earliest embryonic signals, appears to exert a direct impact on the receptive endometrium and to induce major molecular changes that are essential for embryo implantation. Herein we investigate whether hCG can modulate endometrial stromal cell (ESC) receptivity to IL1 during the implantation window and assess the impact on angiogenesis in vitro. Primary cultures of ESCs from normal fertile women during the implantation window were treated for 24 h with different concentrations of hCG (0-100 ng/ml) and stimulated for 24 h with IL1B (0-0.1 ng/ml). IL1 receptors (IL1Rs), IL1R antagonist (IL1RA), and monocyte chemotactic protein (MCP) 1 were analyzed by real-time PCR, ELISA, and Western blotting. The angiogenic activity in vitro was studied using human microvascular endothelial cell line, scratch wound assay, and cell proliferation via BrdU incorporation into DNA. Human CG induced a dose-dependent imbalance in ESC receptivity to IL1 by significantly upregulating the functional signaling IL1R1 and concomitantly downregulating the decoy inhibitory IL1R2 and IL1RA upon subsequent exposure to IL1B. Prior exposure to hCG amplified MCP1 secretion by ESCs in response to IL1B and triggered the release of angiogenic activity in vitro in which MCP1 appeared to play a significant role. Overexpression of IL1R2 using cell transfection inhibited IL1 and hCG/IL1B-mediated MCP1 secretion. These findings suggest that hCG coordinates embryonic signal interaction with the maternal endometrium, and point to a new possible pathway by which it may promote embryonic growth.

Optimization design of a 20-in. elliptical MCP-PMT

International Nuclear Information System (INIS)

Chen, Ping; Tian, Jinshou; Wei, Yonglin; Liu, Hulin; Sai, Xiaofeng; He, Jianping; Chen, Lin; Wang, Xing; Lu, Yu

2017-01-01

This paper describes the simulation work for optimizing the newly developed 20-in. elliptical MCP-PMT by enlarging the outside diameters of the two focusing electrodes and the open area of the glass bulb. Effects of biasing voltages applied to the two focusing electrodes and the MCP input facet are studied. With the new design of the 20 in. MCP-PMT, the transit time spread of the prototype can be less than 3 ns and the collection efficiency is as much as the present prototype.

The photosensor protein Ppr of Rhodocista centenaria is linked to the chemotaxis signalling pathway

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Kiefer Dorothee

2010-11-01

Full Text Available Abstract Background Rhodocista centenaria is a phototrophic α-proteobacterium exhibiting a phototactic behaviour visible as colony movement on agar plates directed to red light. As many phototrophic purple bacteria R. centenaria possesses a soluble photoactive yellow protein (Pyp. It exists as a long fusion protein, designated Ppr, consisting of three domains, the Pyp domain, a putative bilin binding domain (Bbd and a histidine kinase domain (Pph. The Ppr protein is involved in the regulation of polyketide synthesis but it is still unclear, how this is connected to phototaxis and chemotaxis. Results To elucidate the possible role of Ppr and Pph in the chemotactic network we studied the interaction with chemotactic proteins in vitro as well as in vivo. Matrix-assisted coelution experiments were performed to study the possible communication of the different putative binding partners. The kinase domain of the Ppr protein was found to interact with the chemotactic linker protein CheW. The formation of this complex was clearly ATP-dependent. Further results indicated that the Pph histidine kinase domain and CheW may form a complex with the chemotactic kinase CheAY suggesting a role of Ppr in the chemotaxis signalling pathway. In addition, when Ppr or Pph were expressed in Escherichia coli, the chemotactic response of the cells was dramatically affected. Conclusions The Ppr protein of Rhodocista centenaria directly interacts with the chemotactic protein CheW. This suggests a role of the Ppr protein in the regulation of the chemotactic response in addition to its role in chalcone synthesis.

Monocyte Chemoattractant Protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation

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Mitchell, K.; Yang, H.-Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.

2009-01-01

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of CSF production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the SCYA2 gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared to other CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the NF-κβ signaling cascade including TNF-α, IL-1β and IκBα in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding E-selectin, a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during

Complement inhibitory proteins expression in placentas of thrombophilic women Complement inhibitory proteins expression in placentas of thrombophilic women

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Przemysław Krzysztof Wirstlein

2012-10-01

Full Text Available Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry staining
of inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.
Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.
The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Western
blot. We observed a higher transcript (p < 0.05 and protein (p < 0.001 levels of DAF and MCP in the placentas
of thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblast
membranes, but the assessment of staining in all groups did not differ. The observed higher expression level of
proteins that control activation of complement control proteins is only seemingly contradictory to the changes
observed for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changes
associated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas is
an effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry

Electron optics design of an 8-in. spherical MCP-PMT

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Chen, Ping, E-mail: chenping@opt.cn [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, Shanxi (China); Tian, Jinshou [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, Shanxi (China); Qian, Sen; Zhao, Tianchi [Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng; He, Jianping; Wang, Xing; Lu, Yu [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); Chen, Lin; Guo, Lehui; Pei, Chengquan; Hui, Dandan [Key Laboratory of Ultra-fast photoelectric Diagnostics Technology, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences, Xi’an 710119 (China); University of Chinese Academy of Sciences, Beijing 100049 (China)

2017-03-11

This paper discusses the electron optical system of an 8-in. spherical MCP-PMT. The MCP assembly, the supporting pole and the supply voltages are carefully designed to optimize the photoelectron collection efficiency and the transit time spread. Coating the MCP nickel-chromium electrode with an additional high secondary emission material is employed to make a breakthrough on the collection efficiency. With the simulation software CST, the Finite Integration method and the Monte Carlo method are combined to evaluate the collection efficiency, the time properties and the Earth's magnetic field effects. Simulation results show that the photocathode active solid angle is over 3.5 πsr, the average collection efficiency can exceed 95% with the coated MCP and the mean transit time spread is 2.2 ns for a typical electric potential of 500 V applied between the photocathode and the MCP input facet. The prototype and the measured single photoelectron spectrum are also presented.

A novel dioxygenation product of arachidonic acid possesses potent chemotactic activity for human polymorphonuclear leukocytes.

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Shak, S; Perez, H D; Goldstein, I M

1983-12-25

We have found that a novel dioxygenation product of arachidonic acid, 8(S),15(S)-dihydroxy-5,11-cis-9,13-trans-eicosatetraenoic acid (8,15-diHETE), possesses chemotactic activity for human polymorphonuclear leukocytes comparable to that of leukotriene B4. Authentic 8,15-diHETE, identified by gas chromatography-mass spectrometry, was prepared by treating arachidonic acid with soybean lipoxygenase and was purified by reverse-phase high performance liquid chromatography. Using a "leading front" assay, 8,15-diHETE exhibited significant chemotactic activity at a concentration of 5.0 ng/ml. Maximum chemotactic activity was observed at a concentration of 30 ng/ml. The 8,15-diHETE generated by mixed human leukocytes after stimulation with arachidonic acid and the calcium ionophore, A23187, exhibited quantitatively similar chemotactic activity. Two synthetic all-trans conjugated isomers of 8,15-diHETE, however, were not chemotactic at concentrations up to 500 ng/ml. In contrast to its potent chemotactic activity, 8,15-diHETE (at concentrations up to 10 micrograms/ml) was relatively inactive with respect to its ability to provoke either degranulation or generation of superoxide anion radicals by cytochalasin B-treated leukocytes. Both leukotriene B4 and 8,15-diHETE may be important mediators of inflammation.

The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits

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2013-01-01

Background Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play an important role in the early progression of it. The aim of the present study was to evaluate the effect of kaempferol on the inflammatory molecules such as E-selectin (E-sel), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in high cholesterol induced atherosclerosis rabbit models. Methods Thirty male New Zealand white (NZW) rabbits were randomly divided into five groups, control group, model group, fenofibrate (12mg/kg) group and kaempferol groups (150 mg/kg and 30 mg/kg). The rabbits were fed with a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, serum tumour-necrosis factor-alpha (TNF-α) and serum interleukin-1beta (IL-1β) were detected at the end of the sixth and tenth week. Malonaldehyde (MDA) level and superoxide dismutase (SOD) activity in serum were also determined. Lesion areas of the aorta were measured with morphometry analysis after ten weeks. Gene expression of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas was determined by RT-PCR (reverse transcription-polymerase chain reaction). Immunohistochemical staining was employed to measure protein expression of E-sel, ICAM-1, VCAM-1 and MCP-1. Results Model rabbits fed with ten weeks of high-cholesterol diet developed significant progression of atherosclerosis. Compared with the control, levels of blood lipids, TNF-α, IL-1β and MDA increased markedly in serum of model rabbits, while SOD levels decreased. Gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in atherosclerotic aortas increased remarkably in model group. However, comparing to the model rabbits, levels of TNF-α, IL-1β and MDA decreased significantly and serum SOD activity increased, gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas decreased significantly with the treatment of

Anti-Inflammatory Effect of the Blueberry Anthocyanins Malvidin-3-Glucoside and Malvidin-3-Galactoside in Endothelial Cells

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Wu-Yang Huang

2014-08-01

Full Text Available Blueberry fruits have a wide range of health benefits because of their abundant anthocyanins, which are natural antioxidants. The purpose of this study was to investigate the inhibitory effect of blueberry’s two main anthocyanins (malvidin-3-glucoside and malvidin-3-galactoside on inflammatory response in endothelial cells. These two malvidin glycosides could inhibit tumor necrosis factor-alpha (TNF-α induced increases of monocyte chemotactic protein-1 (MCP-1, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1 (VCAM-1 production both in the protein and mRNA levels in a concentration-dependent manner. Mv-3-glc at the concentration of 1 μM could inhibit 35.9% increased MCP-1, 54.4% ICAM-1, and 44.7% VCAM-1 protein in supernatant, as well as 9.88% MCP-1 and 48.6% ICAM-1 mRNA expression (p < 0.05. In addition, they could decrease IκBα degradation (Mv-3-glc, Mv-3-gal, and their mixture at the concentration of 50 μM had the inhibition rate of 84.8%, 75.3%, and 43.2%, respectively, p < 0.01 and block the nuclear translocation of p65, which suggested their anti-inflammation mechanism was mediated by the nuclear factor-kappa B (NF-κB pathway. In general malvidin-3-glucoside had better anti-inflammatory effect than malvidin-3-galactoside. These results indicated that blueberry is good resource of anti-inflammatory anthocyanins, which can be promising molecules for the development of nutraceuticals to prevent chronic inflammation in many diseases.

Urease Plays an Important Role in the Chemotactic Motility of Helicobacter pylori in a Viscous Environment

OpenAIRE

Nakamura, Hiroki; Yoshiyama, Hironori; Takeuchi, Hiroaki; Mizote, Tomoko; Okita, Kiwamu; Nakazawa, Teruko

1998-01-01

Helicobacter pylori exhibits chemotactic responses to urea, flurofamide, acetohydroxamic acid, and sodium bicarbonate. In buffer, the chemotactic activities of a urease-positive strain were higher than those of the isogenic urease-negative strain. Moreover, the chemotactic activities of the urease-positive strain were increased in a viscous solution containing 3% polyvinylpyrrolidone, whereas those of the urease-negative mutant were not. These results are in accordance with the fact that the ...

Physical, chemical and sensory changes of refrigerated yellow pitahaya treated preharvest with 1-MCP

OpenAIRE

Liliana Serna Cock; Laura Sofía Torres Valenzuela; Alfredo Ayala Aponte

2013-01-01

El efecto de la aplicación de soluciones acuosas de 0, 200 y 400 mg L de 1-metilciclopropeno (1-MCP) en pitahaya amarilla en precosecha (Selenicereus megalanthus Haw) fue evaluado. Se midieron los cambios en pérdida de peso, cambio total de la coloración, azucares totales, acidez titulable, ácido ascórbico y análisis sensorial. La pitahaya fue almacenada bajo refrigeración (10°C y 85% de humedad relativa por 29 días). Dos tipos de empaque (Cajas para exportación y canastillas plá...

Meloxicam blocks neuroinflammation, but not depressive-like behaviors, in HIV-1 transgenic female rats.

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Christina L Nemeth

Full Text Available Adolescents living with human immunodeficiency virus (HIV comprise approximately 12% of the HIV-positive population worldwide. HIV-positive adolescents experience a higher rate of clinical depression, a greater risk of sexual and drug abuse behaviors, and a decreased adherence to highly active antiretroviral therapies (HAART. Using adolescent HIV-1 transgenic rats (HIV-1 tg that display related immune response alterations and pathologies, this study tested the hypothesis that developmental expression of HIV-1-related proteins induces a depressive-like phenotype that parallels a decrease in hippocampal cell proliferation and an increase in pro-inflammatory cytokine expression in the hippocampus. Consistent with this hypothesis, adolescent HIV-1 tg rats demonstrated a depressive-like behavioral phenotype, had decreased levels of cell proliferation, and exhibited elevated expression of monocyte chemotactic protein-1 (Mcp-1 in the hippocampus relative to controls. Subsequently, we tested the ability of meloxicam, a selective COX-2 inhibitor, to attenuate behavioral deficits via inflammatory mechanisms. Daily meloxicam treatments did not alter the behavioral profile despite effectively reducing hippocampal inflammatory gene expression. Together, these data support a biological basis for the co-morbid manifestation of depression in HIV-positive patients as early as in adolescence and suggest that modifications in behavior manifest independent of inflammatory activity in the hippocampus.

Characterizations of MCP performance in the hard x-ray range (6–25 keV)

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Wu, Ming, E-mail: minwu@sandia.gov; Rochau, Greg [Sandia National Laboratory, Albuquerque, New Mexico 87185 (United States); Moy, Ken [Special Technology Laboratories, NSTec, Santa Barbara, California 93111-2335 (United States); Kruschwitz, Craig [National Security Technologies, LLC, Los Alamos Operations, Los Alamos, New Mexico 87544 (United States)

2014-11-15

MCP detector performance at hard x-ray energies from 6 to 25 keV was recently investigated using NSLS beamline X15A at BNL. Measurements were made with an NSTec Gen-II (H-CA-65) framing camera, based on a Photonis MCP with ∼10 μm in diameter pores, ∼12 μm center-center spacing, an L/D ratio of 46, and a bias angle of 8°. The MCP characterizations were focused on (1) energy and angle dependent sensitivity, (2) energy and angle dependent spatial resolution, (3) energy dependent gain performance, and (4) energy dependent dynamic range. These measurement corroborated simulation results using a Monte Carlo model that included hard x-ray interactions and the subsequent electron cascade in the MCP.

Murine macrophage response from peritoneal cavity requires signals mediated by chemokine receptor CCR-2 during Staphylococcus aureus infection.

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Nandi, Ajeya; Bishayi, Biswadev

2016-02-01

C-C chemokine receptor-2 (CCR-2) is a cognate receptor for monocyte chemotactic protein-1 (MCP-1), and recent studies revealed that MCP-1-CCR-2 signaling is involved in several inflammatory diseases characterized by macrophage infiltration. Currently, there is no study on the involvement of CCR-2 in the killing of S. aureus by macrophages of Swiss albino mice, and its substantial role in host defense against S. aureus infection in murine macrophages is still unclear. Therefore, the present study was aimed to investigate the functional and interactive role of CCR-2 and MCP-1 in regulating peritoneal macrophage responses with respect to acute S. aureus infection. We found that phagocytosis of S. aureus can serve as an important stimulus for MCP-1 production by peritoneal macrophages, which is dependent directly or indirectly on cytokines, reactive oxygen species and nitric oxide. Neutralization of CCR-2 in macrophages leads to increased production of IL-10 and decreased production of IFN-γ and IL-6. In CCR-2 blocked macrophages, pretreatment with specific blocker of NF-κB or p38-MAPK causes elevation in MCP-1 level and subsequent downregulation of CCR-2 itself. We speculate that CCR-2 is involved in S. aureus-induced MCP-1 production via NF-κB or p38-MAPK signaling. We also hypothesized that unnaturally high level of MCP-1 that build up upon CCR-2 neutralization might allow promiscuous binding to one or more other chemokine receptors, a situation that would not occur in CCR-2 non-neutralized condition. This may be the plausible explanation for such observed Th-2 response in CCR-2 blocked macrophages infected with S. aureus in the present study.

Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome.

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van Setten, P A; van Hinsbergh, V W; van den Heuvel, L P; Preyers, F; Dijkman, H B; Assmann, K J; van der Velden, T J; Monnens, L A

1998-06-01

The epidemic form of the hemolytic uremic syndrome (HUS) in children is hallmarked by endothelial cell damage, most predominantly displayed by the glomerular capillaries. The influx of mononuclear (MO) and polymorphonuclear cells (PMNs) into the glomeruli may be an important event in the initiation, prolongation, and progression of glomerular endothelial cell damage in HUS patients. The molecular mechanisms for the recruitment of these leukocytes into the kidney are unclear, but monocyte chemoattractant protein-1 (MCP-1) and IL-8 are suggested to be prime candidates. In this study, we analyzed the presence of both chemokines in 24-h urinary (n = 15) and serum (n = 14) samples of HUS children by specific ELISAs. Furthermore, kidney biopsies of three different HUS children were examined for MO and PMN cell infiltration by histochemical techniques and electron microscopy. Whereas the chemokines MCP-1 and IL-8 were present in only very limited amounts in urine of 17 normal control subjects, serial samples of HUS patients demonstrated significantly elevated levels of both chemokines. HUS children with anuria showed higher initial and maximum chemokine levels than their counterparts without anuria. A strong positive correlation was observed between urinary MCP-1 and IL-8 levels. Whereas initial serum IL-8 levels were significantly increased in HUS children, serum MCP-1 levels were only slightly elevated compared with serum MCP-1 in control children. No correlation was found between urinary and serum chemokine concentrations. Histologic and EM studies of HUS biopsy specimens clearly showed the presence of MOs and to a lesser extent of PMNs in the glomeruli. The present data suggest an important local role for MOs and PMNs in the process of glomerular endothelial-cell damage. The chemokines MCP-1 and IL-8 may possibly be implicated in the pathogenesis of HUS through the recruitment and activation of MOs and PMNs, respectively.

Preservação dos atributos físicos de frutos de atemoia cv. Gefner com o uso de 1-MCP e atmosfera modificad

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Gláucia Michelle Cosme Silva

2014-12-01

Full Text Available O interesse comercial pela atemoia vem aumentando cada vez mais no Brasil. O aumento da atividade respiratória, acompanhado por modificações rápidas na composição física dos frutos podem inviabilizar sua distribuição a mercados distantes. Neste contexto, objetivou-se com o presente trabalho avaliar os atributos físicos em frutos de atemoia tratados com 1-metilciclopropeno (1-MCP e atmosfera modificada associados à refrigeração. O experimento foi instalado em delineamento experimental inteiramente casualizado, em esquema fatorial 4x5, sendo quatro concentrações de 1-MCP (0; 200; 400 e 600 ŋL L-¹ e cinco períodos de avaliação após a colheita, em intervalo de cinco dias, com quatro repetições e quatro frutos por unidade experimental. As atemoias foram colhidas em pomar comercial, no município de Matias Cardoso-MG, no estádio de maturação fisiológica, lavadas, sanitizadas e secas ao ar, depois tratadas com as concentrações de 1-MCP por oito horas, em temperatura ambiente. Logo após, quatro frutos foram dispostos em bandejas de poliestireno expandido. Alguns permaneceram sem membrana, enquanto outros foram embalados com membrana plástica de PEBD 16µm. As variáveis avaliadas nos frutos foram: perda de biomassa fresca, firmeza, concentração de CO2, etileno e coloração da casca. O uso da atmosfera modificada e do 1-MCP, associados ou não, foi eficiente no atraso do amadurecimento dos frutos, permitindo a conservação de sua qualidade física. Frutos tratados com 1-MCP apresentaram-se mais firmes, além da preservação da coloração, verificada através da luminosidade, cromaticidade e ângulo Hueº, que se mostraram superiores quando comparados aos frutos não tratados.

Monocyte chemoattractant protein-1: a proinflammatory cytokine elevated in sarcopenic obesity

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Lim JP

2015-03-01

Full Text Available Jun Pei Lim,1,2 Bernard P Leung,3 Yew Yoong Ding,1,2 Laura Tay,1,2 Noor Hafizah Ismail,2,4 Audrey Yeo,2 Suzanne Yew,2 Mei Sian Chong1,2 1Department of Geriatric Medicine, 2Institute of Geriatrics and Active Ageing, 3Department of Rheumatology, Allergy and Immunology, 4Department of Community and Continuing Care, Tan Tock Seng Hospital, Singapore Objective: Sarcopenic obesity (SO is associated with poorer physical outcomes and functional status in the older adult. A proinflammatory milieu associated with central obesity is postulated to enhance muscle catabolism. We set out to examine associations of the chemokine monocyte chemoattractant protein-1 (MCP-1 in groups of older adults, with sarcopenia, obesity, and the SO phenotypes.Methods: A total of 143 community dwelling, well, older adults were recruited. Cross-sectional clinical data, physical performance, and muscle mass measurements were collected. Obesity and sarcopenia were defined using revised National Cholesterol Education Program (NCEP obesity guidelines and those of the Asian Working Group for Sarcopenia. Serum levels of MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA.Results: In all, 25.2% of subjects were normal, 15.4% sarcopenic, 48.3% obese, and 11.2% were SO. The SO groups had the lowest appendicular lean mass, highest percentage body fat, and lowest performance scores on the Short Physical Performance Battery and grip strength. The MCP-1 levels were significantly different, with the highest levels found in SO participants (P<0.05.Conclusion: Significantly raised MCP-1 levels in obese and SO subjects support the theory of chronic inflammation due to excess adiposity. Longitudinal studies will reveal whether SO represents a continuum of obesity causing accelerated sarcopenia and cardiovascular events, or the coexistence of two separate conditions with synergistic effects affecting functional performance. Keywords: chemokine C-C motif ligand 2 (CCL-2, elderly

Downregulation of the S1P Transporter Spinster Homology Protein 2 (Spns2 Exerts an Anti-Fibrotic and Anti-Inflammatory Effect in Human Renal Proximal Tubular Epithelial Cells

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Olivier Blanchard

2018-05-01

Full Text Available Sphingosine kinase (SK catalyses the formation of sphingosine 1-phosphate (S1P, which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated. In a further approach, the S1P transporter Spns2, which is known to export S1P and thereby reduces intracellular S1P levels, was stably downregulated in HK2 cells by RNAi. This treatment decreased TGFβ-induced CTGF and fibronectin expression, and it abolished the strong induction of the monocyte chemotactic protein 1 (MCP-1 by the pro-inflammatory cytokines tumor necrosis factor (TNFα and interleukin (IL-1β. Moreover, it enhanced the expression of aquaporin 1, which is an important water channel that is expressed in the proximal tubules, and reverted aquaporin 1 downregulation induced by IL-1β/TNFα. On the other hand, overexpression of a Spns2-GFP construct increased S1P secretion and it resulted in enhanced TGFβ-induced CTGF expression. In summary, our data demonstrate that in human renal proximal tubular epithelial cells, SK-1 downregulation accelerates an inflammatory and fibrotic reaction, whereas Spns2 downregulation has an opposite effect. We conclude that Spns2 represents a promising new target for the treatment of tubulointerstitial inflammation and fibrosis.

Actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

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Westendorf, Christian; Negrete, Jose; Bae, Albert J.; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

2013-01-01

The rapid reorganization of the actin cytoskeleton in response to external stimuli is an essential property of many motile eukaryotic cells. Here, we report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. When averaging the actin response of many cells to a short pulse of the chemoattractant cAMP, we observed a transient accumulation of cortical actin reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. To substantiate that an oscillatory mechanism governs the actin dynamics in these cells, we systematically exposed a large number of cells to periodic pulse trains of different frequencies. Our results indicate a resonance peak at a stimulation period of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the regulatory network of the actin system. To test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and actin-interacting protein 1, as well as knockout mutants that lack Coronin and actin-interacting protein 1. These actin-binding proteins enhance the disassembly of actin filaments and thus allow us to estimate the delay time in the regulatory feedback loop. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed in our periodic stimulation experiments. PMID:23431176

Occupational exposure to diesel engine exhaust and serum cytokine levels.

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Dai, Yufei; Ren, Dianzhi; Bassig, Bryan A; Vermeulen, Roel; Hu, Wei; Niu, Yong; Duan, Huawei; Ye, Meng; Meng, Tao; Xu, Jun; Bin, Ping; Shen, Meili; Yang, Jufang; Fu, Wei; Meliefste, Kees; Silverman, Debra; Rothman, Nathaniel; Lan, Qing; Zheng, Yuxin

2018-03-01

The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross-sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM 2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection. Serum levels of six inflammatory biomarkers including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1β, and monocyte chemotactic protein (MCP)-1 were analyzed in all subjects. Compared to unexposed controls, concentrations of MIP-1β were significantly reduced by ∼37% in DEE exposed workers (P 397 µg/m 3 ) compared to unexposed controls. Further, significant inverse exposure-response relationships for IL-8 and MCP-1 were also found in relation to increasing PM 2.5 levels among the DEE exposed workers. Given that IL-8, MIP-1β, and MCP-1 are chemokines that play important roles in recruitment of immunocompetent cells for immune defense and tumor cell clearance, the observed lower levels of these markers with increasing PM 2.5 exposure may provide insight into the mechanism by which DEE promotes lung cancer. Environ. Mol. Mutagen. 59:144-150, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Defect of netrophil chemotactic function is one of the etiology of aggressive periodontitis.

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Yanti Rusyanti

2016-06-01

Full Text Available Characteristic of progressive destructive periodontal tissue in Aggressive Periodontitis is a features of disruption of the host-homeostasis as the results of imbalance between host response and specific bacterial pathogenic which presents at gingival sulcus. The objective of this study was to evaluate netrophil function of  Aggressive periodontitis molecularly by means of gen polimorphism of Formyl Peptide Receptor (FPR1 at the surface of netrophil cell, the level of IL-8 and netrophil chemotactic. The results of  the study  can be used as an early detection, prevention or to arrest tissue destruction and to restore a health-associated homeostasis in order to get better prognosis of Aggressive Periodontitis. The study was conducted during 20 months in Periodontic Clinic Dental Hospital, Faculty of Dentistry, Padjadjaran University, Genetica Moleculer Medical Laboratory of Research Institution Padjadjaran University Bandung. Research design used case control methode and sample selection is done in concecutive sampling of 32 aggressive periodontitis patients and 29 non aggressive periodontitis patients who were included in the inclusion criteria. Research materials were venous blood and gingival crevicular fluid. PCR-Sequensing methode was used to asses of gene FPR1 Polimorphism. ELISA methode was used to measure IL-8 level in gingival crevicular fluid, and Human CD66abce Microbead Kit by MACS Separation methode was used to asses netrophil chemotactic. Chi-square test, Fisher’s exact, unpaired t tests were employed to analyse the differences of  characteristic, allele frequencies and genotypic, bivariate analysis to analyse of risk factors and biserial point correlation to analyse correlation between risk factors. The results showed the existence of c576T>C>G gene FPR1 polymorphism 5.040 time-fold (p=0.006; OR=5.040 while the down regulation of IL-8( ≤0.064 pg/µl is 34.5 times-fold of having aggressive periodontitis (OR=34, and c576T

Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release

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Claudia Weber

2015-01-01

Insulin solutions displayed cytotoxic and pro-inflammatory potential caused by phenol or m-cresol. We speculate that during insulin pump therapy phenol and m-cresol might induce cell death and inflammatory reactions at the infusion site in vivo. Inflammation is perpetuated by release of MCP-1 by activated monocytic cells leading to enhanced recruitment of inflammatory cells. To minimize acute skin complications caused by phenol/m-cresol accumulation, a frequent change of infusion sets and rotation of the infusion site is recommended.

Transverse Chemotactic Migration of Bacteria from High to Low Permeability Regions in a Dual Permeability Porous Microfluidic Device

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Singh, R.; Olson, M. S.

2011-12-01

to decrease at 9.8 mm and 19.6 mm cross-sections in low permeability regions due to dilution with the injectate from the non-porous channel (Figure 1). However, relative bacterial counts increased in the low permeability region at both downstream cross-sections under chemotactic conditions. A large increase in relative bacterial count in the pore throats just outside the low permeability region was also observed at both cross-sections (Figure 1). The bacterial chemotactic response was observed to decrease linearly with increasing Darcy velocity and at flow rate 0.220 mm/s the chemotactic effect was offset by the advective flow in the porous channel.

The interaction between circulating complement proteins and cutaneous microvascular endothelial cells in the development of childhood Henoch-Schonlein Purpura.

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Yao-Hsu Yang

Full Text Available In addition to IgA, the deposition of complement (C3 in dermal vessels is commonly found in Henoch-Schönlein purpura (HSP. The aim of this study is to elucidate the role of circulating complement proteins in the pathogenesis of childhood HSP.Plasma levels of C3a, C4a, C5a, and Bb in 30 HSP patients and 30 healthy controls were detected by enzyme-linked immunosorbent assay (ELISA. The expression of C3a receptor (C3aR, C5a receptor (CD88, E-selectin, intercellular adhesion molecule 1 (ICAM-1, C3, C5, interleukin (IL-8, monocyte chemotactic protein (MCP-1, and RANTES by human dermal microvascular endothelial cells (HMVEC-d was evaluated either by flow cytometry or by ELISA.At the acute stage, HSP patients had higher plasma levels of C3a (359.5 ± 115.3 vs. 183.3 ± 94.1 ng/ml, p < 0.0001, C5a (181.4 ± 86.1 vs. 33.7 ± 26.3 ng/ml, p < 0.0001, and Bb (3.7 ± 2.6 vs. 1.0 ± 0.6 μg/ml, p < 0.0001, but not C4a than healthy controls. Although HSP patient-derived acute phase plasma did not alter the presentation of C3aR and CD88 on HMVEC-d, it enhanced the production of endothelial C3 and C5. Moreover, C5a was shown in vitro to up-regulate the expression of IL-8, MCP-1, E-selectin, and ICAM-1 by HMVEC-d with a dose-dependent manner.In HSP, the activation of the complement system in part through the alternative pathway may have resulted in increased plasma levels of C3a and C5a, which, especially C5a, may play a role in the disease pathogenesis by activating endothelium of cutaneous small vessels.

Direct and indirect radioiodination of protein: comparative study of chemotactic peptide labeling; Radioiodacao de proteina por via direta e indireta: estudo comparativo da marcacao de peptideo quimiotatico

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Lavinas, Tatiana

2004-07-01

The development of simple methods for protein radioiodination have stimulated the use of radioiodinated peptides in vivo. There are two basic methods for labeling proteins with radioiodine: direct labeling, reaction of an electrophilic radioiodine with functional activated groups on protein, like the phenol ring in the tyrosine residue, and the conjugation of a previously radioiodinated molecule to the protein, referred as indirect method. The great problem related to the direct radioiodination of proteins is the in vivo dehalogenation. This problem can be minimized if a non-phenolic prosthetic group is used in the indirect radioiodination of the peptide. The ATE prosthetic group, N-succinimidyl 3-(tri-n-butylstannyl) benzoate, when radioiodinated by electrophilic iododestannilation produces N-succinimidyl 3-[{sup 123}l/{sup 131}l] iodine benzoate (SIB) that is subsequently conjugated to the protein by the acylation of the lysine group. There are many radiopharmaceuticals employed in scintigraphic images of infection and inflammation used with some limitations. These limitations stimulated the improvement of a new class of radiopharmaceuticals, the receptor-specific related labeled peptides, as the mediators of the inflammatory response, that presents high affinity by receptors expressed in the inflammation process, and fast clearance from blood and non-target tissues. One of these molecules is the synthetic chemotactic peptide fNleLFNIeYK that presents potent chemotaxis for leukocytes, with high affinity by the receptors presented in polymorphonuclear leukocytes and mononuclear phagocytes. The objective of this work included the synthesis of ATE prosthetic group and comparative radioiodination of the chemotactic peptide fNleLFNIeYK by direct and indirect methods, with radiochemical purity determination and evaluation of in vivo and in vitro stability of the compounds. This work presented an original contribution in the comparative biological distribution studies

Chemotactic droplet swimmers in complex geometries

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Jin, Chenyu; Hokmabad, Babak V.; Baldwin, Kyle A.; Maass, Corinna C.

2018-02-01

Chemotaxis1 and auto-chemotaxis are key mechanisms in the dynamics of micro-organisms, e.g. in the acquisition of nutrients and in the communication between individuals, influencing the collective behaviour. However, chemical signalling and the natural environment of biological swimmers are generally complex, making them hard to access analytically. We present a well-controlled, tunable artificial model to study chemotaxis and autochemotaxis in complex geometries, using microfluidic assays of self-propelling oil droplets in an aqueous surfactant solution (Herminghaus et al 2014 Soft Matter 10 7008-22 Krüger et al 2016 Phys. Rev. Lett. 117). Droplets propel via interfacial Marangoni stresses powered by micellar solubilisation. Moreover, filled micelles act as a chemical repellent by diffusive phoretic gradient forces. We have studied these chemotactic effects in a series of microfluidic geometries, as published in Jin et al (2017 Proc. Natl Acad. Sci. 114 5089-94): first, droplets are guided along the shortest path through a maze by surfactant diffusing into the maze from the exit. Second, we let auto-chemotactic droplet swimmers pass through bifurcating microfluidic channels and record anticorrelations between the branch choices of consecutive droplets. We present an analytical Langevin model matching the experimental data. In a previously unpublished experiment, pillar arrays of variable sizes and shapes provide a convex wall interacting with the swimmer and, in the case of attachment, bending its trajectory and forcing it to revert to its own trail. We observe different behaviours based on the interplay of wall curvature and negative autochemotaxis, i.e. no attachment for highly curved interfaces, stable trapping at large pillars, and a narrow transition region where negative autochemotaxis makes the swimmers detach after a single orbit.

Transmission-Line Readout with Good Time and Space Resolutions for Planacon MCP-PMTs

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Tang, F; Byrum, K; Drake, G; Ertley, C; Frisch, H; Genat, J-F; May, E

2008-01-01

With commercially-available multi-anode microchannel plate photomultiplier tubes (MCP-PMT) and electronics, resolutions significantly better than 10 psec have been achieved in small systems with a few readout channels[1,2]. For large-scale time-of-flight systems used in particle physics, which may cover tens of square meters, a solution must be found with a manageable number of electronics channels and low total power consumption on the readout electronics without degrading the system timing resolution. We present here the design of a transmission-line readout for a Photonis Planacon MCP-PMT that has these characteristics. The tube, which is 5 cm square, is characterized by signal pulse rise times in the order of 200 psec and transit time spreads (TTS) in the order of 25 psec[1, 2]. The model 85011-011 MCP has 1024 anode pads laid out in an array of 32 by 32 on the back of the tube. The proposed readout is implemented on a Rogers 4350B printed circuit board with 32 parallel 50-ohm transmission lines on 1.6 mm...

Styrene induces an inflammatory response in human lung epithelial cells via oxidative stress and NF-κB activation

International Nuclear Information System (INIS)

Roeder-Stolinski, Carmen; Fischaeder, Gundula; Oostingh, Gertie Janneke; Feltens, Ralph; Kohse, Franziska; Bergen, Martin von; Moerbt, Nora; Eder, Klaus; Duschl, Albert; Lehmann, Irina

2008-01-01

Styrene is a volatile organic compound (VOC) that is widely used as a solvent in many industrial settings. Chronic exposure to styrene can result in irritation of the mucosa of the upper respiratory tract. Contact of styrene with epithelial cells stimulates the expression of a variety of inflammatory mediators, including the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). To characterise the underlying mechanisms of the induction of inflammatory signals by styrene, we investigated the influence of this compound on the induction of oxidative stress and the activation of the nuclear factor-kappa B (NF-κB) signalling pathway in human lung epithelial cells (A549). The results demonstrate that styrene-induced MCP-1 expression, as well as the expression of the oxidative stress marker glutathione S-transferase (GST), is associated with a concentration dependent pattern of NF-κB activity. An inhibitor of NF-κB, IKK-NBD, and the anti-inflammatory antioxidant N-acetylcysteine (NAC) were both effective in suppressing styrene-induced MCP-1 secretion. In addition, NAC was capable of inhibiting the upregulation of GST expression. Our findings suggest that the activation of the NF-κB signalling pathway by styrene is mediated via a redox-sensitive mechanism

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

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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.

Wound healing activity and mechanisms of action of an antibacterial protein from the venom of the eastern diamondback rattlesnake (Crotalus adamanteus.

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Ramar Perumal Samy

Full Text Available Basic phospholipase A2 was identified from the venom of the eastern diamondback rattlesnake. The Crotalus adamanteus toxin-II (CaTx-II induced bactericidal effects (7.8 µg/ml on Staphylococcus aureus, while on Burkholderia pseudomallei (KHW, and Enterobacter aerogenes were killed at 15.6 µg/ml. CaTx-II caused pore formation and membrane damaging effects on the bacterial cell wall. CaTx-II was not cytotoxic on lung (MRC-5, skin fibroblast (HEPK cells and in mice. CaTx-II-treated mice showed significant wound closure and complete healing by 16 days as compared to untreated controls (**P<0.01. Histological examination revealed enhanced collagen synthesis and neovascularization after treatment with CaTx-II versus 2% Fusidic Acid ointment (FAO treated controls. Measurement of tissue cytokines revealed that interleukin-1 beta (IL-1β expression in CaTx-II treated mice was significantly suppressed versus untreated controls. In contrast, cytokines involved in wound healing and cell migration i.e., monocyte chemotactic protein-1 (MCP-1, fibroblast growth factor-basic (FGF-b, chemokine (KC, granulocyte-macrophage colony-stimulating factor (GM-CSF were significantly enhanced in CaTx-II treated mice, but not in the controls. CaTx-II also modulated nuclear factor-kappa B (NF-κB activation during skin wound healing. The CaTx-II protein highlights distinct snake proteins as a potential source of novel antimicrobial agents with significant therapeutic application for bacterial skin infections.

Colloidal silver nanoparticles/rhamnolipid (SNPRL) composite as novel chemotactic antibacterial agent.

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Bharali, P; Saikia, J P; Paul, S; Konwar, B K

2013-10-01

The antibacterial activity of silver nanoparticles and rhamnolipid are well known individually. In the present research, antibacterial and chemotactic activity due to colloidal silver nanoparticles (SNP), rhamnolipid (RL) and silver nanoparticles/rhamnolipid composite (SNPRL) were evaluated using Staphylococcus aureus (MTCC3160), Escherichia coli (MTCC40), Pseudomonas aeruginosa (MTCC8163) and Bacillus subtilis (MTCC441) as test strains. Further, the SNPRL nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). The observation clearly indicates that SNPRL shows prominent antibacterial and chemotactic activity in comparison to all of its individual precursor components. Copyright © 2013 Elsevier B.V. All rights reserved.

Autoantibodies Targeting AT1 Receptor from Patients with Acute Coronary Syndrome Upregulate Proinflammatory Cytokines Expression in Endothelial Cells Involving NF-κB Pathway

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Weijuan Li

2014-01-01

Full Text Available Our study intended to prove whether agonistic autoantibodies to angiotensin II type 1 receptor (AT1-AAs exist in patients with coronary heart disease (CHD and affect the human endothelial cell (HEC by upregulating proinflammatory cytokines expression involved in NF-κB pathway. Antibodies were determined by chronotropic responses of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (valsartan and AT1-EC2 as described previously. Interleukin-6 (IL-6, vascular cell adhesion molecule-1 (VCAM-1, and monocyte chemotactic protein-1 (MCP-1 expression were improved at both mRNA and protein levels in HEC, while NF-κB in the DNA level was improved detected by electrophoretic mobility shift assays (EMSA. These improvements could be inhibited by specific AT1 receptor blocker valsartan, NF-κB blocker pyrrolidine dithiocarbamate (PDTC, and specific short peptides from the second extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the AT1 receptor, induce expression of proinflammatory cytokines involved in the activation of NF-κB. AT1-AAs may play a great role in the pathogenesis of the acute coronary syndrome by mediating vascular inflammatory effects involved in the NF-κB pathway.

Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis

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Chung-Wei Kao

2018-05-01

Full Text Available Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experimental atherosclerosis. In this work, we synthesized monocyte-targeting iron oxide magnetic nanoparticles (MNPs, which were incorporated with the peptides derived from the chemokine receptor C-C chemokine receptor type 2 (CCR2-binding motif of monocytes chemoattractant protein-1 (MCP-1 as a diagnostic tool for potential atherosclerosis. MCP-1-motif MNPs co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knockout mice (ApoE KO mice, the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS imaging and magnetic resonance imaging (MRI. We also performed Oil Red O staining and Prussian Blue staining to confirm the co-localization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis.

Global solution for a chemotactic haptotactic model of cancer invasion

Science.gov (United States)

Tao, Youshan; Wang, Mingjun

2008-10-01

This paper deals with a mathematical model of cancer invasion of tissue recently proposed by Chaplain and Lolas. The model consists of a reaction-diffusion-taxis partial differential equation (PDE) describing the evolution of tumour cell density, a reaction-diffusion PDE governing the evolution of the proteolytic enzyme concentration and an ordinary differential equation modelling the proteolysis of the extracellular matrix (ECM). In addition to random motion, the tumour cells are directed not only by haptotaxis (cellular locomotion directed in response to a concentration gradient of adhesive molecules along the ECM) but also by chemotaxis (cellular locomotion directed in response to a concentration gradient of the diffusible proteolytic enzyme). In one space dimension, the global existence and uniqueness of a classical solution to this combined chemotactic-haptotactic model is proved for any chemotactic coefficient χ > 0. In two and three space dimensions, the global existence is proved for small χ/μ (where μ is the logistic growth rate of the tumour cells). The fundamental point of proof is to raise the regularity of a solution from L1 to Lp (p > 1). Furthermore, the existence of blow-up solutions to a sub-model in two space dimensions for large χ shows, to some extent, that the condition that χ/μ is small is necessary for the global existence of a solution to the full model.

Commensal bacteria and MAMPs are necessary for stress-induced increases in IL-1β and IL-18 but not IL-6, IL-10 or MCP-1.

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Thomas Maslanik

Full Text Available Regular interactions between commensal bacteria and the enteric mucosal immune environment are necessary for normal immunity. Alterations of the commensal bacterial communities or mucosal barrier can disrupt immune function. Chronic stress interferes with bacterial community structure (specifically, α-diversity and the integrity of the intestinal barrier. These interferences can contribute to chronic stress-induced increases in systemic IL-6 and TNF-α. Chronic stress, however, produces many physiological changes that could indirectly influence immune activity. In addition to IL-6 and TNF-α, exposure to acute stressors upregulates a plethora of inflammatory proteins, each having unique synthesis and release mechanisms. We therefore tested the hypothesis that acute stress-induced inflammatory protein responses are dependent on the commensal bacteria, and more specifically, lipopolysaccharide (LPS shed from Gram-negative intestinal commensal bacteria. We present evidence that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI attenuates increases in some (inflammasome dependent, IL-1 and IL-18, but not all (inflammasome independent, IL-6, IL-10, and MCP-1 inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor. Acute stress did not impact α- or β- diversity measured using 16S rRNA diversity analyses, but selectively reduced the relative abundance of Prevotella. These findings indicate that commensal bacteria contribute to acute stress-induced inflammatory protein responses, and support the presence of LPS-mediated signaling in stress-evoked cytokine and chemokine production. The selectivity of the commensal bacteria in stress-evoked IL-1β and IL-18 responses may implicate the inflammasome in this response.

Activation of macrophages by a laccase-polymerized polyphenol is dependent on phosphorylation of Rac1.

Science.gov (United States)

Tajima, Katsuya; Akanuma, Satoshi; Matsumoto-Akanuma, Akiko; Yamanaka, Daisuke; Ishibashi, Ken-Ichi; Adachi, Yoshiyuki; Ohno, Naohito

2018-01-15

Various physiologically active effects of polymerized polyphenols have been reported. In this study, we synthesized a polymerized polyphenol (mL2a-pCA) by polymerizing caffeic acid using mutant Agaricus brasiliensis laccase and analyzed its physiological activity and mechanism of action. We found that mL2a-pCA induced morphological changes and the production of cytokines and chemokines in C3H/HeN mouse-derived resident peritoneal macrophages in vitro. The mechanisms of action of polymerized polyphenols on in vitro mouse resident peritoneal cells have not been characterized in detail previously. Herein, we report that the mL2a-pCA-induced production of interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in C3H/HeN mouse-derived resident peritoneal cells was inhibited by treatment with the Rac1 inhibitor NSC23766 trihydrochloride. In addition, we found that mL2a-pCA activated the phosphorylation Rac1. Taken together, the results show that mL2a-pCA induced macrophage activation via Rac1 phosphorylation-dependent pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.

Science.gov (United States)

Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy; Musi, Nicolas

2010-11-01

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.

Expression of adhesion molecules, chemokines and matrix metallo- proteinases (MMPs) in viable and degenerating stage of Taenia solium metacestode in swine neurocysticercosis.

Science.gov (United States)

Singh, Satyendra K; Singh, Aloukick K; Prasad, Kashi N; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Tripathi, Mukesh; Gupta, Rakesh K; Husain, Nuzhat

2015-11-30

Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

ASIC proteins regulate smooth muscle cell migration.

Science.gov (United States)

Grifoni, Samira C; Jernigan, Nikki L; Hamilton, Gina; Drummond, Heather A

2008-03-01

The purpose of the present study was to investigate Acid Sensing Ion Channel (ASIC) protein expression and importance in cellular migration. We recently demonstrated that Epithelial Na(+)Channel (ENaC) proteins are required for vascular smooth muscle cell (VSMC) migration; however, the role of the closely related ASIC proteins has not been addressed. We used RT-PCR and immunolabeling to determine expression of ASIC1, ASIC2, ASIC3 and ASIC4 in A10 cells. We used small interference RNA to silence individual ASIC expression and determine the importance of ASIC proteins in wound healing and chemotaxis (PDGF-bb)-initiated migration. We found ASIC1, ASIC2, and ASIC3, but not ASIC4, expression in A10 cells. ASIC1, ASIC2, and ASIC3 siRNA molecules significantly suppressed expression of their respective proteins compared to non-targeting siRNA (RISC) transfected controls by 63%, 44%, and 55%, respectively. Wound healing was inhibited by 10, 20, and 26% compared to RISC controls following suppression of ASIC1, ASIC2, and ASIC3, respectively. Chemotactic migration was inhibited by 30% and 45%, respectively, following suppression of ASIC1 and ASIC3. ASIC2 suppression produced a small, but significant, increase in chemotactic migration (4%). Our data indicate that ASIC expression is required for normal migration and may suggest a novel role for ASIC proteins in cellular migration.

Optimization of the electron collection efficiency of a large area MCP-PMT for the JUNO experiment

International Nuclear Information System (INIS)

Chen, Lin; Tian, Jinshou; Liu, Chunliang; Wang, Yifang; Zhao, Tianchi; Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng; Chen, Ping; Wang, Xing; Lu, Yu; Hui, Dandan; Guo, Lehui; Liu, Shulin; Qian, Sen; Xia, Jingkai; Yan, Baojun; Zhu, Na; Sun, Jianning; Si, Shuguang

2016-01-01

A novel large-area (20-inch) photomultiplier tube based on microchannel plate (MCP-PMTs) is proposed for the Jiangmen Underground Neutrino Observatory (JUNO) experiment. Its photoelectron collection efficiency C e is limited by the MCP open area fraction (A open ). This efficiency is studied as a function of the angular (θ), energy (E) distributions of electrons in the input charge cloud and the potential difference (U) between the PMT photocathode and the MCP input surface, considering secondary electron emission from the MCP input electrode. In CST Studio Suite, Finite Integral Technique and Monte Carlo method are combined to investigate the dependence of C e on θ, E and U. Results predict that C e can exceed A open , and are applied to optimize the structure and operational parameters of the 20-inch MCP-PMT prototype. C e of the optimized MCP-PMT is expected to reach 81.2%. Finally, the reduction of the penetration depth of the MCP input electrode layer and the deposition of a high secondary electron yield material on the MCP are proposed to further optimize C e .

Development of 10×10 Matrix-anode MCP-PMT

Science.gov (United States)

Yang, Jie; Li, Yongbin; Xu, Pengxiao; Zhao, Wenjin

2018-02-01

10×10 matrix-anode is developed by high-temperature co-fired ceramics (HTCC) technology. Based on the new matrix-anode, a new kind of photon counting imaging detector - 10×10 matrix-anode MCP-PMT is developed, and its performance parameters are tested. HTCC technology is suitable for the MCP-PMT's air impermeability and its baking process. Its response uniformity is better than the metal-ceramic or metal-glass sealing anode, and it is also a promising method to realize a higher density matrix-anode.

MCP characterization at the Cu and Mo Kα x-ray energies

International Nuclear Information System (INIS)

Walsh, P.J.; Evans, S.; Schappert, G.T.; Kyrala, G.A.

1998-03-01

The authors are investigating the usefulness of microchannel plate (MCP) intensifiers for imaging x-rays at high photon energies, specifically by using filtered X-rays from an electron bombardment source to generate the K α lines of Cu at 8.04 KeV and Mo at 17.5 KeV. These high energy lines are used to measure the resolution of an MCP based intensifier produced at Los Alamos National Laboratory. They have investigated the spot size of a fielded MCP intensifier by observing, on film, the result of single photon excitation of microchannels. Measurement of the spot size was done with visible light microscopy. They report initial results of the spot size distribution in the stripline direction. They have also begun a measurement of the azimuthal anisotropy in the spatial resolution, accentuated at these energies by the inclination of the axis of the MCP channels. They concentrate on an actual ''fielded instrument'' resolution, rather than ideal, for the purpose of analyzing image data captured at the NOVA Laser Facility

L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-CCAAT/Enhancer Binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

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Xiang-Zhu Xie

2016-01-01

Conclusions: OxLDL induces C/EBPβ protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBPβ signaling pathway may participate in it.

Optimization of the electron collection efficiency of a large area MCP-PMT for the JUNO experiment

Energy Technology Data Exchange (ETDEWEB)

Chen, Lin, E-mail: chenlin@opt.cn [State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi’an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Xi’an Jiaotong University, Xi’an 710049 (China); Tian, Jinshou [Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Liu, Chunliang [Xi’an Jiaotong University, Xi’an 710049 (China); Wang, Yifang; Zhao, Tianchi [Institute of High Energy Physics (IHEP) of CAS, Beijing 100049 (China); Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng [Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Chen, Ping [State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi’an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Wang, Xing; Lu, Yu [Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Hui, Dandan; Guo, Lehui [State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi’an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Liu, Shulin; Qian, Sen; Xia, Jingkai; Yan, Baojun; Zhu, Na [Institute of High Energy Physics (IHEP) of CAS, Beijing 100049 (China); Sun, Jianning; Si, Shuguang [North Night Vision Technology (NNVT) CO., LTD, Nanjing 210110 (China); and others

2016-08-11

A novel large-area (20-inch) photomultiplier tube based on microchannel plate (MCP-PMTs) is proposed for the Jiangmen Underground Neutrino Observatory (JUNO) experiment. Its photoelectron collection efficiency C{sub e} is limited by the MCP open area fraction (A{sub open}). This efficiency is studied as a function of the angular (θ), energy (E) distributions of electrons in the input charge cloud and the potential difference (U) between the PMT photocathode and the MCP input surface, considering secondary electron emission from the MCP input electrode. In CST Studio Suite, Finite Integral Technique and Monte Carlo method are combined to investigate the dependence of C{sub e} on θ, E and U. Results predict that C{sub e} can exceed A{sub open}, and are applied to optimize the structure and operational parameters of the 20-inch MCP-PMT prototype. C{sub e} of the optimized MCP-PMT is expected to reach 81.2%. Finally, the reduction of the penetration depth of the MCP input electrode layer and the deposition of a high secondary electron yield material on the MCP are proposed to further optimize C{sub e}.

Capillary arterialization requires the bone-marrow-derived cell (BMC)-specific expression of chemokine (C-C motif) receptor-2, but BMCs do not transdifferentiate into microvascular smooth muscle.

Science.gov (United States)

Nickerson, Meghan M; Burke, Caitlin W; Meisner, Joshua K; Shuptrine, Casey W; Song, Ji; Price, Richard J

2009-01-01

Chemokine (C-C motif) receptor-2 (CCR2) regulates arteriogenesis and angiogenesis, facilitating the MCP-1-dependent recruitment of growth factor-secreting bone marrow-derived cells (BMCs). Here, we tested the hypothesis that the BMC-specific expression of CCR2 is also required for new arteriole formation via capillary arterialization. Following non-ischemic saphenous artery occlusion, we measured the following in gracilis muscles: monocyte chemotactic protein-1 (MCP-1) in wild-type (WT) C57Bl/6J mice by ELISA, and capillary arterialization in WT-WT and CCR2(-/-)-WT (donor-host) bone marrow chimeric mice, as well as BMC transdifferentiation in EGFP(+)-WT mice, by smooth muscle (SM) alpha-actin immunochemistry. MCP-1 levels were significantly elevated 1 day after occlusion in WT mice. In WT-WT mice at day 7, compared to sham controls, arterial occlusion induced a 34% increase in arteriole length density, a 46% increase in SM alpha-actin(+) vessels, and a 45% increase in the fraction of vessels coated with SM alpha-actin, indicating significant capillary arterialization. However, in CCR2(-/-)-WT mice, no differences were observed between arterial occlusion and sham surgery. In EGFP(+)-WT mice, EGFP and SM alpha-actin never colocalized. We conclude that BMC-specific CCR2 expression is required for skeletal muscle capillary arterialization following arterial occlusion; however, BMCs do not transdifferentiate into smooth muscle.

Cafestol Inhibits Cyclic-Strain-Induced Interleukin-8, Intercellular Adhesion Molecule-1, and Monocyte Chemoattractant Protein-1 Production in Vascular Endothelial Cells

Science.gov (United States)

Hao, Wen-Rui; Sung, Li-Chin; Chen, Chun-Chao; Chen, Jin-Jer

2018-01-01

Moderate coffee consumption is inversely associated with cardiovascular disease mortality; however, mechanisms underlying this causal effect remain unclear. Cafestol, a diterpene found in coffee, has various properties, including an anti-inflammatory property. This study investigated the effect of cafestol on cyclic-strain-induced inflammatory molecule secretion in vascular endothelial cells. Cells were cultured under static or cyclic strain conditions, and the secretion of inflammatory molecules was determined using enzyme-linked immunosorbent assay. The effects of cafestol on mitogen-activated protein kinases (MAPK), heme oxygenase-1 (HO-1), and sirtuin 1 (Sirt1) signaling pathways were examined using Western blotting and specific inhibitors. Cafestol attenuated cyclic-strain-stimulated intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein- (MCP-) 1, and interleukin- (IL-) 8 secretion. Cafestol inhibited the cyclic-strain-induced phosphorylation of extracellular signal-regulated kinase and p38 MAPK. By contrast, cafestol upregulated cyclic-strain-induced HO-1 and Sirt1 expression. The addition of zinc protoporphyrin IX, sirtinol, or Sirt1 silencing (transfected with Sirt1 siRNA) significantly attenuated cafestol-mediated modulatory effects on cyclic-strain-stimulated ICAM-1, MCP-1, and IL-8 secretion. This is the first study to report that cafestol inhibited cyclic-strain-induced inflammatory molecule secretion, possibly through the activation of HO-1 and Sirt1 in endothelial cells. The results provide valuable insights into molecular pathways that may contribute to the effects of cafestol. PMID:29854096

Adiponectin, interleukin-6, monocyte chemoattractant protein-1, and regional fat mass during 12-month randomized treatment with metformin and/or oral contraceptives in polycystic ovary syndrome

DEFF Research Database (Denmark)

Glintborg, Dorte; Mumm, Hanne; Altinok, Magda Lambaa

2014-01-01

CONTEXT: Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. OBJECTIVE: To evaluate if improved body composition during treatment with metformin (M) vs. oral contraceptive pills (OCP) was associated...... with changes in circulating adiponectin, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. PATIENTS AND INTERVENTIONS: Ninety patients with PCOS were randomized to 12-month treatment with M (2 g/day), M + OCP (150 mg desogestrel + 30 microgram ethinylestradiol) or OCP. Adiponectin, IL-6, MCP-1...... during the three types of medical intervention. Treatment with M and M + OCP was superior to OCP regarding decreased regional fat mass. Baseline adiponectin and IL-6 were associated with BMI, waist, and trunk fat mass. Changes in trunk fat were significantly associated with changes in IL-6 and MCP-1...

Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity.

Science.gov (United States)

Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F David; Smith, Roger; Watanabe, Coran M H

2015-10-09

A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

OpenAIRE

Mori, Shogo; Williams, Howard; Cagle, Davey; Karanovich, Kristopher; Horgen, F. David; Smith, Roger; Watanabe, Coran M. H.

2015-01-01

A new bioactive macrolactone, nuiapolide (1) was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol re...

Macrolactone Nuiapolide, Isolated from a Hawaiian Marine Cyanobacterium, Exhibits Anti-Chemotactic Activity

Directory of Open Access Journals (Sweden)

Shogo Mori

2015-10-01

Full Text Available A new bioactive macrolactone, nuiapolide (1 was identified from a marine cyanobacterium collected off the coast of Niihau, near Lehua Rock. The natural product exhibits anti-chemotactic activity at concentrations as low as 1.3 μM against Jurkat cells, cancerous T lymphocytes, and induces a G2/M phase cell cycle shift. Structural characterization of the natural product revealed the compound to be a 40-membered macrolactone with nine hydroxyl functional groups and a rare tert-butyl carbinol residue.

Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet

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Qing-Rong Pan

2014-07-01

Full Text Available Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol. Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB and superoxide dismutase (SOD, the content of malondialdehyde (MDA, and the protein levels of tumor necrosis factor (TNF-α, monocyte chemotactic protein-1 (MCP-1, nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

QUANTIFICATION OF THE EFFICIENCY OF RUMEN MICROBIAL PROTEIN SYNTHESIS IN STEERS FED GREEN TROPICAL GRASS

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MARTHEN L. MULLIK

2012-09-01

Full Text Available ABSTRACT The rate of rumen microbial crude protein (MCP supply to the intestines is a crucial element in the current rumen models to predict respond of ruminants to a certain diet. Data from tropical pastures always below predicted results from the existing rumen models. Thus, quantification of the rumen MCP supply from tropical grass will improve predictive rate under tropical feeding conditions. Four Brahman crossbred steers (457±20.1 kg were used in a metabolism study. Pangola grass (Digitaria erianthe cv. Steudal was harvested every morning and fed to the animals soon after. Parameters measured were EMPS, intake, fractional passage rates, and rumen ammonia concentration. The EMPS was estimated using purine derivative excretion in urine. Crude protein and water soluble carbohydrates content were 6.3 and 7.4% of dry matter (DM respectively. DM intake was 1.6% live weight. Average rumen ammonia concentration was 69 mg/L whilst rumen passage rates were 7.84 and 6.92 %/h for fluid and solids respectively. EMPS was only 72 g MCP/kg digestible organic matter. It might be concluded that EMPS in steers consuming green pangola grass was below the minimum level for forage diets adopted in the current feeding standards. ABSTRAK Tingkat pasokan protein mikroba rumen (MCP ke usus halus merupakan salah satu unsur kunci dalam meramal respon pertumbuhan ruminan terhadap ransum tertentu. Data MCP hijauan tropis selalu berada di bawah nilai prediksi model rumen yang dipakai saat ini. Dengan demikian, kuantifikasi pasokan MCP rumput tropis diharapkan menjadi masukan untuk meningkatkan kemampuan prediksi model rumen untuk pakan daerah tropis. Empat sapi jantan muda Brahman persilangan (457±20,1 kg digunakan dalam sebuah penelitian metabolisme. Rumput pangola (Digitaria erianthe cv. Steudal dipanen setiap pagi dan langsung diberikan kepada ternak dalam kandang metabolis. Parameter yang diukur adalah produksi MCP dan efisiensi sintesis MCP (Emps, konsumsi, laju

Influence of promoting blood circulation to remove blood stasis combined with laparoscopy on serum MCP-1, RANTES, oxidative stress and hormones in infertile patients with endometriosis

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Xiao-Sha Zhang

2017-11-01

Full Text Available Objective: To observe the influence of promoting blood circulation to remove blood stasis combined with laparoscopy on serum MCP-1, RANTES, oxidative stress and hormones in infertile patients with endometriosis. Methods: A total of 60 infertile patients with endometriosis were randomly divided into observation group (30 cases and control group (30 cases. Observation group: promoting blood circulation to remove blood stasis combined with laparoscopy; control group: patients were treated only by laparoscopy. Recording and comparing the levels of MCP-1, RANTES, oxidative stress and hormones before and after treatment. Results: (1 Before treatment, there was no statistically significant difference in the serum MCP-1, RANTES, AOPP, MDA, SOD, levels between the two groups. After treatment, compared with the same group before treatment, the serum RANTES, AOPP, MDA levels of the two groups were significantly lower, the serum SOD level of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. (2 Before treatment, there was no statistically significant difference in the serum FSH, LH, E2, P, PRL levels between the two groups. After treatment, compared with the same group before treatment, the serum FSH, LH, P, PRL levels of the two groups were significantly higher, the serum E2 level of the two groups were significantly lower, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. Conclusion: Promoting blood circulation to remove blood stasis combined with laparoscopy for infertile patients with endometriosis can reduce the levels of serum MCP-1, RANTES, oxidative stress, hormones and be beneficial to protect their uterine function.

Efeito do 1-metilciclopropeno sobre a emissão dos ésteres voláteis de bananas ao longo do amadurecimento Efferct of 1-MCP on esters volatiles eission of bananas along the ripening

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Baraquizio Braga do Nascimento Junior

2008-01-01

Full Text Available Fresh green bananas (Musa sp., subgroup Prata were treated with a dose of only 90 ηg g-1 of 1-MCP for 13 hours and the evolution of the volatile compounds along the ripeness was studied. A method to quantify the emission of esters was developed by cryogenic headspace and gas chromatography. Esters of acetate, butyrate, isobutyrate and isovalerate were found as major compounds. The application of the 1-MCP for 13 hours delayed the appearance of the coloration 8 of the peel for 3 days and decreased quantitatively in about 46% the total production of esters in the banana until the 15° day of harvested.

Simulation of the electron collection efficiency of a PMT based on the MCP coated with high secondary yield material

Energy Technology Data Exchange (ETDEWEB)

Chen, Lin, E-mail: chenlin@opt.cn [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Xi' an Jiaotong University, Xi' an 710049 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006 (China); Tian, Jinshou [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006 (China); Zhao, Tianchi [Institute of High Energy Physics (IHEP) of CAS, Beijing 100049 (China); Liu, Chunliang [Xi' an Jiaotong University, Xi' an 710049 (China); Liu, Hulin; Wei, Yonglin; Sai, Xiaofeng [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Chen, Ping [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China); Wang, Xing; Lu, Yu [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Hui, Dandan [State Key Laboratory of Transient Optics and Photonics, Xi' an Institute of Optics and Precision Mechanics (XIOPM), Chinese Academy of Sciences (CAS), Xi' an 710119 (China); Graduate School of Chinese Academy of Sciences (CAS), Beijing 100049 (China)

2016-11-01

Owning to the serious loss of photoelectrons striking at the input electrode of traditional microchannel plate (MCP), photoelectron collection efficiency (CE) of photomultiplier tubes based on MCP (MCP-PMTs) fluctuates around the MCP open area fraction and cannot make a breakthrough. Depositing a thin film of high secondary electron yield material on the MCP is proposed as an effective approach to improve the CE. The available simulation and experimental data to validate it, however, is sparse. In our work, a three-dimensional small area MCP model is developed in CST Studio Suite to evaluate the collection efficiencies of PMTs based on the traditional MCP and the coated one, respectively. Results predict that CE of the PMT based on the coated MCP has a significant increase and a better uniformity, which is expected to reach 100%.

MyD88 expression in the rat dental follicle: Implications for osteoclastogenesis and tooth eruption

Science.gov (United States)

Liu, Dawen; Yao, Shaomian; Wise, Gary E.

2010-01-01

Myeloid differentiation factor 88 (MyD88) is a key adaptor molecule in the interleukin-1 (IL-1) and IL-18 Toll-like receptor signaling pathway. Because it is present in dental follicle (DF) cells in vitro, the purpose of this study was to determine its chronological expression in vivo, as well as its possible role in osteoclastogenesis and tooth eruption. An oligo DNA microarray was used to determine gene expression of MyD88 in vivo in the DFs from the first mandibular molars of postnatal rats from days 1–11. The results showed that MyD88 was expressed maximally at day 3. Using siRNA to knock down MyD88 expression in the DF cells also reduced the gene expression of nuclear factor-kappa B-1 (NFKB1) and monocyte chemoattractant protein 1 (MCP-1). IL-1α up-regulated the expression of NFKB1, MCP-1 and receptor activator of nuclear factor kappa B ligand (RANKL), but knockdown of MyD88 nullified this IL-1α effect. Conditioned medium from DF cells with MyD88 knocked down reduced chemotactic activity for mononuclear cells and reduced osteoclastogenesis as opposed to controls. In conclusion, the maximal expression of MyD88 at day 3 in the DF may contribute to the major burst of osteoclastogenesis needed for eruption by up-regulating MCP-1 and RANKL expression. PMID:20662905

Comparative study of main dosimetric characteristics between the GR-200A and MCP-N LiF (Mg, Cu, P) TLD chips

International Nuclear Information System (INIS)

Shen Wenxiu; Tang Kaiyong; Wang Shoushan; Cai Gangang; Zhu Hongying; Lu Min

1999-01-01

GR-200A and MCP-N are the same kind of LiF(Mg, Cu, P) chip detectors. The main dosimetric characteristics of two LiF (Mg, Cu, P) chip TLDs (GR-200A made in Solid Dosimetric Detector and Method Laboratory, Beijing, and MCP-N made in Poland) are compared, including glow curve structure, TL sensitivity, anti-moisture, reproducibility, background, detection threshold and photosensitivity. Sensitivity of GR-200a is 1.6 times as much as that of MCP-N. The sensitivity of GR-200A is stable after being used for six times, but the sensitivity of MCP-N dropped 2.8%, and its colour turned from white into light brown. The sensitivity and colour of GR-200A did not vary after being stored for 25 days at 98% RH, by comparison the sensitivity of MCP-N dropped 14%, and its colour turned into light brown. It was found that the GR-200A TLD is superior to the MCP-N TLD in above-mentioned characteristics

Hypoxia-inducible factor-1α regulates chemotactic migration of pancreatic ductal adenocarcinoma cells through directly transactivating the CX3CR1 gene.

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Tiansuo Zhao

Full Text Available CX3CR1 is an important chemokine receptor and regulates the chemotactic migration of pancreatic ductal adenocarcinoma (PDAC cells. Up to now, its regulatory mechanism remains largely undefined. Here, we report that hypoxia upregulates the expression of CX3CR1 in pancreatic cancer cells. When hypoxia-inducible factor (HIF-1α expression was knocked down in vitro and in vivo, the expression of CX3CR1 was significantly decreased. Chromatin immunoprecipitation assay demonstrated that HIF-1α bound to the hypoxia-response element (HRE; 5'-A/GCGTG-3' of CX3CR1 promoter under normoxia, and this binding was significantly enhanced under hypoxia. Overexpression of HIF-1α significantly upregulated the expression of luciferase reporter gene under the control of the CX3CR1 promoter in pancreatic cancer cells. Importantly, we demonstrated that HIF-1α may regulate cancer cell migration through CX3CR1. The HIF-1α/CX3CR1 pathway might represent a valuable therapeutic target to prevent invasion and distant metastasis in PDAC.

Microbial Protein Production and Nitrogen Balance of Local Steer Fed Ammoniated Rice Straws Added

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H Hindratiningrum

2009-05-01

Full Text Available The objective of the experiment was to investigate the kind of energy source feedstuffs on nutrient balance and microbial protein synthesis in local male beef cattle fed with ammoniated rice straws Twenty steers Peranakan Ongole (PO with average age 1-2 years old were used. They were divided 5 groups based on initial body weight as block. Therefore, Completely Randomised Block Design (CBRD was used for this experiment. Data were analysed by analysis variance and continued honestly significant different (HSD to test the differences between means. The result showed that the range MCP and eficiency MCP were 154,61 g/d until 226,54 g/d and 54,08 gMCP/kg DOMR until 62,64 gMCP/kg DOMR. The range of nitrogen balance were 72,28 gram until 111,67 gram. MCP and efficiency MCP were not affected (P>0,05 by the treatments but balance of nitrogen was affected (P<0,05. Diet containing fresh cassava waste as energy source (R2 was lower (P<0,05 than R1 and R4 while between R1,R3 and R4 was similar. This results indicate that feed source of energy (rice brand, wet cassava waste, dry cassava waste and corn can be used in steers with rice straw ensilage as forage. (Animal Production 11(2: 116-121 (2009 Key Words : Microbial protein production, nitrogen balance, rice straw, ensilage

Alteração da eficiência do 1-MCP com o retardo na sua aplicação após a colheita em maçãs 'Fuji suprema' Changes of 1-MPC efficiency by delaying its postharvest application on 'Fuji suprema' apples

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Cassandro Vidal Talamini do Amarante

2010-12-01

Full Text Available Estudos indicam que a eficiência do 1-metilciclopropeno (1-MCP para conservação pós-colheita de maçãs é máxima quando aplicado até uma semana após a colheita. No entanto, o carregamento das câmaras de armazenagem comerciais com maçãs 'Fuji' pode extender-se por mais de uma semana. Os efeitos da aplicação tardia do 1-MCP para maçãs 'Fuji' não têm sido reportados. Este trabalho teve por objetivo avaliar os efeitos do retardo na aplicação de 1-MCP, a partir da data de colheita, na preservação da firmeza de polpa, acidez titulável (AT e sólidos solúveis (SS, e na prevenção de escaldadura superficial, escurecimento da polpa e podridões em maçãs 'Fuji Suprema'. Os frutos foram colhidos em pomares comerciais do Estado de Santa Catarina, nas regiões de Fraiburgo (quatro pomares, Bom Retiro (três pomares e São Joaquim (três pomares, em abril de 2006. Os frutos foram refrigerados 12 h após a colheita e mantidos durante nove meses sob atmosfera do ar a 0,5 ± 0,5 ºC e 90-95% de UR. Os frutos foram tratados com ar (controle ou 1-MCP (1 µL.L-1, durante 24h, na mesma temperatura de armazenamento, aos 0; 4; 8; 12; 16 ou 20 dias após a colheita. A qualidade dos frutos foi determinada após o armazenamento refrigerado, mais sete dias a 23 ºC. O retardo na aplicação do 1-MCP, por até 20 dias após a colheita, não reduziu sua eficiência na conservação da firmeza da polpa e na prevenção do escurecimento da polpa e podridões, em frutos colhidos nas três regiões, bem como na preservação do teor de SS em frutos colhidos em Bom Retiro e São Joaquim. No entanto, a eficiência do 1-MCP sobre a prevenção da escaldadura superficial foi reduzida quando sua aplicação foi atrasada por 16 ou 20 dias a partir da data de colheita, especialmente nos frutos das regiões que apresentaram maior suscetibilidade ao distúrbio (Fraiburgo e São Joaquim. Os benefícios do 1-MCP sobre a conservação da AT foram reduzidos quando

Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers

DEFF Research Database (Denmark)

Shaker, S.B.; Wachenfeldt, K.A. von; Larsson, S.

2008-01-01

Introduction: Inflammation is an important constituent of the pathology of chronic obstructive pulmonary disease (COPD), leading to alveolar destruction and airway remodelling. Objective: The aim of this study was to assess the difference in plasma biomarkers of inflammation between asymptomatic...... smokers and patients with COPD. Methods: We used commercially available enzyme-linked immunosorbent assay kits to measure the plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), tissue inhibitor...... of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) on two occasions with a 2-week interval in patients with COPD (n = 20), asymptomatic smokers (n = 10) and healthy life-long non-smokers (n = 10). The participants were characterised clinically, physiologically and by quantitative...

Decreased numbers of chemotactic factor receptors in chronic neutropenia with defective chemotaxis: spontaneous recovery from the neutrophil abnormalities during early childhood

International Nuclear Information System (INIS)

Yasui, K.; Yamazaki, M.; Miyagawa, Y.; Komiyama, A.; Akabane, T.

1987-01-01

Childhood chronic neutropenia with decreased numbers of chemotactic factor receptors as well as defective chemotaxis was first demonstrated in an 8-month-old girl. Chemotactic factor receptors on neutrophils were assayed using tritiated N-formyl-methionyl-leucyl-phenylalanine ( 3 H-FMLP). The patient's neutrophils had decreased numbers of the receptors: numbers of the receptors were 20,000 (less than 3 SD) as compared with those of control cells of 52,000 +/- 6000 (mean +/- SD) (n = 10). The neutropenia disappeared spontaneously by 28 months of age parallel with the improvement of chemotaxis and increase in numbers of chemotactic factor receptors. These results demonstrate a transient decrease of neutrophil chemotactic factor receptors as one of the pathophysiological bases of a transient defect of neutrophil chemotaxis in this disorder

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-01-30

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

Neutrophil chemotactic activity in bronchoalveolar lavage fluid of patients with AIDS-associated Pneumocystis carinii pneumonia

DEFF Research Database (Denmark)

Benfield, T L; Kharazmi, A; Larsen, C G

1997-01-01

been shown to confer a poor prognosis in PCP. We therefore investigated the potential of BAL fluid from 17 patients with PCP to induce neutrophil chemotaxis. BAL fluid from patients induced considerable neutrophil chemotactic activity compared to normal controls. Elevated levels of IL-8 were detected...... in patient samples as compared to controls. A specific anti-IL-8 antibody significantly reduced chemotactic activity of patient samples by more than 50%. In conclusion, IL-8 appears to be a significant participant of neutrophil chemotaxis in AIDS-associated PCP, and may participate in the recruitment...

Influence of 1-MCP on texture, related enzymes, quality and their relative gene expression in 'Amrapali' mango (Mangifera indica L.) fruits.

Science.gov (United States)

Reddy, S V R; Sharma, R R; Barthakur, S

2017-11-01

The mango fruits remain biologically active even after harvest as they continue respiration, transpiration and other bio-chemical processes. Being highly perishable, the fruit quality deteriorates fast under ambient conditions (30 ± 5 °C and 50 ± 5% RH), rendering them unmarketable within 5-6 days. In order to extend the shelf-life of 'Amrapali' mango fruits, we have treated them with three different concentrations (500, 750 and 1000 ppb) of 1-Methylcyclopropene (1-MCP) @ 20 °C and stored at ambient conditions. Among all the treatments, 1000 ppb was found to be an effective in extending shelf-life till twelfth day with minimum physiological loss in weight (19.24%), maximum firmness (10.43 N), highest retention of quality parameters such as soluble solid concentrates (27.88 °B), ascorbic acid (28.49 mg 100 g -1 FW) and total antioxidant activity (675.41 µmol Trolox g -1 FW) compared to untreated mango fruits (21.79%, 5.45 N, 23.17 °B, 19.55 mg 100 g -1 FW and 265.41 µmol Trolox g -1 FW, respectively). Gene expression studies have revealed that the texture related gene expansin was significantly repressed till fifth day of storage with increasing concentrations of 1-MCP.

The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells.

Science.gov (United States)

Yang, Chih-Wei; Wu, Mai-Szu; Pan, Ming-Jeng; Hsieh, Wang-Ju; Vandewalle, Alain; Huang, Chiu-Ching

2002-08-01

Tubulointerstitial nephritis is a main renal manifestation caused by pathogenic leptospira that accumulate mostly in the proximal tubules, thereby inducing tubular injury and tubulointerstitial nephritis. To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells. A dose-dependent increase of monocyte chemoattractant protein-1 (MCP-1), RANTES, nitrite, and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant was observed 48 h after incubating Leptospira shermani outer membrane proteins with mouse proximal tubule cells. RT competitive-PCR experiments showed that Leptospira shermani outer membrane proteins (0.2 microg/ml) increased the expression of MCP-1, nitric oxide synthase (iNOS), RANTES, and TNF-alpha mRNA by 3.0-, 9.4-, 2.5-, and 2.5-fold, respectively, when compared with untreated cells. Outer membrane proteins extract from avirulent Leptospira patoc did not induce significant effects. The pathogenic outer membrane proteins extract contain a major component of a 32-kD lipoprotein (LipL32), which is absent in the nonpathogenic leptospira outer membrane. An antibody raised against LipL32 prevented the stimulatory effect of Leptospira shermani outer membrane proteins extract on MCP-1 and iNOS mRNA expression in cultured proximal tubule cells, whereas recombinant LipL32 significantly stimulated the expression of MCP-1 and iNOS mRNAs and augmented nuclear binding of nuclear factor-kappaB (NF-kappaB) and AP-1 transcription factors in proximal tubule cells. An antibody raised against LipL32 also blunted the effects induced by the recombinant LipL32. This study demonstrates that LipL32 is a major component of pathogenic leptospira outer membrane proteins involved in the pathogenesis of tubulointerstitial nephritis.

Statins, inflammation and deep vein thrombosis: a systematic review

Science.gov (United States)

Rodriguez, April L.; Wojcik, Brandon M.; Wrobleski, Shirley K.; Myers, Daniel D.; Wakefield, Thomas W.

2012-01-01

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin. The effects of statins on thrombosis are unclear, prompting this literature review. A literature search was performed (1950 to February 2011) with MEDLINE, EMBASE, and PUBMED databases including the following keywords: “statins”, “hydroxymethylglutaryl-CoA reductase inhibitors”, “VTE”, “PE”, “DVT”, and either “anti-coagulation” or “inflammation”. Editorials, reviews, case reports, meta-analysis and duplicates were excluded. Inflammatory biomarkers of DVT, include interleukin (IL)-6, CRP, IL-8, and monocyte chemotactic protein 1 (MCP-1). Statin therapy reduces IL-6 expression of CRP and MCP-1, usually elevated in VTE. Reduction of IL-6 induced MCP-1 has been linked to vein wall fibrosis, promoting post thrombotic syndrome (PTS) and recurrent DVT in patients. Also, our review suggests that the anti-thrombotic effects are likely exhibited through the anti-inflammatory properties of statins. This work supports that statin therapy has the ability to decrease the incidence and recurrence of VTE and the potential to decrease PTS. This is mainly due to the anti-inflammatory effects of statins and may explain why normolipidemic patients, with elevated CRP, appear to have the greatest reduction in VTE. Given their low risk of bleeding, statins have the potential to serve as a safe adjunctive pharmacological therapy to current treatments in select patients with VTE, however further investigations into this concept are needed and essential. PMID:22278047

Ureaplasma isolates stimulate pro-inflammatory CC chemokines and matrix metalloproteinase-9 in neonatal and adult monocytes

Science.gov (United States)

Silwedel, Christine; Fehrholz, Markus; Henrich, Birgit; Waaga-Gasser, Ana Maria; Claus, Heike; Speer, Christian P.

2018-01-01

Being generally regarded as commensal bacteria, the pro-inflammatory capacity of Ureaplasma species has long been debated. Recently, we confirmed Ureaplasma–driven pro-inflammatory cytokine responses and a disturbance of cytokine equilibrium in primary human monocytes in vitro. The present study addressed the expression of CC chemokines and matrix metalloproteinase-9 (MMP-9) in purified term neonatal and adult monocytes stimulated with serovar 8 of Ureaplasma urealyticum (Uu) and serovar 3 of U. parvum (Up). Using qRT-PCR and multi-analyte immunoassay, we assessed mRNA and protein expression of the monocyte chemotactic proteins 1 and 3 (MCP-1/3), the macrophage inflammatory proteins 1α and 1β (MIP-1α/β) as well as MMP-9. For the most part, both isolates stimulated mRNA expression of all given chemokines and MMP-9 in cord blood and adult monocytes (pUreaplasma isolates in vitro, adding to our previous data. Findings from co-stimulated cells indicate that Ureaplasma may modulate monocyte immune responses to a second stimulus. PMID:29558521

The actin cytoskeleton of chemotactic amoebae operates close to the onset of oscillations

Science.gov (United States)

Westendorf, Christian; Negrete, Jose, Jr.; Bae, Albert; Sandmann, Rabea; Bodenschatz, Eberhard; Beta, Carsten

2013-03-01

We report evidence that the actin machinery of chemotactic Dictyostelium cells operates close to an oscillatory instability. The averaged F-actin response of many cells to a short-time pulse of cAMP is reminiscent of a damped oscillation. At the single-cell level, however, the response dynamics ranged from short, strongly damped responses to slowly decaying, weakly damped oscillations. Furthermore, in a small subpopulation, we observed self-sustained oscillations in the cortical F-actin concentration. We systematically exposed a large number of cells to periodic pulse trains. The results indicate a resonance peak at periodic inputs of around 20 s. We propose a delayed feedback model that explains our experimental findings based on a time-delay in the actin regulatory network. To quantitatively test the model, we performed stimulation experiments with cells that express GFP-tagged fusion proteins of Coronin and Aip1. These served as markers of the F-actin disassembly process and thus allow us to estimate the delay time. Based on this independent estimate, our model predicts an intrinsic period of 20 s, which agrees with the resonance observed experimentally. Financial support by the Max-Planck Society and the DFG (SFB 937).

Two micron pore size MCP-based image intensifiers

Science.gov (United States)

Glesener, John; Estrera, Joseph

2010-02-01

Image intensifiers (I2) have many advantages as detectors. They offer single photon sensitivity in an imaging format, they're light in weight and analog I2 systems can operate for hours on a single AA battery. Their light output is such as to exploit the peak in color sensitivity of the human eye. Until recent developments in CMOS sensors, they also were one of the highest resolution sensors available. The closest all solid state solution, the Texas Instruments Impactron chip, comes in a 1 megapixel format. Depending on the level of integration, an Impactron based system can consume 20 to 40 watts in a system configuration. In further investing in I2 technology, L-3 EOS determined that increasing I2 resolution merited a high priority. Increased I2 resolution offers the system user two desirable options: 1) increased detection and identification ranges while maintaining field-of-view (FOV) or 2) increasing FOV while maintaining the original system resolution. One of the areas where an investment in resolution is being made is in the microchannel plate (MCP). Incorporation of a 2 micron MCP into an image tube has the potential of increasing the system resolution of currently fielded systems. Both inverting and non-inverting configurations are being evaluated. Inverting tubes are being characterized in night vision goggle (NVG) and sights. The non-inverting 2 micron tube is being characterized for high resolution I2CMOS camera applications. Preliminary measurements show an increase in the MTF over a standard 5 micron pore size, 6 micron pitch plate. Current results will be presented.

Development and tests of MCP based timing and multiplicity detector for MIPs

Science.gov (United States)

Feofilov, G.; Kondratev, V.; Stolyarov, O.; Tulina, T.; Valiev, F.; Vinogradov, L.

2017-01-01

We present summary of technological developments and tests of the MCP based large area detector aimed at precise timing and charged particles multiplicity measurements. Results obtained in course of these developments of isochronous (simultaneity) precise signal readout, passive summation of 1 ns signals, fast (1 GHz) front-end electronics, miniature vacuum systems, etc. could be potentially interesting for a number of future applications in different fields.

Adiponectin, interleukin-6, monocyte chemoattractant protein-1, and regional fat mass during 12-month randomized treatment with metformin and/or oral contraceptives in polycystic ovary syndrome.

Science.gov (United States)

Glintborg, Dorte; Mumm, Hanne; Altinok, Magda Lambaa; Richelsen, Bjørn; Bruun, Jens Meldgaard; Andersen, Marianne

2014-08-01

Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. To evaluate if improved body composition during treatment with metformin (M) vs. oral contraceptive pills (OCP) was associated with changes in circulating adiponectin, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. Ninety patients with PCOS were randomized to 12-month treatment with M (2 g/day), M + OCP (150 mg desogestrel + 30 microgram ethinylestradiol) or OCP. Adiponectin, IL-6, MCP-1, whole body DXA scans, and clinical evaluations were performed before and after the intervention period in the 65 study completers. Changes in inflammatory markers and changes in total and regional fat mass estimates. Adiponectin, IL-6, and MCP-1 levels were unchanged during the three types of medical intervention. Treatment with M and M + OCP was superior to OCP regarding decreased regional fat mass. Baseline adiponectin and IL-6 were associated with BMI, waist, and trunk fat mass. Changes in trunk fat were significantly associated with changes in IL-6 and MCP-1 during M + OCP. Long-term treatment with M alone or in combination with OCP was associated with improved body composition compared to OCP, whereas inflammatory markers were unchanged. OCP was not associated with increased inflammatory markers despite a small but significant weight gain.

Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls

Directory of Open Access Journals (Sweden)

Hillenbrand Andreas

2012-11-01

Full Text Available Abstract Background Obesity has been associated with increased incidence of colorectal cancer. Adipose tissue dysfunction accompanied with alterations in the release of adipocytokines has been proposed to contribute to cancer pathogenesis and progression. The aim of this study was to analyze plasma concentrations of several adipose tissue expressed hormones in colorectal cancer patients (CRC and morbidly obese (MO patients and to compare these concentrations to clinicopathological parameters. Methods Plasma concentrations of adiponectin, resistin, leptin, active plasminogen activator inhibitor (PAI-1, monocyte chemotactic protein (MCP-1, interleukin (IL-1 alpha, and tumor necrosis factor (TNF-alpha were determined in 67 patients operated on for CRC (31 rectal cancers, 36 colon cancers, 37 patients operated on for morbid obesity and 60 healthy blood donors (BD. Results Compared to BD, leptin concentrations were lowered in CRC patients whereas those of MO patients were elevated. Adiponectin concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1, and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF-alpha were similarly expressed in MO and CRC patients compared to BD. Resistin concentrations positively correlated with tumor staging (p Conclusions The results suggest that both MO and CRC have low-grade inflammation as part of their etiology.

Biological ageing and frailty markers in breast cancer patients.

Science.gov (United States)

Brouwers, Barbara; Dalmasso, Bruna; Hatse, Sigrid; Laenen, Annouschka; Kenis, Cindy; Swerts, Evalien; Neven, Patrick; Smeets, Ann; Schöffski, Patrick; Wildiers, Hans

2015-05-01

Older cancer patients are a highly heterogeneous population in terms of global health and physiological reserves, and it is often difficult to determine the best treatment. Moreover, clinical tools currently used to assess global health require dedicated time and lack a standardized end score. Circulating markers of biological age and/or fitness could complement or partially substitute the existing screening tools. In this study we explored the relationship of potential ageing/frailty biomarkers with age and clinical frailty. On a population of 82 young and 162 older non-metastatic breast cancer patients, we measured mean leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also developed a new tool to summarize clinical frailty, designated Leuven Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi-continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL-6 levels were associated with chronological age in both groups and with clinical frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1 only correlated with age. Plasma IL-6 should be further explored as frailty biomarker in cancer patients.

Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls

International Nuclear Information System (INIS)

Hillenbrand, Andreas; Fassler, Juliane; Huber, Nadine; Xu, Pengfei; Henne-Bruns, Doris; Templin, Markus; Schrezenmeier, Hubert; Wolf, Anna Maria; Knippschild, Uwe

2012-01-01

Obesity has been associated with increased incidence of colorectal cancer. Adipose tissue dysfunction accompanied with alterations in the release of adipocytokines has been proposed to contribute to cancer pathogenesis and progression. The aim of this study was to analyze plasma concentrations of several adipose tissue expressed hormones in colorectal cancer patients (CRC) and morbidly obese (MO) patients and to compare these concentrations to clinicopathological parameters. Plasma concentrations of adiponectin, resistin, leptin, active plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1 alpha, and tumor necrosis factor (TNF)-alpha were determined in 67 patients operated on for CRC (31 rectal cancers, 36 colon cancers), 37 patients operated on for morbid obesity and 60 healthy blood donors (BD). Compared to BD, leptin concentrations were lowered in CRC patients whereas those of MO patients were elevated. Adiponectin concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1, and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF-alpha were similarly expressed in MO and CRC patients compared to BD. Resistin concentrations positively correlated with tumor staging (p<0.002) and grading (p=0.015) of rectal tumor patients. The results suggest that both MO and CRC have low-grade inflammation as part of their etiology

Development of a dual MCP framing camera for high energy x-rays

Energy Technology Data Exchange (ETDEWEB)

Izumi, N., E-mail: izumi2@llnl.gov; Hall, G. N.; Carpenter, A. C.; Allen, F. V.; Cruz, J. G.; Felker, B.; Hargrove, D.; Holder, J.; Lumbard, A.; Montesanti, R.; Palmer, N. E.; Piston, K.; Stone, G.; Thao, M.; Vern, R.; Zacharias, R.; Landen, O. L.; Tommasini, R.; Bradley, D. K.; Bell, P. M. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); and others

2014-11-15

Recently developed diagnostic techniques at LLNL require recording backlit images of extremely dense imploded plasmas using hard x-rays, and demand the detector to be sensitive to photons with energies higher than 50 keV [R. Tommasini et al., Phys. Phys. Plasmas 18, 056309 (2011); G. N. Hall et al., “AXIS: An instrument for imaging Compton radiographs using ARC on the NIF,” Rev. Sci. Instrum. (these proceedings)]. To increase the sensitivity in the high energy region, we propose to use a combination of two MCPs. The first MCP is operated in a low gain regime and works as a thick photocathode, and the second MCP works as a high gain electron multiplier. We tested the concept of this dual MCP configuration and succeeded in obtaining a detective quantum efficiency of 4.5% for 59 keV x-rays, 3 times larger than with a single plate of the thickness typically used in NIF framing cameras.

Impact of anesthesia, analgesia, and euthanasia technique on the inflammatory cytokine profile in a rodent model of severe burn injury.

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Al-Mousawi, Ahmed M; Kulp, Gabriela A; Branski, Ludwik K; Kraft, Robert; Mecott, Gabriel A; Williams, Felicia N; Herndon, David N; Jeschke, Marc G

2010-09-01

Anesthetics used in burn and trauma animal models may be influencing results by modulating inflammatory and acute-phase responses. Accordingly, we determined the effects of various anesthetics, analgesia, and euthanasia techniques in a rodent burn model. Isoflurane (ISO), ketamine-xylazine (KX), or pentobarbital (PEN) with or without buprenorphine were administered before scald-burn in 72 rats that were euthanized without anesthesia by decapitation after 24 h and compared with unburned shams. In a second experiment, 120 rats underwent the same scald-burn injury using KX, and 24 h later were euthanized under anesthesia or carbon dioxide (CO2). In addition, we compared euthanasia by exsanguination with that of decapitation. Serum cytokine levels were determined by an enzyme-linked immunosorbent assay. In the first experiment, ISO was associated with elevation of cytokine-induced neutrophil chemoattractant 2 (CINC-2) and monocyte chemotactic protein 1 (MCP-1), and KX and PEN was associated with elevation of CINC-1,CINC-2, IL-6, and MCP-1. Pentobarbital also decreased IL-1". IL-6 increased significantly when ISO or PEN were combined with buprenorphine. In the second experiment, euthanasia performed by exsanguination under ISO was associated with reduced levels of IL-1", CINC-1, CINC-2, and MCP-1, whereas KX reduced CINC-2 and increased IL-6 levels. Meanwhile, PEN reduced levels of IL-1" and MCP-1, and CO2 reduced CINC-2 and MCP-1. In addition,decapitation after KX, PEN, or CO2 decreased IL-1" and MCP-1, although we found no significant difference between ISO and controls. Euthanasia by exsanguination compared with decapitation using the same agent also led to modulation of several cytokines. Differential expression of inflammatory markers with the use of anesthetics and analgesics should be considered when designing animal studies and interpreting results because these seem to have a significant modulating impact. Our findings indicate that brief anesthesia with ISO

Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells.

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David Bauer

Full Text Available Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFα plays a central orchestrating role. TNFα acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2. These proteins direct inward infiltration/migration of tumor-associated macrophages (TAMs, tumor-associated neutrophils (TANs, myeloid-derived suppressor cells (MDSCs, T-regulatory cells (Tregs, T helper IL-17-producing cells (Th17s, metastasis-associated macrophages (MAMs and cancer-associated fibroblasts (CAFs. Tumor embedded infiltrates collectively enable immune evasion, tumor growth, angiogenesis, and metastasis. In the current study, we investigate the potential of apigenin, a known anti-inflammatory constituent of parsley, to downregulate TNFα mediated release of chemokines from human triple-negative cells (MDA-MB-231 cells. The results show that TNFα stimulation leads to large rise of CCL2, granulocyte macrophage colony-stimulating factor (GMCSF, IL-1α and IL-6, all suppressed by apigenin. While many aspects of the transcriptome for NFkB signaling were evaluated, the data show signaling patterns associated with CCL2 were blocked by apigenin and mediated through suppressed mRNA and protein synthesis of IKBKe. Moreover, the data show that the attenuation of CCL2 by apigenin in the presence TNFα paralleled the suppression of phosphorylated extracellular signal-regulated kinase 1 (ERK 1/ 2. In summary, the obtained findings suggest that there exists a TNFα evoked release of CCL2 and other LSP recruiting cytokines from human breast cancer cells, which can be attenuated by apigenin.

Retinoic acid suppresses growth of lesions, inhibits peritoneal cytokine secretion, and promotes macrophage differentiation in an immunocompetent mouse model of endometriosis.

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Wieser, Friedrich; Wu, Juanjuan; Shen, Zhaoju; Taylor, Robert N; Sidell, Neil

2012-06-01

To determine the effects of all-trans-retinoic acid (RA) on establishment and growth of endometrial lesions, peritoneal interleukin-6 (IL-6) and macrophage chemotactic factor-1 (MCP-1) concentrations, and CD38, CD11b, and F4/80 expression on peritoneal macrophages in an immunocompetent mouse model of endometriosis. Experimental transplantation study using mice. Academic medical center. C57BL/6 recipient mice and syngeneic green fluorescent protein transgenic (GFP+) mice. Recipient mice were inoculated with GFP+ minced uterine tissue to induce endometriosis and treated with RA (400 nmol/day) or vehicle for 17 days (3 days before to 14 days after tissue injection). Total number of GFP+ implants in recipient mice, number of implants showing visible blood vessels, total volume of established lesions per mouse, concentrations of IL-6 and MCP-1 in peritoneal fluid, and expression of CD11b, F4/80, and CD38 on peritoneal macrophages. Retinoic acid treatment for 17 days reduced the number of implants versus controls and decreased the frequency of lesions with vessels. Peritoneal washings in RA-treated animals had lower concentrations of IL-6 and MCP-1 than controls 3 days after endometrial inoculation and lower levels of IL-6 on day 14 after inoculation. Concomitant with these effects on day 14, CD38, CD11b, and F4/80 were higher on macrophages from RA-treated mice versus controls. The development of endometriotic implants is inhibited by RA. This effect may be caused, at least in part, by reduced IL-6 and MCP-1 production and enhanced differentiation of peritoneal macrophages. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effects of Garlic Oil on the Migration of Neutrophil-Like Cell Studied by Using a Chemotactic Gradient Labchip

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Po-Chen Shih

2010-01-01

Full Text Available We have designed and fabricated a novel chemotactic gradient Labchip for studying cell migration quantitatively. Owing to the great potential of garlic and its preparations in developing antiinflammatory drugs, the aim of the present study is to investigate the effect of garlic oil on the locomotion of a neutrophil-like cell by measuring the dynamic features of cell migration including migration direction, average migration speed, chemotactic index (CI, and motility index (MI with the newly designed Labchip. We found that garlic oil treatment lowered the values of CI and MI and reduced the average speed of cell migration from 13 to 8 μm/min. The results indicate that garlic oil is a potential inhibitor for neutrophil-like cell migration and chemotactic responsiveness. By comparing with the effects of nocodazole and cytochalasin B, we also suggest that the antiinflammatory activity exhibited by garlic oil was mainly through inhibiting the assembly-disassembly processes of the cytoskeleton.

Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium nitrite: Effects on tissue fibrosis and apoptosis.

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Al-Gayyar, Mohammed M H; Hassan, Hanan M; Alyoussef, Abdullah; Abbas, Ahmed; Darweish, Mohamed M; El-Hawwary, Amany A

2016-03-01

Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO). Seventy adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid-Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK. NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.

RELATIONSHIP OF ADIPOKINES AND PROINFLAMMATORY CYTOKINES AMONG ASIAN INDIANS WITH OBESITY AND YOUTH ONSET TYPE 2 DIABETES.

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Gokulakrishnan, Kuppan; Amutha, Anandakumar; Ranjani, Harish; Bibin, Subramanian Y; Balakumar, Mahalingam; Pandey, Gautam Kumar; Anjana, Ranjit Mohan; Ali, Mohammed K; Narayan, K M Venkat; Mohan, Viswanathan

2015-10-01

It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y). We recruited individuals with T2DM-Y (age at onset obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and monocyte chemotactic protein-1 [MCP-1]) across groups. Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 μg/mL, Pobese T2DM-Y (141 pg/mL, Pobese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM. In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.

Stroke Status Evoked Adhesion Molecule Genetic Alterations in Astrocytes Isolated from Stroke-Prone Spontaneously Hypertensive Rats and the Apigenin Inhibition of Their Expression

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Kazuo Yamagata

2010-01-01

Full Text Available We examined the possibility that the expression of adhesion molecules is regulated differently in cultured astrocytes from stroke-prone spontaneously hypertensive rats (SHRSP/IZM rats than in those from Wistar Kyoto rats (WKY/IZM by tumor necrosis factor-alpha (TNF- or hypoxia and reoxygenation (H/R and the inhibitory effects of apigenin. It was found that the expression of vascular cell adhesion molecule-1 (VCAM-1 by TNF- in astrocytes isolated from SHRSP/IZM was increased compared with that in WKY/IZM. The expression of monocyte chemotactic protein-1 (MCP-1 mRNA induced by H/R in SHRSP/IZM astrocytes was increased compared with that in normal oxygen concentrations. Apigenin strongly attenuated TNF--induced VCAM-1 mRNA and protein expression and suppressed the adhesion of U937 cells and SHRSP/IZM astrocytes. These results suggest that the expression levels of adhesion molecules during H/R affect disease outcome and can drive SHRSP/IZM to stroke. It is suggested that apigenin regulates adhesion molecule expression in reactive astrocytes during ischemia.

Fast front-end L0 trigger electronics for ALICE FMD-MCP tests and performance

CERN Document Server

Efimov, L G; Kasatkan, V; Klempt, W; Kuts, V; Lenti, V; Platanov, V; Rudge, A; Stolyarov, O I; Tsimbal, F A; Valiev, F F; Villalobos Baillie, O; Vinogradov, L I; Zhigunov, O

1997-01-01

We present design details and new measurements of the performance of fast electronics for the Forward Multiplicity Detector for ALICE. These detectors based on sector type Microchannel Plates (MCP) forming several disks gave the very first trigger decision in the experiment (L0). Fast passive summators integrated with the detectors are used for linear summation of up to eight isochronous signal channels from MCP pads belonging to one sector. Two types of microelectronics design thin film summators were produced. We present test results for these summators, working in the frequency range up to 1 Ghz. New low noise preamplifiers have been built to work with these summators. The new design shows a good performance with the usable frequency range extended up to 1 Ghz. An upgrade of the functional scheme for the L0 ALICE pre-trigger design is also presented.Abstract:List of figures Figure 1: ALICE L0 Trigger Front-End Electronics Functional Scheme. Figure 2: UHF design for a fast passive summator based on direct...

Promoter analysis of the Chilo iridescent virus DNA polymerase and major capsid protein genes

International Nuclear Information System (INIS)

Nalcacioglu, Remziye; Marks, Hendrik; Vlak, Just M.; Demirbag, Zihni; Oers, Monique M. van

2003-01-01

The DNA polymerase (DNApol) and major capsid protein (MCP) genes were used as models to study promoter activity in Chilo iridescent virus (CIV). Infection of Bombyx mori SPC-BM-36 cells in the presence of inhibitors of DNA or protein synthesis showed that DNApol, as well as helicase, is an immediate-early gene and confirmed that the major capsid protein (MCP) is a late gene. Transcription of DNApol initiated 35 nt upstream and that of MCP 14 nt upstream of the translational start site. In a luciferase reporter gene assay both promoters were active only when cells were infected with CIV. For DNApol sequences between position -27 and -6, relative to the transcriptional start site, were essential for promoter activity. Furthermore, mutation of a G within the sequence TTGTTTT located just upstream of the DNApol transcription initiation site reduced the promoter activity by 25%. Sequences crucial for MCP promoter activity are located between positions -53 and -29

Extracellular cyclophilin levels associate with parameters of asthma in phenotypic clusters.

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Stemmy, Erik J; Benton, Angela S; Lerner, Jennifer; Alcala, Sarah; Constant, Stephanie L; Freishtat, Robert J

2011-12-01

Leukocyte persistence during chronic (quiescent) phases of asthma is a major hallmark of the disease. The mechanisms regulating these persistent leukocyte populations are not clearly understood. An alternative family of chemoattracting proteins, cyclophilins (Cyps), has recently been shown to contribute to leukocyte recruitment in animal models of allergic asthma. The goals of this study were to determine whether Cyps are present in asthma patients during the chronic phase of the disease and to investigate whether levels of Cyps associate with clinical parameters of disease severity. Nasal wash samples from an urban cohort of 137 patients of age 6-20 years with physician-diagnosed asthma were examined for the presence of cyclophilin A (CypA), cyclophilin B (CypB), as well as several other classical chemokines. Linear, logistic, or ordinal regressions were performed to identify associations between Cyps, chemokines, and clinical parameters of asthma. The asthma cohort was further divided into previously established phenotypic clusters (cluster 1: n = 55; cluster 2: n = 31; and cluster 3: n = 51) and examined for associations. Levels of CypB in the asthma group were highly elevated compared to nonasthmatic controls, while a slight increase in Monocyte Chemotactic Protein-1 (MCP-1) was also observed. CypA and MCP-1 were associated with levels of eosinophil cationic protein (ECP; a marker of eosinophil activation). Cluster-specific associations were found for CypA and CypB and clinical asthma parameters [e.g. forced expiratory volume in 1 second (FEV(1)) and ECP]. Cyps are present in nasal wash samples of asthma patients and may be a novel biomarker for clinical parameters of asthma severity.

Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response.

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Emily C Moorefield

Full Text Available Amniotic fluid stem (AFS cells are broadly multipotent, can be expanded extensively in culture, are not tumorigenic and can be readily cryopreserved for cell banking. Mesenchymal stem cells (MSC show immunomodulatory activity and secrete a wide spectrum of cytokines and chemokines that suppress inflammatory responses, block mixed lymphocyte reactions (MLR and other immune reactions, and have proven therapeutic against conditions such as graft-versus-host disease. AFS cells resemble MSCs in many respects including surface marker expression and differentiation potential. We therefore hypothesized that AFS cells may exhibit similar immunomodulatory capabilities. We present data to demonstrate that direct contact with AFS cells inhibits lymphocyte activation. In addition, we show that cell-free supernatants derived from AFS cells primed with total blood monocytes or IL-1β, a cytokine released by monocytes and essential in mediation of the inflammatory response, also inhibited lymphocyte activation. Further investigation of AFS cell-free supernatants by protein array revealed secretion of multiple factors in common with MSCs that are known to be involved in immune regulation including growth related oncogene (GRO and monocyte chemotactic protein (MCP family members as well as interleukin-6 (IL-6. AFS cells activated by PBMCs released several additional cytokines as compared to BM-MSCs, including macrophage inflammatory protein-3α (MIP-3α, MIP-1α and Activin. AFS cells also released higher levels of MCP-1 and lower levels of MCP-2 compared to BM-MSCs in response to IL-1β activation. This suggests that there may be some AFS-specific mechanisms of inhibition of lymphocyte activation. Our results indicate that AFS cells are able to suppress inflammatory responses in vitro and that soluble factors are an essential component in the communication between lymphocytes and AFS cells. Their extensive self-renewal capacity, possibility for banking and

Cytokine and nitric oxide levels in patients with sepsis--temporal evolvement and relation to platelet mitochondrial respiratory function

DEFF Research Database (Denmark)

Sjövall, Fredrik; Morota, Saori; Frostner, Eleonor Åsander

2014-01-01

the correlation between observed changes in platelet mitochondrial respiration and a set of pro- and anti-inflammatory cytokines as well as NO plasma levels in patients with sepsis. METHODS AND RESULTS: Platelet mitochondrial respiration and levels of TNFα, MCP-1 (monocyte chemotactic protein-1), INFγ (interferon......-γ), IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-17 and NO were analyzed in 38 patients with severe sepsis or septic shock at three time points during one week following admission to the ICU. Citrate synthase, mitochondrial DNA and cytochrome c were measured as markers of cellular mitochondrial content....... All mitochondrial respiratory states increased over the week analyzed (prespiration on day 6-7 (p = 0.02, r2 = 0.22) and was also higher in non-survivors compared to survivors on day 3-4 and day 6-7 (p = 0.03 respectively). Neither NO nor any...

Gut Microbiota in Type 2 Diabetes Individuals and Correlation with Monocyte Chemoattractant Protein1 and Interferon Gamma from Patients Attending a Tertiary Care Centre in Chennai, India

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Premalatha Pushpanathan

2016-01-01

Full Text Available Background: Type 2 diabetes mellitus (T2DM and obesity are associated with changes in gut microbiota and characterized by chronic low-grade inflammation. Monocyte chemoattractant protein-1 (MCP-1 and interferon gamma (IFNγ are proinflammatory cytokines which play an important role in the development of T2DM. We undertook this study to analyze the gut microbiota of T2DM and nondiabetic subjects and to determine the profile of MCP 1 and IFNγ in the same subjects attending a tertiary care center in Chennai, Tamil Nadu, India. Methods: The study included 30 subjects with clinical details. Stool and blood samples were collected from all the subjects. DNA was extracted from fecal samples and polymerase chain reaction was done using fusion primers. Metagenomic analysis was performed using ion torrent sequencing. The reads obtained were in FASTA format and reported as operational taxonomic units. Human MCP 1 and IFNγ enzyme linked immunosorbent assay (ELISA were performed for 23 serum samples. Results: The study consisted of 30 subjects; 17 were T2DM and 13 were nondiabetics. The gut microbiota among T2DM consisted predominantly of Gram negative bacteria; Escherichia and Prevotella, when compared with the nondiabetic group with predominantly Gram positive organisms suchas Faecalibacterium, Eubacterium, and Bifidobacterium. The mean MCP-1 values in the diabetic group were 232.8 pg/ml and in the nondiabetic group 170.84 pg/ml. IFNγ (mean 385.5 pg/ml was raised in glycated hemoglobin (HbA1c group of 6.5–7.5% which was statistically significant. Association of Escherichia with T2DM and association of Bifidobacteria in the nondiabetics were also statistically significant. Conclusion: Escherichia counts were elevated in T2DM with HbA1c of 6.5–8.5% which was statistically significant suggesting that lipopolysaccharides present in the cell wall of Gram-negative bacteria may be responsible for low-grade inflammation as evidenced by elevated MCP-1 and

Subclinical chronic kidney disease modifies the diagnosis of experimental acute kidney injury.

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Succar, Lena; Pianta, Timothy J; Davidson, Trent; Pickering, John W; Endre, Zoltán H

2017-09-01

Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Effect of the immersion in 1-MCP on the physicochemical and physiological properties of yellow pitahaya fruit (Selenicereus megalanthus How with minimum processing

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Segura Rojas Diego Fernando

2011-09-01

Full Text Available

La pitahaya amarilla (Selenicereus megalanthus How es una fruta exótica con gran potencial comercial. No obstante, sólo ha sido aprovechada comercialmente como fruta entera, sin procedimientos que le den valor agregado y mayor tiempo de vida de anaquel. En este trabajo se evaluó la aplicación de 200 mg/lt de 1-MCP en pitahaya amarilla mínimamente procesada (rodajas con cáscara y sin cáscara, empacada al vacío y almacenada bajo refrigeración, sobre la intensidad respiratoria y parámetros de calidad como sólidos solubles, acidez total titulable, pérdida de peso, azücares totales, firmeza y color. La aplicación de 1-MCP aumentó la producción de CO2, lo cual se manifestó en mayores contenidos de sólidos solubles y azúcares totales, pero no incidió en la pérdida de peso, variación de la acidez total titulable, cambios de color y retención de la firmeza. En ambos tipos de procesamientos se logró reducir durante el almacenamiento la pérdida de vitamina C.

Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

International Nuclear Information System (INIS)

Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A.

1990-01-01

Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons

Cooperation of decay-accelerating factor and membrane cofactor protein in regulating survival of human cervical cancer cells

International Nuclear Information System (INIS)

Gao, Ling-Juan; Guo, Shu-Yu; Cai, You-Qun; Gu, Ping-Qing; Su, Ya-Juan; Gong, Hui; Liu, Yun; Chen, Chen

2009-01-01

Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) are the key molecules involved in cell protection against autologus complement, which restricts the action of complement at critical stages of the cascade reaction. The cooperative effect of DAF and MCP on the survival of human cervical cancer cell (ME180) has not been demonstrated. In this study we applied, for the first time, short hairpin RNA (shRNA) to knock down the expression of the DAF and MCP with the aim of exploiting complement more effectively for tumor cell damage. Meanwhile, we investigated the cooperative effects of DAF and MCP on the viability and migration, moreover the proliferation of ME180 cell. The results showed that shRNA inhibition of DAF and MCP expression enhanced complement-dependent cytolysis (CDC) up to 39% for MCP and up to 36% for DAF, and the combined inhibition of both regulators yielded further additive effects in ME180 cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two protein individually. These data indicated that combined DAF and MCP shRNA described in this study may offer an additional alternative to improve the efficacy of antibody-and complement-based cancer immunotherapy

Enhanced basophil histamine release and neutrophil chemotactic activity predispose grain dust-induced airway obstruction.

Science.gov (United States)

Park, H; Jung, K; Kang, K; Nahm, D; Cho, S; Kim, Y

1999-04-01

The pathogenic mechanism of grain dust (GD)-induced occupational asthma (OA) remains unclear. To understand further the mechanism of GD-induced OA. Fifteen employees working in a same GD industry, complaining of work-related respiratory symptoms, were enrolled and were divided into two groups according to the GD-bronchoprovocation test (BPT) result: six positive responders were grouped as group III, nine negative responders as group II and five healthy controls as group I. Serum GD-specific immunoglobulin (Ig)E (sIgE), specific IgG (sIgG) and specific IgG4 (sIgG4) antibodies were detected by enzyme-linked immunosorbent assay. Basophil histamine release was measured by the autofluorometric method, and changes of serum neutrophil chemotactic activity were observed by the Boyden chamber method. For clinical parameters such as degree of airway hyperresponsiveness to methacholine, duration of respiratory symptoms, exposure duration, and prevalences of serum sIgE, sIgG and sIgG4 antibodies, there were no significant differences between group II and III (P > 0.05, respectively). Serum neutrophil chemotactic activity increased significantly at 30 min and decreased at 240 min after the GD-BPT in group III subjects (P 0.05). Basophil histamine release induced by GD was significantly higher in group III than those of group I or group II (P < 0.05, respectively), while minimal release of anti-IgG4 antibodies was noted in all three groups. These results suggest that enhanced basophil histamine release and serum neutrophil chemotactic activity might contribute to the development of GD-induced occupational asthma.

LEGO bricks used as chemotactic chambers: evaluation by a computer-assisted image analysis technique.

Science.gov (United States)

Azzarà, A; Chimenti, M

2004-01-01

One of the main techniques used to explore neutrophil motility, employs micropore filters in chemotactic chambers. Many new models have been proposed, in order to perform multiple microassays in a rapid, inexpensive and reproducible way. In this work, LEGO bricks have been used as chemotactic chambers in the evaluation of neutrophil random motility and chemotaxis and compared with conventional Boyden chambers in a "time-response" experiment. Neutrophil motility throughout the filters was evaluated by means of an image-processing workstation, in which a dedicated algorithm recognizes and counts the cells in several fields and focal planes throughout the whole filter; correlates counts and depth values; performs a statistical analysis of data; calculates the true value of neutrophil migration; determines the distribution of cells; and displays the migration pattern. By this method, we found that the distances travelled by the cells in conventional chambers and in LEGO bricks were perfectly identical, both in random migration and under chemotactic conditions. Moreover, no interference with the physiological behaviour of neutrophils was detectable. In fact, the kinetics of migration was identical both in random migration (characterized by a gaussian pattern) and in chemotaxis (characterized by a typical stimulation peak, previously identified by our workstation). In conclusion, LEGO bricks are extremely precise devices. They are simple to use and allow the use of small amounts of chemoattractant solution and cell suspension, supplying by itself a triplicate test. LEGO bricks are inexpensive, fast and suitable for current diagnostic activity or for research investigations in every laboratory.

Dipeptidyl Peptidase-4 Inhibitor Anagliptin Prevents Intracranial Aneurysm Growth by Suppressing Macrophage Infiltration and Activation.

Science.gov (United States)

Ikedo, Taichi; Minami, Manabu; Kataoka, Hiroharu; Hayashi, Kosuke; Nagata, Manabu; Fujikawa, Risako; Higuchi, Sei; Yasui, Mika; Aoki, Tomohiro; Fukuda, Miyuki; Yokode, Masayuki; Miyamoto, Susumu

2017-06-19

Chronic inflammation plays a key role in the pathogenesis of intracranial aneurysms (IAs). DPP-4 (dipeptidyl peptidase-4) inhibitors have anti-inflammatory effects, including suppressing macrophage infiltration, in various inflammatory models. We examined whether a DPP-4 inhibitor, anagliptin, could suppress the growth of IAs in a rodent aneurysm model. IAs were surgically induced in 7-week-old male Sprague Dawley rats, followed by oral administration of 300 mg/kg anagliptin. We measured the morphologic parameters of aneurysms over time and their local inflammatory responses. To investigate the molecular mechanisms, we used lipopolysaccharide-treated RAW264.7 macrophages. In the anagliptin-treated group, aneurysms were significantly smaller 2 to 4 weeks after IA induction. Anagliptin inhibited the accumulation of macrophages in IAs, reduced the expression of MCP-1 (monocyte chemotactic protein 1), and suppressed the phosphorylation of p65. In lipopolysaccharide-stimulated RAW264.7 cells, anagliptin treatment significantly reduced the production of tumor necrosis factor α, MCP-1, and IL-6 (interleukin 6) independent of GLP-1 (glucagon-like peptide 1), the key mediator in the antidiabetic effects of DPP-4 inhibitors. Notably, anagliptin activated ERK5 (extracellular signal-regulated kinase 5), which mediates the anti-inflammatory effects of statins, in RAW264.7 macrophages. Preadministration with an ERK5 inhibitor blocked the inhibitory effect of anagliptin on MCP-1 and IL-6 expression. Accordingly, the ERK5 inhibitor also counteracted the suppression of p65 phosphorylation in vitro. A DPP-4 inhibitor, anagliptin, prevents the growth of IAs via its anti-inflammatory effects on macrophages. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The natural compound berberine positively affects macrophage functions involved in atherogenesis.

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Zimetti, F; Adorni, M P; Ronda, N; Gatti, R; Bernini, F; Favari, E

2015-02-01

We investigated the effect of berberine (BBR), an alkaloid showing antiatherogenic properties beyond the cholesterol lowering capacity, on macrophage cholesterol handling upon exposure to human serum and on macrophage responses to excess free cholesterol (FC) loading. Mouse and human macrophages were utilized as cellular models. Cholesterol content was measured by a fluorimetric assay; cholesterol efflux, cytotoxicity and membrane FC distribution were evaluated by radioisotopic assays. Monocyte chemotactic protein-1 (MCP-1) secretion was measured by ELISA; membrane ruffling and macropinocytosis were visualized by confocal microscopy. Exposure of cholesterol-enriched MPM to serum in the presence of 1 μM BBR resulted in a reduction of intracellular cholesterol content twice greater than exposure to serum alone (-52%; p microscope analysis revealed that BBR inhibited macropinocytosis, an independent-receptor process involved in LDL internalization. Macrophage FC-enrichment increased MCP-1 release by 1.5 folds, increased cytotoxicity by 2 fold, and induced membrane ruffling; all these responses were markedly inhibited by BBR. FC-enrichment led to an increase in plasma membrane cholesterol by 4.5 folds, an effect counteracted by BBR. We showed novel potentially atheroprotective activities of BBR in macrophages, consisting in the inhibition of serum-induced cholesterol accumulation, occurring at least in part through an impairment of macropinocytosis, and of FC-induced deleterious effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Cellular Stoichiometry of Methyl-Accepting Chemotaxis Proteins in Sinorhizobium meliloti.

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Zatakia, Hardik M; Arapov, Timofey D; Meier, Veronika M; Scharf, Birgit E

2018-03-15

The chemosensory system in Sinorhizobium meliloti has several important deviations from the widely studied enterobacterial paradigm. To better understand the differences between the two systems and how they are optimally tuned, we determined the cellular stoichiometry of the methyl-accepting chemotaxis proteins (MCPs) and the histidine kinase CheA in S. meliloti Quantitative immunoblotting was used to determine the total amount of MCPs and CheA per cell in S. meliloti The MCPs are present in the cell in high abundance (McpV), low abundance (IcpA, McpU, McpX, and McpW), and very low abundance (McpY and McpZ), whereas McpT was below the detection limit. The approximate cellular ratio of these three receptor groups is 300:30:1. The chemoreceptor-to-CheA ratio is 23.5:1, highly similar to that seen in Bacillus subtilis (23:1) and about 10 times higher than that in Escherichia coli (3.4:1). Different from E. coli , the high-abundance receptors in S. meliloti are lacking the carboxy-terminal NWETF pentapeptide that binds the CheR methyltransferase and CheB methylesterase. Using transcriptional lacZ fusions, we showed that chemoreceptors are positively controlled by the master regulators of motility, VisNR and Rem. In addition, FlbT, a class IIA transcriptional regulator of flagellins, also positively regulates the expression of most chemoreceptors except for McpT and McpY, identifying chemoreceptors as class III genes. Taken together, these results demonstrate that the chemosensory complex and the adaptation system in S. meliloti deviates significantly from the established enterobacterial paradigm but shares some similarities with B. subtilis IMPORTANCE The symbiotic soil bacterium Sinorhizobium meliloti is of great agricultural importance because of its nitrogen-fixing properties, which enhances growth of its plant symbiont, alfalfa. Chemotaxis provides a competitive advantage for bacteria to sense their environment and interact with their eukaryotic hosts. For a better

Production of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta by human polymorphonuclear neutrophils stimulated with Porphyromonas endodontalis lipopolysaccharide.

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Ko, Hyun Jung; Lim, Sung Sam

2002-11-01

This study was undertaken to investigate the capacity of polymorphonuclear neutrophils (PMNs) to secrete Macrophage Inflammatory Protein (MIP)-1alpha and MIP-1beta after stimulation with Porphyromonas endodontalis lipopolysaccharide (LPS). Escherichia coli LPS was used as a positive control. Venous blood was collected and PMNs were isolated from healthy volunteers. Cells were cultured with various concentrations of LPS for different periods of time. Cell supernatants were assayed by enzyme-linked immunosorbent assay. The levels of chemokine secretion in PMNs stimulated with each LPS were found to be significantly higher than in the unstimulated control cells (p endodontalis LPS. These findings demonstrated that P. endodontalis LPS is capable of stimulating PMNs to produce chemotactic cytokines and suggested that PMNs stimulated with P. endodontalis LPS may play a crucial role in the inflammatory and immunopathological reactions of pulpal and periapical diseases.

Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans.

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John Axelsson

Full Text Available BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. METHODS: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h followed by 5 days with restricted sleep (03.00-07.00 h. On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α, interleukin (IL -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1 after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA. Also leukocyte numbers, mononuclear cells and cortisol were analysed. RESULTS: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05. A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05. In addition, all variables varied across the 24 h day. CONCLUSIONS: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco) and Its Active Site for Chemotaxis

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Dawar, Farman Ullah; Tu, Jiagang; Xiong, Yang; Lan, Jiangfeng; Dong, Xing Xing; Liu, Xiaoling; Khattak, Muhammad Nasir Khan; Mei, Jie; Lin, Li

2016-01-01

Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA), a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase) activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS). The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals) at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics. PMID:27589721

Chemotactic Activity of Cyclophilin A in the Skin Mucus of Yellow Catfish (Pelteobagrus fulvidraco and Its Active Site for Chemotaxis

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Farman Ullah Dawar

2016-08-01

Full Text Available Fish skin mucus is a dynamic barrier for invading pathogens with a variety of anti-microbial enzymes, including cyclophilin A (CypA, a multi-functional protein with peptidyl-prolyl cis/trans isomerase (PPIase activity. Beside various other immunological functions, CypA induces leucocytes migration in vitro in teleost. In the current study, we have discovered several novel immune-relevant proteins in yellow catfish skin mucus by mass spectrometry (MS. The CypA present among them was further detected by Western blot. Moreover, the CypA present in the skin mucus displayed strong chemotactic activity for yellow catfish leucocytes. Interestingly, asparagine (like arginine in mammals at position 69 was the critical site in yellow catfish CypA involved in leucocyte attraction. These novel efforts do not only highlight the enzymatic texture of skin mucus, but signify CypA to be targeted for anti-inflammatory therapeutics.

Plant-Adapted Escherichia coli Show Increased Lettuce Colonizing Ability, Resistance to Oxidative Stress and Chemotactic Response

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Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Lett, Lina; Curatti, Leonardo

2014-01-01

Background Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety. Methods/Principal Findings This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency. Conclusion/Significance These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues. PMID:25313845

The cross-validated AUC for MCP-logistic regression with high-dimensional data.

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Jiang, Dingfeng; Huang, Jian; Zhang, Ying

2013-10-01

We propose a cross-validated area under the receiving operator characteristic (ROC) curve (CV-AUC) criterion for tuning parameter selection for penalized methods in sparse, high-dimensional logistic regression models. We use this criterion in combination with the minimax concave penalty (MCP) method for variable selection. The CV-AUC criterion is specifically designed for optimizing the classification performance for binary outcome data. To implement the proposed approach, we derive an efficient coordinate descent algorithm to compute the MCP-logistic regression solution surface. Simulation studies are conducted to evaluate the finite sample performance of the proposed method and its comparison with the existing methods including the Akaike information criterion (AIC), Bayesian information criterion (BIC) or Extended BIC (EBIC). The model selected based on the CV-AUC criterion tends to have a larger predictive AUC and smaller classification error than those with tuning parameters selected using the AIC, BIC or EBIC. We illustrate the application of the MCP-logistic regression with the CV-AUC criterion on three microarray datasets from the studies that attempt to identify genes related to cancers. Our simulation studies and data examples demonstrate that the CV-AUC is an attractive method for tuning parameter selection for penalized methods in high-dimensional logistic regression models.

LAMP-1-chimeric DNA vaccines enhance the antibody response in Japanese flounder, Paralichthys olivaceus.

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Rondón-Barragán, Iang; Nozaki, Reiko; Hirono, Ikuo; Kondo, Hidehiro

2017-08-01

DNA vaccination is one method to protect farmed fish from viral and bacterial diseases. Chimeric antigens encoded by DNA vaccines have been shown to increase the resistance to viral diseases. Here, we sequenced the gene encoding lysosome-associated membrane protein-1 from Japanese flounder, Paralichthys olivaceus, (JfLAMP-1) and assessed its use in a chimeric DNA vaccine fused with the major capsule protein (MCP) from red seabream iridovirus (RSIV). JfLAMP-1 cDNA has a length of 1248 bp encoding 415 aa, which contains transmembrane and cytoplasmic domains. JfLAMP-1 is constitutively expressed in several tissues and its expression in spleen was upregulated following injection of formalin-killed cells (FKC) of Edwardsiella tarda. Immunofluorescence analysis showed that JfLAMP-1 is distributed in the small and large granules in the cytoplasm and groups close to the nucleus. The DNA encoding the luminal domain of JfLAMP-1 was replaced with the gene for the RSIV MCP, and the construct was cloned in an expression vector (pCIneo). Fish vaccinated with pCLAMP-MCP had significantly higher antibody levels than fish vaccinated with pCIneo vector harboring the MCP gene (p day 30 post-vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modular Engine Noise Component Prediction System (MCP) Program Users' Guide

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Golub, Robert A. (Technical Monitor); Herkes, William H.; Reed, David H.

2004-01-01

This is a user's manual for Modular Engine Noise Component Prediction System (MCP). This computer code allows the user to predict turbofan engine noise estimates. The program is based on an empirical procedure that has evolved over many years at The Boeing Company. The data used to develop the procedure include both full-scale engine data and small-scale model data, and include testing done by Boeing, by the engine manufacturers, and by NASA. In order to generate a noise estimate, the user specifies the appropriate engine properties (including both geometry and performance parameters), the microphone locations, the atmospheric conditions, and certain data processing options. The version of the program described here allows the user to predict three components: inlet-radiated fan noise, aft-radiated fan noise, and jet noise. MCP predicts one-third octave band noise levels over the frequency range of 50 to 10,000 Hertz. It also calculates overall sound pressure levels and certain subjective noise metrics (e.g., perceived noise levels).

Monte Carlo Simulations of High-speed, Time-gated MCP-based X-ray Detectors: Saturation Effects in DC and Pulsed Modes and Detector Dynamic Range

International Nuclear Information System (INIS)

Kruschwitz, Craig; Ming Wu; Moy, Ken; Rochau, Greg

2008-01-01

We present here results of continued efforts to understand the performance of microchannel plate (MCP)-based, high-speed, gated, x-ray detectors. This work involves the continued improvement of a Monte Carlo simulation code to describe MCP performance coupled with experimental efforts to better characterize such detectors. Our goal is a quantitative description of MCP saturation behavior in both static and pulsed modes. We have developed a new model of charge buildup on the walls of the MCP channels and measured its effect on MCP gain. The results are compared to experimental data obtained with a short-pulse, high-intensity ultraviolet laser; these results clearly demonstrate MCP saturation behavior in both DC and pulsed modes. The simulations compare favorably to the experimental results. The dynamic range of the detectors in pulsed operation is of particular interest when fielding an MCP-based camera. By adjusting the laser flux we study the linear range of the camera. These results, too, are compared to our simulations

Substrate-driven chemotactic assembly in an enzyme cascade

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Zhao, Xi; Palacci, Henri; Yadav, Vinita; Spiering, Michelle M.; Gilson, Michael K.; Butler, Peter J.; Hess, Henry; Benkovic, Stephen J.; Sen, Ayusman

2018-03-01

Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor

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Chávez-Vargas, Lydia; Adame-García, Sendi Rafael; Cervantes-Villagrana, Rodolfo Daniel; Castillo-Kauil, Alejandro; Bruystens, Jessica G. H.; Fukuhara, Shigetomo; Taylor, Susan S.; Mochizuki, Naoki; Reyes-Cruz, Guadalupe; Vázquez-Prado, José

2016-01-01

Morphology of migrating cells is regulated by Rho GTPases and fine-tuned by protein interactions and phosphorylation. PKA affects cell migration potentially through spatiotemporal interactions with regulators of Rho GTPases. Here we show that the endogenous regulatory (R) subunit of type I PKA interacts with P-Rex1, a Rac guanine nucleotide exchange factor that integrates chemotactic signals. Type I PKA holoenzyme interacts with P-Rex1 PDZ domains via the CNB B domain of RIα, which when expressed by itself facilitates endothelial cell migration. P-Rex1 activation localizes PKA to the cell periphery, whereas stimulation of PKA phosphorylates P-Rex1 and prevents its activation in cells responding to SDF-1 (stromal cell-derived factor 1). The P-Rex1 DEP1 domain is phosphorylated at Ser-436, which inhibits the DH-PH catalytic cassette by direct interaction. In addition, the P-Rex1 C terminus is indirectly targeted by PKA, promoting inhibitory interactions independently of the DEP1-PDZ2 region. A P-Rex1 S436A mutant construct shows increased RacGEF activity and prevents the inhibitory effect of forskolin on sphingosine 1-phosphate-dependent endothelial cell migration. Altogether, these results support the idea that P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism, initiated by interaction with the PDZ domains of P-Rex1 followed by direct phosphorylation at the first DEP domain and putatively indirect regulation of the C terminus, thus promoting inhibitory intramolecular interactions. This reciprocal regulation between PKA and P-Rex1 might represent a key node of integration by which chemotactic signaling is fine-tuned by PKA. PMID:26797121

Respiratory syncytial virus and TNFalpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappaB1

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Roebuck Kenneth A

2002-03-01

Full Text Available Abstract Background Respiratory syncytial virus (RSV infection of airway epithelial cells stimulates the expression and secretion of a variety of cytokines including the chemotactic cytokines interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, and RANTES (regulated upon activation, normal T cell expressed and secreted. Chemokines are important chemoattractants for the recruitment of distinct sets of leukocytes to airway sites of inflammation. Results We have shown previously that chemokine expression is regulated in airway epithelial cells (A549 in a stimulus-specific manner in part through the redox-responsive transcription factors AP-1 and NF-κB. In this study, we examined the NF-κB-mediated effects of RSV and the proinflammatory cytokine TNFα on the induction of IL-8, MCP-1 and RANTES chemokine gene expression in A549 epithelial cells. The results demonstrate that RSV induces chemokine expression with distinct kinetics that is associated with a specific pattern of NF-κB binding activity. This distinction was further demonstrated by the differential effects of the NF-κB inhibitors dexamethasone (DEX and N-acetyl-L-cysteine (NAC. NAC preferentially inhibited RSV induced chemokine expression, whereas DEX preferentially inhibited TNFα induced chemokine expression. DNA binding studies using NF-κB subunit specific binding ELISA demonstrated that RSV and TNFα induced different NF-κB binding complexes containing Rel A (p65 and NF-κB1 (p50. Both TNFα and RSV strongly induced Rel A the activation subunit of NF-κB, whereas only TNFα was able to substantially induce the p50 subunit. Consistent with the expression studies, RSV but not TNFα induction of Rel A and p50 were markedly inhibited by NAC, providing a mechanism by which TNFα and RSV can differentially activate chemokine gene expression via NF-κB. Conclusions These data suggest that RSV induction of chemokine gene expression, in contrast to TNFα, involves redox

Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice.

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Motoko Kawashima

Full Text Available BACKGROUND: Decrease in lacrimal gland secretory function is related to age-induced dry eye disease. Lactoferrin, the main glycoprotein component of tears, has multiple functions, including anti-inflammatory effects and the promotion of cell growth. We investigated how oral administration of lactoferrin affects age-related lacrimal dysfunction. METHODS AND FINDINGS: Twelve-month-old male C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral lactoferrin treatment group. Tear function was measured at a 6-month time-point. After euthanasia, the lacrimal glands were subjected to histological examination with 8-hydroxy-2'-deoxyguanosine (8-OHdG antibodies, and serum concentrations of 8-OHdG and hexanoyl-lysine adduct (HEL were evaluated. Additionally, monocyte chemotactic protein-1(MCP-1 and tumor necrosis factor-α (TNF-α gene expression levels were determined by real-time PCR. The volume of tear secretion was significantly larger in the treated group than in the control. Lactoferrin administration reduced inflammatory cell infiltration and the MCP-1 and TNF-α expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin group were lower than those in the control group and were associated with attenuated 8-OHdG immunostaining of the lacrimal glands. CONCLUSION: Oral lactoferrin administration preserves lacrimal gland function in aged mice by attenuating oxidative damage and suppressing subsequent gland inflammation.