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Sample records for chemoattractants

  1. Monocyte chemoattractants in pigeon aortic atherosclerosis.

    OpenAIRE

    Denholm, E. M.; Lewis, J. C.

    1987-01-01

    Atherosclerosis occurs in the aorta of White Carneau pigeons proximal to the celiac bifurcation, where monocyte adhesion and migration into lesions have been demonstrated. This study documents chemoattractants that might be responsible for monocyte adherence and migration. Ten-week-old pigeons were fed either a cholesterol-free (normal) diet or a 0.4% cholesterol diet for 12 or 24 weeks. Birds with a normal diet did not have lesions in the lesion-prone area of the aorta, whereas birds fed a c...

  2. Two Types of Assays for Detecting Frog Sperm Chemoattraction

    OpenAIRE

    Burnett, Lindsey A.; Tholl, Nathan; Chandler, Douglas E.

    2011-01-01

    Sperm chemoattraction in invertebrates can be sufficiently robust that one can place a pipette containing the attractive peptide into a sperm suspension and microscopically visualize sperm accumulation around the pipette1. Sperm chemoattraction in vertebrates such as frogs, rodents and humans is more difficult to detect and requires quantitative assays. Such assays are of two major types - assays that quantitate sperm movement to a source of chemoattractant, so-called sperm accumulation assay...

  3. Mathematics of Experimentally Generated Chemoattractant Gradients.

    Science.gov (United States)

    Postma, Marten; van Haastert, Peter J M

    2016-01-01

    Many eukaryotic cells move in the direction of a chemical gradient. Several assays have been developed to measure this chemotactic response, but no complete mathematical models of the spatial and temporal gradients are available to describe the fundamental principles of chemotaxis. Here we provide analytical solutions for the gradients formed by release of chemoattractant from a point source by passive diffusion or forced flow (micropipettes) and gradients formed by laminar diffusion in a Zigmond chamber. The results show that gradients delivered with a micropipette are formed nearly instantaneously, are very steep close to the pipette, and have a steepness that is strongly dependent on the distance from the pipette. In contrast, gradients in a Zigmond chamber are formed more slowly, are nearly independent of the distance from the source, and resemble the temporal and spatial properties of the natural cAMP wave that Dictyostelium cells experience during cell aggregation. PMID:27271915

  4. Sperm navigation along helical paths in 3D chemoattractant landscapes

    Science.gov (United States)

    Jikeli, Jan F.; Alvarez, Luis; Friedrich, Benjamin M.; Wilson, Laurence G.; Pascal, René; Colin, Remy; Pichlo, Magdalena; Rennhack, Andreas; Brenker, Christoph; Kaupp, U. Benjamin

    2015-08-01

    Sperm require a sense of direction to locate the egg for fertilization. They follow gradients of chemical and physical cues provided by the egg or the oviduct. However, the principles underlying three-dimensional (3D) navigation in chemical landscapes are unknown. Here using holographic microscopy and optochemical techniques, we track sea urchin sperm navigating in 3D chemoattractant gradients. Sperm sense gradients on two timescales, which produces two different steering responses. A periodic component, resulting from the helical swimming, gradually aligns the helix towards the gradient. When incremental path corrections fail and sperm get off course, a sharp turning manoeuvre puts sperm back on track. Turning results from an `off' Ca2+ response signifying a chemoattractant stimulation decrease and, thereby, a drop in cyclic GMP concentration and membrane voltage. These findings highlight the computational sophistication by which sperm sample gradients for deterministic klinotaxis. We provide a conceptual and technical framework for studying microswimmers in 3D chemical landscapes.

  5. The biophysical model for accuracy of cellular sensing spatial gradients of multiple chemoattractants

    International Nuclear Information System (INIS)

    Spatial gradients of surrounding chemoattractants are the key factors in determining the directionality of eukaryotic cell movement. Thus, it is important for cells to accurately measure the spatial gradients of surrounding chemoattractants. Here, we study the precision of sensing the spatial gradients of multiple chemoattractants using cooperative receptor clusters. Cooperative receptors on cells are modeled as an Ising chain of Monod–Wyman–Changeux clusters subject to multiple chemical-gradient fields to study the physical limits of multiple chemoattractants spatial gradients sensing. We found that eukaryotic cells cannot sense each chemoattractant gradient individually. Instead, cells can only sense a weighted sum of surrounding chemical gradients. Moreover, the precision of sensing one chemical gradient is signicantly affected by coexisting chemoattractant concentrations. These findings can provide a further insight into the role of chemoattractants in immune response and help develop novel treatments for inflammatory diseases. (paper)

  6. Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants

    OpenAIRE

    Weinberger, Barry; Laskin, Debra L.; Mariano, Thomas M.; Sunil, Vasanthi R.; DeCoste, Christina J.; Heck, Diane E.; Carol R. Gardner; Laskin, Jeffrey D.

    2001-01-01

    Potential mechanisms underlying impaired chemotactic responsiveness of neonatal neutrophils were investigated. Two distinct chemoattractants were compared: bacterially derived N-formyl-methionyl-leucyl-phenylalanine (fMLP) and a unique chemotactic monoclonal antibody, designated DL1.2, which binds to a neutrophil antigen with an apparent molecular mass of 120 kDa. Chemotaxis of neutrophils toward fMLP, as well as DL1.2, was reduced in neonates when compared with adult cells. This did not appe...

  7. Consequences of Interference of Milk with Chemoattractants for Enzyme-Linked Immunosorbent Assay Quantifications▿

    OpenAIRE

    RAINARD, P

    2010-01-01

    Concentrations of the chemoattractants CXCL1, CXCL2, CXCL3, CXCL8, and C5a in milk were reduced by the preparation of milk whey by high-speed centrifugation or with rennet. About half of the chemoattractants (35 to 65%) were associated with the casein micelle sediment, except when whey was prepared by acidification. Consequently, quantification of chemoattractants should be carried out preferentially with skimmed milk samples or, whenever whey is needed, with acidic whey samples. The interfer...

  8. Arachidonic acid is a chemoattractant for Dictyostelium discoideum cells

    Indian Academy of Sciences (India)

    Ralph H Schaloske; Dagmar Blaesius; Christina Schlatterer; Daniel F Lusche

    2007-12-01

    Cyclic AMP (cAMP) is a natural chemoattractant of the social amoeba Dictyostelium discoideum. It is detected by cell surface cAMP receptors. Besides a signalling cascade involving phosphatidylinositol 3,4,5-trisphosphate (PIP3), Ca2+ signalling has been shown to have a major role in chemotaxis. Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca2+ concentration by causing the release of Ca2+ from intracellular stores and activating influx of extracellular Ca2+. Here we report that AA is a chemoattractant for D. discoideum cells differentiated for 8–9 h. Motility towards a glass capillary filled with an AA solution was dose-dependent and qualitatively comparable to cAMP-induced chemotaxis. Ca2+ played an important role in AA chemotaxis of wild-type Ax2 as ethyleneglycolbis(b-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA) added to the extracellular buffer strongly inhibited motility. In the HM1049 mutant whose iplA gene encoding a putative Ins(1,4,5)P3-receptor had been knocked out, chemotaxis was only slightly affected by EGTA. Chemotaxis in the presence of extracellular Ca2+ was similar in both strains. Unlike cAMP, addition of AA to a cell suspension did not change cAMP or cGMP levels. A model for AA chemotaxis based on the findings in this and previous work is presented.

  9. Oscillatory behavior of neutrophils under opposing chemoattractant gradients supports a winner-take-all mechanism.

    Directory of Open Access Journals (Sweden)

    Matthew B Byrne

    Full Text Available Neutrophils constitute the largest class of white blood cells and are the first responders in the innate immune response. They are able to sense and migrate up concentration gradients of chemoattractants in search of primary sites of infection and inflammation through a process known as chemotaxis. These chemoattractants include formylated peptides and various chemokines. While much is known about chemotaxis to individual chemoattractants, far less is known about chemotaxis towards many. Previous studies have shown that in opposing gradients of intermediate chemoattractants (interleukin-8 and leukotriene B4, neutrophils preferentially migrate toward the more distant source. In this work, we investigated neutrophil chemotaxis in opposing gradients of chemoattractants using a microfluidic platform. We found that primary neutrophils exhibit oscillatory motion in opposing gradients of intermediate chemoattractants. To understand this behavior, we constructed a mathematical model of neutrophil chemotaxis. Our results suggest that sensory adaptation alone cannot explain the observed oscillatory motion. Rather, our model suggests that neutrophils employ a winner-take-all mechanism that enables them to transiently lock onto sensed targets and continuously switch between the intermediate attractant sources as they are encountered. These findings uncover a previously unseen behavior of neutrophils in opposing gradients of chemoattractants that will further aid in our understanding of neutrophil chemotaxis and the innate immune response. In addition, we propose a winner-take-all mechanism allows the cells to avoid stagnation near local chemical maxima when migrating through a network of chemoattractant sources.

  10. Using Chemoattractants to Lure Bacteria to Contact-Killing Surfaces.

    Science.gov (United States)

    Jain, Rishabh; Faith, Nancy G; Milkowski, Andrew; Nelson, Kevin; Busche, David; Lynn, David M; Czuprynski, Charles J; Abbott, Nicholas L

    2016-05-01

    Antimicrobial surfaces with covalently attached biocidal functionalities only kill microbes that come into direct contact with the surfaces (contact-killing surfaces). Herein, the activity of contact-killing surfaces is shown to be enhanced by using gradients in the concentration of soluble chemoattractants (CAs) to attract bacteria to the surfaces. Two natural and nonbiocidal CAs (aspartate and glucose) were used to attract bacteria to model surfaces decorated with quaternary ammonium groups (known to kill bacteria that come into contact with them). These results demonstrate the killing of Escherichia coli and Salmonella typhimurium, two common pathogens, at levels 10- to 20-times greater than that of the native surfaces alone. This approach is general and provides new strategies for the design of active or dynamic contact-killing surfaces with enhanced antimicrobial activities. PMID:27059788

  11. Expression of monocyte chemoattractant protein-1 in the pancreas of mice

    Institute of Scientific and Technical Information of China (English)

    LI Dong; ZHU Su-wen; LIU Dong-juan; LIU Guo-liang; SHAN Zhong-yan

    2005-01-01

    Background Type 1 diabetes has been recognized as an organ specific autoimmune disease owing to the immune destruction of pancreatic islet β cells in genetically susceptible individuals.In both human and rodent models of type 1 diabetes, such as nonobese diabetic (NOD) mice, biobreeding rats, the disease has a distinct stage characterized by immune cells infiltrating in the pancreas (insulitis).The major populations of infiltrating cells are macrophages and T lymphocytes.Therefore, immune cell infiltration of pancreatic islets may be a crucial step in the pathogenesis of type 1 diabetes.Monocyte chemoattractant protein-1 can specifically attract monocytes in vivo.Interferon induced protein-10 has chemoattractant effects on the activated lymphocytes.In this study, we analysed the expression of monocyte chemoattractant protein-1 in the pancreas of mice and interferon inducible protein-10 mRNA in the pancreas of NOD mice, and discussed their possible role in the pathogenesis of type 1 diabetes.Methods The immunohistochemical method and immunoelectronmicroscopy were used to evaluate the expression of monocyte chemoattractant protein-1 in the pancreas of NOD mice and BALB/c mice.RT-PCR was used to evaluate the expression of monocyte chemoattractant protein-1 and interferon inducible protein mRNA in NOD mice.Results Monocyte chemoattractant protein-1 was positive in the pancreas of NOD mice, whereas negative in the pancreas of BALB/C mice.RT-PCR showed that monocyte chemoattractant protein-1 and interferon inducible protein-10 mRNA could be found in the pancreas of NOD mice.Immunoelectronmicroscopy demonstrated that monocyte chemoattractant protein-1 was produced by β cells and stored in the cytoplasm of the cells.Conclusions Pancreatic islet β cells produce monocyte chemoattractantprotein-1 in NOD mice.Monocyte chemoattractant protein-1 may play an important part in the pathogenesis of type 1 diabetes by attracting monocytes/macrophages to infiltrate pancreatic

  12. Chemoattractant receptors in drug discovery: FPR2 and CCR2-two potential targets

    OpenAIRE

    Kalderén, Christina

    2012-01-01

    Chemoattractants and chemoattractant receptors have many important functions in multicellular organisms, not least for their role in regulating migration of leukocytes. The receptors are also involved in many pathologies and they have, since they were cloned in the 1990ies, been regarded as attractive targets for development of drugs against cancer, viral infections, and inflammatory/autoimmune diseases. Although chemotactic molecules are very heterogeneous in terms of chemi...

  13. Circulating monocyte chemoattractant protein-1 in women with gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Mariusz Kuzmicki

    2008-04-01

    Full Text Available Monocyte chemoattractant protein 1 (MCP-1 has been implicated as a key factor in the recruitment and activation of peripheral blood leukocytes in atherosclerotic lesions and adipose tissue. Elevated levels of circulating MCP-1 have been found in patients with type 1 and type 2 diabetes, as well as with coronary artery disease. In this study we compared serum MCP-1 concentrations between pregnant women with normal glucose tolerance (NGT, gestational diabetes mellitus (GDM and non-pregnant healthy women. The group studied consisted of 62 patients with GDM (mean age 30.1 +/- 5.0 years at 29.0 +/- 3.5 week of gestation, 64 pregnant women with NGT (mean age 30.0 +/- 4.7 years at 29.2 +/- 2.9 week of gestation and 34 non-pregnant healthy women (mean age 29.8 +/- 4.7 years. Serum MCP-1 concentration was measured using an enzyme - linked immunosorbent assay. Median MCP-1 concentrations did not differ significantly between women with GDM (median 342.3 [interquartile range 267.9-424.4] pg/ml and NGT (338.0 [274.7-408.2] pg/ml, but were markedly lower than those found in non-pregnant women (485.2 [409.6-642.4] pg/ml, p<0.0001. After adjusting for glucose, the difference between pregnant and non-pregnant women remained highly significant (p<0.0001. In GDM patients MCP-1 levels correlated significantly with fasting glucose (r=0.2665, p=0.0363, insulin (r=0.4330, p=0.0004, HOMA-IR (r=0.4402, p=0.0003, ISQUICKI (r=-0.4402, p=0.0003, HbA1c (r=0.2724, p=0.0322, as well as with prepregnancy and current BMI (r=0.3501, p=0.0057 and r=0.3250, p=0.0106, respectively. Multiple regression analysis revealed that MCP1 concentrations were significantly predicted only by plasma glucose ( beta=0.3489, p=0.00004. Our results suggest that MCP1 levels are decreased in pregnant women, irrespective of their glucose tolerance status.

  14. Multiple Degradation Pathways of Chemoattractant Mediated Cyclic GMP Accumulation in Dictyostelium

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Lookeren Campagne, Michiel M. van; Kesbeke, Fanja

    1983-01-01

    Chemoattractants induce a transient accumulation of cGMP levels in Dictyostelium. Intracellular cGMP levels reach a peak at 10 s and prestimulated cGMP levels are recovered at about 30 s. Intracellular and extracellular cGMP levels were detected simultaneously after stimulation of D. lacteum cells w

  15. Chemoattractant lymphokines specific for the helper/inducer T-lymphocyte subset.

    Science.gov (United States)

    Berman, J S; Cruikshank, W W; Center, D M; Theodore, A C; Beer, D J

    1985-10-01

    The cellular content of T-lymphocyte-rich inflammatory sites is dependent in part on the in situ elaboration of chemoattractant factors. We have previously described three T-lymphocyte-specific chemoattractant lymphokines; a chemokinetic factor, lymphocyte chemoattractant factor (LCF, MW 56,000), and two distinct lymphocyte migration inhibitory factors (LyMIF75K, MW 75,000; and LyMIF35K, MW 35,000). These factors are produced by human T cells in response to antigen, concanavalin A, or histamine stimulation. In this communication, we report that LCF and LyMIF35K are produced by OKT8+ (suppressor/cytotoxic) and OKT4+ (helper/inducer) lymphocytes, respectively, and are selectively chemoattractant for the OKT4+ lymphocyte subset. LyMIF75K is produced by OKT4+ cells and inhibits both OKT4+ and OKT8+ lymphocyte migration. Production of LCF and LyMIF35K by infiltrating lymphocyte subsets may be one mechanism whereby unactivated helper/inducer T lymphocytes are selectively recruited to sites of inflammation. PMID:3161625

  16. Progesterone from the cumulus cells is the sperm chemoattractant secreted by the rabbit oocyte cumulus complex.

    Directory of Open Access Journals (Sweden)

    Héctor Alejandro Guidobaldi

    Full Text Available Sperm chemotaxis in mammals have been identified towards several female sources as follicular fluid (FF, oviduct fluid, and conditioned medium from the cumulus oophorus (CU and the oocyte (O. Though several substances were confirmed as sperm chemoattractant, Progesterone (P seems to be the best chemoattractant candidate, because: 1 spermatozoa express a cell surface P receptor, 2 capacitated spermatozoa are chemotactically attracted in vitro by gradients of low quantities of P; 3 the CU cells produce and secrete P after ovulation; 4 a gradient of P may be kept stable along the CU; and 5 the most probable site for sperm chemotaxis in vivo could be near and/or inside the CU. The aim of this study was to verify whether P is the sperm chemoattractant secreted by the rabbit oocyte-cumulus complex (OCC in the rabbit, as a mammalian animal model. By means of videomicroscopy and computer image analysis we observed that only the CU are a stable source of sperm attractants. The CU produce and secrete P since the hormone was localized inside these cells by immunocytochemistry and in the conditioned medium by enzyme immunoassay. In addition, rabbit spermatozoa express a cell surface P receptor detected by western blot and localized over the acrosomal region by immunocytochemistry. To confirm that P is the sperm chemoattractant secreted by the CU, the sperm chemotactic response towards the OCC conditioned medium was inhibited by three different approaches: P from the OCC conditioned medium was removed with an anti-P antibody, the attractant gradient of the OCC conditioned medium was disrupted by a P counter gradient, and the sperm P receptor was blocked with a specific antibody. We concluded that only the CU but not the oocyte secretes P, and the latter chemoattract spermatozoa by means of a cell surface receptor. Our findings may be of interest in assisted reproduction procedures in humans, animals of economic importance and endangered species.

  17. A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis

    OpenAIRE

    Nau, Gerard J.; Guilfoile, Patrick; Chupp, Geoffrey L.; Berman, Jeffrey S.; Kim, Sue J.; Kornfeld, Hardy; Young, Richard A.

    1997-01-01

    Chronic inflammation and granuloma formation are associated with mononuclear cell infiltrates and are characteristic pathologic responses in tuberculosis. To identify host cell genes involved in tuberculous pathology, we screened macrophage cDNA libraries for genes induced by mycobacterial infection. One gene isolated in this screen, osteopontin (also known as early T lymphocyte activation protein 1 or Eta-1), was of particular interest because it is a cytokine and macrophage chemoattractant....

  18. Exendin-4 Improves Cardiac Function in Mice Overexpressing Monocyte Chemoattractant Protein-1 in Cardiomyocytes

    OpenAIRE

    Younce, Craig W; Niu, Jianli; Ayala, Jennifer; Burmeister, Melissa A.; Smith, Layton H.; Kolattukudy, Pappachan; Julio E Ayala

    2014-01-01

    The incretin hormone glucagon-like peptide-1 (Glp1) is cardioprotective in models of ischemia-reperfusion injury, myocardial infarction and gluco/lipotoxicity. Inflammation is a factor in these models, yet it is unknown whether Glp1 receptor (Glp1r) agonists are protective against cardiac inflammation. We tested the hypothesis that the Glp1r agonist Exendin-4 (Ex4) is cardioprotective in mice with cardiac-specific monocyte chemoattractant protein-1 overexpression. These MHC-MCP1 mice exhibit ...

  19. Effect of steady and unsteady flow on chemoattractant plume formation and sperm taxis

    Science.gov (United States)

    Bell, Allison F.; Crimaldi, John P.

    2015-08-01

    The formation of chemoattractant plumes around benthic invertebrate eggs in steady and unsteady shear flows is investigated for a range of shear rates, and the ability of sperm to navigate within these plumes is assessed using several chemotactic strategies. Although many of the details of sperm taxis remain uncertain, we investigate the role of basic processes using a toy model in two dimensions. Search strategies in 2D are intrinsically less complex than 3D, but many of the basic components are similar, and the simplified geometry permits an understanding and identification of the key factors of navigation tactics. Numerical simulations are used to model the advection and diffusion of the chemoattractant within the different flows, using three different sperm swimming behaviors. A Monte-Carlo approach is then used to determine the probability of a sperm reaching an egg for a range of flow conditions, initial conditions, and swimming behaviors. The spatial structure of chemoattractant plumes at the scale of the gametes is also investigated. Success rates for locating an egg decrease monotonically with increasing shear rates, and a definitive hierarchical ordering of the tested swimming strategies is identified. A conceptual framework to study and identify important aspects of this fundamental process to support further studies is provided.

  20. Monocyte chemoattractant protein-1 plays a key role in type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    Dong Li; Guoliang Liu

    2005-01-01

    Type 1 diabetes is an autoimmune disease resulting from the selective destruction of β cells in the pancreatic islets.In both human and rodent models of type 1 diabetes, the clinical disease is preceded by a progressive mononuclear cell invasion of the pancreatic islets (insulitis). In the early stage of insulitis, the major components are monocyte/macrophages, and the recruitment of mononuclear cells is a critical step in the pathogenesis of the type 1 diabetes. Studies have revealed that Monocyte chemoattractant protein-1(MCP-1)specifically recruits monocytes/macrophages into pancreas and plays an important role in the development of insulitis and diabetes.

  1. Extracellular galectin-3 counteracts adhesion and exhibits chemoattraction in Helicobacter pylori-infected gastric cancer cells.

    Science.gov (United States)

    Subhash, Vinod Vijay; Ling, Samantha Shi Min; Ho, Bow

    2016-08-01

    Galectin-3 (Gal-3) is a β-galactoside lectin that is upregulated and rapidly secreted by gastric epithelial cells in response to Helicobacter pylori infection. An earlier study reported the involvement of H. pylori cytotoxin-associated gene A (cagA) in the expression of intracellular Gal-3. However, the role of extracellular Gal-3 and its functional significance in H. pylori-infected cells remains uncharacterized. Data presented here demonstrate secretion of Gal-3 is an initial host response event in gastric epithelial cells during H. pylori infection and is independent of CagA. Previously, Gal-3 was shown to bind to H. pylori LPS. The present study elaborates the significance of this binding, as extracellular recombinant Gal-3 (rGal-3) was shown to inhibit the adhesion of H. pylori to the gastric epithelial cells. Interestingly, a decrease in H. pylori adhesion to host cells also resulted in a decrease in apoptosis. Furthermore, the study also demonstrated a chemoattractant role of extracellular rGal-3 in the recruitment of THP-1 monocytes. This study outlines the previously unidentified roles of extracellular Gal-3 where it acts as a negative regulator of H. pylori adhesion and apoptosis in gastric epithelial cells, and as a chemoattractant to THP-1 monocytes. Our findings could contribute to the better understanding of how Gal-3 acts as a modulator under H. pylori-induced pathological conditions. PMID:27283429

  2. Differential and time-dependent expression of monocyte chemoattractant protein-1 mRNA by astrocytes and macrophages in rat brain : Effects of ischemia and peripheral lipopolysaccharide administration

    NARCIS (Netherlands)

    Gourmala, NG; Buttini, M; Limonta, S; Sauter, A; Boddeke, HWGM

    1997-01-01

    Increasing evidence indicates a key role of chemoattractant cytokines in the accumulation of leukocytes in the central nervous system (CNS) during the course of inflammatory processes. Monocyte chemoattractant protein (MCP-1/JE), a member of the beta-chemokine (C-C chemokine) family, functions as a

  3. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kun ZENG; Daniel G REMICK; Xian WANG

    2004-01-01

    AIM: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood. METHODS: Human whole blood or different type of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP- 1 and IL-8 level were measured by ELISA assay. RESULTS: Hcy 10-1000 μmol/L induced production of MCP-1 and IL-8 in cultured human whole blood (P<0.05). The major cellular source of these chemokines comed from monocytes.Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/L in the cultured whole blood.secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism.

  4. Soluble Pityrosporum-derived chemoattractant for polymorphonuclear leukocytes of psoriatic patients.

    Science.gov (United States)

    Bunse, T; Mahrle, G

    1996-01-01

    The chemoattraction of polymorphonuclear leukocytes (PMNs) from psoriatic patients, atopic patients and healthy control persons by Pityrosporum orbicularelovale was investigated using the Boyden chamber method. The chemotactical attraction of PMNs from psoriatic patients by Pityrosporum (stimulation index SI = 58 +/- 50) was significantly increased (p < 0.05) compared to PMNs from atopic patients (SI = 20 +/- 17) and control persons (SI = 26 +/- 24). This effect seems to be specific for Pityrosporum, since the chemotactical response to Staphylococcus epidermidis was not increased in psoriasis. The chemotactical factor produced by Pityrosporum is hydrophilic and is destroyed by acid hydrolysis, indicating its protein nature. The yeast Pityrosporum may thus play a role in the koebnerization of psoriasis. PMID:8721481

  5. Bacterial chemoattraction towards jasmonate plays a role in the entry of Dickeya dadantii through wounded tissues.

    Science.gov (United States)

    Antunez-Lamas, Maria; Cabrera, Ezequiel; Lopez-Solanilla, Emilia; Solano, Roberto; González-Melendi, Pablo; Chico, Jose Manuel; Toth, Ian; Birch, Paul; Pritchard, Leighton; Prichard, Leighton; Liu, Hui; Rodriguez-Palenzuela, Pablo

    2009-11-01

    Jasmonate is a key signalling compound in plant defence that is synthesized in wounded tissues. In this work, we have found that this molecule is also a strong chemoattractant for the phythopathogenic bacteria Dickeya dadantii (ex-Erwinia chysanthemi). Jasmonic acid induced the expression of a subset of bacterial genes possibly involved in virulence/survival in the plant apoplast and bacterial cells pre-treated with jasmonate showed increased virulence in chicory and Saintpaulia leaves. We also showed that tissue wounding induced bacterial spread through the leaf surface. Moreover, the jasmonate-deficient aos1 Arabidopsis thaliana mutant was more resistant to bacterial invasion by D. dadantii than wild-type plants. These results are consistent with the hypothesis that sensing jasmonic acid by this bacterium helps the pathogen to ingress inside plant tissues. PMID:19818025

  6. Slime mould solves maze in one pass ... assisted by gradient of chemo-attractants

    CERN Document Server

    Adamatzky, Andrew

    2011-01-01

    Plasmodium of Physarum polycephalum is a large cell, visible by unaided eye, which exhibits sophisticated patterns of foraging behaviour. The plasmodium's behaviour is well interpreted in terms of computation, where data are spatially extended configurations of nutrients and obstacles, and results of computation are networks of protoplasmic tubes formed by the plasmodium. In laboratory experiments and numerical simulation we show that if plasmodium of Physarum is inoculated in a maze's peripheral channel and an oat flake (source of attractants) in a the maze's central chamber then the plasmodium grows toward target oat flake and connects the flake with the site of original inoculation with a pronounced protoplasmic tube. The protoplasmic tube represents a path in the maze. The plasmodium solves maze in one pass because it is assisted by a gradient of chemo-attractants propagating from the target oat flake.

  7. Double localization of F-actin in chemoattractant-stimulated polymorphonuclear leucocytes.

    Science.gov (United States)

    Lepidi, H; Benoliel, A M; Mege, J L; Bongrand, P; Capo, C

    1992-09-01

    Uniform concentrations of chemoattractants such as formylpeptides induced a morphological polarization of human polymorphonuclear leucocytes (PMNs) and a concentration of F-actin at the cell front. They also induced a transient increase in filamentous actin (F-actin) which preceded the cell shape change. We combined fluorescence microscopy and image analysis to study the localization of F-actin, as revealed by a specific probe (bodipyTM phallacidin) in suspended PMNs stimulated by chemoattractants. F-actin exhibited remarkable concentration in focal points after a 30 s exposure to 10(-8) M formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe), although no shape change of PMNs was detectable. A 10-min incubation with formylpeptide (10(-6) to 10(-9) M) induced the morphological polarization of PMNs and the appearance of a principal focus of F-actin in the cell head region and a secondary focus in the cell posterior end. The distribution of F-actin-associated fluorescence in 2D images of polarized PMNs might be due to an actual concentration of F-actin in privileged areas, to a local concentration of plasma membrane drawing filamentous actin or to variations in the cell volume. Then, we studied the distribution of a cytoplasmic marker, fluorescein diacetate and a membrane probe, TMA-DPH, in unstimulated rounded PMNs and in spherical and morphologically polarized PMNs stimulated by formylpeptide. The distribution of neither of these probes was correlated with F-actin distribution, especially in rounded PMNs stimulated 30 s with 10(-8) M fMet-Leu-Phe, suggesting that F-actin was concentrated in two foci located in the cell head region and in the cell posterior end. In addition, zymosan-activated serum induced the morphological polarization of PMNs and the appearance of two foci of filamentous actin, demonstrating that binding of formylpeptide to its specific receptor was not required for F-actin reorganization. We conclude that the accumulation of F-actin probably

  8. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kunZENG; DanielGREMICK; XianWANG

    2004-01-01

    AIM: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattract antprotein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood. METHODS: Human whole blood or differenttype of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP-1 and IL-8 level were measured by ELISA assay. RESULTS: Hcy 10-1000 μmol/L induced production of MCP-1and IL-8 in cultured human whole blood (P<0.05). The major cellular source of these chemokines comed from monocytes. Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/L in the cultured whole blood.The intracellular ROS, particular the OH radicals, play extremely important role in the Hcy-induced MCP-1 and IL-8 production. CONCLUSION: Increased Hcy level in plasma (hyperhomocysteinemia) induced MCP-1 and IL-8secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism,

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

    International Nuclear Information System (INIS)

    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.)

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

    Directory of Open Access Journals (Sweden)

    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

  11. An ion mobility-mass spectrometry investigation of monocyte chemoattractant protein-1

    Science.gov (United States)

    Schenauer, Matthew R.; Leary, Julie A.

    2009-10-01

    In the present article we describe the gas-phase dissociation behavior of the dimeric form of monocyte chemoattractant protein-1 (MCP-1) using quadrupole-traveling wave ion mobility spectrometry-time of flight mass spectrometry (q-TWIMS-TOF MS) (Waters Synapt(TM)). Through investigation of the 9+ charge state of the dimer, we were able to monitor dissociation product ion (monomer) formation as a function of activation energy. Using ion mobility, we were able to observe precursor ion structural changes occurring throughout the activation process. Arrival time distributions (ATDs) for the 5+ monomeric MCP-1 product ions, derived from the gas-phase dissociation of the 9+ dimer, were then compared with ATDs obtained for the 5+ MCP-1 monomer isolated directly from solution. The results show that the dissociated monomer is as compact as the monomer arising from solution, regardless of the trap collision energy (CE) used in the dissociation. The solution-derived monomer, when collisionally activated, also resists significant unfolding within measure. Finally, we compared the collisional activation data for the MCP-1 dimer with an MCP-1 dimer non-covalently bound to a single molecule of the semi-synthetic glycosaminoglycan (GAG) analog Arixtra(TM); the latter a therapeutic anti-thrombin III-activating pentasaccharide. We observed that while dimeric MCP-1 dissociated at relatively low trap CEs, the Arixtra-bound dimer required much higher energies, which also induced covalent bond cleavage in the bound Arixtra molecule. Both the free and Arixtra-bound dimers became less compact and exhibited longer arrival times with increasing trap CEs, albeit the Arixtra-bound complex at slightly higher energies. That both dimers shifted to longer arrival times with increasing activation energy, while the dissociated MCP-1 monomers remained compact, suggests that the longer arrival times of the Arixtra-free and Arixtra-bound dimers may represent a partial breach of non

  12. Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like differentiation of monocytes.

    Science.gov (United States)

    Spoettl, T; Hausmann, M; Herlyn, M; Gunckel, M; Dirmeier, A; Falk, W; Herfarth, H; Schoelmerich, J; Rogler, G

    2006-07-01

    Monocytes (MO) migrating into normal, non-inflamed intestinal mucosa undergo a specific differentiation resulting in a non-reactive, tolerogenic intestinal macrophage (IMAC). Recently we demonstrated the differentiation of MO into an intestinal-like macrophage (MAC) phenotype in vitro in a three-dimensional cell culture model (multi-cellular spheroid or MCS model). In the mucosa of patients with inflammatory bowel disease (IBD) in addition to normal IMAC, a reactive MAC population as well as increased levels of monocyte chemoattractant protein 1 (MCP-1) is found. The aim of this study was to investigate the influence of MCP-1 on the differentiation of MO into IMAC. MCS were generated from adenovirally transfected HT-29 cells overexpressing MCP-1, macrophage inflammatory protein 3 alpha (MIP-3alpha) or non-transfected controls and co-cultured with freshly elutriated blood MO. After 7 days of co-culture MCS were harvested, and expression of the surface antigens CD33 and CD14 as well as the intracellular MAC marker CD68 was determined by flow-cytometry or immunohistochemistry. MCP-1 and MIP-3alpha expression by HT-29 cells in the MCS was increased by transfection at the time of MCS formation. In contrast to MIP-3alpha, MCP-1 overexpression induced a massive migration of MO into the three-dimensional aggregates. Differentiation of IMAC was disturbed in MCP-1-transfected MCS compared to experiments with non-transfected control aggregates, or the MIP-3alpha-transfected MCS, as indicated by high CD14 expression of MO/IMAC cultured inside the MCP-1-transfected MCS, as shown by immunohistochemistry and FACS analysis. Neutralization of MCP-1 was followed by an almost complete absence of monocyte migration into the MCS. MCP-1 induced migration of MO into three-dimensional spheroids generated from HT-29 cells and inhibited intestinal-like differentiation of blood MO into IMAC. It may be speculated that MCP-1 could play a role in the disturbed IMAC differentiation in IBD mucosa

  13. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Who-Whong Wang

    Full Text Available Early diagnosis of hepatocellullar carcinoma (HCC remains a challenge. The current practice of serum alpha-fetoprotein (AFP measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV carrier samples from the Singapore General Hospital (SGH using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group, confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1 were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974 had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001. In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as

  14. Identification of serum monocyte chemoattractant protein-1 and prolactin as potential tumor markers in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Who-Whong; Ang, Soo Fan; Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential

  15. Monocyte chemoattractant protein-1 but not tumor necrosis factor-alpha is correlated with monocyte infiltration in mouse lipid lesions

    Energy Technology Data Exchange (ETDEWEB)

    Reckless, Jill; Rubin, Edward M.; Verstuyft, Judy B.; Metcalfe, James C.; Grainger, David J.

    1999-01-11

    The infiltration of monocytes into the vascular wall and their transformation into lipid-laden foam cells characterize early atherogenesis. This focal accumulation of lipids, together with smooth muscle cell proliferation and migration, and the synthesis of extracellular matrix in the intima of large arteries result in the formation of an atherosclerotic plaque. The extent to which the plaque is infiltrated with monocytes appears to be an important determinant of plaque stability. It has been proposed that macrophages secrete an excess of matrix-degrading enzymes over their inhibitors, resulting in conversion of a stable plaque into anunstable plaque that is likely to rupture, resulting in acutemyocardial infarction. Macrophages and T cells constitute {approx}40 percent of the total population of cells in the lipid core region of atherosclerotic plaques. Their recruitment to the lesion may depend on alterations in the adhesive properties of the endothelial surface. Increased endothelial cell permeability and endothelial cell activation are among the earliest changes associated with developing lesions of atherosclerosis. Many of the cell adhesion molecules involved in monocyte recruitment are expressed at low or undetectable levels on normal endothelium but are substantially elevated on the endothelium overlaying atherosclerotic lesions In addition to endothelial cell activation, numerous chemotactic cytokines have also been postulated to be involved in monocyte recruitment. For example, interleukin (IL)-1 and tumor necrosis factor-a (TNF-a) are direct chemoattractants for human monocytes but additionally induce cytoskeletal changes in the endothelium that result in increased permeability. This increased permeability, together with stimulated expression of adhesion molecules such as E-selectin, plays an important part in the local inflammation mediated by TNF-a and IL-1. In addition, a large number of other proinflammatory cytokines, including macrophage

  16. Pattern recognition of monocyte chemoattractant protein-1 (MCP-1) in whole blood samples using new platforms based on nanostructured materials

    Science.gov (United States)

    Stefan-van Staden, Raluca-Ioana; Gugoasa, Livia Alexandra; Biris, Alexandru Radu

    2015-09-01

    Four stochastic microsensors based on nanostructured materials (graphene, maltodextrin (MD), and diamond) integrated in miniaturized platforms were proposed. Monocyte chemoattractant protein-1 (MCP-1) is a pro-inflammatory cytokine whose main function is to regulate cell trafficking. It is correlated with the incidence of cardiovascular diseases and obesity, and was used as the model analyte in this study. The screening of whole blood samples for MCP-1 can be done for concentrations ranging from 10-12 to 10-8 g mL-1. The method was used for both qualitative and quantitative assessments of MCP-1 in whole blood samples. The lowest quantification limits for the assay of MCP-1 (1 pg mL-1) were reached when the microsensors based on protoporphyrin IX/Graphene-Au-3 and on MD/Graphene were employed in the platform design.

  17. Dopamine attenuates the chemoattractant effect of interleukin-8: a novel role in the systemic inflammatory response syndrome.

    LENUS (Irish Health Repository)

    Sookhai, S

    2012-02-03

    Activated neutrophil (PMN) adherence to vascular endothelium comprises a key step for both transendothelial migration and initiation of potentially deleterious release of PMN products. The biogenic amine, dopamine (DA), has been used for several decades in patients to maintain hemodynamic stability. The effect of dopamine on PMN transendothelial migration and adhesion receptor expression and on the endothelial molecules, E-selectin and ICAM-1, was evaluated. PMN were isolated from healthy controls, stimulated with lipopolysaccharide (LPS), and tumor necrosis factor-alpha (TNF-alpha) and treated with dopamine. CD 11b and CD 18 PMN adhesion receptor expression were assessed flow cytometrically. In a separate experiment, the chemoattractant peptide, IL-8, was placed in the lower chamber of transwells, and PMN migration was assessed. Human umbilical vein endothelial cells (HUVEC) were stimulated with LPS\\/TNF-alpha and incubated with dopamine. ICAM-1 and E-selectin endothelial molecule expression were assessed flow cytometrically. There was a significant increase in transendothelial migration in stimulated PMN compared with normal PMN (40 vs. 14%, P < 0.001). In addition, PMN CD11b\\/CD18 was significantly upregulated in stimulated PMN compared with normal PMN (252.4\\/352.4 vs. 76.7\\/139.4, P < 0.001) as were endothelial E-selectin\\/ICAM-1 expression compared with normal EC (8.1\\/9 vs. 3.9\\/3.8, P < 0.05). After treatment with dopamine, PMN transmigration was significantly decreased compared with stimulated PMN (8% vs. 40%, P < 0.001). Furthermore, dopamine also attenuated PMN CD11b\\/CD18 and the endothelial molecules E-selectin and ICAM-1 compared with stimulated PMN\\/EC that were not treated dopamine (174\\/240 vs. 252\\/352, P < 0.05 and 4\\/4.4 vs. 8.1\\/9, P < 0.05. respectively). The chemoattractant effect of IL-8 was also attenuated. These results identify for the first time that dopamine attenuates the initial interaction between PMN and the endothelium

  18. The therapeutic role of monocyte chemoattractant protein-1 in a renal tissue engineering strategy for diabetic patients.

    Directory of Open Access Journals (Sweden)

    Hao Yin

    Full Text Available In this study we aim to boost the functional output of the intra-kidney islet transplantation for diabetic patients using a tissue engineered polymeric scaffold. This highly porous electrospun scaffold featured randomly distributed fibers composed of polycaprolactone (PCL and poliglecaprone (PGC. It successfully sustained murine islets in vitro for up to 4 weeks without detected cytotoxicity. The in vivo study showed that the islet population proliferated by 89% within 12 weeks when they were delivered by the scaffold but only 18% if freely injected. Correspondingly, the islet population delivered by the scaffold unleashed a greater capability to produce insulin that in turn further drove down the blood glucose within 12 weeks after the surgery. Islets delivered by the scaffold most effectively prevented diabetic deterioration of kidney as evidenced by the lack of a kidney or glomerular enlargement and physiological levels of creatinine, urea nitrogen and albumin through week 12 after the surgery. Unlike traditional wisdom in diabetic research, the mechanistic study suggested that monocytes chemoattractant protein-1 (MCP-1 was responsible for the improved preservation of renal functions. This study revealed a therapeutic role of MCP-1 in rescuing kidneys in diabetic patients, which can be integrated into a tissue engineered scaffold to simultaneously preserved renal functions and islet transplantation efficacy. Also, this study affords a simple yet effective solution to improve the clinical output of islet transplantation.

  19. Neural crest migration: interplay between chemorepellents, chemoattractants, contact inhibition, epithelial-mesenchymal transition, and collective cell migration.

    Science.gov (United States)

    Theveneau, Eric; Mayor, Roberto

    2012-01-01

    Neural crest (NC) cells are induced at the border of the neural plate and subsequently leave the neuroepithelium during a delamination phase. This delamination involves either a complete or partial epithelium-to-mesenchyme transition, which is directly followed by an extensive cell migration. During migration, NC cells are exposed to a wide variety of signals controlling their polarity and directionality, allowing them to colonize specific areas or preventing them from invading forbidden zones. For instance, NC cells are restricted to very precise pathways by the presence of inhibitory signals at the borders of each route, such as Semaphorins, Ephrins, and Slit/Robo. Although specific NC chemoattractants have been recently identified, there is evidence that repulsive interactions between the cells, in a process called contact inhibition of locomotion, is one of the major driving forces behind directional migration. Interestingly, in cellular and molecular terms, the invasive behavior of NC is similar to the invasion of cancer cells during metastasis. NC cells eventually settle in various places and make an immense contribution to the vertebrate body. They form the major constituents of the skull, the peripheral nervous system, and the pigment cells among others, which show the remarkable diversity and importance of this embryonic-stem cell like cell population. Consequently, several birth defects and craniofacial disorders, such as Treacher Collins syndrome, are due to improper NC cell migration. PMID:23801492

  20. Higher expression of monocyte chemoattractant protein 1 and its receptor in brain tissue of intractable epilepsy patients.

    Science.gov (United States)

    Wang, Chunyan; Yang, Lihua; Zhang, Jiadong; Lin, Zhiguo; Qi, Jiping; Duan, Shurong

    2016-06-01

    We aimed to explore the pathogenesis of monocyte chemoattractant protein-1 (MCP1) and CC chemokine receptor 2 (CCR2) in brain tissue of patients with intractable epilepsy (IE). Hippocampi or temporal lobe tissues were obtained from 40 patients with IE and five patients without IE who had undergone surgical decompression and debridement. The levels of MCP1 and CCR2 were evaluated using immunohistochemistry. Pearson correlation analysis was employed to evaluate the correlation between levels of MCP1 and CCR2 in IE with or without hippocampal sclerosis (HS) and the disease duration, along with age. Higher levels of MCP1 (11.68±4.68% versus 1.72±1.54%) and CCR2 (11.54±4.65% versus 1.52±1.29%; Pcorrelated with the disease duration. However, no correlation was found in IE patients without HS. There was also no correlation between levels of MCP1 and CCR2 in IE patients with age, either with HS or without HS. These results suggest that MCP1 and its receptor may play a role in the pathogenesis and progression of IE. PMID:26810469

  1. Chemoattractive capacity of different lengths of nerve fragments bridging regeneration chambers for the repair of sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Jiren Zhang; Yubo Wang; Jincheng Zhang

    2012-01-01

    A preliminary study by our research group showed that 6-mm-long regeneration chamber bridging is equivalent to autologous nerve transplantation for the repair of 12-mm nerve defects.In this study,we compared the efficacy of different lengths (6,8,10 mm) of nerve fragments bridging 6-mm regeneration chambers for the repair of 12-mm-long nerve defects.At 16 weeks after the regeneration chamber was implanted,the number,diameter and myelin sheath thickness of the regenerated nerve fibers,as well as the conduction velocity of the sciatic nerve and gastrocnemius muscle wet weight ratio,were similar to that observed with autologous nerve transplantation.Our results demonstrate that 6-,8-and 10-mm-long nerve fragments bridging 6-mm regeneration chambers effectively repair 12-mm-long nerve defects.Because the chemoattractive capacity is not affected by the length of the nerve fragment,we suggest adopting 6-mm-long nerve fragments for the repair of peripheral nerve defects.

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

    International Nuclear Information System (INIS)

    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.

  3. Urine Monocyte Chemoattractant Protein-1 and Lupus Nephritis Disease Activity: Preliminary Report of a Prospective Longitudinal Study

    Directory of Open Access Journals (Sweden)

    Sabah Alharazy

    2015-01-01

    Full Text Available Objective. This longitudinal study aimed to determine the urine monocyte chemoattractant protein-1 (uMCP-1 levels in patients with biopsy-proven lupus nephritis (LN at various stages of renal disease activity and to compare them to current standard markers. Methods. Patients with LN—active or inactive—had their uMCP-1 levels and standard disease activity markers measured at baseline and 2 and 4 months. Urinary parameters, renal function test, serological markers, and renal SLE disease activity index-2K (renal SLEDAI-2K were analyzed to determine their associations with uMCP-1. Results. A hundred patients completed the study. At each visit, uMCP-1 levels (pg/mg creatinine were significantly higher in the active group especially with relapses and were significantly associated with proteinuria and renal SLEDAI-2K. Receiver operating characteristic (ROC curves showed that uMCP-1 was a potential biomarker for LN. Whereas multiple logistic regression analysis showed that only proteinuria and serum albumin and not uMCP-1 were independent predictors of LN activity. Conclusion. uMCP-1 was increased in active LN. Although uMCP-1 was not an independent predictor for LN activity, it could serve as an adjunctive marker when the clinical diagnosis of LN especially early relapse remains uncertain. Larger and longer studies are indicated.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Genome-wide association replicates the association of Duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children

    OpenAIRE

    Voruganti, V. Saroja.; Laston, Sandra; Haack, Karin; Mehta, Nitesh R.; Smith, C. Wayne; Cole, Shelley A.; Butte, Nancy F.; Comuzzie, Anthony G.

    2012-01-01

    Obesity is associated with a chronic low inflammatory state characterized by elevated levels of chemokines. Monocyte chemoattractant protein-1 (MCP-1) is a member of the cysteine-cysteine (CC) chemokine family and is increased in obesity. The purpose of this study was to identify loci regulating serum MCP-1 in obese Hispanic children from the Viva La Familia Study. A genome-wide association (GWA) analysis was performed in 815 children, ages 4-19 years, using genotypes assayed with the Illumin...

  6. Mycobacterium avium subsp. paratuberculosis Infection Causes Suppression of RANTES, Monocyte Chemoattractant Protein 1, and Tumor Necrosis Factor Alpha Expression in Peripheral Blood of Experimentally Infected Cattle

    OpenAIRE

    Buza, Joram J.; Mori, Yasuyuki; Bari, Abusaleh M.; Hikono Aodon-geril, Hirokazu; Hirayama, Sachiyo; Shu, Yujing; Momotani, Eiichi

    2003-01-01

    Blood from cattle with subclinical Mycobacterium avium subsp. paratuberculosis infection was stimulated with M. avium subsp. paratuberculosis antigens, and expression of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), RANTES, monocyte chemoattractant protein 1 (MCP-1), and IL-8 was measured. Expression of TNF-α, RANTES, and MCP-1 was lower in infected than in uninfected cattle. The reduced response may weaken protective immunity and perpetuate infection.

  7. Circulating levels of monocyte chemoattractant protein-1 and interleukin-7 in women who have undergone bilateral salpingo-oophorectomy

    Directory of Open Access Journals (Sweden)

    Tani A

    2013-12-01

    Full Text Available Anna Tani,1 Toshiyuki Yasui,2 Sumika Matsui,1 Takeshi Kato,1 Naoko Tsuchiya,3 Mitsutoshi Yuzurihara,3 Yoshio Kase,3 Minoru Irahara11Department of Obstetrics and Gynecology, 2Department of Reproductive Technology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan; 3Pharmacology Research Department, Tsumura Central Research Institute, Ibaraki, JapanPurpose: The aim of the study reported here was to determine the effect of surgical menopause by bilateral salpingo-oophorectomy (BSO on circulating levels of cytokines and chemokines related to the pathogenesis of atherosclerosis.Patients and methods: A total of 110 women were recruited for this study from the outpatient clinic of our facility. We divided the women into three groups: 1 women with a regular menstrual cycle, 2 women in whom less than 5 years had passed since their BSO, and 3 women in whom 5 years or more had passed since their BSO. Concentrations of nine cytokines and chemokines in serum were measured.Results: The serum monocyte chemoattractant protein-1 (MCP-1 level in women in whom less than 5 years had passed since their BSO was significantly higher than in women with a regular menstrual cycle (P<0.05. There were significant differences in serum interleukin (IL-7 among the three groups (P=0.035. MCP-1 showed a significant positive correlation (r=0.320, P=0.008 with follicle-stimulating hormone in women with a regular menstrual cycle and in women in whom less than 5 years had passed since their BSO.Conclusion: A hypoestrogenic state due to BSO induced changes in MCP-1 and IL-7 levels. MCP-1 level showed a significant increase in the early period after BSO, while IL-7 level showed a significant decrease in the late period after BSO.Keywords: follicle-stimulating hormone, cytokines, chemokines, hypoestrogenism, surgical menopause

  8. Developmentally regulated monocyte recruitment and bone resorption are modulated by functional deletion of the monocytic chemoattractant protein-1 gene.

    Science.gov (United States)

    Graves, D T; Alsulaimani, F; Ding, Y; Marks, S C

    2002-08-01

    Tooth eruption involves the movement of a tooth from its site of development within the alveolar bone to its functional position in the oral cavity. Because this process is dependent upon monocytes and formation of osteoclasts, it represents an excellent model for examination of these processes under developmental regulation. We investigated the functional role of monocyte chemoattractant protein-1 (MCP-1) in monocyte recruitment and its impact on bone resorption by examining each parameter in MCP-1(-/-) mice as compared with wild-type controls during tooth eruption. The peak number of monocytes occurred on day 5 in the MCP-1(-/-) mice and on day 9 in the wild-type mice. The peak number of osteoclasts followed the same pattern, occurring sooner in the MCP-1(-/-) (day 5) than in wild-type mice (day 9). Consistent with this, MCP-1(-/-) mice had an accelerated rate of tooth eruption in the early phase when the teeth first entered the oral cavity as compared with the wild-type mice. However, there was accelerated eruption in the wild-type group in the later phase of tooth eruption. When examined at the molecular level, inducible nitric oxide synthase (iNOS) and interleukin-11 and -6 were expressed at considerably higher levels in the experimental group with accelerated tooth eruption. This is the first report identifying these factors as potential modulators of bone resorption that can accelerate the rate of tooth eruption. We conclude that, at early timepoints, monocyte recruitment occurs by MCP-1-independent mechanisms. However, at a later timepoint, MCP-1 may play a contributory role in the recruitment of monocytic cells, allowing the wild-type animals to catch up. PMID:12151080

  9. The therapeutic effect of monocyte chemoattractant protein-1 delivered by an electrospun scaffold for hyperglycemia and nephrotic disorders

    Directory of Open Access Journals (Sweden)

    Yong C

    2014-02-01

    Full Text Available Cai Yong,2,* Zhengxin Wang,1,* Xing Zhang,3 Xiaomin Shi,1 Zhijia Ni,1 Hong Fu,1 Guoshan Ding,1 Zhiren Fu,1 Hao Yin1,3 1Department of Surgery, Organ Transplant Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Transplantation, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, People's Republic of China; 3Department of Surgery, University of Chicago, Chicago, IL, USA *These authors contributed equally to this article Abstract: Here, we investigated in diabetic mice the therapeutic effect of monocyte chemoattractant protein-1 (MCP-1, locally delivered by an electrospun scaffold, on transplanted islets. This therapeutic scheme is expected to exert a synergistic effect to ameliorate hyperglycemia and its associated nephrotic disorders. The cumulative amount of MCP-1 released from the scaffold in vitro within a 3-week window was 267.77±32.18 ng, without a compromise in bioactivity. After 8 weeks following the transplantation, the islet population stimulated by MCP-1 was 35.14%±7.23% larger than the non-stimulated islet population. Moreover, MCP-1 increased concentrations of blood insulin and C-peptide 2 by 49.83%±5.29% and 43.49%±9.21%, respectively. Consequently, the blood glucose concentration in the MCP-1 group was significantly lower than that in the control group at week 2 post-surgery. MCP-1 also enhanced the tolerance of sudden oral glucose challenge. The rapid decrease of blood creatinine, urine creatinine, and blood urea nitrogen suggested that the recovery of renal functions compromised by hyperglycemia could also be attributed to MCP-1. Our study shed new light on a synergistic strategy to alleviate hyperglycemia and nephrotic disorders in diabetic patients. Keywords: MCP-1, electrospinning, islet transplantation, diabetes

  10. Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis

    Science.gov (United States)

    Graupera, Isabel; Solà, Elsa; Fabrellas, Núria; Moreira, Rebeca; Solé, Cristina; Huelin, Patricia; de la Prada, Gloria; Pose, Elisa; Ariza, Xavier; Risso, Alessandro; Albertos, Sonia; Morales-Ruiz, Manuel; Jiménez, Wladimiro; Ginès, Pere

    2016-01-01

    MCP-1 (monocyte chemoattractant protein-1) is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis. AIM: To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis. METHODS: Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN), trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, β2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed. RESULTS: 69 patients(32%) had at least one readmission during the 3-month period of follow-up and 30 patients died(14%). Urine MCP-1 and OPN levels, were associated with 3-month probability of readmission (0.85 (0.27–2.1) and 2003 (705–4586) ug/g creat vs 0.47 (0.2–1.1) and 1188 (512–2958) ug/g creat, in patients with and without readmission, respectively; phepatic encephalopathy, bacterial infections or AKI. Urine MCP-1 was an independent predictive factor of hospital readmission and combined end-point of readmission or dead at 3 months. Plasma levels of MCP-1 did not correlated with outcomes. CONCLUSION: Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These results suggest that in cirrhosis there is an inflammatory response that is associated with poor outcomes. PMID:27359339

  11. The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction

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    Hicks Amy M

    2010-05-01

    Full Text Available Abstract Background Spontaneous regression/complete resistance (SR/CR mice are a unique colony of mice that possess an inheritable, natural cancer resistance mediated primarily by innate cellular immunity. This resistance is effective against sarcoma 180 (S180 at exceptionally high doses and these mice remain healthy. Methods In this study, we challenged SR/CR mice with additional lethal transplantable mouse cancer cell lines to determine their resistance spectrum. The ability of these transplantable cancer cell lines to induce leukocyte infiltration was quantified and the percentage of different populations of responding immune cells was determined using flow cytometry. Results In comparison to wild type (WT mice, SR/CR mice showed significantly higher resistance to all cancer cell lines tested. However, SR/CR mice were more sensitive to MethA sarcoma (MethA, B16 melanoma (B16, LL/2 lung carcinoma (LL/2 and J774 lymphoma (J774 than to sarcoma 180 (S180 and EL-4 lymphoma (EL-4. Further mechanistic studies revealed that this lower resistance to MethA and LL/2 was due to the inability of these cancer cells to attract SR/CR leukocytes, leading to tumor cell escape from resistance mechanism. This escape mechanism was overcome by co-injection with S180, which could attract SR/CR leukocytes allowing the mice to resist higher doses of MethA and LL/2. S180-induced cell-free ascites fluid (CFAF co-injection recapitulated the results obtained with live S180 cells, suggesting that this chemoattraction by cancer cells is mediated by diffusible molecules. We also tested for the first time whether SR/CR mice were able to resist additional cancer cell lines prior to S180 exposure. We found that SR/CR mice had an innate resistance against EL-4 and J774. Conclusions Our results suggest that the cancer resistance in SR/CR mice is based on at least two separate processes: leukocyte migration/infiltration to the site of cancer cells and recognition of common

  12. The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction

    International Nuclear Information System (INIS)

    Spontaneous regression/complete resistance (SR/CR) mice are a unique colony of mice that possess an inheritable, natural cancer resistance mediated primarily by innate cellular immunity. This resistance is effective against sarcoma 180 (S180) at exceptionally high doses and these mice remain healthy. In this study, we challenged SR/CR mice with additional lethal transplantable mouse cancer cell lines to determine their resistance spectrum. The ability of these transplantable cancer cell lines to induce leukocyte infiltration was quantified and the percentage of different populations of responding immune cells was determined using flow cytometry. In comparison to wild type (WT) mice, SR/CR mice showed significantly higher resistance to all cancer cell lines tested. However, SR/CR mice were more sensitive to MethA sarcoma (MethA), B16 melanoma (B16), LL/2 lung carcinoma (LL/2) and J774 lymphoma (J774) than to sarcoma 180 (S180) and EL-4 lymphoma (EL-4). Further mechanistic studies revealed that this lower resistance to MethA and LL/2 was due to the inability of these cancer cells to attract SR/CR leukocytes, leading to tumor cell escape from resistance mechanism. This escape mechanism was overcome by co-injection with S180, which could attract SR/CR leukocytes allowing the mice to resist higher doses of MethA and LL/2. S180-induced cell-free ascites fluid (CFAF) co-injection recapitulated the results obtained with live S180 cells, suggesting that this chemoattraction by cancer cells is mediated by diffusible molecules. We also tested for the first time whether SR/CR mice were able to resist additional cancer cell lines prior to S180 exposure. We found that SR/CR mice had an innate resistance against EL-4 and J774. Our results suggest that the cancer resistance in SR/CR mice is based on at least two separate processes: leukocyte migration/infiltration to the site of cancer cells and recognition of common surface properties on cancer cells. The infiltration of SR

  13. Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

    Science.gov (United States)

    Fufaa, Gudeta D.; Weil, E. Jennifer; Nelson, Robert G.; Hanson, Robert L.; Knowler, William C.; Rovin, Brad H.; Wu, Haifeng; Klein, Jon B.; Mifflin, Theodore E.; Feldman, Harold I.; Vasan, Ramachandran S.; Kimmel, Paul L.; Kusek, John W.; Mauer, Michael; Zinman, Bernard; Donnelly, Sandra; Canada, Toronto; Gardiner, Robert; Suissa, Samy; Drummond, Keith; Goodyer, Paul; Sinaiko, Alan; Strand, Trudy; Gubler, Marie Claire; Klein, Ronald

    2015-01-01

    Background Urinary monocyte chemoattractant protein-1 (MCP-1) and hepcidin are potential biomarkers of renal inflammation. We examined their association with development of diabetic nephropathy (DN) lesions in normotensive normoalbuminuric subjects with type 1 diabetes (T1D) from the Renin-Angiotensin System Study. Methods Biomarker concentrations were measured in baseline urine samples from 224 subjects who underwent kidney biopsies at baseline and after 5 years. Fifty-eight urine samples below the limit of quantitation (LOQ, 28.8 pg/mL) of the MCP-1 assay were assigned concentrations of LOQ/√2 for analysis. Relationships between ln(MCP-1/Cr) or ln(hepcidin/Cr) and morphometric variables were assessed by sex using multiple linear regression after adjustment for age, T1D duration, HbA1c, mean arterial pressure, albumin excretion rate (AER) and glomerular filtration rate (GFR). In models that examined changes in morphometric variables, the baseline morphometric value was also included. Results Baseline mean age was 24.6 years, mean duration of T1D 11.2 years, median AER 6.4 µg/min and mean iohexol GFR 129 mL/min/1.73 m2. No associations were found between hepcidin/Cr and morphometric variables. Higher MCP-1/Cr was associated with higher interstitial fractional volume at baseline and after 5 years in women (baseline partial r = 0.244, P = 0.024; 5-year partial r = 0.299, P = 0.005), but not in men (baseline partial r = −0.049, P = 0.678; 5-year partial r = 0.026, P = 0.830). MCP-1 was not associated with glomerular lesions in either sex. Conclusions Elevated urinary MCP-1 concentration measured before clinical findings of DN in women with T1D was associated with changes in kidney interstitial volume, suggesting that inflammatory processes may be involved in the pathogenesis of early interstitial changes in DN. PMID:25648911

  14. The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory events,including monocyte/macrophage infiltration in the brain,glial immune activation and release of neurotoxic substances.In these events,astrocytic-derived monocyte chemoattractant protein-1(MCP-1)plays an important role,whose release is elevated by HIV transactivator of transcription(HIV tat)and...

  15. Interleukin-17A and Toll-Like Receptor 3 Ligand Poly(I:C Synergistically Induced Neutrophil Chemoattractant Production by Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Hirotaka Matsuzaki

    Full Text Available Chronic inflammatory airway diseases, such as bronchial asthma and chronic obstructive pulmonary disease, are common respiratory disorders worldwide. Exacerbations of these diseases are frequent and worsen patients' respiratory condition and overall health. However, the mechanisms of exacerbation have not been fully elucidated. Recently, it was reported that interleukin (IL-17A might play an important role in neutrophilic inflammation, which is characteristic of such exacerbations, through increased production of neutrophil chemoattractants. Therefore, we hypothesized that IL-17A was involved in the pathogenesis of acute exacerbation, due to viral infection in chronic inflammatory airway diseases. In this study, we assessed chemokine production by bronchial epithelial cells and investigated the underlying mechanisms. Comprehensive chemokine analysis showed that, compared with poly(I:C alone, co-stimulation of BEAS-2B cells with IL-17A and poly(I:C strongly induced production of such neutrophil chemoattractants as CXC chemokine ligand (CXCL8, growth-related oncogene (GRO, and CXCL1. Co-stimulation synergistically induced CXCL8 and CXCL1 mRNA and protein production by BEAS-2B cells and normal human bronchial epithelial cells. Poly(I:C induced chemokine expression by BEAS-2B cells mainly via Toll-like receptor 3/TIR-domain-containing adapter-inducing interferon-β-mediated signals. The co-stimulation with IL-17A and poly(I:C markedly activated the p38 and extracellular-signal-regulated kinase 1/2 pathway, compared with poly(I:C, although there was little change in nuclear factor-κB translocation into the nucleus or the transcriptional activities of nuclear factor-κB and activator protein 1. IL-17A promoted stabilization of CXCL8 mRNA in BEAS-2B cells treated with poly(I:C. In conclusion, IL-17A appears to be involved in the pathogenesis of chronic inflammatory airway disease exacerbation, due to viral infection by promoting release of neutrophil

  16. 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

  17. Cessation of neutrophil influx in C5a-induced acute experimental arthritis is associated with loss of chemoattractant activity from the joint space

    International Nuclear Information System (INIS)

    Neutrophil emigration is a critical component of the inflammatory process and is generally thought to play a role in host defense as well as in the tissue injury that often accompanies inflammation. Most inflammatory reactions exhibit a sequence of emigrating cell types, thus clearly demonstrating that the neutrophil influx eventually ceases and that the neutrophils are then removed from the lesion. It has been our premise that in order to understand the processes that lead to the progressive inflammatory reactions that underly so many disease processes, it is important to determine the mechanism by which the ''normal'' inflammatory response resolves. The purpose of this study was to identify the time of cessation of neutrophil influx in experimental arthritis induced by the injection of C5 fragments (C5f) and to investigate mechanisms underlying the cessation process. The migration of i.v. delivery pulses to inflamed joints was assessed by lavage of the joint space and by external scintigraphy. We found no evidence for the development of inhibitory systems against chemotactic factors or ''desensitization'' of the inflamed site, because a second injection of C5f into joints which had been injected previously with C5f resulted in enhancement rather than inhibition of migration. Neither was evidence found for altered tissue barriers to migration or for desensitization of neutrophils as possible explanations for cessation of influx. The major mechanism appeared to be a loss of chemoattractant activity in the joint space between 2 h and 6 h after C5f injection which was detected by transfer into a fresh joint. Radiolabeled C5a des-Arg had a t1/2 of disappearance from the joint of less than 1 h, which suggested that the transferred chemoattractant must, in part, have been due to the generation of new chemotaxins by C5f injection

  18. Functional characteristics of histamine receptor-bearing mononuclear cells. I. Selective production of lymphocyte chemoattractant lymphokines with histamine used as a ligand.

    Science.gov (United States)

    Center, D M; Cruikshank, W W; Berman, J S; Beer, D J

    1983-10-01

    Mitogens and antigens have been the traditional ligands for activating lymphocytes in vitro for the elaboration of lymphokines. Recently, histamine, by interaction with histamine-type 2 receptors on T lymphocytes, has been found to induce the production of one lymphokine, histamine-induced suppressor factor (HSF), that inhibits lymphocyte proliferation and lymphokine production in vitro. Because the biologic effects of HSF appear to be confined to alterations in lymphocyte function, we assessed the ability of soluble products of histamine-stimulated human blood mononuclear cells to affect another lymphocyte function, motility. Utilizing a modified Boyden chamber assay to assess lymphocyte migration, we identified chemoattractant activity for human blood and rat splenic T lymphocytes in histamine-induced mononuclear cell supernatants. No neutrophil or monocyte chemoattractant activity was present. Sephadex G-100 gel filtration of histamine-induced supernatants showed the lymphotactic activity eluted with a 56,000 m.w. This activity was cationic as determined by its elution pattern from a Sephadex QAE anion exchange matrix with a single pl of 9.0 to 9.4 determined by isoelectric focusing in sucrose. Its biologic activity is predominantly chemokinetic in nature, is stable to heating at 56 degrees C for 30 min, but is sensitive to the effects of trypsin and neuraminidase. These physicochemical and functional characteristics establish it as identical to a recently described concanavalin A-induced (Con A) lymphotactic lymphokine (LCF). Mononuclear cells that did not adhere to a histamine affinity matrix were unable to produce LCF when subsequently stimulated with histamine or Con A. Mononuclear cells incubated with histamine and diphenhydramine produced LCF; the addition of cimetidine eliminated LCF production. In fact, supernatants from cells incubated with histamine and cimetidine significantly inhibited lymphocyte migration, a phenomenon explainable by the two regions

  19. Association of monocyte chemoattractant protein-1 (MCP-1)-2518A>G polymorphism with susceptibility to coronary artery disease: a meta-analysis.

    Science.gov (United States)

    Bai, Xiao-Yan; Li, Shujing; Wang, Miao; Qu, Xinjian; Hu, Gaolei; Xu, Zhaowei; Chen, Min; He, Guo-Wei; Wu, Huijian

    2015-05-01

    We attempted to systematically elucidate the association between monocyte chemoattractant protein-1 (MCP-1) -2518A>G polymorphism and risk of coronary artery disease (CAD). Eligible studies were identified through PubMed, EBSCO, and Web of Science Databases. The magnitude of MCP-1 polymorphism effect and its possible mode of action on CAD were estimated. The odds ratio (OR) with 95% confidence intervals (CI) were pooled in a specific genetic model to assess the association. A total of 21 studies were involved. There was significant gene effect on CAD risk in the overall population (likelihood ratio test: p pFDR = 0.005) in the recessive model. In the ethnicity-stratified analysis, significant association was observed in the Caucasian population (OR = 1.492; 95% CI: 1.106-2.014; puncorrected = 0.009, pFDR = 0.015), whereas no statistical significant association was detected in the Asian population (adjusted p = 0.124). The results suggested that MCP-1 -2518A>G polymorphism may be associated with susceptibility to CAD, especially in Caucasians. PMID:25875728

  20. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2012-02-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  1. Mechanism of sphingosine 1-phosphate- and lysophosphatidic Acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells.

    LENUS (Irish Health Repository)

    Costello, Richard W

    2011-05-01

    The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-protein coupled receptors S1P(1-5) and LPA(1-3) respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The G(i) coupled receptors S1P(1), S1P(3), LPA(1), LPA(2) and LPA(3) were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and G(i)-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and G(i)-dependent up-regulation of the eosinophil chemoattractant, CCL-26. The eosinophil granule protein eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P(1), LPA(1), LPA(2) and LPA(3), providing the situation whereby eosinophil granule proteins may enhance S1P- and\\/or LPA- induced eosinophil accumulation at nerve cells in allergic conditions.

  2. Olmesartan inhibits the expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α and improves vascular remodeling after vascular injury in mouse

    Institute of Scientific and Technical Information of China (English)

    李震; 陈小东; 倪少凯; 李建文; 林木生

    2004-01-01

    Objective: To investigate the neointima formation and the expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in cuff-induced vascular injury in mouse model, and to examine the effect of angiotensin II type 1 receptor (AT1) blocker, olmesartan, on MCP-1 and TNF-α expression and consequently vascular remodeling.Methods: Vascular injury was induced by polyethylene cuff-placement around the mouse femoral artery. Some mice were treated with AT1 receptor blocker, olmesartan, at the dose of 3 mg*kg-1*day-1 with an osmotic minipump. Neointima formation and the proliferation of vascular smooth muscle cells (VSMCs) were measured by morphometric analysis and bromodeoxyuridine (BrdU) incorporation. MCP-1 and TNF-α expression was detected by Western blot and immunohistochemical staining.Results: We observed neointima formation 14 days after cuff placement as well as VSMCs proliferation in the media and neointima. Cuff placement also induced MCP-1 and TNF-α expression in the media and neointima that the VSMCs specifically existed. Treatment of mice with olmesartan at a dose of 3 mg*kg-1*day-1, which did not influence systolic blood pressure, significantly decreased neointima formation and the proliferation of VSMCs. Olmesartan also inhibited MCP-1 and TNF-α expression in the injured arteries.Conclusions: Our results demonstrate that blockade of AT1 receptor inhibits MCP-1 and TNF-α expression and thereby improves vascular remodeling.

  3. 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.

  4. Induction of Monocyte Chemoattractant Proteins in Macrophages via the Production of Granulocyte/Macrophage Colony-Stimulating Factor by Breast Cancer Cells

    Science.gov (United States)

    Yoshimura, Teizo; Imamichi, Tomozumi; Weiss, Jonathan M.; Sato, Miwa; Li, Liangzhu; Matsukawa, Akihiro; Wang, Ji Ming

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1)/CCL2 plays an important role in the initiation and progression of cancer. We previously reported that in 4T1 murine breast cancer, non-tumor stromal cells, including macrophages, were the major source of MCP-1. In the present study, we analyzed the potential mechanisms by which MCP-1 is upregulated in macrophages infiltrating 4T1 tumors. We found that cell-free culture supernatants of 4T1 cells (4T1-sup) markedly upregulated MCP-1 production by peritoneal inflammatory macrophages. 4T1-sup also upregulated other MCPs, such as MCP-3/CCL7 and MCP-5/CCL12, but modestly upregulated neutrophil chemotactic chemokines, such as KC/CXCL1 or MIP-2/CXCL2. Physicochemical analysis indicated that an approximately 2–3 kDa 4T1 cell product was responsible for the capacity of 4T1-sup to upregulate MCP-1 expression by macrophages. A neutralizing antibody against granulocyte/macrophage colony-stimulating factor (GM-CSF), but not macrophage CSF, almost completely abrogated MCP-1-inducing activity of 4T1-sup, and recombinant GM-CSF potently upregulated MCP-1 production by macrophages. The expression levels of GM-CSF in 4T1 tumors in vivo were higher than other tumors, such as Lewis lung carcinoma. Treatment of mice with anti-GM-CSF antibody significantly reduced the growth of 4T1 tumors at the injection sites but did not reduce MCP-1 production or lung metastasis in tumor-bearing mice. These results indicate that 4T1 cells have the capacity to directly upregulate MCP-1 production by macrophages by releasing GM-CSF; however, other mechanisms are also involved in increased MCP-1 levels in the 4T1 tumor microenvironment. PMID:26834744

  5. Interleukin-1β,Tumor Necrosis Factor-α and Lipopolysaccharide Induce Expression of Monocyte Chemoattractant Protein-1 in Calf Aortic Smooth Muscle Cells

    Institute of Scientific and Technical Information of China (English)

    MENG Feng; DENG Zhongduan; NI Juan

    2000-01-01

    To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1)mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL- 1β, 20 ng/mlTNF-lα and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expression of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32p-end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cultured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cultured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-Iβ, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2.3-fold and 1.6-fold, respectively).ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9-fold, 1.7-fold and 1.1-fold, respectively ). The results suggest that calf aortic SMCs could express MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP- 1mRNA and protein, and the former is more effective than the latter.

  6. Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    YANG Xiaoyun; WANG Lin; ZENG Hesong; DUBEY Laxman; ZHOU Ning; PU Jun

    2006-01-01

    To observe the effects of simvastatin on nuclear factor kappaB (NF-κB)-DNA binding activity and on the expression of monocyte chemoattractant protein-1 (MCP-1) in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects.Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group (LC), highcholesterol group (HC), high-cholesterol+ simvastatin group (HC+S) and then were fed for 12weeks. At the end of theexperiment, standard enzymatic assays, electrophoretic mobility shift assay (EMSA), immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-κB-DNA binding activity, MCP-1 protein expression, intima thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-κB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC+S groups were significantly lower than those in the HC group (P<0.05). There was no significant difference in the serum lipids between the LC and HC+S groups (P>0.05), but the NF-κB-DNA binding activity, the expression of MCP-1 protein and the intima thickness and plaque area of aorta in the HC+S group were significantly decreased as compared to the LC group (P<0.05). This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NFκB-DNA binding activity and by reducing the expression of MCP-1 protein.

  7. Induction of Monocyte Chemoattractant Proteins in Macrophages via the Production of Granulocyte-macrophage Colony Stimulating Factor by Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Teizo eYoshimura

    2016-01-01

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1/CCL2 plays an important role in the initiation and progression of cancer. We previously reported that in 4T1 murine breast cancer, non-tumor stromal cells, including macrophages, were the major source of MCP-1. In the present study, we analyzed the potential mechanisms by which MCP-1 is upregulated in macrophages infiltrating 4T1 tumors. We found that cell-free culture supernatants of 4T1 cells (4T1-sup markedly upregulated MCP-1 production by peritoneal inflammatory macrophages. 4T1-sup also upregulated other MCPs, such as MCP-3/CCL7 and MCP-5/CCL12, but modestly neutrophil chemotactic chemokines, such as KC/CXCL1 or MIP-2/CXCL2. Physicochemical analysis indicated that an approximately 2 to 3 kDa 4T1 cell product was responsible for the capacity of 4T1-sup to upregulate MCP-1 expression by macrophages. A neutralizing antibody against granulocyte-macrophage-colony stimulating factor (GM-CSF, but not macrophage-colony stimulating factor, almost completely abrogated MCP-1-inducing activity of 4T1-sup, and recombinant GM-CSF potently up-regulated MCP-1 production by macrophages. The expression levels of GM-CSF in 4T1 tumors in vivo were higher than other tumors, such as Lewis lung carcinoma. Treatment of mice with anti-GM-CSF antibody significantly reduced the growth of 4T1 tumors at the injection sites but did not reduce MCP-1 production or lung metastasis in tumor-bearing mice. These results indicate that 4T1 cells have the capacity to directly up-regulate MCP-1 production by macrophages by releasing GM-CSF; however, other mechanisms are also involved in increased MCP-1 levels in the 4T1 tumor microenvironment.

  8. Genome-wide association replicates the association of Duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children.

    Science.gov (United States)

    Voruganti, V Saroja; Laston, Sandra; Haack, Karin; Mehta, Nitesh R; Smith, C Wayne; Cole, Shelley A; Butte, Nancy F; Comuzzie, Anthony G

    2012-12-01

    Obesity is associated with a chronic low inflammatory state characterized by elevated levels of chemokines. Monocyte chemoattractant protein-1 (MCP-1) is a member of the cysteine-cysteine (CC) chemokine family and is increased in obesity. The purpose of this study was to identify loci regulating serum MCP-1 in obese Hispanic children from the Viva La Familia Study. A genome-wide association (GWA) analysis was performed in 815 children, ages 4-19 years, using genotypes assayed with the Illumina HumanOmni1-Quad v1.0 BeadChips. All analyses were performed in SOLAR using a linear regression-based test under an additive model of allelic effect, while accounting for the relatedness of family members via a kinship variance component. The strongest association for MCP-1 levels was found with a non-synonymous single nucleotide polymorphism (SNP), rs12075, resulting in an amino acid substitution (Asp42Gly) in the Duffy antigen receptor for chemokines (DARC) gene product (minor allele frequency=43.6%, p=1.3 × 10(-21)) on chromosome 1. Four other DARC SNPs were also significantly associated with MCP-1 levels (p<10(-16)-10(-6)). The Asp42Gly variant was associated with higher levels of MCP-1 and accounted for approximately 10% of its variability. In addition, MCP-1 levels were significantly associated with SNPs in chemokine receptor 3 (CCR3) and caspase recruitment domain family, member 9 (CARD9). In summary, the association of the DARC Asp42Gly variant with MCP-1 levels replicates previous GWA results substantiating a potential role for DARC in the regulation of pro-inflammatory cytokines. PMID:23017229

  9. Plasma Levels of Monocyte Chemoattractant Protein-1, n-Terminal Fragment of Brain Natriuretic Peptide and Calcidiol Are Independently Associated with the Complexity of Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    Roberto Martín-Reyes

    Full Text Available We investigated the relationship of the Syntax Score (SS and coronary artery calcification (CAC, with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field.We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0-1 and high-grade (2-3 calcification, measured with a semiquantitative scale ranging from 0 (none to 3 (severe. For the SS study patients were divided in SS<14 and SS≥14. Multivariate linear and logistic regression analyses were performed.MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08-3.39]; p = 0.040, along with NT-proBNP (RC = 0.17 [95%CI = 0.05-0.28]; p = 0.004, male sex (RC = 4.15 [95%CI = 1.47-6.83]; p = 0.003, age (RC = 0.13 [95%CI = 0.02-0.24]; p = 0.020, hypertension (RC = 3.64, [95%CI = 0.77-6.50]; p = 0.013, hyperlipidemia (RC = 2.78, [95%CI = 0.28-5.29]; p = 0.030, and statins (RC = 6.12 [95%CI = 1.28-10.96]; p = 0.013. Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36-0.90]; p = 0.013 along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19-0.78]; p = 0.006, diabetes (OR = 2.35 [95%CI = 1.11-4.98]; p = 0.028 and age (OR = 1.37 [95%CI = 1.18-1.59]; p<0.001. During follow-up (1.79 [0.94-2.86] years, 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome.MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels are associated with CAC. More studies are needed to confirm these data.

  10. 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

    Science.gov (United States)

    Pushpanathan, Premalatha; Srikanth, Padma; Seshadri, Krishna G.; Selvarajan, Sribal; Pitani, Ravi Shankar; Kumar, Thomas David; Janarthanan, R.

    2016-01-01

    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 IFNγ levels in T

  11. Plasma Levels of Monocyte Chemoattractant Protein-1, n-Terminal Fragment of Brain Natriuretic Peptide and Calcidiol Are Independently Associated with the Complexity of Coronary Artery Disease

    Science.gov (United States)

    Martín-Reyes, Roberto; Franco-Peláez, Juan Antonio; Lorenzo, Óscar; González-Casaus, María Luisa; Pello, Ana María; Aceña, Álvaro; Carda, Rocío; Martín-Ventura, José Luis; Blanco-Colio, Luis; Martín-Mariscal, María Luisa; Martínez-Milla, Juan; Villa-Bellosta, Ricardo; Piñero, Antonio; Navarro, Felipe; Egido, Jesús; Tuñón, José

    2016-01-01

    Background and Objectives We investigated the relationship of the Syntax Score (SS) and coronary artery calcification (CAC), with plasma levels of biomarkers related to cardiovascular damage and mineral metabolism, as there is sparse information in this field. Methods We studied 270 patients with coronary disease that had an acute coronary syndrome (ACS) six months before. Calcidiol, fibroblast growth factor-23, parathormone, phosphate and monocyte chemoattractant protein-1 [MCP-1], high-sensitivity C-reactive protein, galectin-3, and N-terminal pro-brain natriuretic peptide [NT-proBNP] levels, among other biomarkers, were determined. CAC was assessed by coronary angiogram as low-grade (0–1) and high-grade (2–3) calcification, measured with a semiquantitative scale ranging from 0 (none) to 3 (severe). For the SS study patients were divided in SS<14 and SS≥14. Multivariate linear and logistic regression analyses were performed. Results MCP-1 predicted independently the SS (RC = 1.73 [95%CI = 0.08–3.39]; p = 0.040), along with NT-proBNP (RC = 0.17 [95%CI = 0.05–0.28]; p = 0.004), male sex (RC = 4.15 [95%CI = 1.47–6.83]; p = 0.003), age (RC = 0.13 [95%CI = 0.02–0.24]; p = 0.020), hypertension (RC = 3.64, [95%CI = 0.77–6.50]; p = 0.013), hyperlipidemia (RC = 2.78, [95%CI = 0.28–5.29]; p = 0.030), and statins (RC = 6.12 [95%CI = 1.28–10.96]; p = 0.013). Low calcidiol predicted high-grade calcification independently (OR = 0.57 [95% CI = 0.36–0.90]; p = 0.013) along with ST-elevation myocardial infarction (OR = 0.38 [95%CI = 0.19–0.78]; p = 0.006), diabetes (OR = 2.35 [95%CI = 1.11–4.98]; p = 0.028) and age (OR = 1.37 [95%CI = 1.18–1.59]; p<0.001). During follow-up (1.79 [0.94–2.86] years), 27 patients developed ACS, stroke, or transient ischemic attack. A combined score using SS and CAC predicted independently the development of the outcome. Conclusions MCP-1 and NT-proBNP are independent predictors of SS, while low calcidiol plasma levels

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

    Directory of Open Access Journals (Sweden)

    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

  13. Plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha are increased in patients with polycystic ovary syndrome (PCOS) and associated with adiposity, but unaffected by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Andersen, Marianne; Richelsen, Bjørn;

    2009-01-01

    OBJECTIVE: Hirsutism is most often caused by polycystic ovary syndrome (PCOS). PCOS patients are characterized by insulin resistance, abdominal obesity and low-grade inflammation. Insulin sensitizing treatment reduces the inflammatory state, but the effect on serum levels of migration inhibitor...... factor (MIF), monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha have not been evaluated before in PCOS. RESEARCH DESIGN AND METHODS: Plasma chemokine levels (MCP-1, MIP-1alpha and MIF) were measured in two study designs. (i) 51 hirsute patients and 63 matched...... controls and (ii) 30 PCOS patients before and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks. Clinical evaluations and whole body DXA-scans were performed in all participants. RESULTS: Hirsute patients (n = 51) had significantly increased MCP-1 [121 (15-950) vs. 81 (18-365) pg...

  14. Monocyte chemoattractant protein-1, trans-forming growth factor-β1, nerve growth factor, resistin and hyaluronic acid as serum markers:comparison between recurrent acute and chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Ganesh Kamath; C Ganesh Pai; Asha Kamath; Annamma Kurien

    2016-01-01

    BACKGROUND: Diagnostic parameters that can predict the presence of chronic pancreatitis (CP) in patients with recur-rent pain due to pancreatitis would help to direct appropri-ate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β1 (TGF-β1), nerve growth factor (NGF), resis-tin and hyaluronic acid (HA) in patients with recurrent acute pancreatitis (RAP) and CP to assess their ability to differenti-ate the two conditions. METHODS: Levels of serum markers assessed by enzyme-linked immunosorbent assay (ELISA) were prospectively com-pared in consecutive patients with RAP, CP and in controls, and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP. RESULTS: One hundred and thirteen consecutive patients (RAP=32, CP=81) and 78 healthy controls were prospectively enrolled. The mean (SD) age of the patients was 32.0 (14.0) years; 89 (78.8%) were male. All markers were signiifcantly higher in CP patients than in the controls (P CONCLUSION: Serum resistin is a promising marker to dif-ferentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

  15. Ex vivo expanded human regulatory T cells delay islet allograft rejection via inhibiting islet-derived monocyte chemoattractant protein-1 production in CD34+ stem cells-reconstituted NOD-scid IL2rγnull mice.

    Directory of Open Access Journals (Sweden)

    Fang Xiao

    Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune disease caused by immune-mediated destruction of insulin-secreting β cells of the pancreas. Near complete dependence on exogenous insulin makes T1DM very difficult to control, with the result that patients are exposed to high blood glucose and risk of diabetic complications and/or intermittent low blood glucose that can cause unconsciousness, fits and even death. Allograft transplantation of pancreatic islets restores normoglycemia with a low risk of surgical complications. However, although successful immediately after transplantation, islets are progressively lost, with most of the patients requiring exogenous insulin within 2 years post-transplant. Therefore, there is an urgent requirement for the development of new strategies to prevent islet rejection. In this study, we explored the importance of human regulatory T cells in the control of islets allograft rejection. We developed a pre-clinical model of human islet transplantation by reconstituting NOD-scid IL2rγnull mice with cord blood-derived human CD34+ stem cells and demonstrated that although the engrafted human immune system mediated the rejection of human islets, their survival was significantly prolonged following adoptive transfer of ex vivo expanded human Tregs. Mechanistically, Tregs inhibited the infiltration of innate immune cells and CD4+ T cells into the graft by down-regulating the islet graft-derived monocyte chemoattractant protein-1. Our findings might contribute to the development of clinical strategies for Treg therapy to control human islet rejection. We also show for the first time that CD34+ cells-reconstituted NOD-scid IL2rγnull mouse model could be beneficial for investigating human innate immunity in vivo.

  16. Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.

    Science.gov (United States)

    Li, A; Wang, J; Zhu, D; Zhang, X; Pan, R; Wang, R

    2015-01-01

    Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work. PMID:25968940

  17. Mathematics of Experimentally Generated Chemoattractant Gradients

    NARCIS (Netherlands)

    M. Postma; P.J.M. van Haastert

    2016-01-01

    Many eukaryotic cells move in the direction of a chemical gradient. Several assays have been developed to measure this chemotactic response, but no complete mathematical models of the spatial and temporal gradients are available to describe the fundamental principles of chemotaxis. Here we provide a

  18. Mast cell chemotaxis - chemoattractants and signaling pathways

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr

    2012-01-01

    Roč. 3, May (2012), s. 119. ISSN 1664-3224 R&D Projects: GA MŠk LD12073; GA ČR GA301/09/1826; GA ČR GAP302/10/1759 Grant ostatní: ECST(XE) BM1007; AV ČR(CZ) MC200520901 Institutional support: RVO:68378050 Keywords : mast cell * IgE receptor * plasma membrane Subject RIV: EB - Genetics ; Molecular Biology

  19. Effect of folic acid supplementation on levels of circulating Monocyte Chemoattractant Protein-1 and the presence of intravascular ultrasound derived virtual histology thin-cap fibroatheromas in patients with stable angina pectoris.

    Directory of Open Access Journals (Sweden)

    Kjetil H Løland

    Full Text Available BACKGROUND: Virtual Histology Intravascular Ultrasound (VH-IVUS may be used to detect early signs of unstable coronary artery disease. Monocyte Chemoattractant Protein-1 (MCP-1 is linked with coronary atherosclerosis and plaque instability and could potentially be modified by folic acid treatment. METHODS: In a randomized, prospective study, 102 patients with stable angina pectoris (SAP received percutaneous coronary intervention and established medical treatment as well as either homocysteine-lowering folic acid/vitamin B12 (± B6 or placebo (± B6 for 1 year before VH-IVUS was performed. The presence of VH-Thin-Cap Fibroatheroma (VH-TCFA in non-intervened coronary vessels was registered and serum levels of MCP-1 were measured. The patients were subsequently followed for incident myocardial infarction (MI. RESULTS: Patients treated with folic acid/vitamin B12 had a geometric mean (SD MCP-1 level of 79.95 (1.49 versus 86.00 (1.43 pg/mL for patients receiving placebo (p-value 0.34. VH-TCFA lesions were present in 7.8% of patients and did not differ between intervention arms (p-value 0.47. Serum levels of MCP-1 were 1.46 (95% CI 1.12 to 1.92 times higher in patients with VH-TCFA lesions than in those without (p-value 0.005. Afterwards, patients were followed for median 2.1 years and 3.8% experienced a myocardial infarction (MI, which in post-hoc Cox regression analyses was independently predicted by both MCP-1 (P-value 0.006 and VH-TCFA (p-value 0.01. CONCLUSIONS: In patients with SAP receiving established medical treatment, folic acid supplementation is not associated with either presence of VH-TCFA or levels of MCP-1. MCP-1 is however associated with VH-TCFA, a finding corroborated by increased risk for future MI. ClinicalTrials.gov Identifier: NCT00354081.

  20. 超声造影联合血清单核细胞趋化蛋白1和细胞黏附分子1检测确定胃癌术前分期%Contrast enhanced ultrasonography with monocyte chemoattractant protein-1 and cellular adhesion molecule-1 detection in preoperative staging of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    张超贤; 秦咏梅; 李光艳

    2016-01-01

    Objective To explore the clinical value of oral ultrasonic contrast agent ultrasonography (OUCAUS) combined with serum monocyte chemoattractant protein-1 (MCP-1) and cell adhesion molecule-1 (CAM-1) measurement in preoperative staging of stomach carcinoma.Methods 800 gastric cancer patients were diagnosed by electric gastroscopy and OUCAUS.The preoperative staging was measured by OUCAUS and compared with pathologic staging,and serum levels of MCP-1 and CAM-1 were measured with ELISA.Results The total accuracy rate of OUCAUS was 79.9% in estimating invasive depth of stomach neoplasm,82.9% in estimating lymphatic metastasis and 88.6% in estimating distant metastasis respectively.The expression levels of MCP-1 and CAM-1 in serum were closely correlated with invasive degree,lymphatic metastasis,distant metastasis and pathologic staging (all P < 0.05).The total accuracy rate of combining OUCAUS and MCP-1,CAM-1 was 93.0 % in estimating invasive depth,93.9% in estimating lymphatic metastasis and 98.6% in estimating distant metastasis respectively.The total accuracy rate of combining OUCAUS and MCP-1,CAM-1 in estimating invasive depth,lymphatic metastasis and distant metastasis was significantly higher than that of by OUCAUS alone.Conclusions MCP-1 and CAM-1 serum levels are closely correlated to pathologic staging of gastric cancer.Combining OUCAUS and MCP-1,CAM-1 can increase the accuracy rate determining invasion and metastasis in gastric cancer.%目的 探讨口服超声助显剂超声检查(oral ultrasonic contrast agent ultrasonography,OUCAUS)联合血清单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)和细胞黏附分子1(cell adhesion molecule-1,CAM-1)检测对胃癌术前分期的临床价值.方法 对新乡医学院第一附属医院800例胃癌患者术前行胃镜和OUCAUS检查并进行术前分期,同时用ELISA法检测其术前血清MCP-1和CAM-1水平,并与术后病理分期比较.结果 OUCAUS对胃癌侵犯深度、

  1. Aspects of chemoattractant recognition by the alga Dunaliella tertiolecta

    International Nuclear Information System (INIS)

    Studies on the molecular nature of algal chemotaxis were performed using the halophilic chlorophyte Dunaliella tertiolecta as a model. Several physical and chemical parameters for generation of maximum chemotactic response in capillary assays are described. Inhibition of chemotaxis to NH4+ and several aromatic amino acid by sublethal concentrations of certain heavy metals, including Zn2+, Co2+, Ni2+, Cu2+, and Hg2+ is demonstrated. Inhibition by Zn2 of the response of NH4+ is partially reversed by increased concentrations of Ca2+. Attraction of L-phenylalanine, L-tyrosine, L-tryptophan, their structural analogs, and other compounds has been quantified using a capillary assay. Radiolabeled L-phenylalanine was used as a ligand to investigate algal binding and uptake. No internalization of the amino acid by D. tertiolectra occurred, even after 3 hr. Specific binding of 3H-L-phenylalanine was below 100 molecules per alga at 10-8 M L-phenylalanine. No evidence for the alteration of L-phenylalnine by D. tertiolecta was found following 22 hr incubation with the substrate in light or darkness. To further probe the molecular components of the chemosensory system of D. tertiolecta, a procedure for isolation and purification of trinitrobenzene sulfonic acid (TNBS)-labeled plasma membrane vesicles was developed. Plasma membrane purity was assessed by criteria of chlorophyll content, succinic dehydrogenase activity and protein pattern

  2. Lysophosphatidic acid is a chemoattractant for Dictyostelium discoideum amoebae.

    OpenAIRE

    Jalink, K.; Moolenaar, W H; Duijn, B., Van

    1993-01-01

    The naturally occurring phospholipid lysophosphatidic acid (LPA) can induce a number of physiological responses in vertebrate cells, including platelet aggregation, smooth muscle contraction, and fibroblast proliferation. LPA is thought to activate a specific G-protein-coupled receptor, thereby triggering classic second messenger pathways such as stimulation of phospholipase C and inhibition of adenylate cyclase. Here we report that 1-oleoyl-LPA, at submicromolar concentrations, evokes a chem...

  3. Chemoattraction of Ichthyophthirius multifiliis (Ciliophora) theronts to host molecules

    DEFF Research Database (Denmark)

    Buchmann, Kurt; Nielsen, Michael Engelbrecht

    1999-01-01

    not attract theronts. In contrast, sera and mucus from a range of teleosts (including marine fish) were effective attractants. Fractionation by gel filtration of fish serum allowed determination of the molecular size of the attracting proteins. Further biochemical studies suggested the...

  4. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B;

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the...... circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP)....

  5. Slime mould solves maze in one pass ... assisted by gradient of chemo-attractants

    OpenAIRE

    Adamatzky, Andrew

    2011-01-01

    Plasmodium of Physarum polycephalum is a large cell, visible by unaided eye, which exhibits sophisticated patterns of foraging behaviour. The plasmodium's behaviour is well interpreted in terms of computation, where data are spatially extended configurations of nutrients and obstacles, and results of computation are networks of protoplasmic tubes formed by the plasmodium. In laboratory experiments and numerical simulation we show that if plasmodium of Physarum is inoculated in a maze's periph...

  6. Blow-up of weak solutions to a chemotaxis system under influence of an external chemoattractant

    Science.gov (United States)

    Black, Tobias

    2016-06-01

    We study nonnnegative radially symmetric solutions of the parabolic–elliptic Keller–Segel whole space system {ut=Δu‑∇ṡ(u∇v), x∈Rn,t>0,0=Δv+u+f(x), x∈Rn,t>0,u(x,0)=u0(x), x∈Rn, with prototypical external signal production f(x):={f0|x|‑α,if |x|⩽R‑ρ,0,if |x|⩾R+ρ, for R\\in (0,1) and ρ \\in ≤ft(0,\\frac{R}{2}\\right) , which is still integrable but not of class {{L}\\frac{n{2}+{δ0}}}≤ft({{{R}}n}\\right) for some {δ0}\\in ≤ft[0,1\\right) . For corresponding parabolic-parabolic Neumann-type boundary-value problems in bounded domains Ω , where f\\in {{L}\\frac{n{2}+{δ0}}}(Ω ){\\cap}{{C}α}(Ω ) for some {δ0}\\in (0,1) and α \\in (0,1) , it is known that the system does not emit blow-up solutions if the quantities \\parallel {{u}0}{{\\parallel}{{L\\frac{n{2}+{δ0}}}(Ω )}},\\parallel f{{\\parallel}{{L\\frac{n{2}+{δ0}}}(Ω )}} and \\parallel {{v}0}{{\\parallel}{{Lθ}(Ω )}} , for some θ >n , are all bounded by some \\varepsilon >0 small enough. We will show that whenever {{f}0}>\\frac{2n}α(n-2)(n-α ) and {{u}0}\\equiv {{c}0}>0 in \\overline{{{B}1}(0)} , a measure-valued global-in-time weak solution to the system above can be constructed which blows up immediately. Since these conditions are independent of R\\in (0,1) and c 0  >  0, we obtain a strong indication that in fact {δ0}=0 is critical for the existence of global bounded solutions under a smallness conditions as described above.

  7. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43

    OpenAIRE

    Maslowski, Kendle M.; Vieira, Angelica T.; Ng, Aylwin; Kranich, Jan; Sierro, Frederic; Yu, Di; Schilter, Heidi C; Rolph, Michael S.; Mackay, Fabienne; Artis, David; Xavier, Ramnik J.; Teixeira, Mauro M; Mackay, Charles R.

    2009-01-01

    The immune system responds to pathogens by a variety of pattern recognition molecules such as the Toll-like receptors (TLRs), which promote recognition of dangerous foreign pathogens. However, recent evidence indicates that normal intestinal microbiota might also positively influence immune responses, and protect against the development of inflammatory diseases1,2. One of these elements may be short-chain fatty acids (SCFAs), which are produced by fermentation of dietary fibre by intestinal m...

  8. Urocanic acid is a major chemoattractant for the skin-penetrating parasitic nematode Strongyloides stercoralis

    OpenAIRE

    Safer, Daniel; Brenes, Mario; Dunipace, Seth; Schad, Gerhard

    2007-01-01

    Host-seeking behavior by parasitic nematodes relies heavily on chemical cues emanating from potential hosts. Nonspecific cues for Strongyloides stercoralis, a nematode that infects humans and a few other mammals, include carbon dioxide and sodium chloride; however, the characteristic species specificity of this parasite suggested the existence of other, more specific cues. Here we show that the infective larva of S. stercoralis is strongly attracted to an extract of mammalian skin and that th...

  9. Effect of prostaglandin I2 analogs on monocyte chemoattractant protein-1 in human monocyte and macrophage.

    Science.gov (United States)

    Tsai, Ming-Kai; Hsieh, Chong-Chao; Kuo, Hsuan-Fu; Lee, Min-Sheng; Huang, Ming-Yii; Kuo, Chang-Hung; Hung, Chih-Hsing

    2015-08-01

    Chemokines play essential roles during inflammatory responses and in pathogenesis of inflammatory diseases. Monocyte chemotactic protein-1 (MCP-1) is a critical chemokine in the development of atherosclerosis and acute cardiovascular syndromes. MCP-1, by its chemotactic activity, causes diapedesis of monocytes from the lumen to the subendothelial space that leads to atherosclerotic plaque formation. Prostaglandin I2 (PGI2) analogs are used clinically for patients with pulmonary hypertension and have anti-inflammatory effects. However, little is known about the effect of PGI2 analogs on the MCP-1 production in human monocytes and macrophages. We investigated the effects of three conventional (iloprost, beraprost and treprostinil) and one new (ONO-1301) PGI2 analogs, on the expression of MCP-1 expression in human monocytes and macrophages. Human monocyte cell line, THP-1 cell, was treated with PGI2 analogs after LPS stimulation. Supernatants were harvested to measure MCP-1 levels and measured by ELISA. To explore which receptors involved the effects of PGI2 analogs on the expression of MCP-1 expression, IP and EP, PPAR-α and PPAR-γ receptor antagonists were used. Forskolin, a cAMP activator, was used to further confirm the involvement of cAMP on MCP-1 production in human monocytes. Three PGI2 analogs suppressed LPS-induced MCP-1 production in THP-1 cells and THP-1-induced macrophages. Higher concentrations of ONO-1301 also had the suppressive effect. CAY 10449, an IP receptor antagonist, could reverse the effects on MCP-1 production of iloprost on THP-1 cells. Other reported PGI2 receptor antagonists including EP1, EP2, EP4, PPAR-α and PPAR-γ antagonists could not reverse the effect. Forskolin, a cAMP activator, also suppressed MCP-1 production in THP-1 cells. PGI2 analogs suppressed LPS-induced MCP-1 production in human monocytes and macrophages via the IP receptor and cAMP pathway. The new PGI2 analog (ONO-1301) was not better than conventional PGI2 analog in the suppression of MCP-1 production in human monocytes. PMID:25154882

  10. Monocyte chemoattractant protein-1 (MCP-1 regulates macrophage cytotoxicity in abdominal aortic aneurysm.

    Directory of Open Access Journals (Sweden)

    Qiwei Wang

    Full Text Available AIMS: In abdominal aortic aneurysm (AAA, macrophages are detected in the proximity of aortic smooth muscle cells (SMCs. We have previously demonstrated in a murine model of AAA that apoptotic SMCs attract monocytes and other leukocytes by producing MCP-1. Here we tested whether infiltrating macrophages also directly contribute to SMC apoptosis. METHODS AND RESULTS: Using a SMC/RAW264.7 macrophage co-culture system, we demonstrated that MCP-1-primed RAWs caused a significantly higher level of apoptosis in SMCs as compared to control macrophages. Next, we detected an enhanced Fas ligand (FasL mRNA level and membrane FasL protein expression in MCP-1-primed RAWs. Neutralizing FasL blocked SMC apoptosis in the co-culture. In situ proximity ligation assay showed that SMCs exposed to primed macrophages contained higher levels of receptor interacting protein-1 (RIP1/Caspase 8 containing cell death complexes. Silencing RIP1 conferred apoptosis resistance to SMCs. In the mouse elastase injury model of aneurysm, aneurysm induction increased the level of RIP1/Caspase 8 containing complexes in medial SMCs. Moreover, TUNEL-positive SMCs in aneurysmal tissues were frequently surrounded by CD68(+/FasL(+ macrophages. Conversely, elastase-treated arteries from MCP-1 knockout mice display a reduction of both macrophage infiltration and FasL expression, which was accompanied by diminished apoptosis of SMCs. CONCLUSION: Our data suggest that MCP-1-primed macrophages are more cytotoxic. MCP-1 appears to modulate macrophage cytotoxicity by increasing the level of membrane bound FasL. Thus, we showed that MCP-1-primed macrophages kill SMCs through a FasL/Fas-Caspase8-RIP1 mediated mechanism.

  11. Neural regeneration protein is a novel chemoattractive and neuronal survival-promoting factor

    International Nuclear Information System (INIS)

    Neurogenesis and neuronal migration are the prerequisites for the development of the central nervous system. We have identified a novel rodent gene encoding for a neural regeneration protein (NRP) with an activity spectrum similar to the chemokine stromal-derived factor (SDF)-1, but with much greater potency. The Nrp gene is encoded as a forward frameshift to the hypothetical alkylated DNA repair protein AlkB. The predicted protein sequence of NRP contains domains with homology to survival-promoting peptide (SPP) and the trefoil protein TFF-1. The Nrp gene is first expressed in neural stem cells and expression continues in glial lineages. Recombinant NRP and NRP-derived peptides possess biological activities including induction of neural migration and proliferation, promotion of neuronal survival, enhancement of neurite outgrowth and promotion of neuronal differentiation from neural stem cells. NRP exerts its effect on neuronal survival by phosphorylation of the ERK1/2 and Akt kinases, whereas NRP stimulation of neural migration depends solely on p44/42 MAP kinase activity. Taken together, the expression profile of Nrp, the existence in its predicted protein structure of domains with similarities to known neuroprotective and migration-inducing factors and the high potency of NRP-derived synthetic peptides acting in femtomolar concentrations suggest it to be a novel gene of relevance in cellular and developmental neurobiology

  12. Chemoattractant-Regulated Mobilization of a Novel Intracellular Compartment in Human Neutrophils

    Science.gov (United States)

    Borregaard, N.; Miller, L. J.; Springer, T. A.

    1987-09-01

    A novel mobilizable intracellular compartment was identified in human neutrophils by latent alkaline phosphatase activity. This compartment is mobilized to the plasma membrane much more readily than any identified granule subset and has kinetics of up-regulation in the membrane similar to those reported for a variety of receptor proteins. Triton X-100 permeabilization of both intact human neutrophils and subcellular fractions obtained by density-gradient centrifugation revelaed that 70 percent of the alkaline phosphatase is located in an intracellular compartment distinct from primary, secondary, and gelatinase granules and from the plasma membrane. This compartment fully translocates to the plasma membrane after stimulation with nanomolar concentrations of the chemotactic peptide N-formylmethionylleucylphenylalanine.

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

    OpenAIRE

    Chong, Mei Sian; Lim,Jun Pei; Leung, Bernard; Ding, Yew Yoong; Tay, Laura; Ismail, Noor Hafizah; Yeo, Audrey; Yew,Suzanne

    2015-01-01

    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 a...

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

    OpenAIRE

    Lim JP; Leung BP; Ding YY; Tay L; NH Ismail; Yeo A; Yew S; Chong MS

    2015-01-01

    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 a...

  15. Neuropilin-1 mediates myeloid cell chemoattraction and influences retinal neuroimmune crosstalk

    Science.gov (United States)

    Dejda, Agnieszka; Mawambo, Gaelle; Cerani, Agustin; Miloudi, Khalil; Shao, Zhuo; Daudelin, Jean-Francois; Boulet, Salix; Oubaha, Malika; Beaudoin, Felix; Akla, Naoufal; Henriques, Sullivan; Menard, Catherine; Stahl, Andreas; Delisle, Jean-Sébastien; Rezende, Flavio A.; Labrecque, Nathalie; Sapieha, Przemyslaw

    2014-01-01

    Immunological activity in the CNS is largely dependent on an innate immune response and is heightened in diseases, such as diabetic retinopathy, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease. The molecular dynamics governing immune cell recruitment to sites of injury and disease in the CNS during sterile inflammation remain poorly defined. Here, we identified a subset of mononuclear phagocytes (MPs) that responds to local chemotactic cues that are conserved among central neurons, vessels, and immune cells. Patients suffering from late-stage proliferative diabetic retinopathy (PDR) had elevated vitreous semaphorin 3A (SEMA3A). Using a murine model, we found that SEMA3A acts as a potent attractant for neuropilin-1–positive (NRP-1–positive) MPs. These proangiogenic MPs were selectively recruited to sites of pathological neovascularization in response to locally produced SEMA3A as well as VEGF. NRP-1–positive MPs were essential for disease progression, as NRP-1–deficient MPs failed to enter the retina in a murine model of oxygen-induced retinopathy (OIR), a proxy for PDR. OIR mice with NRP-1–deficient MPs exhibited decreased vascular degeneration and diminished pathological preretinal neovascularization. Intravitreal administration of a NRP-1–derived trap effectively mimicked the therapeutic benefits observed in mice lacking NRP-1–expressing MPs. Our findings indicate that NRP-1 is an obligate receptor for MP chemotaxis, bridging neural ischemia to an innate immune response in neovascular retinal disease. PMID:25271625

  16. Identification of Serum Monocyte Chemoattractant Protein-1 and Prolactin as Potential Tumor Markers in Hepatocellular Carcinoma

    OpenAIRE

    Who-Whong Wang; Soo Fan Ang; Rajneesh Kumar; Charmain Heah; Andi Utama; Navessa Padma Tania; Huihua Li; Sze Huey Tan; Desmond Poo; Su Pin Choo; Wan Cheng Chow; Chee Kiat Tan; Han Chong Toh

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Ar...

  17. Identification of Serum Monocyte Chemoattractant Protein-1 and Prolactin as Potential Tumor Markers in Hepatocellular Carcinoma

    NARCIS (Netherlands)

    Wang, Who-Whong; Ang, Soo Fan; Kumar, Rajneesh; Heah, Charmain; Utama, Andi; Tania, Navessa Padma; Li, Huihua; Tan, Sze Huey; Poo, Desmond; Choo, Su Pin; Chow, Wan Cheng; Tan, Chee Kiat; Toh, Han Chong

    2013-01-01

    Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the

  18. The spectrum of resistance in SR/CR mice: the critical role of chemoattraction in the cancer/leukocyte interaction

    OpenAIRE

    Hicks Amy M; Sanders Anne M; Blanks Michael J; Stehle John R; Adams Jonathan; Riedlinger Gregory; Willingham Mark C; Cui Zheng

    2010-01-01

    Abstract Background Spontaneous regression/complete resistance (SR/CR) mice are a unique colony of mice that possess an inheritable, natural cancer resistance mediated primarily by innate cellular immunity. This resistance is effective against sarcoma 180 (S180) at exceptionally high doses and these mice remain healthy. Methods In this study, we challenged SR/CR mice with additional lethal transplantable mouse cancer cell lines to determine their resistance spectrum. The ability of these tran...

  19. Chemotaxis in Dictyostelium discoideum : Effect of Concanavalin A on Chemoattractant Mediated Cyclic GMP Accumulation and Light Scattering Decrease

    NARCIS (Netherlands)

    Mato, José M.; Haastert, Peter J.M. van; Krens, Frans A.; Konijn, Theo M.

    1978-01-01

    In cells of the cellular slime mold Dictyostelium discoideum concanavalin A (Con A), at a concentration of 100 µg per ml, inhibits folic acid and cyclic AMP induced decrease in light scattering. Con A has no effect on folic acid mediated cyclic GMP accumulation and increases cyclic AMP mediated cycl

  20. Reduction of Monocyte Chemoattractant Protein-1 Expression in Rheumatoid Arthritis Rat Joints with Light-Emitting Diode Phototherapy

    OpenAIRE

    Kuboyama, Noboru; Abiko, Yoshimitsu

    2012-01-01

    Background: Rheumatoid arthritis (RA) is a systemic autoimmune disorder that involves inflammation and pain of the joints. Light-Emitting Diode (LED) irradiation is being evaluated for treating RA; however, the mechanism is unclear. Monocyte chemotaxis protein (MCP)-1 is a key chemokine in the inflammatory status of RA, and MCP-1 levels in plasma are described as a marker for joint inflammation in RA.

  1. MIP-3alpha/CCL20 in renal transplantation and its possible involvement as dendritic cell chemoattractant in allograft rejection.

    Science.gov (United States)

    Woltman, Andrea M; de Fijter, Johan W; van der Kooij, Sandra W; Jie, Kim E; Massacrier, Catherine; Caux, Christophe; Daha, Mohamed R; van Kooten, Cees

    2005-09-01

    Graft-infiltrating dendritic cells (DC) and alloreactive T lymphocytes play a critical role in renal allograft rejection. Renal proximal tubular epithelial cells (TEC) are considered as active players in the attraction of leukocytes during renal inflammatory responses. Macrophage inflammatory protein (MIP)-3alpha/CCL20 is a major chemokine expressed by epithelial cells that attracts immature DC. In the present study, we present evidence that also the transplanted kidney can be a major source of MIP-3alpha/CCL20. Renal transplant recipients with rejection showed significantly increased excretion of urinary MIP-3alpha/CCL20 that correlated with transplant function. The tubular staining for MIP-3alpha/CCL20 in renal biopsies of patients with rejection as well as in vitro studies with primary human TEC indicated that TEC might be responsible for the increased urinary MIP-3alpha/CCL20. Furthermore, MIP-3alpha/CCL20 produced by activated TEC was highly potent in the attraction of CD1a+CD34+-derived DC precursors. These data suggest a role for MIP-3alpha/CCL20 in amplification of the immune response during renal allograft rejection by attraction of CCR6+ inflammatory cells, which may include DC, to the site of inflammation. PMID:16095490

  2. Chemoattractive capacity of different lengths of nerve fragments bridging regeneration chambers for the repair of sciatic nerve defects

    OpenAIRE

    Zhang, Jiren; Wang, Yubo; Zhang, Jincheng

    2012-01-01

    A preliminary study by our research group showed that 6-mm-long regeneration chamber bridging is equivalent to autologous nerve transplantation for the repair of 12-mm nerve defects. In this study, we compared the efficacy of different lengths (6, 8, 10 mm) of nerve fragments bridging 6-mm regeneration chambers for the repair of 12-mm-long nerve defects. At 16 weeks after the regeneration chamber was implanted, the number, diameter and myelin sheath thickness of the regenerated nerve fibers, ...

  3. Urinary monocyte chemoattractant protein-1 and hepcidin and early diabetic nephropathy lesions in type 1 diabetes mellitus

    OpenAIRE

    Fufaa, Gudeta D.; Weil, E. Jennifer; Nelson, Robert G; Hanson, Robert L.; Knowler, William C.; Rovin, Brad H; Wu, Haifeng; Jon B Klein; Mifflin, Theodore E.; Feldman, Harold I.; Vasan, Ramachandran S.; Kimmel, Paul L.; Kusek, John W.; Mauer, Michael; Zinman, Bernard

    2015-01-01

    …the residual risk of renal disease progression in patients with diabetic nephropathy is still extremely high despite current optimal treatment; innate immunity, MCP-1 and macrophage tissue infiltration seem very promising targets for future treatment of diabetic nephropathy on top of the standard of care with RAAS inhibition.

  4. The Therapeutic Role of Monocyte Chemoattractant Protein-1 in a Renal Tissue Engineering Strategy for Diabetic Patients

    OpenAIRE

    Yin, Hao; Gao, Ming; Leoni, Lara; Han, Huifang; Zhang, Xing; Fu, Zhiren

    2013-01-01

    In this study we aim to boost the functional output of the intra-kidney islet transplantation for diabetic patients using a tissue engineered polymeric scaffold. This highly porous electrospun scaffold featured randomly distributed fibers composed of polycaprolactone (PCL) and poliglecaprone (PGC). It successfully sustained murine islets in vitro for up to 4 weeks without detected cytotoxicity. The in vivo study showed that the islet population proliferated by 89% within 12 weeks when they we...

  5. Adult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury

    OpenAIRE

    Neirinckx, Virginie; Agirman, Gulistan; Coste, Cécile; Marquet, Alice; Dion, Valérie; Rogister, Bernard; Franzen, Rachelle; Wislet, Sabine

    2015-01-01

    Introduction Stem cells from adult tissues were considered for a long time as promising tools for regenerative therapy of neurological diseases, including spinal cord injuries (SCI). Indeed, mesenchymal (MSCs) and neural crest stem cells (NCSCs) together constitute the bone marrow stromal stem cells (BMSCs) that were used as therapeutic options in various models of experimental SCI. However, as clinical approaches remained disappointing, we thought that reducing BMSC heterogeneity should be a...

  6. Production of interleukin 8 and Monocyte chemoattractant protein-1 on human umbilical vein endothelial cells stimulated by Porphyromonas gingivalis with different fimA genotypes

    Institute of Scientific and Technical Information of China (English)

    Shu-Yu Cai; Song Ge

    2015-01-01

    Objective:To study the effects ofPorphyromonas gingivalis (Pg) with different fimA genotypes on IL-8 and MCP-1 produciton by human umbilical vein endothelial cells and to reveal their the possible role in the development of atherosclerosis.Methods: Pg with different fimA genotypes were cultured with anaerobic and were used to infect HUVEC cells at a MOI of 100. Supernatant IL-8 and MCP-1 contents of cultured HUVEC cells after Pg stimulation at 2 h, 6 h and 24 h, respectively, were detected by ELISA.Results: Supernatant IL-8 and MCP-1 contents of HUVEC cells after Pg stimulation at 2 h, 6 h and 24 h were significantly higher than those in un-stimulation groups (P<0.05), and supernatant IL-8 and MCP-1 contents of HUVEC cells after II fimA and IV fimA genotypes Pg stimulation were significantly higher than those after I fimA genotypes Pg stimulation (P<0.05). Also, supernatant IL-8 and MCP-1 contents of HUVEC cells after II fimA genotypes Pg stimulation were significantly higher than those after IV fimA genotypes Pg stimulation.Conclusion: Pg with II fimA genotypes show a stronger ability to stimulate HUVEC cells to express IL-8 and MCP-1,which may lead a functional disorder of vascular endothelial.

  7. Stromal cell derived factor-1α (SDF-1α) directed chemoattraction of transiently CXCR4 overexpressing mesenchymal stem cells into functionalized three-dimensional biomimetic scaffolds

    DEFF Research Database (Denmark)

    Thieme, S; Ryser, Martin; Gentsch, Marcus;

    2009-01-01

    Three-dimensional (3D) bone substitute material should not only serve as scaffold in large bone defects but also attract mesenchymal stem cells, a subset of bone marrow stromal cells (BMSCs) that are able to form new bone tissue. An additional crucial step is to attract BMSCs from the surface int...

  8. Role of p38 Mitogen-activated Protein Kinase in Mediating Monocyte Chemoattractant Protein-1 in Human Umbilical Vein Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    李艳波; 邓华聪; 郑丹; 李呼伦

    2004-01-01

    @@ p38 mitogen-activated protein kinase (p38MAPK)is a member of the mitogen-activated protein kinase (MAPK) family. p38MAPK pathway is one of the most widely studied signaling pathways involved in the transduction of intracellular signals including survival, growth,differentiation and death.

  9. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma.

    Science.gov (United States)

    Lee, Yong Gyu; Jeong, Jong Jin; Nyenhuis, Sharmilee; Berdyshev, Evgeny; Chung, Sangwoon; Ranjan, Ravi; Karpurapu, Manjula; Deng, Jing; Qian, Feng; Kelly, Elizabeth A B; Jarjour, Nizar N; Ackerman, Steven J; Natarajan, Viswanathan; Christman, John W; Park, Gye Young

    2015-06-01

    Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. PMID:25360868

  10. Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line

    DEFF Research Database (Denmark)

    Benfield, T L; Lundgren, Bettina; Shelhamer, J H;

    1999-01-01

    BACKGROUND: The major surface glycoprotein (MSG) is an abundant, immunogenic glycoprotein located on the surface of Pneumocystis carinii. Little is known about the proinflammatory effects of MSG. DESIGN: We have investigated the effect of human MSG on the secretion of the chemokines interleukin 8...... in response to MSG stimulation occurred by 4 h and persisted throughout 8 h of stimulation. CONCLUSION: These findings suggest that MSG can alter alveolar epithelial cytokine release and may be capable of modulating the local inflammatory response in this manner....

  11. 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...

  12. The Effects of Two Chemo-attractants and Different First Feeds on the Growth Performances of African Catfish (Clarias gariepinus, Burchell, 1822) at Different Larval Stages

    OpenAIRE

    Yilmaz, Erdal

    2005-01-01

    In this study, 4 days old African catfish larvae were fed with trout starter diet, minced beef liver and fresh water mussel, dried tubifex, DL-alanine and betaine supplemented trout starter, artemia nauplii and a combined diet consisting of boiled chicken egg yolk, minced mussel and dried tubifex as the first feed after yolk absorption for a week. At the end of the first period, it was observed that DL-alanine and betaine supplementation did not improve the larval growth and survival compared...

  13. Dermatan sulfate reduces monocyte chemoattractant protein 1 and TGF-β production, as well as macrophage recruitment and myofibroblast accumulation in mice with unilateral ureteral obstruction

    Directory of Open Access Journals (Sweden)

    C.L.R. Belmiro

    2011-07-01

    Full Text Available Selectins play an essential role in most inflammatory reactions, mediating the initial leukocyte-rolling event on activated endothelium. Heparin and dermatan sulfate (DS bind and block P- and L-selectin function in vitro. Recently, we reported that subcutaneous administration of DS inhibits colon inflammation in rats by reducing macrophage and T-cell recruitment and macrophage activation. In the present study, we examined the effect of porcine intestinal mucosa DS on renal inflammation and fibrosis in mice after unilateral ureteral obstruction (UUO. Twenty-four adult male Swiss mice weighing 20-25 g were divided into 4 groups: group C (N = 6 was not subjected to any surgical manipulation; group SH (N = 6 was subjected to surgical manipulation but without ureter ligation; group UUO (N = 6 was subjected to unilateral ureteral obstruction and received no treatment; group UUO plus DS (N = 6 was subjected to UUO and received DS (4 mg/kg subcutaneously daily for 14 days. An immunoblot study was also performed for TGF-β. Collagen (stained area ~3700 µm², MCP-1 (stained area ~1700 µm², TGF-β (stained area ~13% of total area, macrophage (number of cells ~40, and myofibroblast (stained area ~1900 µm² levels were significantly (P < 0.05 higher in the UUO group compared to control. DS treatment significantly (P < 0.05 reduced the content of collagen (stained area ~700 µm², MCP-1 (stained area ~160 µm² and TGF-β (stained area ~5% of total area, in addition to myofibroblast (stained area ~190 µm² and macrophage (number of cells ~32 accumulation in the obstructed kidney. Overall, these results indicate that DS attenuates kidney inflammation by reducing macrophage recruitment, myofibroblast population and fibrosis in mice submitted to UUO.

  14. Xanthohumol from Hop (Humulus lupulus L.) Is an Efficient Inhibitor of Monocyte Chemoattractant Protein-1 and Tumor Necrosis Factor-a Release in LPS-Stimulated RAW 264.7 Mouse Macrophages and U937 Human Monocytes

    NARCIS (Netherlands)

    Lupinacci, E.; Meijerink, J.; Vincken, J.P.; Gabriele, B.; Gruppen, H.; Witkamp, R.F.

    2009-01-01

    Activated macrophages in adipose tissue play a major role in the chronic inflammatory process that has been linked to the complications of overweight and obesity. The hop plant (Humulus lupulus L.) has been described to possess both anti-inflammatory and antidiabetic effects. In the present study, t

  15. Candesartan ameliorates acute myocardial infarction in rats through inducible nitric oxide synthase, nuclear factor‑κB, monocyte chemoattractant protein‑1, activator protein‑1 and restoration of heat shock protein 72.

    Science.gov (United States)

    Lin, Xuefeng; Wu, Min; Liu, Bo; Wang, Junkui; Guan, Gongchang; Ma, Aiqun; Zhang, Yong

    2015-12-01

    Candesartan, an angiotensin II type 1 receptor antagonist, has a variety of biological activities, including antioxidant, anti‑inflammatory and anticancer activities, with specific pharmacological effects. The present study investigated the mechanisms and protective effect of candesartan on acute myocardial infarction in rats. Male Wistar rats (8‑week‑old) were induced as a model of acute myocardial infarction and treated with candesartan (0.25 mg/kg) for 2 weeks. The present study first measured the activities of casein kinase (CK), the MB isoenzyme of creatine kinase (CK‑MB) and lactate dehydrogenase (LDH), the level of cardiac troponin T (cTnT) and infarct size. Subsequently, western blot analysis was performed to analyze the protein expression levels of inducible nitric oxide synthase (iNOS) and heat shock protein 72 (HSP72) in the rats. An enzyme linked immunosorbent assay was used to detect iNOS and nuclear factor‑κB (NF‑κB) activity. In addition, gene expression levels of monocyte chemotactic protein‑1 (MCP‑1) and activating protein‑1 (AP‑1) were determined using reverse transcription‑quantitative polymerase chain reaction analysis. Finally, the activities of caspase‑3 and caspase‑9 were examined using colorimetric assay kits. In the serum of the rat model of acute myocardial infarction, candesartan significantly increased the activities of CK, CK‑MB and LDH, and the level of cTnT. The infarction size was perfected by candesartan treatment. Candesartan significantly reduced the protein expression and activity of iNOS, the activity of NF‑κB p65, and the gene expression levels of MCP‑1 and AP‑1 in the rat model of acute myocardial infarction. Candesartan increased the protein expression of HSP‑72 in the acute myocardial infarction rat model. However, candesartan did not effect the levels of caspase‑3 or caspase‑9 in the rat model of acute myocardial infarction. These results suggested that candesartan ameliorates acute myocardial infarction in rats through iNOS, NF‑κB, MCP‑1 and AP‑1, and the restoration of HSP72. PMID:26499133

  16. Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice

    Directory of Open Access Journals (Sweden)

    LaFerla Frank M

    2005-10-01

    Full Text Available Abstract Background Alzheimer's disease is a complex neurodegenerative disorder characterized pathologically by a temporal and spatial progression of beta-amyloid (Aβ deposition, neurofibrillary tangle formation, and synaptic degeneration. Inflammatory processes have been implicated in initiating and/or propagating AD-associated pathology within the brain, as inflammatory cytokine expression and other markers of inflammation are pronounced in individuals with AD pathology. The current study examines whether inflammatory processes are evident early in the disease process in the 3xTg-AD mouse model and if regional differences in inflammatory profiles exist. Methods Coronal brain sections were used to identify Aβ in 2, 3, and 6-month 3xTg-AD and non-transgenic control mice. Quantitative real-time RT-PCR was performed on microdissected entorhinal cortex and hippocampus tissue of 2, 3, and 6-month 3xTg-AD and non-transgenic mice. Microglial/macrophage cell numbers were quantified using unbiased stereology in 3xTg-AD and non-transgenic entorhinal cortex and hippocampus containing sections. Results We observed human Aβ deposition at 3 months in 3xTg-AD mice which is enhanced by 6 months of age. Interestingly, we observed a 14.8-fold up-regulation of TNF-α and 10.8-fold up-regulation of MCP-1 in the entorhinal cortex of 3xTg-AD mice but no change was detected over time in the hippocampus or in either region of non-transgenic mice. Additionally, this increase correlated with a specific increase in F4/80-positive microglia and macrophages in 3xTg-AD entorhinal cortex. Conclusion Our data provide evidence for early induction of inflammatory processes in a model that develops amyloid and neurofibrillary tangle pathology. Additionally, our results link inflammatory processes within the entorhinal cortex, which represents one of the earliest AD-affected brain regions.

  17. Identification of 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (setipiprant/ACT-129968), a potent, selective, and orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist.

    Science.gov (United States)

    Fretz, Heinz; Valdenaire, Anja; Pothier, Julien; Hilpert, Kurt; Gnerre, Carmela; Peter, Oliver; Leroy, Xavier; Riederer, Markus A

    2013-06-27

    Herein we describe the discovery of the novel CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 28 (setipiprant/ACT-129968), a clinical development candidate for the treatment of asthma and seasonal allergic rhinitis. A lead optimization program was started based on the discovery of the recently disclosed CRTh2 antagonist 2-(2-benzoyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 5. An already favorable and druglike profile could be assessed for lead compound 5. Therefore, the lead optimization program mainly focused on the improvement in potency and oral bioavailability. Data of newly synthesized analogs were collected from in vitro pharmacological, physicochemical, in vitro ADME, and in vivo pharmacokinetic studies in the rat and the dog. The data were then analyzed using a traffic light selection tool as a visualization device in order to evaluate and prioritize candidates displaying a balanced overall profile. This data-driven process and the excellent results of the PK study in the rat (F = 44%) and the dog (F = 55%) facilitated the identification of 28 as a potent (IC50 = 6 nM), selective, and orally available CRTh2 antagonist. PMID:23721423

  18. Chemotaxis of horse polymorphonuclear leukocytes to N-formyl-L-methionyl-L-leucyl-L-phenylalanine.

    Science.gov (United States)

    Zinkl, J G; Brown, P D

    1982-04-01

    Horse polymorphonuclear leukocytes (PMN) isolated from horse blood by sedimentation and isotonic lysis and having about 25% accompanying lymphocytes were as effective at chemotaxis as nearly pure PMN isolated by density gradient techniques. N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), used as a representative of the formylmethionyl peptides (produced by prokaryocytic organisms), was effective as a chemoattractant only at the high concentration of 10(-4) M. When serum was preincubated with FMLP at concentrations as low as 10(-8) M, the serum attracted horse PMN. This activity was not generated when heat-inactivated (56 to 60 C for 30 minutes) serum was used. A combination of FMLP and zymosan was no more effective than zymosan alone in generating serum chemoattractants. The results of this study indicate that the FMLP is a weak chemoattractant for horse PMN, but that FMLP has the capability similar to that of zymosan to activate complement to produce PMN chemoattractants. PMID:7073083

  19. On-Chip Open Microfluidic Devices for Chemotaxis Studies

    OpenAIRE

    Wright, Gus A.; Costa, Lino; Terekhov, Alexander; Jowhar, Dawit; Hofmeister, William; Janetopoulos, Christopher

    2012-01-01

    Microfluidic devices can provide unique control over both the chemoattractant gradient and the migration environment of the cells. Our work incorporates laser-machined micro and nanofluidic channels into bulk fused silica and cover slip-sized silica wafers. We have designed “open” chemotaxis devices that produce passive chemoattractant gradients without an external micropipette system. Since the migration area is unobstructed, cells can be easily loaded and strategically placed into the devic...

  20. Regulation of cell proliferation and migration in glioblastoma: New therapeutic approach

    Directory of Open Access Journals (Sweden)

    YangjinKim

    2013-03-01

    biophysical properties of cells, dynamics of the core control system, and microenvironment as well as glucose injection methods. We developed a new type of therapeutic approaches: effective injection of chemoattractant for bring invasive cells back to the surgical site after initial surgery, followed by glucose injection at the same location. The model suggests that a good combination of chemoattractant and glucose injection at appropriate time frames may lead to an effective therapeutic strategy of eradicating tumor cells.

  1. The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis

    OpenAIRE

    Wang, Fei

    2009-01-01

    Chemotaxis—the directed movement of cells in a gradient of chemoattractant—is essential for neutrophils to crawl to sites of inflammation and infection and for Dictyostelium discoideum (D. discoideum) to aggregate during morphogenesis. Chemoattractant-induced activation of spatially localized cellular signals causes cells to polarize and move toward the highest concentration of the chemoattractant. Extensive studies have been devoted to achieving a better understanding of the mechanism(s) use...

  2. Suppression of polymorphonuclear leucocyte chemotaxis by Pseudomonas aeruginosa elastase in vitro: a study of the mechanisms and the correlation with ring abscess in pseudomonal keratitis.

    OpenAIRE

    Ijiri, Y; Matsumoto, K.; Kamata, R; Nishino, N.; Okamura, R.; Kambara, T; Yamamoto, T.

    1994-01-01

    Bacteria, or the culture supernatants of an elastase non-producing strain of Pseudomonas aeruginosa, elicited a chemotactic response from polymorphonuclear leucocytes (PMN) in vitro. The chemoattractive capacity was diminished under the presence of Boc-Phe-Leu-Phe-Leu-Phe, a receptor antagonist of N-formyl-Met-Leu-Phe (fMLP) which is a bacterial chemotactic peptide to PMN. This indicated that the chemoattractant derived from Pseudomonas aeruginosa was a fMLP-like molecule(s). In contrast, cul...

  3. Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease

    OpenAIRE

    Noah P Zimmerman; Vongsa, Rebecca A.; Wendt, Michael K; Michael B Dwinell

    2008-01-01

    Chemokines, a large family of small chemoattractive cytokines, and their receptors play an integral role in the regulation of the immune response and homeostasis. The ability of chemokines to attract specific populations of immune cells sets them apart from other chemoattractants. Chemokines produced within the gastrointestinal mucosa, are critical players in directing the balance between physiological and pathophysiological inflammation in health, inflammatory bowel disease and the progressi...

  4. The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity.

    Science.gov (United States)

    Kehrl, John H

    2016-08-15

    Leukocyte chemoattractant receptors are members of the G-protein coupled receptor (GPCR) family. Signaling downstream of these receptors directs the localization, positioning and homeostatic trafficking of leukocytes; as well as their recruitment to, and their retention at, inflammatory sites. Ligand induced changes in the molecular conformation of chemoattractant receptors results in the engagement of heterotrimeric G-proteins, which promotes α subunits to undergo GTP/GDP exchange. This results in the functional release of βγ subunits from the heterotrimers, thereby activating downstream effector molecules, which initiate leukocyte polarization, gradient sensing, and directional migration. Pertussis toxin ADP ribosylates Gαi subunits and prevents chemoattractant receptors from triggering Gαi nucleotide exchange. The use of pertussis toxin revealed the essential importance of Gαi subunit nucleotide exchange for chemoattractant receptor signaling. More recent studies have identified a range of regulatory mechanisms that target these receptors and their associated heterotrimeric G-proteins, thereby helping to control the magnitude, kinetics, and duration of signaling. A failure in these regulatory pathways can lead to impaired receptor signaling and immunopathology. The analysis of mice with targeted deletions of Gαi isoforms as well as some of these G-protein regulatory proteins is providing insights into their roles in chemoattractant receptor signaling. PMID:27071343

  5. Aggregation Patterns in Stressed Bacteria

    CERN Document Server

    Tsimring, L S; Aranson, I S; Ben-Jacob, E; Cohen, I; Shochet, O; Tsimring, Lev; Levine, Herbert; Aranson, Igor; Ben-Jacob, Eshel; Cohen, Inon; Shochet, Ofer

    1995-01-01

    We study the formation of spot patterns seen in a variety of bacterial species when the bacteria are subjected to oxidative stress due to hazardous byproducts of respiration. Our approach consists of coupling the cell density field to a chemoattractant concentration as well as to nutrient and waste fields. The latter serves as a triggering field for emission of chemoattractant. Important elements in the proposed model include the propagation of a front of motile bacteria radially outward form an initial site, a Turing instability of the uniformly dense state and a reduction of motility for cells sufficiently far behind the front. The wide variety of patterns seen in the experiments is explained as being due the variation of the details of the initiation of the chemoattractant emission as well as the transition to a non-motile phase.

  6. Steady-State Chemotactic Response in E. coli

    CERN Document Server

    Kafri, Yariv

    2007-01-01

    The bacterium E. coli maneuvers itself to regions with high chemoattractant concentrations by performing two stereotypical moves: `runs', in which it moves in near straight lines, and `tumbles', in which it does not advance but changes direction randomly. The duration of each move is stochastic and depends upon the chemoattractant concentration experienced in the recent past. We relate this stochastic behavior to the steady-state density of a bacterium population, and we derive the latter as a function of chemoattractant concentration. In contrast to earlier treatments, here we account for the effects of temporal correlations and variable tumbling durations. A range of behaviors obtains, that depends subtly upon several aspects of the system - memory, correlation, and tumbling stochasticity in particular.

  7. Auto-chemotactic micro-swimmer suspensions: modeling, analysis and simulations

    CERN Document Server

    Lushi, Enkeleida; Shelley, Michael J

    2013-01-01

    Microorganisms can preferentially orient and move along gradients of a chemo-attractant (i.e., chemotax) while colonies of many microorganisms can collectively undergo complex dynamics in response to chemo-attractants that they themselves produce. For colonies or groups of micro-swimmers we investigate how an "auto-chemotactic" response that should lead to swimmer aggregation is affected by the non-trivial fluid flows that are generated by collective swimming. For this, we consider chemotaxis models based upon a hydrodynamic theory of motile suspensions that are fully coupled to chemo-attractant production, transport, and diffusion. Linear analysis of isotropically ordered suspensions reveals both an aggregative instability due to chemotaxis that occurs independently of swimmer type, and a hydrodynamic instability when the swimmers are "pushers". Nonlinear simulations show nonetheless that hydrodynamic interactions can significantly modify the chemotactically-driven aggregation dynamics in suspensions of "pus...

  8. Ti plasmid-specified chemotaxis of Agrobacterium tumefaciens C58C1 toward vir-inducing phenolic compounds and soluble factors from monocotyledonous and dicotyledonous plants.

    OpenAIRE

    Ashby, A M; Watson, M D; Loake, G J; Shaw, C H

    1988-01-01

    Twelve phenolic compounds with related structures were analyzed for their ability to act as chemoattractants for Agrobacterium tumefaciens C58C1 and as inducers of the Ti plasmid virulence operons. The results divided the phenolic compounds into three groups: compounds that act as strong vir inducers and are chemoattractants for A. tumefaciens C58C1 harboring the nopaline Ti plasmid pDUB1003 delta 31, but not the isogenic cured strain; compounds that are at best weak vir inducers and are weak...

  9. The stability of a homogeneous suspension of chemotactic bacteria

    Science.gov (United States)

    Subramanian, G.; Koch, Donald L.; Fitzgibbon, Sean R.

    2011-04-01

    The linear stability of a homogeneous dilute suspension of chemotactic bacteria in a constant chemoattractant gradient is analyzed. The bacteria execute a run-and-tumble motion, typified by the species E. coli, wherein periods of smooth swimming (runs) are interrupted by abrupt uncorrelated changes in swimming direction (tumbles). Bacteria tumble less frequently when swimming toward regions of higher chemoattractant concentration, leading to a mean bacterial orientation and velocity in the base state. The stability of an unbounded suspension, both with and without a chemoattractant, is controlled by coupled long wavelength perturbations of the fluid velocity and bacterial orientation fields. In the former case, the most unstable perturbations have their wave vector oriented along the chemoattractant gradient. Chemotaxis reduces the critical bacteria concentration, for the onset of collective swimming, compared with that predicted by Subramanian and Koch ["Critical bacterial concentration for the onset of collective swimming," J. Fluid Mech. 632, 359 (2009)] in the absence of a chemoattractant. A part of this decrease may be attributed to the increase in the mean tumbling time in the presence of a chemoattractant gradient. A second destabilizing influence comes from the ability of the shearing motion, associated with a velocity perturbation in which the velocity and chemical gradients are aligned, to sweep prealigned bacteria into the local extensional quadrant thereby creating a stronger destabilizing active stress than in an initially isotropic suspension. The chemoattractant gradient also fundamentally alters the unstable spectrum for any finite wavenumber. In suspensions of bacteria that do not tumble, Saintillan and Shelley ["Instabilities and pattern formation in active particle suspensions: Kinetic theory and continuum simulations," Phys. Rev. Lett. 100, 178103 (2008); "Instabilities, pattern formation and mixing in active suspensions," Phys. Fluids 20

  10. High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A

    NARCIS (Netherlands)

    Toelle, Markus; Huang, Tao; Schuchardt, Mirjam; Jankowski, Vera; Pruefer, Nicole; Jankowski, Joachim; Tietge, Uwe J. F.; Zidek, Walter; van der Giet, Markus

    2012-01-01

    Aims High-density lipoprotein (HDL) is known to have potent anti-inflammatory properties. Monocyte chemoattractant protein-1 is an important pro-inflammatory cytokine in early atherogenesis. There is evidence that HDL can lose its protective function during inflammatory disease. In patients with end

  11. Early Embryonic Vascular Patterning by Matrix-Mediated Paracrine Signalling: A Mathematical Model Study

    OpenAIRE

    Köhn-Luque, Alvaro; Back, Walter de; Starruß, Jörn; Mattiotti, Andrea; Deutsch, Andreas; Pérez-Pomares, José María; Herrero, Miguel A.

    2011-01-01

    During embryonic vasculogenesis, endothelial precursor cells of mesodermal origin known as angioblasts assemble into a characteristic network pattern. Although a considerable amount of markers and signals involved in this process have been identified, the mechanisms underlying the coalescence of angioblasts into this reticular pattern remain unclear. Various recent studies hypothesize that autocrine regulation of the chemoattractant vascular endothelial growth factor (VEGF) is responsible for...

  12. Dual role of CCR2 during initiation and progression of collagen-induced arthritis: Evidence for regulatory activity of CCR2(+) T cells

    Czech Academy of Sciences Publication Activity Database

    Brühl, H.; Čihák, J.; Schneider, M. A.; Plachý, Jiří; Rupp, T.; Wenzel, I.; Shakaremi, M.; Milz, J. W.; Stangassinger, M.; Schlöndorf, D.; Mack, M.

    2004-01-01

    Roč. 2004, č. 172 (2004), s. 890-898. ISSN 0022-1767 Institutional research plan: CEZ:AV0Z5052915 Keywords : Chemokine receptor 2 * monocyte chemoattractant protein * adjuvant-induced arthritis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 6.486, year: 2004

  13. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation

    DEFF Research Database (Denmark)

    Uller, Lena; Mathiesen, Jesper Mosolff; Alenmyr, Lisa;

    2007-01-01

    BACKGROUND: Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells...... inflammation even to the extent that this mechanism can explain the efficacy of ramatroban Udgivelsesdato: february...

  14. Physarum attraction: Why slime mold behaves as cats do?

    OpenAIRE

    Adamatzky, Andrew; Costello, Ben de Lacy

    2012-01-01

    We discuss potential chemical substances responsible for attracting acellular slime mold Physarun polycephalum to valerian root. The contributes toward fundamental research into pheromones and chemo-attracts of primitive organisms such as slime molds. The results show that significant information could be gained about the action of compounds on higher organisms.

  15. Chemotactic Behavior of Pathogenic and Nonpathogenic Leptospira Species

    OpenAIRE

    Lambert, Ambroise; Takahashi, Naoko; Charon, Nyles W.; Picardeau, Mathieu

    2012-01-01

    We have developed a capillary tube assay in combination with real-time PCR to quantitate the number of chemoattracted Leptospira cells. We identified Tween 80, glucose, sucrose, and pyruvate as attractants for Leptospira cells; amino acids and vitamin B12 were found to be nonchemotactic or weakly chemotactic. This assay has the general applicability to further our understanding of leptospiral chemotaxis.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2 have been strongly implicated in disease pathogenesis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on the CCL2-CCR2 axis are scarce in MS. We studied the...

  17. Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

    DEFF Research Database (Denmark)

    Jinquan, T; Frydenberg, Jane; Mukaida, N;

    1995-01-01

    activate neutrophils, whereas it induces chemotaxis, exocytosis, and a respiratory burst in neutrophils. To date, its functions on T lymphocytes have not been well established. We report here that recombinant human (rh)GRO-alpha is a potent chemoattractant for freshly isolated T lymphocytes, but not for...

  18. T cell behaviour in the pathogenesis of atopic dermatitis : how they get in and how to get them out

    NARCIS (Netherlands)

    Hijnen, D.J.

    2007-01-01

    AD skin is characterized by the infiltration of CD4+ T cells in the dermis and epidermis. Chemokines (chemoattracting cytokines), including TARC and CTACK play a pivotal role in the recruitment of T cells to the skin of AD patients. In chapter two we describe that the serum levels of chemokines TARC

  19. The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge

    DEFF Research Database (Denmark)

    Mamsen, Linn Salto; Brøchner, Christian Beltoft; Byskov, Anne Grete;

    2012-01-01

    system in this process. Sixteen human specimens, 5-14 wpc obtained from legal abortions were included. On serial paraffin sections, PGCs were detected immunohistochemically by expression of OCT4 and c-Kit, nerve fibers by ß-III-tubulin and stem cell factor (SCF) as a possible chemoattractive cue for PGC...

  20. Maze-solving by chemotaxis

    Science.gov (United States)

    Reynolds, A. M.

    2010-06-01

    Here, we report on numerical simulations showing that chemotaxis will take a body through a maze via the shortest possible route to the source of a chemoattractant. This is a robust finding that does not depend on the geometrical makeup of the maze. The predictions are supported by recent experimental studies which have shown that by moving down gradients in pH , a droplet of organic solvent can find the shortest of multiple possible paths through a maze to an acid-soaked exit. They are also consistent with numerical and experimental evidence that plant-parasitic nematodes take the shortest route through the labyrinth of air-filled pores within soil to preferred host plants that produce volatile chemoattractants. The predictions support the view that maze-solving is a robust property of chemotaxis and is not specific to particular kinds of maze or to the fractal structure of air-filled channels within soils.

  1. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device

    Science.gov (United States)

    Ayuso, Jose M.; Basheer, Haneen A.; Monge, Rosa; Sánchez-Álvarez, Pablo; Doblaré, Manuel; Shnyder, Steven D.; Vinader, Victoria; Afarinkia, Kamyar

    2015-01-01

    We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it. PMID:26444904

  2. Nutrient exposure of chemotactic organisms in small-scale turbulent flows

    Energy Technology Data Exchange (ETDEWEB)

    Munoz-Garcia, Javier [Systems Biology Ireland and Grupo Interdisciplinar de Sistemas Complejos (GISC), University College Dublin, Belfield, Dublin 4 (Ireland); Neufeld, Zoltan [School of Mathematical Sciences and Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin 4 (Ireland); Torney, Colin, E-mail: javiermunozgarcia@gmail.co [Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ 08544 (United States)

    2010-10-15

    Micro-organisms living in a turbulent fluid environment often use directed motility to locate regions of higher than average nutrient concentrations. Here, we consider a simple continuum model for the distribution of such chemotactic particles when the particles and the chemoattractant are both advected by a turbulent flow. The influence of chemotactic sensitivity on the spatial distribution of the particles is characterized for different types of advected chemical fields. Using an effective diffusion approximation, we obtain an analytical expression for the nutrient exposure resulting from the chemotactic activity of the particles, generalizing previous results obtained for the case of phototaxis in flows. We show that the biological advantage of chemotaxis in such systems is determined by the spatial variability of the averaged chemoattractant field and the effective diffusivity of the turbulent flow.

  3. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    Directory of Open Access Journals (Sweden)

    Ritankar Majumdar

    2016-01-01

    Full Text Available Leukotriene B4 (LTB4 is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments.

  4. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    Science.gov (United States)

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. PMID:26741884

  5. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device.

    Directory of Open Access Journals (Sweden)

    Jose M Ayuso

    Full Text Available We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC-19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC-19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.

  6. Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device.

    Science.gov (United States)

    Ayuso, Jose M; Basheer, Haneen A; Monge, Rosa; Sánchez-Álvarez, Pablo; Doblaré, Manuel; Shnyder, Steven D; Vinader, Victoria; Afarinkia, Kamyar; Fernández, Luis J; Ochoa, Ignacio

    2015-01-01

    We report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC-19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC-19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it. PMID:26444904

  7. Host microenvironment in breast cancer development: Inflammatory and immune cells in tumour angiogenesis and arteriogenesis

    International Nuclear Information System (INIS)

    Breast cancer progression is associated with and dependent upon robust neovascularization. It is becoming clear that tumour-associated 'normal' cells, such as immune/inflammatory cells, endothelial cells and stromal cells, conspire with cancer cells in promoting this process. In particular, infiltrating immune/inflammatory cells secrete a diverse repertoire of growth factors and proteases that enable them to enhance tumour growth by stimulating angiogenesis and, as we suggest here, by promoting 'tumour arteriogenesis' – enlargement of feeding vessels supplying the expanding tumour capillary bed. Macrophages and their chemoattractants (e.g. macrophage chemoattractant protein-1) are critical for the arteriogenic process in ischaemia, and probably also in breast neoplasia. A better understanding of these various cellular and molecular constituents of breast cancer neovascularization may be useful in designing more effective therapies

  8. Single-cell twitching chemotaxis in developing biofilms.

    Science.gov (United States)

    Oliveira, Nuno M; Foster, Kevin R; Durham, William M

    2016-06-01

    Bacteria form surface-attached communities, known as biofilms, which are central to bacterial biology and how they affect us. Although surface-attached bacteria often experience strong chemical gradients, it remains unclear whether single cells can effectively perform chemotaxis on surfaces. Here we use microfluidic chemical gradients and massively parallel automated tracking to study the behavior of the pathogen Pseudomonas aeruginosa during early biofilm development. We show that individual cells can efficiently move toward chemoattractants using pili-based "twitching" motility and the Chp chemosensory system. Moreover, we discovered the behavioral mechanism underlying this surface chemotaxis: Cells reverse direction more frequently when moving away from chemoattractant sources. These corrective maneuvers are triggered rapidly, typically before a wayward cell has ventured a fraction of a micron. Our work shows that single bacteria can direct their motion with submicron precision and reveals the hidden potential for chemotaxis within bacterial biofilms. PMID:27222583

  9. Individual-based models for bacterial chemotaxis in the diffusion asymptotics

    CERN Document Server

    Rousset, Mathias

    2011-01-01

    We discuss velocity-jump models for chemotaxis of bacteria with an internal state that allows the velocity jump rate to depend on the memory of the chemoattractant concentration along their path of motion. Using probabilistic techniques, we provide a pathwise result that shows that the considered process converges to an advection-diffusion process in the (long-time) diffusion limit. We also (re-)prove using the same approach that the same limiting equation arises for a related, simpler process with direct sensing of the chemoattractant gradient. Additionally, we propose a time discretization technique that retains these diffusion limits exactly, i.e., without error that depends on the time discretization. In the companion paper \\cite{variance}, these results are used to construct a coupling technique that allows numerical simulation of the process with internal state with asymptotic variance reduction, in the sense that the variance vanishes in the diffusion limit.

  10. Reperfusion pulmonary edema

    International Nuclear Information System (INIS)

    Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B4 and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. The authors conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability

  11. The stochastic dance of circling sperm cells: sperm chemotaxis in the plane

    International Nuclear Information System (INIS)

    Biological systems such as single cells must function in the presence of fluctuations. It has been shown in a two-dimensional experimental setup that sea urchin sperm cells move toward a source of chemoattractant along planar trochoidal swimming paths, i.e. drifting circles. In these experiments, a pronounced variability of the swimming paths is observed. We present a theoretical description of sperm chemotaxis in two dimensions which takes fluctuations into account. We derive a coarse-grained theory of stochastic sperm swimming paths in a concentration field of chemoattractant. Fluctuations enter as multiplicative noise in the equations for the sperm swimming path. We discuss the stochastic properties of sperm swimming and predict a concentration-dependence of the effective diffusion constant of sperm swimming which could be tested in experiments.

  12. New insights into the role of stromal cell-derived factor 1 (SDF-1/CXCL12) in the pathophysiology of multiple sclerosis.

    Science.gov (United States)

    Khorramdelazad, Hossein; Bagheri, Vahid; Hassanshahi, Gholamhossein; Zeinali, Masoud; Vakilian, Alireza

    2016-01-15

    The etiology of several autoimmune diseases, including multiple sclerosis (MS) is still not clarified. MS is defined as an autoimmune disease with clinical features of a chronic, inflammatory, and demyelinating autoimmune disorder, which affects the central nervous system. Phases of remission and relapse are the major course of the disease, which could be exacerbated in terms of both severity and duration. As a subfamily of the cytokines, chemokines act as chemoattractants for a wide variety of cells, including immune cells. CXCL12, which is an important member of the CXC subfamily, has been widely explored in the hematopoietic system. In the peripheral immune system, CXCL12/CXCR4 performs pleiotropic functions. CXCL12 is a highly effective chemoattractant for lymphocytes and monocytes but not neutrophils. CXCL12 is present in the cerebrospinal fluid (CSF) of patients with MS and other inflammatory neurological disorders. The aim of this study is to summarize recent findings regarding the relationship between CXCL12 and MS. PMID:26711573

  13. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

    Science.gov (United States)

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A.

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4 receptor-dependent manner. Inhibition of exosome release leads to loss of directional motility with concomitant loss of LTB4 release. Our findings establish that the exosomal pool of LTB4 acts in an autocrine fashion to sensitize neutrophils towards the primary chemoattractant, and in a paracrine fashion to mediate the recruitment of neighboring neutrophils in trans. We envision that this mechanism is used by other signals to foster communication between cells in harsh extracellular environments. PMID:26741884

  14. The stochastic dance of circling sperm cells: sperm chemotaxis in the plane

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, B M; Juelicher, F [Max Planck Institute for the Physics of Complex Systems, Noethnitzer Strasse 38, 01187 Dresden (Germany)], E-mail: ben@pks.mpg.de, E-mail: julicher@pks.mpg.de

    2008-12-15

    Biological systems such as single cells must function in the presence of fluctuations. It has been shown in a two-dimensional experimental setup that sea urchin sperm cells move toward a source of chemoattractant along planar trochoidal swimming paths, i.e. drifting circles. In these experiments, a pronounced variability of the swimming paths is observed. We present a theoretical description of sperm chemotaxis in two dimensions which takes fluctuations into account. We derive a coarse-grained theory of stochastic sperm swimming paths in a concentration field of chemoattractant. Fluctuations enter as multiplicative noise in the equations for the sperm swimming path. We discuss the stochastic properties of sperm swimming and predict a concentration-dependence of the effective diffusion constant of sperm swimming which could be tested in experiments.

  15. mRNA concentrations of MIF in subcutaneous abdominal adipose cells are associated with adipocyte size and insulin action

    OpenAIRE

    Koska, Juraj; Stefan, Norbert; Dubois, Severine; Trinidad, Cathy; Considine, Robert V; Funahashi, Tohru; Bunt, Joy C.; Ravussin, Eric; Permana, Paska A.

    2009-01-01

    Objective To determine whether the mRNA concentrations of inflammation response genes in isolated adipocytes and in cultured preadipocytes are related to adipocyte size and in vivo insulin action in obese individuals. Design Cross-sectional inpatient study. Subjects Obese Pima Indians with normal glucose tolerance. Measurements Adipocyte diameter (by microscope technique; n=29), expression of candidate genes (by quantitative real-time PCR) in freshly isolated adipocytes (monocyte chemoattract...

  16. Eosinophilic inflammation in allergic asthma

    OpenAIRE

    IolandaFátima Lopes CalvoTibério; CarlaMáximoPrado

    2013-01-01

    Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modu...

  17. Eosinophilic Inflammation in Allergic Asthma

    OpenAIRE

    Possa, Samantha S.; Leick, Edna A; Carla M. Prado; Martins, Mílton A.; Tibério, Iolanda F. L. C.

    2013-01-01

    Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL)-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR)3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modu...

  18. The effects of second-hand smoke on biological processes important in atherogenesis

    OpenAIRE

    Schneider Matthias; Yao Min; Zafarani Mohammed; Ma Chongze; Bhattacharya Monideepa; Wong Lina S; Yuan Hongwei; Pitas Robert E; Martins-Green Manuela

    2007-01-01

    Abstract Background Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs) from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis. Methods To...

  19. Fluid Shear Stress Increases Neutrophil Activation via Platelet-Activating Factor

    OpenAIRE

    Mitchell, Michael J.; Lin, Kimberly S.; King, Michael R.

    2014-01-01

    Leukocyte exposure to hemodynamic shear forces is critical for physiological functions including initial adhesion to the endothelium, the formation of pseudopods, and migration into tissues. G-protein coupled receptors on neutrophils, which bind to chemoattractants and play a role in neutrophil chemotaxis, have been implicated as fluid shear stress sensors that control neutrophil activation. Recently, exposure to physiological fluid shear stresses observed in the microvasculature was shown to...

  20. ELR+ CXC chemokine expression in benign and malignant colorectal conditions

    OpenAIRE

    Brittner Brigitte; Gräber Stefan; Schuld Jochen; Wagner Mathias; Frick Vilma; Rubie Claudia; Bohle Rainer M; Schilling Martin K

    2008-01-01

    Abstract Background CXCR2 chemokine ligands CXCL1, CXCL5 and CXCL6 were shown to be involved in chemoattraction, inflammatory responses, tumor growth and angiogenesis. Here, we comparatively analyzed their expression profile in resection specimens from patients with colorectal adenoma (CRA) (n = 30) as well as colorectal carcinoma (CRC) (n = 48) and corresponding colorectal liver metastases (CRLM) (n = 16). Methods Chemokine expression was assessed by microdissection, quantitative real-time P...

  1. Mobilization of stem and progenitor cells in cardiovascular diseases

    OpenAIRE

    Wojakowski, W; Landmesser, U.; Bachowski, R; Jadczyk, T; M. Tendera

    2012-01-01

    Circulating bone marrow (BM)-derived stem and progenitor cells (SPCs) participate in turnover of vascular endothelium and myocardial repair after acute coronary syndromes. Acute myocardial infarction (MI) produces a generalized inflammatory reaction, including mobilization of SPCs, increased local production of chemoattractants in the ischemic myocardium, as well as neural and humoral signals activating the SPC egress from the BM. Several types of circulating BM cells were identified in the p...

  2. Evaluation of local MCP-1 and IL-12 nanocoatings for infection prevention in open fractures#

    OpenAIRE

    Li, Bingyun; Jiang, Bingbing; Dietz, Matthew J.; Smith, E. Suzanne; Clovis, Nina B.; Krishna Rao, K. Murali

    2010-01-01

    The increasing incidence of bacterial infection and the appearance of Staphylococcus aureus (S. aureus) strains that are resistant to commonly used antibiotics has made it important to develop non-antibiotic approaches for infection prevention. The aim of this study was to develop local monocyte chemoattractant protein-1 (MCP-1) and interleukin-12 p70 (IL-12 p70) therapies to prevent S. aureus infection by enhancing the recruitment and activation of macrophages, which are believed to play an ...

  3. Secreted proteome of the murine multipotent hematopoietic progenitor cell line DKmix.

    Science.gov (United States)

    Luecke, Nina; Templin, Christian; Muetzelburg, Marika Victoria; Neumann, Detlef; Just, Ingo; Pich, Andreas

    2010-03-15

    Administration of the multipotent hematopoietic progenitor cell (HPC) line DKmix improved cardiac function after myocardial infarction and accelerated dermal wound healing due to paracrine mechanisms. The aim of this study was to analyse the secreted proteins of DKmix cells in order to identify the responsible paracrine factors and assess their relevance to the wide spectrum of therapeutic effects. A mass spectrometry (MS)-based approach was used to identify secreted proteins of DKmix cells. Serum free culture supernatants of DKmix-conditioned medium were collected and the proteins present were separated, digested by trypsin and the resulting peptides were then analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) MS. Overall 95 different proteins were identified. Among them, secretory proteins galectin-3 and gelsolin were identified. These proteins are known to stimulate cell migration and influence wound healing and cardiac remodelling. The remaining proteins originate from intracellular compartments like cytoplasm (69%), nucleus (12%), mitochondria (4%), and cytoplasmic membrane (3%) indicating permeable or leaky DKmix cells in the conditioned medium. Additionally, a sandwich immunoassay was used to detect and quantify cytokines and chemokines. Interleukin-6 (IL-6), interleukin-13 (IL-13), monocyte-chemoattractant protein-1 (MCP-1), monocyte-chemoattractant protein-3 (MCP-3), monocyte-chemoattractant protein-1alpha (MIP-1alpha) and monocyte-chemoattractant protein-1beta (MIP-1beta) were detected in low concentrations. This study identified a subset of proteins present in the DKmix-conditioned medium that act as paracrine modulators of tissue repair. Moreover, it suggests that DKmix-derived conditioned medium might have therapeutic potency by promoting tissue regeneration. PMID:20127908

  4. Entwickung eines zellfreien, dreidimensionalen Implantates zur Behandlung von Defekten knorpelartiger Gewebe

    OpenAIRE

    Haberstroh, Kathrin

    2010-01-01

    The objective of the presented studies was the development of a cell-free implant, inducing the migration of precursor cells from the adjacent tissue or bone marrow by chemoattractive substances. Subsequently, these cells should be stimulated to differentiate and generate cartilage like repair tissue. Possible applications of such cell-free implants are the treatment of articular cartilage defects, for example of the knee or the substitution of the nucleus pulposus after its exstirpation. ...

  5. Experimental Autoimmune Encephalomyelitis (EAE) in CCR2−/− Mice: Susceptibility in Multiple Strains

    OpenAIRE

    Gaupp, Stefanie; Pitt, David; Kuziel, William A.; Cannella, Barbara; Raine, Cedric S.

    2003-01-01

    Chemokines are low molecular weight cytokines which act as chemoattractants for infiltrating cells bearing appropriate receptors (CCR) to sites of inflammation. It has been proposed that CCR2 on monocytes is responsible for their recruitment into the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, and two previous reports have described resistance of CCR2−/− mice to EAE. The present study examined three different mouse strains w...

  6. Sat-Nav for T cells: Role of PI3K isoforms and lipid phosphatases in migration of T lymphocytes.

    Science.gov (United States)

    Ward, Stephen G; Westwick, John; Harris, Stephanie

    2011-07-01

    Phosphoinositide 3-kinase (PI3K)-dependent signaling has been placed at the heart of conserved biochemical mechanisms that facilitate cell migration of leukocytes in response to a range of chemoattractant stimuli. This review assesses the evidence for and against PI3K-dependent mechanisms of T lymphocyte migration and whether pharmacological targeting of PI3K isoforms is likely to offer potential benefit for T cell mediated pathologies. PMID:21333676

  7. Characterization of buffalo interleukin 8 (IL-8) and its expression in endometritis

    OpenAIRE

    Ahlam A. Abou Mossallam; El Nahas, Soheir M; Eman R. Mahfouz; Osman, Noha M

    2015-01-01

    River buffalo (Bubalus bubalis bubalis) with a population over 135 million heads is an important livestock. Interleukin 8 (IL-8) is a member of the chemokine family and is an important chemoattractant for neutrophils associated with a wide variety of inflammatory diseases such as endometritis. Tissue samples from the mammary gland, uterus and ovary were obtained from river buffalo (Mediterranean type) with and without endometritis. Bacteriological examination showed the presence of both gram ...

  8. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    OpenAIRE

    Jaiswal Pundrik; Soldati Thierry; Thewes Sascha; Baskar Ramamurthy

    2012-01-01

    Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factor...

  9. A meta-analysis for C-X-C chemokine receptor type 4 as a prognostic marker and potential drug target in hepatocellular carcinoma

    OpenAIRE

    Hu, Fei

    2015-01-01

    Fei Hu, Lin Miao, Yu Zhao, Yuan-Yuan Xiao, Qing XuDepartment of Medical Oncology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, People’s Republic of ChinaAbstract: Chemokines (CKs), small proinflammatory chemoattractant cytokines that bind to specific G-protein coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. C-X-C chemokine receptor type 4 (CXCR4) has gained tremendous attention over th...

  10. Determination of the Cardiovascular Phenotype of Different Transgenic Mouse Models

    OpenAIRE

    Wolfram, Swen

    2002-01-01

    Background: Fibroblast growth factors 1 and 2 (FGF–1 and FGF–2), potent mitogens for endothelial cells and vascular smooth cells, are implicated in arterial and capillary growth as well as in cardioprotection. Monocyte chemoattractant protein 1 (MCP–1) is involved in various inflammatory conditions. Utilizing transgenic mice (TG) overexpressing FGF–1, FGF–2, or MCP–1 and nontransgenic controls (NTG), the effects of these factors on vascular development, cellular protection, cardiac p...

  11. Release of Ca2+ from the Endoplasmic Reticulum Contributes to Ca2+ Signaling in Dictyostelium discoideum

    OpenAIRE

    Wilczynska, Zofia; Happle, Kathrin; Müller-Taubenberger, Annette; Schlatterer, Christina; Malchow, Dieter; Fisher, Paul R.

    2005-01-01

    Ca2+ responses to two chemoattractants, folate and cyclic AMP (cAMP), were assayed in Dictyostelium D. discoideum mutants deficient in one or both of two abundant Ca2+-binding proteins of the endoplasmic reticulum (ER), calreticulin and calnexin. Mutants deficient in either or both proteins exhibited enhanced cytosolic Ca2+ responses to both attractants. Not only were the mutant responses greater in amplitude, but they also exhibited earlier onsets, faster rise rates, earlier peaks, and faste...

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

    OpenAIRE

    Murea Mariana; Register Thomas C; Divers Jasmin; Bowden Donald W; Carr J Jeffrey; Hightower Caresse R; Xu Jianzhao; Smith S Carrie; Hruska Keith A; Langefeld Carl D; Freedman Barry I

    2012-01-01

    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 plaqu...

  13. Evidence for a self-enforcing inflammation in neutrophil-mediated chronic diseases

    OpenAIRE

    Overbeek, S.A.

    2011-01-01

    In summary, this thesis provides evidence for the self-sustaining role of neutrophils in the inflammatory state in the pathogenesis of COPD and CD. In active disease, neutrophils release proteolytic enzymes that breakdown collagen. One of the collagen fragments can be neutrophilic chemoattractant N-ac-PGP, which leads to enhanced neutrophil inflammation and further inflammation. In COPD, cigarette smoking initiates a vicious circle of events leading to collagen breakdown, PGP generation and P...

  14. N-α-PGP and PGP, potential biomarkers and therapeutic targets for COPD

    OpenAIRE

    Gaggar Amit; Dransfield Mark; Parker Suzanne; Noerager Brett; Jackson Patricia L; O'Reilly Philip; Blalock J Edwin

    2009-01-01

    Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder for which new diagnostic and therapeutic approaches are required. Hallmarks of COPD are matrix destruction and neutrophilic airway inflammation in the lung. We have previously described two tri-peptides, N-α-PGP and PGP, which are collagen fragments and neutrophil chemoattractants. In this study, we investigate if N-α-PGP and PGP are biomarkers and potential therapeutic targets for COPD. Methods ...

  15. Sputum PGP is reduced by azithromycin treatment in patients with COPD and correlates with exacerbations

    OpenAIRE

    O'Reilly, Philip J.; Jackson, Patricia L; Wells, J. Michael; Dransfield, Mark T; Scanlon, Paul D.; Blalock, J Edwin

    2013-01-01

    Rationale Proline–glycine–proline (PGP), a neutrophil chemoattractant derived from the enzymatic breakdown of collagen, is elevated in sputum of patients with chronic obstructive pulmonary disease (COPD) and may contribute to disease progression. Whether sputum levels of PGP respond to therapy for COPD or predict outcomes is unknown. Objectives We conducted a study ancillary to a multicenter trial of the efficacy of azithromycin treatment for 1 year in preventing COPD exacerbations to test wh...

  16. Molecular aspects of mammalian fertilization

    Institute of Scientific and Technical Information of China (English)

    Hector Serrano; Dolores Garcia-Suarez

    2001-01-01

    Mammalian fertilization is a highly regulated process, much of which are not clearly understood. Here we present some information in order to elaborate a working hypothesis for this process, beginning with the sperm modifications in the epidydimis up to sperm and egg plasmalemma interaction and fusion. We also discuss the still poorly understood capacitation process, the phenomenon of sperm chemo-attraction that brings the capacitated sperm to interact with the oocyte vestments and certain aspects of the acrosome reaction.

  17. Doxycycline decreases production of interleukin-8 in a549 human lung epithelial cells

    OpenAIRE

    Hoyt JC; Ballering JG; Hayden JM; Robbins RA

    2013-01-01

    Doxycycline is an antibiotic that possess anti-inflammatory properties. These anti-inflammatory properties make doxycycline an attractive candidate for possible treatments for a variety of common chronic obstructive airway diseases. Interleukin-8 (IL-8) is a major inflammatory chemokine and a powerful chemo-attractant for both neutrophils and monocytes. We hypothesized that doxycycline might exert its anti-inflammatory effects, at least in part, by modulating IL-8 production. To test this ...

  18. EATING OURSELVES TO DEATH AND DESPAIR: THE CONTRIBUTION OF ADIPOSITY AND INFLAMMATION TO DEPRESSION

    OpenAIRE

    Shelton, Richard C.; Miller, Andrew H.

    2010-01-01

    Obesity and related metabolic conditions are of epidemic proportions in most of the world, affecting both adults and children. The accumulation of lipids in the body in the form of white adipose tissue in the abdomen is now known to activate innate immune mechanisms. Lipid accumulation causes adipocytes to directly secrete the cytokines interleukin (IL) 6 and tumor necrosis factor α (TNFα), but also monocyte chemoattractant protein 1 (MCP-1), which results in the accumulation of leukocytes in...

  19. Rho GTPases orient directional sensing in chemotaxis

    OpenAIRE

    Wang, Yu; Senoo, Hiroshi; Sesaki, Hiromi; Iijima, Miho

    2013-01-01

    During chemotaxis, cells recognize an extracellular chemical gradient and produce amplified intracellular responses independently of the actin cytoskeleton. This process is called directional sensing and observed as the activation of Ras GTPase and the production of phosphatidylinositol (3,4,5)-triphosphate (PIP3) toward higher concentrations of chemoattractants. How directional sensing is controlled is largely unknown. In our current study, we demonstrate that a Rho GTPase (RacE) and a Rho g...

  20. Modulation of choroidal neovascularization by subretinal injection of retinal pigment epithelium and polystyrene microbeads

    OpenAIRE

    Schmack, Ingo; Berglin, Lennart; Nie, Xiaoyan; Wen, Jing; Kang, Shin J; Marcus, Adam I.; Yang, Hua; Lynn, Michael J.; Kapp, Judith A.; Grossniklaus, Hans E.

    2009-01-01

    Purpose The study was conducted to create a rapidly developing and reproducible animal model of subretinal choroidal neovascularization (CNV) that allows a time-dependent evaluation of growth dynamics, histopathologic features, and cytokine expression. Methods C57BL/6 and chemoattractant leukocyte protein-2 deficient (∆Ccl-2) mice were studied. Mice received single or combined subretinal injections of cultured retinal pigment epithelium (RPE; C57BL/6-derived), polystyrene microbeads, or phosp...

  1. SDF-1α and CXCR4 as therapeutic targets in cardiovascular disease

    OpenAIRE

    Wen, Jessica; Zhang, Jian-qing; Huang, Wei; Wang, Yigang

    2011-01-01

    SDF-1α/CXCR4 signaling is important for endogenous processes, including organogenesis and hematopoeisis, as well as in response to tissue injury. The secretion of SDF-1α acts as a chemoattractant to facilitate the homing of circulating CXCR4 positive cells as well as other stem cells to the site of injury for the initiation organ regeneration and repair. In the case of cardiovascular disease, and particularly myocardial infarction, this signaling axis is implicated in many of these processes,...

  2. Canonical and Noncanonical G-Protein Signaling Helps Coordinate Actin Dynamics To Promote Macrophage Phagocytosis of Zymosan

    OpenAIRE

    Huang, Ning-Na; Becker, Steven; Boularan, Cedric; Kamenyeva, Olena; Vural, Ali; Hwang, Il-Young; Shi, Chong-Shan; Kehrl, John H

    2014-01-01

    Both chemotaxis and phagocytosis depend upon actin-driven cell protrusions and cell membrane remodeling. While chemoattractant receptors rely upon canonical G-protein signaling to activate downstream effectors, whether such signaling pathways affect phagocytosis is contentious. Here, we report that Gαi nucleotide exchange and signaling helps macrophages coordinate the recognition, capture, and engulfment of zymosan bioparticles. We show that zymosan exposure recruits F-actin, Gαi proteins, an...

  3. Gradient sensing in defined chemotactic fields

    OpenAIRE

    Skoge, Monica; Adler, Micha; Groisman, Alex; Levine, Herbert; Loomis, William F.; Rappel, Wouter-Jan

    2010-01-01

    Cells respond to a variety of secreted molecules by modifying their physiology, growth patterns, and behavior. Motile bacteria and eukaryotic cells can sense extracellular chemoattractants and chemorepellents and alter their movement. In this way fibroblasts and leukocytes can find their ways to sites of injury and cancer cells can home in on sites that are releasing growth factors. Social amoebae such as Dictyostelium are chemotactic to cAMP which they secrete several hours after they have i...

  4. Enhanced Aortic Macrophage Lipid Accumulation and Inflammatory Response in LDL Receptor Null Mice Fed an Atherogenic Diet

    OpenAIRE

    Wang, Shu; Wu, Dayong; Matthan, Nirupa R.; Lamon-Fava, Stefania; Lecker, Jaime L; Lichtenstein, Alice H

    2010-01-01

    The effect of an atherogenic diet on inflammatory response and elicited peritoneal macrophage (Mφ) cholesterol accumulation in relation to aortic lesion formation was assessed in LDL receptor null (LDLr−/−) mice. Mice were fed an atherogenic or control diet for 32 weeks. The atherogenic relative to control diet resulted in significantly higher plasma monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) concentrations, more aortic wall Mφ depo...

  5. Chemotaxis to aromatic and hydroaromatic acids: comparison of Bradyrhizobium japonicum and Rhizobium trifolii.

    OpenAIRE

    Parke, D; Rivelli, M; Ornston, L N

    1985-01-01

    Rhizobia are bacteria well known for their ability to fix nitrogen in symbiosis with leguminous plants. Members of diverse rhizobial species grow at the expense of hydroaromatic and aromatic compounds commonly found in plant cells and plant litter. Using a quantitative capillary assay to measure chemotaxis, we tested the ability of hydroaromatic acids, selected aromatic acids, and their metabolites to serve as chemoattractants for two distantly related rhizobial species, Bradyrhizobium japoni...

  6. Variant assumptions made in deriving equilibrium solutions to Little et al (PLoS Comput Biol 2009 5(10) e1000539)

    OpenAIRE

    Little, Mark P; Gola, Anna; Tzoulaki, Ioanna; Vandoolaeghe, Wendy

    2009-01-01

    The paper of Little et al. (PloS Comput Biol 2009 5(10) e1000539) outlined a system of reaction-diffusion equations that were used to describe induction of atherosclerotic disease. These were solved by considering an equilibrium solution and small perturbations around this equilibrium. Here we consider slight variant sets of assumptions that could be used to derive equilibrium solutions. In general they do not imply any change in the numerical results relating to monocyte chemo-attractant pro...

  7. "A system for the intracellular generation of triple helix-forming oligonucleotides (TFOs) and the sequence-specific inhibition of human MCP-1 gene expression"

    OpenAIRE

    Kautz, Kordula

    2006-01-01

    Chemokines play a key role in the cellular infiltration of inflamed tissue. They are released by a wide variety of cell types during the initial phase of host response to injury, allergens, antigens, or invading microorganisms, and selectively attract leukocytes to inflammatory foci, inducing both migration and activation. Monocyte chemoattractant protein-1 (MCP-1), a member of the CC chemokine superfamily, functions in attracting monocytes, T lymphocytes, and basophils to sites of inflammati...

  8. Expression of adhesion molecules on human granulocytes after stimulation with Helicobacter pylori membrane proteins: comparison with membrane proteins from other bacteria.

    OpenAIRE

    Enders, G; Brooks, W.; von Jan, N; Lehn, N.; Bayerdörffer, E; Hatz, R

    1995-01-01

    Type B gastritis in its active form is characterized by a dense infiltration of the lamina propria with granulocytes. Since the bacterium Helicobacter pylori does not invade the epithelial barrier, a signaling pathway chemoattractive for granulocytes must exist across this mucosal boarder. One possible mechanism tested was whether granulocytes are directly activated by water-soluble membrane proteins (WSP) from H. pylori. These findings were compared with the effects of WSP from other bacteri...

  9. Pathophysiology and clinical relevance of Helicobacter pylori.

    OpenAIRE

    Halter, F.; Hurlimann, S.; Inauen, W

    1992-01-01

    Considerable knowledge has recently accumulated on the mechanism by which Helicobacter pylori (H. pylori) induces chronic gastritis. Although H. pylori is not an invasive bacterium, soluble surface constituents can provoke pepsinogen release from gastric chief cells or trigger local inflammation in the underlying tissue. Urease appears to be one of the prime chemoattractants for recruitment and activation of inflammatory cells. Release of cytokines, such as tumor necrosis factor alpha, interl...

  10. Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke–induced emphysema in mice

    OpenAIRE

    Clauss, Matthias; Voswinckel, Robert; Rajashekhar, Gangaraju; Sigua, Ninotchka L.; Fehrenbach, Heinz; Rush, Natalia I.; Schweitzer, Kelly S.; Yildirim, Ali Ö.; Kamocki, Krzysztof; Fisher, Amanda J.; Gu, Yuan; Safadi, Bilal; Nikam, Sandeep; Hubbard, Walter C.; Tuder, Rubin M

    2011-01-01

    Pulmonary emphysema is a disease characterized by alveolar cellular loss and inflammation. Recently, excessive apoptosis of structural alveolar cells has emerged as a major mechanism in the development of emphysema. Here, we investigated the proapoptotic and monocyte chemoattractant cytokine endothelial monocyte-activating protein 2 (EMAPII). Lung-specific overexpression of EMAPII in mice caused simplification of alveolar structures, apoptosis, and macrophage accumulation, compared with that ...

  11. Wogonin, a plant flavone from Scutellariae radix, attenuated ovalbumin-induced airway inflammation in mouse model of asthma via the suppression of IL-4/STAT6 signaling

    OpenAIRE

    Ryu, Eun Kyung; Kim, Tae-Hyun; Jang, Eun Jeong; Choi, Yoon Suk; Kim, Seon Tae; Hahm, Ki Baik; Lee, Ho-Jae

    2015-01-01

    Bronchial asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils at the site of inflammation. Eotaxins are potent chemoattractants for eosinophils and play important roles in pathogenesis of asthma. In the course of screening for eotaxin-3 inhibitors, we found that wogonin showed potent inhibitory activity of interleukin-4 (IL-4)-induced eotaxin-3 expression in BEAS-2B cells. In this study, we examined the effects of wogonin on IL-4/STAT6...

  12. Controlling Interneuron Activity in Caenorhabditis Elegans to Evoke Chemotactic Behaviour

    OpenAIRE

    Kocabas, Askin; Shen, Ching-Han; Guo, Zengcai V.; Ramanathan, Sharad

    2012-01-01

    Animals locate and track chemoattractive gradients in the environment to find food. With its small nervous system, Caenorhabditis elegans is a good model system in which to understand how the dynamics of neural activity control this search behaviour. Extensive work on the nematode has identified the neurons that are necessary for the different locomotory behaviours underlying chemotaxis through the use of laser ablation, activity recording in immobilized animals and the study of mutants. Howe...

  13. Antiatherogenic effect of Mezzetia parviflora BECC. extract in high cholesterol fed rats

    OpenAIRE

    Murdifin, Mufidah

    2015-01-01

    The investigation of anti-atherosclerotic activity of M. parviflora and the mechanisms responsible for the extract???s effects (antihypolipidemic, anti-lipidperoxidation, and monocyte chemoattractant protein-1 (MCP-1) inhibition activities) has been performed. In this study, atherogenesis was induced by feeding rats with a hypercholesterolemic diet (200 mg/Kg day -1 ) for 3 months. The cholesterol intake was administered along with simvastatin 3.6 mg/Kg or M. parvifloraextract at doses of...

  14. Effect of Sipjeondaebo-Tang on Cancer-Induced Anorexia and Cachexia in CT-26 Tumor-Bearing Mice

    OpenAIRE

    Youn Kyung Choi; Ki Yong Jung; Sang-Mi Woo; Yee Jin Yun; Chan-Yong Jun; Jong Hyeong Park; Yong Cheol Shin; Sung-Gook Cho; Seong-Gyu Ko

    2014-01-01

    Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α ). In addition, glucagon like peptide-1...

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

    OpenAIRE

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

    2011-01-01

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

  16. Reactivation of Desensitized Formyl Peptide Receptors by Platelet Activating Factor: A Novel Receptor Cross Talk Mechanism Regulating Neutrophil Superoxide Anion Production

    OpenAIRE

    Forsman, Huamei; Önnheim, Karin; Andréasson, Emil; Christenson, Karin; Karlsson, Anna; Bylund, Johan; Dahlgren, Claes

    2013-01-01

    Neutrophils express different chemoattractant receptors of importance for guiding the cells from the blood stream to sites of inflammation. These receptors communicate with one another, a cross talk manifested as hierarchical, heterologous receptor desensitization. We describe a new receptor cross talk mechanism, by which desensitized formyl peptide receptors (FPRdes) can be reactivated. FPR desensitization is induced through binding of specific FPR agonists and is reached after a short perio...

  17. Candida albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration

    OpenAIRE

    Hargarten, Jessica C.; Moore, Tyler C.; Petro, Thomas M.; Nickerson, Kenneth W.; Atkin, Audrey L.

    2015-01-01

    The polymorphic commensal fungus Candida albicans causes life-threatening disease via bloodstream and intra-abdominal infections in immunocompromised and transplant patients. Although host immune evasion is a common strategy used by successful human fungal pathogens, C. albicans provokes recognition by host immune cells less capable of destroying it. To accomplish this, C. albicans white cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages, a phagocyte that they ar...

  18. Anwendung eines GL261-Tumormodells in CCR2-defizienten Mäusen

    OpenAIRE

    Felsenstein, Matthäus

    2016-01-01

    Objective: Glioblastoma multiforme (GBM) belongs to the most malignant glial tumor type (WHO IV°) with poor prognosis. Therefore, more profound tumor-immunological understanding is necessary. Glioma consist of large amounts of infiltrated microglia/macrophages (5-20%). These cells are recruited through chemo-attractants such as CCL2 released to a great extend by tumor cells. Microglia/macrophages presumably possess pro-tumoral and pro-angiogenic properties affecting tumor development. The aim...

  19. Slime mould tactile sensor

    OpenAIRE

    Adamatzky, Andrew

    2013-01-01

    Slime mould P. polycephalum is a single cells visible by unaided eye. The cells shows a wide spectrum of intelligent behaviour. By interpreting the behaviour in terms of computation one can make a slime mould based computing device. The Physarum computers are capable to solve a range of tasks of computational geometry, optimisation and logic. Physarum computers designed so far lack of localised inputs. Commonly used inputs --- illumination and chemo-attractants and -repellents --- usually act...

  20. Interference with granulocyte function by Staphylococcus epidermidis slime.

    OpenAIRE

    Johnson, G M; Lee, D A; Regelmann, W E; Gray, E. D.; Peters, G; Quie, P. G.

    1986-01-01

    The interaction of Staphylococcus epidermidis slime with human neutrophils (PMN) was examined by using isolated slime and allowing bacteria to elaborate slime and other extracellular products in situ. S. epidermidis slime was found to contain a chemoattractant. Incubation of PMN with 50 micrograms or more of slime per ml inhibited subsequent chemotaxis of the PMN to n-formyl-methionyl-leucyl-phenylalanine by 27% and to zymosan-activated serum by 44 to 67% with increasing slime concentrations....

  1. iPLA2β: front and center in human monocyte chemotaxis to MCP-1

    OpenAIRE

    Mishra, Ravi S.; Carnevale, Kevin A.; Cathcart, Martha K.

    2008-01-01

    Monocyte chemoattractant protein-1 (MCP-1) directs migration of blood monocytes to inflamed tissues. Despite the central role of chemotaxis in immune responses, the regulation of chemotaxis by signal transduction pathways and their in vivo significance remain to be thoroughly deciphered. In this study, we examined the intracellular location and functions of two recently identified regulators of chemotaxis, Ca2+-independent phospholipase (iPLA2β) and cytosolic phospholipase (cPLA2α), and subst...

  2. Mechanisms of Leukocyte Accumulation and Activation in Chorioamnionitis: Interleukin 1β and Tumor Necrosis Factor α Enhance Colony Stimulating Factor 2 Expression in Term Decidua

    OpenAIRE

    Arcuri, Felice; Toti, Paolo; Buchwalder, Lynn; Casciaro, Alessandra; Cintorino, Marcella; Schatz, Frederick; Rybalov, Basya; Lockwood, Charles J.

    2009-01-01

    Chorioamnionitis is a major cause of prematurity as well as perinatal morbidity and mortality. The present study observed a marked increase in immunohistochemical staining for Colony Stimulating Factor 2 (CSF2; also known as granulocyte macrophage-colony stimulating factor), a potent neutrophil and macrophage chemoattractant and activator, in the decidua of patients with CAM compared with controls (n = 8; P = .001). To examine the regulation of this CSF2, cultured decidual cells primed with e...

  3. Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

    OpenAIRE

    Lee, W. L.; Shalita, A R; Suntharalingam, K; Fikrig, S M

    1982-01-01

    The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorph...

  4. Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides

    Science.gov (United States)

    Totti, Noel; McCusker, Kevin T.; Campbell, Edward J.; Griffin, Gail L.; Senior, Robert M.

    1984-01-01

    Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at ~ 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

  5. High Pre-Transplant Serum Levels of CXCL10 Predict Early Renal Allograft Failure

    OpenAIRE

    Salvadori, M; De Serio, M.; G. La Villa; V. FOSSOMBRONI; F. Pradella; Lazzeri, E.; Lasagni, L; A.Buonamano; A. Rosati; M. ROTONDI; Romagnani, P.; E. Bertoni

    2003-01-01

    Background: The chemokine CXCL10 is a potent chemoattractant for activated lymphocytes and dendritic cells and mediates vascular injury by inducing intimal hyperplasia and inhibition of endothelial cell growth. Neutralisation of CXCL10 prolongs allograft survival and transplant knock-out models have shown that this chemokine is required for the initiation and development of graft failure due to both acute and chronic rejection. In the present study, we investigated whether pre-transplant CXCL...

  6. Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis.

    Directory of Open Access Journals (Sweden)

    Melissa L Burke

    Full Text Available Schistosomiasis continues to be an important cause of parasitic morbidity and mortality world-wide. Determining the molecular mechanisms regulating the development of granulomas and fibrosis will be essential for understanding how schistosome antigens interact with the host environment. We report here the first whole genome microarray analysis of the murine liver during the progression of Schistosoma japonicum egg-induced granuloma formation and hepatic fibrosis. Our results reveal a distinct temporal relationship between the expression of chemokine subsets and the recruitment of cells to the infected liver. Genes up-regulated earlier in the response included T- and B-cell chemoattractants, reflecting the early recruitment of these cells illustrated by flow cytometry. The later phases of the response corresponded with peak recruitment of eosinophils, neutrophils, macrophages and myofibroblasts/hepatic stellate cells (HSCs and the expression of chemokines with activity for these cells including CCL11 (eotaxin 1, members of the Monocyte-chemoattractant protein family (CCL7, CCL8, CCL12 and the Hepatic Stellate Cell/Fibrocyte chemoattractant CXCL1. Peak expression of macrophage chemoattractants (CCL6, CXCL14 and markers of alternatively activated macrophages (e.g. Retnla during this later phase provides further evidence of a role for these cells in schistosome-induced pathology. Additionally, we demonstrate that CCL7 immunolocalises to the fibrotic zone of granulomas. Furthermore, striking up-regulation of neutrophil markers and the localisation of neutrophils and the neutrophil chemokine S100A8 to fibrotic areas suggest the involvement of neutrophils in S. japonicum-induced hepatic fibrosis. These results further our understanding of the immunopathogenic and, especially, chemokine signalling pathways that regulate the development of S. japonicum-induced granulomas and fibrosis and may provide correlative insight into the pathogenesis of other

  7. Mutant MCP-1 Protein Delivery from Layer-by-Layer Coatings on Orthopaedic Implants to Modulate Inflammatory Response

    OpenAIRE

    Keeney, Michael; Waters, Heather; Barcay, Katie; Jiang, Xinyi; Yao, Zhenyu; Pajarinen, Jukka; Egashira, Kensuke; Goodman, Stuart; Yang, Fan

    2013-01-01

    Total joint replacement (TJR) is a common and effective surgical procedure for hip or knee joint reconstruction. However, the production of wear particles is inevitable for all TJRs, which activates macrophages and initiates an inflammatory cascade often resulting in bone loss, prosthetic loosening and eventual TJR failure. Macrophage Chemoattractant Protein-1 (MCP-1) is one of the most potent cytokines responsible for macrophage cell recruitment, and previous studies suggest that mutant MCP-...

  8. Adiponectin Stimulates Angiogenesis by Promoting Cross-talk between AMP-activated Protein Kinase and Akt Signaling in Endothelial Cells*

    OpenAIRE

    Ouchi, Noriyuki; Kobayashi, Hideki; Kihara, Shinji; Kumada, Masahiro; Sato, Kaori; Inoue, Tatsuya; Funahashi, Tohru; Walsh, Kenneth

    2003-01-01

    Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro and in vivo. Adiponectin stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures in vitro and functioned as a chemoattractant in migration assays. Adiponectin promoted the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase Akt/protein ...

  9. Role of Shwachman-Bodian-Diamond syndrome protein in translation machinery and cell chemotaxis: a comparative genomics approach

    OpenAIRE

    Vasieva O

    2011-01-01

    Olga VasievaInstitute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; Fellowship for the Interpretation of Genomes, Burr Ridge, IL, USAAbstract: Shwachman-Bodian-Diamond syndrome (SBDS) is linked to a mutation in a single gene. The SBDS proinvolved in RNA metabolism and ribosome-associated functions, but SBDS mutation is primarily linked to a defect in polymorphonuclear leukocytes unable to orient correctly in a spatial gradient of chemoattractants. Results of data...

  10. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis.

    OpenAIRE

    Ritankar Majumdar; Aidin Tavakoli Tameh; Carole A Parent

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4...

  11. Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis

    OpenAIRE

    Majumdar, Ritankar; Tavakoli Tameh, Aidin; Carole A Parent

    2016-01-01

    Leukotriene B4 (LTB4) is secreted by chemotactic neutrophils, forming a secondary gradient that amplifies the reach of primary chemoattractants. This strategy increases the recruitment range for neutrophils and is important during inflammation. Here, we show that LTB4 and its synthesizing enzymes localize to intracellular multivesicular bodies that, upon stimulation, release their content as exosomes. Purified exosomes can activate resting neutrophils and elicit chemotactic activity in a LTB4...

  12. Demethylation of the human eotaxin-3 gene promoter leads to the elevated expression of eotaxin-3

    OpenAIRE

    Lim, Eunjin; Rothenberg, Marc E.

    2013-01-01

    DNA demethylation has been primarily studied in the context of development biology, cell fate, and cancer, with less attention on inflammation. Herein, we investigate the association between DNA methylation and production of the chemoattractant cytokine eotaxin-3 in the tissue of patients with allergic disease. Regions of the human eotaxin-3 promoter were found to be hypomethylated in primary epithelial cells obtained from allergic tissue compared with normal control tissue (CTL). The demethy...

  13. The impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia

    OpenAIRE

    Chou, Chung-Wei; Lin, Fang-Chi; Tsai, Han-Chen; Chang, Shi-Chuan

    2014-01-01

    Background Concurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown. Methods We measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-β1 and IL-1 ...

  14. Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; van Steenwijk, R; Nielsen, T L;

    1995-01-01

    Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins ...... suggests a role of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear....

  15. Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury

    Directory of Open Access Journals (Sweden)

    Reyes Livia

    2005-06-01

    Full Text Available Abstract Background Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury. Methods Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumulation and expression of inflammatory mediators were determined. To further analyze in vivo observations, in vitro experiments with alveolar epithelial cells and alveolar macrophages were performed. Results A 320% increase of polymorphonuclear leukocytes in bronchoalveolar lavage fluid was observed in macrophage-depleted compared to macrophage-competent lipopolysaccharide-animals. This neutrophil recruitment was also confirmed in the interstitial space. Monocyte chemoattractant protein-1 concentration in bronchoalveolar lavage fluid was significantly increased in the absence of alveolar macrophages. This phenomenon was underlined by in vitro experiments with alveolar epithelial cells and alveolar macrophages. Neutralizing monocyte chemoattractant protein-1 in the airways diminished neutrophil accumulation. Conclusion These data suggest that alveolar macorphages play an important role in early endotoxin-induced lung injury. They prevent neutrophil influx by controlling monocyte chemoattractant protein-1 production through alveolar epithelial cells. Alveolar macrophages might therefore possess robust anti-inflammatory effects.

  16. Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

    Science.gov (United States)

    Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan

    2016-01-01

    Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion. PMID:27367541

  17. Characterizing asthma from a drop of blood using neutrophil chemotaxis.

    Science.gov (United States)

    Sackmann, Eric Karl-Heinz; Berthier, Erwin; Schwantes, Elizabeth A; Fichtinger, Paul S; Evans, Michael D; Dziadzio, Laura L; Huttenlocher, Anna; Mathur, Sameer K; Beebe, David J

    2014-04-22

    Asthma is a chronic inflammatory disorder that affects more than 300 million people worldwide. Asthma management would benefit from additional tools that establish biomarkers to identify phenotypes of asthma. We present a microfluidic solution that discriminates asthma from allergic rhinitis based on a patient's neutrophil chemotactic function. The handheld diagnostic device sorts neutrophils from whole blood within 5 min, and generates a gradient of chemoattractant in the microchannels by placing a lid with chemoattractant onto the base of the device. This technology was used in a clinical setting to assay 34 asthmatic (n = 23) and nonasthmatic, allergic rhinitis (n = 11) patients to establish domains for asthma diagnosis based on neutrophil chemotaxis. We determined that neutrophils from asthmatic patients migrate significantly more slowly toward the chemoattractant compared with nonasthmatic patients (P = 0.002). Analysis of the receiver operator characteristics of the patient data revealed that using a chemotaxis velocity of 1.55 μm/min for asthma yields a diagnostic sensitivity and specificity of 96% and 73%, respectively. This study identifies neutrophil chemotaxis velocity as a potential biomarker for asthma, and we demonstrate a microfluidic technology that was used in a clinical setting to perform these measurements. PMID:24711384

  18. Bacterial strategies for chemotaxis response.

    Science.gov (United States)

    Celani, Antonio; Vergassola, Massimo

    2010-01-26

    Regular environmental conditions allow for the evolution of specifically adapted responses, whereas complex environments usually lead to conflicting requirements upon the organism's response. A relevant instance of these issues is bacterial chemotaxis, where the evolutionary and functional reasons for the experimentally observed response to chemoattractants remain a riddle. Sensing and motility requirements are in fact optimized by different responses, which strongly depend on the chemoattractant environmental profiles. It is not clear then how those conflicting requirements quantitatively combine and compromise in shaping the chemotaxis response. Here we show that the experimental bacterial response corresponds to the maximin strategy that ensures the highest minimum uptake of chemoattractants for any profile of concentration. We show that the maximin response is the unique one that always outcompetes motile but nonchemotactic bacteria. The maximin strategy is adapted to the variable environments experienced by bacteria, and we explicitly show its emergence in simulations of bacterial populations in a chemostat. Finally, we recast the contrast of evolution in regular vs. complex environments in terms of minimax vs. maximin game-theoretical strategies. Our results are generally relevant to biological optimization principles and provide a systematic possibility to get around the need to know precisely the statistics of environmental fluctuations. PMID:20080704

  19. Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells.

    Science.gov (United States)

    Okuda, Satohiro; Tsutsui, Hiroki; Shiina, Keiko; Sprunck, Stefanie; Takeuchi, Hidenori; Yui, Ryoko; Kasahara, Ryushiro D; Hamamura, Yuki; Mizukami, Akane; Susaki, Daichi; Kawano, Nao; Sakakibara, Takashi; Namiki, Shoko; Itoh, Kie; Otsuka, Kurataka; Matsuzaki, Motomichi; Nozaki, Hisayoshi; Kuroiwa, Tsuneyoshi; Nakano, Akihiko; Kanaoka, Masahiro M; Dresselhaus, Thomas; Sasaki, Narie; Higashiyama, Tetsuya

    2009-03-19

    For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules. However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Emerging data indicate that two synergid cells on the side of the egg cell emit a diffusible, species-specific signal to attract the pollen tube at the last step of pollen tube guidance. Here we report that secreted, cysteine-rich polypeptides (CRPs) in a subgroup of defensin-like proteins are attractants derived from the synergid cells. We isolated synergid cells of Torenia fournieri, a unique plant with a protruding embryo sac, to identify transcripts encoding secreted proteins as candidate molecules for the chemoattractant(s). We found two CRPs, abundantly and predominantly expressed in the synergid cell, which are secreted to the surface of the egg apparatus. Moreover, they showed activity in vitro to attract competent pollen tubes of their own species and were named as LUREs. Injection of morpholino antisense oligomers against the LUREs impaired pollen tube attraction, supporting the finding that LUREs are the attractants derived from the synergid cells of T. fournieri. PMID:19295610

  20. Chronic photo-oxidative stress and subsequent MCP-1 activation as causative factors for age-related macular degeneration.

    Science.gov (United States)

    Suzuki, Mihoko; Tsujikawa, Motokazu; Itabe, Hiroyuki; Du, Zhao-Jiang; Xie, Ping; Matsumura, Nagakazu; Fu, Xiaoming; Zhang, Renliang; Sonoda, Koh-hei; Egashira, Kensuke; Hazen, Stanley L; Kamei, Motohiro

    2012-05-15

    Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Although pathogenic factors, such as oxidative stress, inflammation and genetics are thought to contribute to the development of AMD, little is known about the relationships and priorities between these factors. Here, we show that chronic photo-oxidative stress is an environmental factor involved in AMD pathogenesis. We first demonstrated that exposure to light induced phospholipid oxidation in the mouse retina, which was more prominent in aged animals. The induced oxidized phospholipids led to an increase in the expression of monocyte chemoattractant protein-1, which then resulted in macrophage accumulation, an inflammatory process. Antioxidant treatment prevented light-induced phospholipid oxidation and the subsequent increase of monocyte chemoattractant protein-1 (also known as C-C motif chemokine 2; CCL2), which are the beginnings of the light-induced changes. Subretinal application of oxidized phospholipids induced choroidal neovascularization, a characteristic feature of wet-type AMD, which was inhibited by blocking monocyte chemoattractant protein-1. These findings strongly suggest that a sequential cascade from photic stress to inflammatory processes through phospholipid oxidation has an important role in AMD pathogenesis. Finally, we succeeded in mimicking human AMD in mice with low-level, long-term photic stress, in which characteristic pathological changes, including choroidal neovascularization formation, were observed. Therefore, we propose a consecutive pathogenic pathway involving photic stress, oxidation of phospholipids and chronic inflammation, leading to angiogenesis. These findings add to the current understanding of AMD pathology and suggest protection from oxidative stress or suppression of the subsequent inflammation as new potential therapeutic targets for AMD. PMID:22357958

  1. Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague.

    Directory of Open Access Journals (Sweden)

    Yaron Vagima

    2015-05-01

    Full Text Available Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully virulent Y. pestis strain, no significant changes were observed in the lungs in the levels of neutrophils infiltrate, expression of adhesion molecules, or the expression of the major neutrophil chemoattractants keratinocyte cell-derived chemokine (KC, macrophage inflammatory protein 2 (MIP-2 and granulocyte colony stimulating factor (G-CSF. In contrast, early induction of chemokines, rapid neutrophil infiltration and a reduced bacterial burden were observed in the lungs of mice infected with an avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a YopJ mutant revealed the involvement of YopJ in the inhibition of chemoattractants expression. However, the recruitment of neutrophils to the lungs of mice infected with the mutant was still delayed and associated with rapid bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF mRNA levels in the lungs were up-regulated early after infection with the mutant, their protein levels remained constant, suggesting that Y. pestis may employ additional mechanisms to suppress early chemoattractants induction in the lung. It therefore seems that prevention of the early influx of neutrophils to the lungs is of major importance for Y. pestis virulence. Indeed, pulmonary instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to rapid homing of neutrophils to the lung followed by a reduction in bacterial counts at 24 hr post-infection and improved survival rates. These observations shed new light on the virulence mechanisms of Y. pestis during pneumonic plague, and have implications for the

  2. Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell-derived factor-1.

    Science.gov (United States)

    McQuibban, G A; Butler, G S; Gong, J H; Bendall, L; Power, C; Clark-Lewis, I; Overall, C M

    2001-11-23

    Chemokines provide directional cues for leukocyte migration and activation that are essential for normal leukocytic trafficking and for host responses during processes such as inflammation, infection, and cancer. Recently we reported that matrix metalloproteinases (MMPs) modulate the activity of the CC chemokine monocyte chemoattractant protein-3 by selective proteolysis to release the N-terminal tetrapeptide. Here we report the N-terminal processing, also at position 4-5, of the CXC chemokines stromal cell-derived factor (SDF)-1alpha and beta by MMP-2 (gelatinase A). Robustness of the MMP family for chemokine cleavage was revealed from identical cleavage site specificity of MMPs 1, 3, 9, 13, and 14 (MT1-MMP) toward SDF-1; selectivity was indicated by absence of cleavage by MMPs 7 and 8. Efficient cleavage of SDF-1alpha by MMP-2 is the result of a strong interaction with the MMP hemopexin C domain at an exosite that overlaps the monocyte chemoattractant protein-3 binding site. The association of SDF-1alpha with different glycosaminoglycans did not inhibit cleavage. MMP cleavage of SDF-1alpha resulted in loss of binding to its cognate receptor CXCR-4. This was reflected in a loss of chemoattractant activity for CD34(+) hematopoietic progenitor stem cells and pre-B cells, and unlike full-length SDF-1alpha, the MMP-cleaved chemokine was unable to block CXCR-4-dependent human immunodeficiency virus-1 infection of CD4(+) cells. These data suggest that MMPs may be important regulatory proteases in attenuating SDF-1 function and point to a deep convergence of two important networks, chemokines and MMPs, to regulate leukocytic activity in vivo. PMID:11571304

  3. Methods for Pseudopodia Purification and Proteomic Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yingchun; Ding, Shi-Jian; Wang, Wei; Yang, Feng; Jacobs, Jon M.; Camp, David G.; Smith, Richard D.; Klemke, Richard L.

    2007-08-21

    Directional cell migration (chemotaxis) plays a central role in a wide spectrum of physiological and pathological processes, including embryo development, wounding healing, immunity, and cancer metastasis (1, 2). The process of chemotaxis is characterized by the sustained migration of cells in the direction of an increasing concentration of chemoattractant and/or ECM protein. Upon sensing the chemoattractant cells response with localized amplification of signals on the side facing the gradient (3-7). The spatial signal propagation facilitates reorganization of the actin-myosin cytoskeleton leading to extension of a dominant pseudopodium (PD) only in the direction of chemoattractant (7-10). While it is clear that localized signaling is critical for pseudopodium formation and chemotaxis, the molecular mechanisms that mediate this response remain poorly defined. To investigate mechanisms of pseudopodia formation, we recently described a novel approach to separate the PD and cell body (CB) compartments for large scale proteomic and phosphoproteomic analyses using chambers equipped with microporous filters (Fig. 1) (3, 7, 11). This in vitro system recapitulates physiological events associates with pseudopodial protrusion through small openings in the ECM and the vessel wall during immune cell intravasation and cancer cell metastasis (12, 13). The model system has been used to reveal important signaling pathways and novel proteins that mediate cell migration. This model, combined with the state-of-the-art proteomics and phosphoproteomics technology, will provide an effective approach to systematically analyze the proteins that differentially localized or phosphorylated in the front and the back of polarized migrating cells. In the following sections, we will describe in detail the protocols used to purify the PD and CB compartments for large-scale proteomic and phosphoproteomic analyses using mass spectrometry.

  4. Structural and functional implications of the complement convertase stabilized by a staphylococcal inhibitor

    OpenAIRE

    Rooijakkers, Suzan H.M.; Wu, Jin; Ruyken, Maartje; van Domselaar, Robert; Planken, Karel L.; Tzekou, Apostolia; Ricklin, Daniel; Lambris, John D.; Janssen, Bert J.C.; van Strijp, Jos A. G.; Gros, Piet

    2009-01-01

    Activation of the complement system generates potent chemoattractants and opsonizes cells for immune clearance. Short-lived protease complexes cleave complement component C3 into anaphylatoxin C3a and opsonin C3b. Here we report the crystal structure of the C3 convertase formed by C3b and the protease fragment Bb, which was stabilized by the bacterial immune-evasion protein SCIN. The data suggest that the proteolytic specificity and activity depends on dimerization of C3 with C3b of the conve...

  5. Evidence for an association between TSH and IGF-1 receptors: A tale of two antigens implicated in Graves’ disease1

    OpenAIRE

    Tsui, Shanli; Naik, Vibha; Hoa, Neil; Hwang, Catherine J.; Afifyan, Nikoo F.; Hikim, Amiya Sinha; Gianoukakis, Andrew G.; Douglas, Raymond S.; Smith, Terry J.

    2008-01-01

    TSH receptor (TSHR) plays a central role in regulating thyroid function and is targeted by IgGs in Graves’ disease (GD-IgG). Whether TSHR is involved in the pathogenesis of thyroid associated ophthalmopathy, the orbital manifestation of GD, remains uncertain. TSHR signaling overlaps with that of insulin-like grow factor 1 receptor (IGF-1R). GD-IgG can activate fibroblasts derived from donors with GD to synthesize T cell chemoattractants and hyaluronan, actions mediated through IGF-1R. Here we...

  6. Effect of breviscapine on fractalkine expression in chronic hypoxic rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-ju; CHENG De-yun; YANG Li; XIA Xiu-qiong; GUAN Jian

    2006-01-01

    @@ Fractalkine (FKN) is the only known chemokine that fulfils the dual functions of an adhesive molecule and a soluble chemoattractant.1 FKN expression was reported increase in lungs of patients with severe pulmonary arterial hypertension,2 suggesting that FKN may participate in pathogenesis of pulmonary hypertension.Breviscapine is a flavonoid extracted from Erigeron breviscapus (Vant.) Hand. Mazz. Breviscapine can prevent the development of hypoxic pulmonary hypertension3 but the mechanism is unknown. This study evaluated the role of FKN in the pathogenesis of hypoxic pulmonary hypertension and the effect of breviscapine on FKN in hypoxic pulmonary hypertension.

  7. On a competitive system under chemotactic effects with non-local terms

    International Nuclear Information System (INIS)

    In this paper, we study a system of partial differential equations describing the evolution of a population under chemotactic effects with non-local reaction terms. We consider an external application of chemoattractant in the system and study the cases of one and two populations in competition. By introducing global competitive/cooperative factors in terms of the total mass of the populations, we obtain, for a range of parameters, that any solution with positive and bounded initial data converges to a spatially homogeneous state with positive components. The proofs rely on the maximum principle for spatially homogeneous sub- and super-solutions. (paper)

  8. A cell's sense of direction.

    Science.gov (United States)

    Parent, C A; Devreotes, P N

    1999-04-30

    In eukaryotic cells directional sensing is mediated by heterotrimeric guanine nucleotide-binding protein (G protein)-linked signaling pathways. In Dictyostelium discoideum amoebae and mammalian leukocytes, the receptors and G-protein subunits are uniformly distributed around the cell perimeter. Chemoattractants induce the transient appearance of binding sites for several pleckstrin homology domain-containing proteins on the inner face of the membrane. In gradients of attractant these sites are persistently present on the side of the cell facing the higher concentration, even in the absence of a functional actin cytoskeleton or cell movement. Thus, the cell senses direction by spatially regulating the activity of the signal transduction pathway. PMID:10221901

  9. Novel Anti-Inflammatory Strategies Through Protein Engineering of Evasins

    OpenAIRE

    Pauline Bonvin

    2013-01-01

    We have identified 3 chemokine binding proteins (ChBP) from a tick salivary gland library which were named Evasin-1, -3 and -4. Evasin-1 and -4 bind CC-chemokines, the first being highly selective whilst the second has a broad pattern of selectivity. Evasin-3 binds the neutrophil chemoattractant ELR CXC-chemokines. In order to create therapeutic modalities for the treatment of chronic inflammatory diseases, the Evasins have been fused to Fc to produce molecules with a long half-life. The fusi...

  10. The effect of a lignan complex isolated from flaxseed on inflammation markers in healthy postmenopausal women

    DEFF Research Database (Denmark)

    Hallund, Jesper; Tetens, Inge; Bugel, S.; Tholstrup, T.; Bruun, J. M.

    2008-01-01

    /d of secoisolariciresinol diglucoside, on inflammatory markers. Methods and results: Healthy postmenopausal women (n = 22) completed a randomised double-blind, placebo-controlled crossover study. Women consumed daily a Low-fat muffin, with or without a lignan complex, for 6 weeks, separated by a 6-week......, and monocyte chemoattractant protein-1 were found between the lignan complex intervention period and placebo period. Conclusion: Daily consumption for 6 week of a low-fat muffin enriched with a lignan complex may reduce CRP concentrations compared to a low-fat muffin with no lignans added....

  11. Ca2+ spikes in the flagellum control chemotactic behavior of sperm

    OpenAIRE

    Böhmer, Martin; Van, Qui; Weyand, Ingo; Hagen, Volker; Beyermann, Michael; Matsumoto, Midori; Hoshi, Motonori; Hildebrand, Eilo; Kaupp, Ulrich Benjamin

    2005-01-01

    The events that occur during chemotaxis of sperm are only partly known. As an essential step toward determining the underlying mechanism, we have recorded Ca2+ dynamics in swimming sperm of marine invertebrates. Stimulation of the sea urchin Arbacia punctulata by the chemoattractant or by intracellular cGMP evokes Ca2+ spikes in the flagellum. A Ca2+ spike elicits a turn in the trajectory followed by a period of straight swimming (‘turn-and-run'). The train of Ca2+ spikes gives rise to repeti...

  12. Chemokine Receptors and Transplantation

    Institute of Scientific and Technical Information of China (English)

    Jinquan Tan; Gang Zhou

    2005-01-01

    A complex process including both the innate and acquired immune responses results in allograft rejection. Some chemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but also in facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage of the allogeneic response. This review focuses on the impact of these chemoattractant proteins on transplant outcome and novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokine receptors and/or their ligands. Cellular & Molecular Immunology.

  13. The mouse CCR2 gene is regulated by two promoters that are responsive to plasma cholesterol and peroxisome proliferator-activated receptor γ ligands

    International Nuclear Information System (INIS)

    We have previously shown that the expression of monocyte CCR2, the receptor for monocyte chemoattractant protein-1, is induced by plasma cholesterol. The present study examines the mechanisms that regulate monocyte CCR2 expression in hypercholesterolemia using a mouse model. Our data demonstrate that in the mouse, CCR2 expression in circulating monocytes is controlled by two promoters P1 and P2. The two distinct transcripts, which encode the same protein, are produced by alternative splicing in the 5'-untranslated region. Both promoters are constitutively active, but only P2 is stimulated by cholesterol. However, both promoters are repressed by peroxisome proliferator-activated receptor γ

  14. The Role of Sphingosine 1-Phosphate in Migration of Osteoclast Precursors; an Application of Intravital Two-Photon Microscopy

    OpenAIRE

    Ishii, Taeko; Shimazu, Yutaka; Nishiyama, Issei; Kikuta, Junichi; Ishii, Masaru

    2011-01-01

    Sphingosine-1-phosphate (S1P), a biologically active lysophospholipid that is enriched in blood, controls the trafficking of osteoclast precursors between the circulation and bone marrow cavities via G protein-coupled receptors, S1PRs. While S1PR1 mediates chemoattraction toward S1P in bone marrow, where S1P concentration is low, S1PR2 mediates chemorepulsion in blood, where the S1P concentration is high. The regulation of precursor recruitment may represent a novel therapeutic strategy for c...

  15. Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-κB pathway in primary rat microglia

    OpenAIRE

    Wang, Jing; Du, Jun-Rong; Wang, Yu; Kuang, Xi; Wang, Cheng-Yuan

    2010-01-01

    Aim: To investigate the anti-inflammatory effect of Z-ligustilide (LIG) on lipopolysaccharide (LPS)-activated primary rat microglia. Methods: Microglia were pretreated with LIG 1 h prior to stimulation with LPS (1 μg/mL). After 24 h, cell viability was tested with MTT, nitric oxide (NO) production was assayed with Griess reagent, and the content of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein (MCP-1) was measured with ELISA. Protein expression ...

  16. 14–3-3 Inhibits the Dictyostelium Myosin II Heavy-Chain-specific Protein Kinase C Activity by a Direct Interaction: Identification of the 14–3-3 Binding Domain

    OpenAIRE

    Matto-Yelin, Meirav; Aitken, Alastair; Ravid, Shoshana

    1997-01-01

    Myosin II heavy chain (MHC) specific protein kinase C (MHC-PKC), isolated from Dictyostelium discoideum, regulates myosin II assembly and localization in response to the chemoattractant cyclic AMP. Immunoprecipitation of MHC-PKC revealed that it resides as a complex with several proteins. We show herein that one of these proteins is a homologue of the 14–3-3 protein (Dd14–3-3). This protein has recently been implicated in the regulation of intracellular signaling pathways via its interaction ...

  17. Inflammation but no DNA (deoxyribonucleic acid) damage in mice exposed to airborne dust from a biofuel plant

    DEFF Research Database (Denmark)

    Madsen, Anne Mette; Saber, Anne Thoustrup; Nordly, Pernille; Sharma, Anoop Kumar; Wallin, Hakan; Vogel, Ulla Birgitte

    2008-01-01

    not been studied in detail. This study investigated whether exposure to dust from biofuel plants induces DNA (deoxyribonucleic acid) damage and inflammation in exposed mice. Methods DNA damage and inflammation were evaluated in mice exposed through the intratracheal installation of airborne dust...... of dust, the lung tissue mRNA (messenger ribonucleic acid) levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) were increased more than 10-fold if the dust was from the boiler room and 30- to 60-fold if the dust came from the straw...

  18. Slime mould logical gates: exploring ballistic approach

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    Plasmodium of \\emph{Physarum polycephalum} is a single cell visible by unaided eye. On a non-nutrient substrate the plasmodium propagates as a traveling localization, as a compact wave-fragment of protoplasm. The plasmodium-localization travels in its originally predetermined direction for a substantial period of time even when no gradient of chemo-attractants is present. We utilize this property of \\emph{Physarum} localizations to design a two-input two-output Boolean logic gates $ \\to $ and $ \\to $. We verify the designs in laboratory experiments and computer simulations. We cascade the logical gates into one-bit half-adder and simulate its functionality.

  19. In-chip fabrication of free-form 3D constructs for directed cell migration analysis

    DEFF Research Database (Denmark)

    Olsen, Mark Holm; Hjortø, Gertrud Malene; Hansen, Morten;

    2013-01-01

    Free-form constructs with three-dimensional (3D) microporosity were fabricated by two-photon polymerization inside the closed microchannel of an injection-molded, commercially available polymer chip for analysis of directed cell migration. Acrylate constructs were produced as woodpile topologies...... with a range of pore sizes from 5 × 5 μm to 15 × 15 μm and prefilled with fibrillar collagen. Dendritic cells seeded into the polymer chip in a concentration gradient of the chemoattractant CCL21 efficiently negotiated the microporous maze structure for pore sizes of 8 × 8 μm or larger. The cells...

  20. Structural and functional characterization of the interactions of platelet derived chemokines CCL5, CXCL4 and CXCL4L1

    OpenAIRE

    Sarabi, Alisina

    2011-01-01

    Chemokines play an important role in the development of inflammation and in the recruitment of leukocytes from the vessel into the inflamed tissue. Activated platelets serve as a rich source of chemokines, e.g. CCL5, CXCL4 and its closely related variant CXCL4L1. The pro-inflammatory CCL5 is a known potent chemoattractant for monocytes and also responsible for its arrest on inflamed endothelium. Since this arrest is enhanced by the interaction of CCL5 with CXCL4, we aimed to determine the str...

  1. Prognostic value of interleukin-8 in AIDS-associated Pneumocystis carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; Vestbo, Jørgen; Junge, Jette;

    1995-01-01

    Interleukin-8 (IL-8) is a potent neutrophil chemoattractant and activator. Pneumocystis carinii pneumonia is associated with an accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid. Thus, we hypothesized that IL-8 is involved in the pathogenesis of P. carinii pneumonia. BAL fluid and...... serum were prospectively collected in 76 consecutive HIV-infected patients with a primary episode of P. carinii pneumonia, as well as in 10 healthy control subjects. Patients were found to have elevated levels of IL-8 in BAL fluid compared with control subjects (p < 0.01). Nine patients died during the...

  2. Rainbow trout CK9, a CCL25-like ancient chemokine that attracts and regulates B cells and macrophages, the main antigen presenting cells in fish

    Science.gov (United States)

    Aquilino, Carolina; Granja, Aitor G.; Castro, Rosario; Wang, Tiehui; Abos, Beatriz; Parra, David; Secombes, Christopher J.; Tafalla, Carolina

    2016-01-01

    CK9 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to mammalian CCL25. Although CK9 is known to be transcriptionally regulated in response to inflammation particularly in mucosal tissues, its functionality has never been revealed. In the current work, we have demonstrated that CK9 is chemoattractant for antigen presenting cells (APCs) expressing major histocompatibility complex class II (MHC II) on the cell surface. Among these APCs, CK9 has a strong chemotactic capacity for both B cells (IgM+ and IgT+) and macrophages. Along with its chemotactic capacities, CK9 modulated the MHC II turnover of B lymphocytes and up-regulated the phagocytic capacity of both IgM+ cells and macrophages. Although CK9 had no lymphoproliferative effects, it increased the survival of IgT+ lymphocytes. Furthermore, we have established that the chemoattractant capacity of CK9 is strongly increased after pre-incubation of leukocytes with a T-independent antigen, whereas B cell receptor (BCR) cross-linking strongly abrogated their capacity to migrate to CK9, indicating that CK9 preferentially attracts B cells at the steady state or under BCR-independent stimulation. These results point to CK9 being a key regulator of B lymphocyte trafficking in rainbow trout, able to modulate innate functions of teleost B lymphocytes and macrophages. PMID:27003360

  3. ELMO1 Directly Interacts with Gβγ Subunit to Transduce GPCR Signaling to Rac1 Activation in Chemotaxis

    Science.gov (United States)

    Wang, Youhong; Xu, Xuehua; Pan, Miao; Jin, Tian

    2016-01-01

    Diverse chemokines bind to G protein-coupled receptors (GPCRs) to activate the small GTPase Rac to regulate F-actin dynamics during chemotaxis. ELMO and Dock proteins form complexes that function as guanine nucleotide exchange factors (GEFs) for Rac activation. However, the linkage between GPCR activation and the ELMO/Dock-mediated Rac activation is not fully understood. In the present study, we show that chemoattractants induce dynamic membrane translocation of ELMO1 in mammalian cells. ELMO1 plays an important role in GPCR-mediated chemotaxis. We also reveal that ELMO1 and Dock1 form a stable complex. Importantly, activation of chemokine GPCR promotes the interaction between ELMO1 and Gβγ. The ELMO1-Gβγ interaction is through the N-terminus of ELMO1 protein and is important for the membrane translocation of ELMO1. ELMO1 is required for Rac1 activation upon chemoattractant stimulation. Our results suggest that chemokine GPCR-mediated interaction between Gβγ and ELMO1/Dock1 complex might serve as an evolutionarily conserved mechanism for Rac activation to regulate actin cytoskeleton for chemotaxis of human cells.

  4. The Molecular Basis of Radial Intercalation during Tissue Spreading in Early Development.

    Science.gov (United States)

    Szabó, András; Cobo, Isidoro; Omara, Sharif; McLachlan, Sophie; Keller, Ray; Mayor, Roberto

    2016-05-01

    Radial intercalation is a fundamental process responsible for the thinning of multilayered tissues during large-scale morphogenesis; however, its molecular mechanism has remained elusive. Using amphibian epiboly, the thinning and spreading of the animal hemisphere during gastrulation, here we provide evidence that radial intercalation is driven by chemotaxis of cells toward the external layer of the tissue. This role of chemotaxis in tissue spreading and thinning is unlike its typical role associated with large-distance directional movement of cells. We identify the chemoattractant as the complement component C3a, a factor normally linked with the immune system. The mechanism is explored by computational modeling and tested in vivo, ex vivo, and in vitro. This mechanism is robust against fluctuations of chemoattractant levels and expression patterns and explains expansion during epiboly. This study provides insight into the fundamental process of radial intercalation and could be applied to a wide range of morphogenetic events. PMID:27165554

  5. Role of G protein-coupled receptors in inflammation

    Institute of Scientific and Technical Information of China (English)

    Lei SUN; Richard DYE

    2012-01-01

    G protein-coupled receptors (GPCRs) play important roles in inflammation.Inflammatory cells such as polymorphonuclear leuko-cytes (PMN),monocytes and macrophages express a large number of GPCRs for classic chemoattractants and chemokines.These receptors are critical to the migration of phagocytes and their accumulation at sites of inflammation,where these cells can exacer-bate inflammation but also contribute to its resolution.Besides chemoattractant GPCRs,protease activated receptors (PARs) such as PAR1 are involved in the regulation of vascular endothelial permeability.Prostaglandin receptors play different roles in inflam-matory cell activation,and can mediate both proinflammatory and anti-inflammatory functions.Many GPCRs present in inflammatory cells also mediate transcription factor activation,resulting in the synthesis and secretion of inflammatory factors and,in some cases,molecules that suppress inflammation.An understanding of the signaling paradigms of GPCRs in inflammatory cells is likely to facilitate translational research and development of improved anti-inflammatory therapies.

  6. Does it make sense to target one tumor cell chemotactic factor or its receptor when several chemotactic axes are involved in metastasis of the same cancer?

    Science.gov (United States)

    Ratajczak, Mariusz Z; Suszynska, Malwina; Kucia, Magda

    2016-12-01

    The major problem with cancer progression and anti-cancer therapy is the inherent ability of cancer cells to migrate and establish distant metastases. This ability to metastasize correlates with the presence in a growing tumor of cells with a more malignant phenotype, which express certain cancer stem cell markers. The propensity of malignant cells to migrate and their resistance to radio-chemotherapy somewhat mimics the properties of normal developmentally early stem cells that migrate during organogenesis in the developing embryo. In the past, several factors, including cell migration-promoting cytokines, chemokines, growth factors, bioactive lipids, extracellular nucleotides, and even H(+) ions, were found to influence the metastasis of cancer cells. This plethora of pro-migratory factors demonstrates the existence of significant redundancy in the chemoattractants for cancer cells. In spite of this obvious fact, significant research effort has been dedicated to demonstrating the crucial involvement of particular pro-metastatic factor-receptor axes and the development of new drugs targeting one receptor or one chemoattractant. Based on our own experience working with a model of metastatic rhabdomyosarcoma as well as the work of others, in this review we conclude that targeting a single receptor-ligand pro-metastatic axis will not effectively prevent metastasis and that we should seek other more effective therapeutic options. PMID:27510263

  7. An endothelial laminin isoform, laminin 8 (alpha4beta1gamma1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis.

    Science.gov (United States)

    Wondimu, Zenebech; Geberhiwot, Tarekegn; Ingerpuu, Sulev; Juronen, Erkki; Xie, Xun; Lindbom, Lennart; Doi, Masayuki; Kortesmaa, Jarkko; Thyboll, Jill; Tryggvason, Karl; Fadeel, Bengt; Patarroyo, Manuel

    2004-09-15

    During extravasation, neutrophils migrate through the perivascular basement membrane (BM), a specialized extracellular matrix rich in laminins. Laminins 8 (LN-8) (alpha4beta1gamma1) and 10 (LN-10) (alpha5beta1gamma1) are major components of the endothelial BM, but expression, recognition, and use of these laminin isoforms by neutrophils are poorly understood. In the present study, we provide evidence, using a panel of novel monoclonal antibodies against human laminin alpha4 (LNalpha4) chain, that neutrophils contain and secrete LN-8, and that this endogenous laminin contributes to chemoattractant-induced, alphaMbeta2-integrin-dependent neutrophil migration through albumin-coated filters. Phorbol ester-stimulated neutrophils adhered to recombinant human (rh) LN-8, rhLN-10, and mouse LN-1 (mLN-1) (alpha1beta1gamma1) via alphaMbeta2-integrin, and these laminin isoforms strongly promoted chemoattractant-induced neutrophil migration via the same integrin. However, only rhLN-8 enhanced the spontaneous migration. In addition, recruitment of neutrophils into the peritoneum following an inflammatory stimulus was impaired in LNalpha4-deficient mice. rhLN-8 also protected isolated neutrophils from spontaneous apoptosis. This study is the first to identify a specific laminin isoform in neutrophils and provides evidence for the role of LN-8 in the adhesion, migration, extravasation, and survival of these cells. PMID:15172971

  8. Induction of various immune modulatory molecules in CD34(+) hematopoietic cells

    DEFF Research Database (Denmark)

    Umland, Oliver; Heine, Holger; Miehe, Michaela;

    2004-01-01

    necrosis factor alpha (TauNF-alpha), but not LPS alone, can activate nuclear factor-kappaB in KG-1a cells. By cDNA subtraction and multiplex polymerase chain reaction, we revealed differential expression of cellular inhibitor of apoptosis protein-1, inhibitor of kappaB (IkappaB)/IkappaBalpha (MAD-3), and...... intercellular adhesion molecule-1 (ICAM-1) in SUP(LPS)-stimulated KG-1a cells and up-regulation of interferon (IFN)-inducible T cell-chemoattractant, interleukin (IL)-8, macrophage-inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES, CD70, granulocyte macrophage-colony stimulating factor, and IL-1beta...... in stimulated KG-1a cells and CD34(+) BMCs. Although monokine induced by IFN-gamma, IFN-inducible protein 10, and IFN-gamma were exclusively up-regulated in KG-1a cells, differential expression of monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine, myeloid progenitor inhibitory...

  9. In the eye of the neutrophil swarm-navigation signals that bring neutrophils together in inflamed and infected tissues.

    Science.gov (United States)

    Lämmermann, Tim

    2016-07-01

    Neutrophils are sentinel cells that express in higher vertebrates >30 chemokine and chemoattractant receptors to sense and quickly react to tissue damage signals. Intravital microscopy studies in mouse models of wounding, inflammation, and infection have revealed that neutrophils form cell swarms at local sites of tissue injury and cell death. This swarming response is choreographed by chemokines, lipids, and other chemoattractants, controlling sequential phases of highly coordinated chemotaxis, intercellular signal relay, and cluster formation among neutrophils. This review will give a brief overview about the basic principles and key molecules that have led to the refined multistep model of how neutrophils come together to isolate sites of tissue injury and microbial invasion from healthy tissue. Whereas auto- and paracrine signaling among neutrophils during later phases of swarming can provide a level of self-organization for robust navigation in diverse inflammatory settings, guidance factors from primary tissue lesions, resident bystander cells, and dying cells regulate the initial phases of the swarming response. This review will discuss how the specific environmental context and mixture of attractants at the locally inflamed site can lead to variants of the multistep attraction model and influence the extent of neutrophil swarming, ranging from accumulations of only few individual cells to the aggregation of several hundreds of neutrophils, as found in abscesses. Given the critical roles of neutrophils in both host protection and tissue destruction, novel insights on neutrophil swarming might provide useful for the therapeutic modulation of neutrophil-dependent inflammatory processes. PMID:26416718

  10. Sperm chemotaxis promotes individual fertilization success in sea urchins.

    Science.gov (United States)

    Hussain, Yasmeen H; Guasto, Jeffrey S; Zimmer, Richard K; Stocker, Roman; Riffell, Jeffrey A

    2016-05-15

    Reproductive success fundamentally shapes an organism's ecology and evolution, and gamete traits mediate fertilization, which is a critical juncture in reproduction. Individual male fertilization success is dependent on the ability of sperm from one male to outcompete the sperm of other males when searching for a conspecific egg. Sperm chemotaxis, the ability of sperm to navigate towards eggs using chemical signals, has been studied for over a century, but such studies have long assumed that this phenomenon improves individual male fitness without explicit evidence to support this claim. Here, we assessed fertilization changes in the presence of a chemoattractant-digesting peptidase and used a microfluidic device coupled with a fertilization assay to determine the effect of sperm chemotaxis on individual male fertilization success in the sea urchin Lytechinus pictus We show that removing chemoattractant from the gametic environment decreases fertilization success. We further found that individual male differences in chemotaxis to a well-defined gradient of attractant correlate with individual male differences in fertilization success. These results demonstrate that sperm chemotaxis is an important contributor to individual reproductive success. PMID:26994183

  11. External and internal constraints on eukaryotic chemotaxis.

    Science.gov (United States)

    Fuller, Danny; Chen, Wen; Adler, Micha; Groisman, Alex; Levine, Herbert; Rappel, Wouter-Jan; Loomis, William F

    2010-05-25

    Chemotaxis, the chemically guided movement of cells, plays an important role in several biological processes including cancer, wound healing, and embryogenesis. Chemotacting cells are able to sense shallow chemical gradients where the concentration of chemoattractant differs by only a few percent from one side of the cell to the other, over a wide range of local concentrations. Exactly what limits the chemotactic ability of these cells is presently unclear. Here we determine the chemotactic response of Dictyostelium cells to exponential gradients of varying steepness and local concentration of the chemoattractant cAMP. We find that the cells are sensitive to the steepness of the gradient as well as to the local concentration. Using information theory techniques, we derive a formula for the mutual information between the input gradient and the spatial distribution of bound receptors and also compute the mutual information between the input gradient and the motility direction in the experiments. A comparison between these quantities reveals that for shallow gradients, in which the concentration difference between the back and the front of a 10-mum-diameter cell is <5%, and for small local concentrations (<10 nM) the intracellular information loss is insignificant. Thus, external fluctuations due to the finite number of receptors dominate and limit the chemotactic response. For steeper gradients and higher local concentrations, the intracellular information processing is suboptimal and results in a smaller mutual information between the input gradient and the motility direction than would have been predicted from the ligand-receptor binding process. PMID:20457897

  12. Effects of organic chemicals derived from ambient particulate matter on lung inflammation related to lipopolysaccharide

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Ken-ichiro; Yanagisawa, Rie; Hirano, Seishiro; Kobayashi, Takahiro [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Takano, Hirohisa [National Institute for Environmental Studies, Environmental Health Sciences Division, Tsukuba, Ibaraki (Japan); Kyoto Prefectural University of Medicine, Inflammation and Immunology, Graduate School of Medical Science, Kyoto (Japan); Ichinose, Takamichi [Oita University of Nursing and Health Sciences, Department of Health Science, Oita (Japan); Yoshikawa, Toshikazu [Kyoto Prefectural University of Medicine, Inflammation and Immunology, Graduate School of Medical Science, Kyoto (Japan)

    2006-12-15

    The effects of components of ambient particulate matter (PM) on individuals with predisposing respiratory disorders are not well defined. We have previously demonstrated that airway exposure to diesel exhaust particles (DEP) or organic chemicals (OC) extracted from DEP (DEP-OC) enhances lung inflammation related to bacterial endotoxin (lipopolysaccharide, LPS). The present study aimed to examine the effects of airway exposure to OC extracted from urban PM (PM-OC) on lung inflammation related to LPS. ICR mice were divided into four experimental groups that intratracheally received vehicle, LPS (2.5 mg/kg), PM-OC (4 mg/kg), or PM-OC + LPS. Lung inflammation, lung water content, and lung expression of cytokines were evaluated 24 h after intratracheal administration. LPS challenge elicited lung inflammation evidenced by cellular profiles of bronchoalveolar lavage fluid and lung histology, which was further aggravated by the combined challenge with PM-OC. The combination with PM-OC and LPS did not significantly exaggerate LPS-elicited pulmonary edema. LPS instillation induced elevated lung expression of interleukin-1{beta}, macrophage inflammatory protein-1{alpha}, macrophage chemoattractant protein-1, and keratinocyte chemoattractant, whereas the combined challenge with PM-OC did not influence these levels. All the results were consistent with our previous reports on DEP-OC. These results suggest that the extracted organic chemicals from PM exacerbate infectious lung inflammation. The mechanisms underlying the enhancing effects are not mediated via the enhanced local expression of proinflammatory cytokines. (orig.)

  13. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

    Science.gov (United States)

    Viswanathan, Kavitha; Dhabhar, Firdaus S.

    2005-04-01

    Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

  14. Candida albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration.

    Science.gov (United States)

    Hargarten, Jessica C; Moore, Tyler C; Petro, Thomas M; Nickerson, Kenneth W; Atkin, Audrey L

    2015-10-01

    The polymorphic commensal fungus Candida albicans causes life-threatening disease via bloodstream and intra-abdominal infections in immunocompromised and transplant patients. Although host immune evasion is a common strategy used by successful human fungal pathogens, C. albicans provokes recognition by host immune cells less capable of destroying it. To accomplish this, C. albicans white cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages, a phagocyte that they are able to survive within and eventually escape from. C. albicans opaque cells do not secrete this chemoattractive stimulant(s). We report here a physiological mechanism that contributes to the differences in the interaction of C. albicans white and opaque cells with macrophages. E,E-Farnesol, which is secreted by white cells only, is a potent stimulator of macrophage chemokinesis, whose activity is enhanced by yeast cell wall components and aromatic alcohols. E,E-farnesol results in up to an 8.5-fold increase in macrophage migration in vitro and promotes a 3-fold increase in the peritoneal infiltration of macrophages in vivo. Therefore, modulation of farnesol secretion to stimulate host immune recognition by macrophages may help explain why this commensal is such a successful pathogen. PMID:26195556

  15. Chemokines and chemokine receptors in mucosal homeostasis at the intestinal epithelial barrier in inflammatory bowel disease.

    Science.gov (United States)

    Zimmerman, Noah P; Vongsa, Rebecca A; Wendt, Michael K; Dwinell, Michael B

    2008-07-01

    Chemokines, a large family of small chemoattractive cytokines, and their receptors play an integral role in the regulation of the immune response and homeostasis. The ability of chemokines to attract specific populations of immune cells sets them apart from other chemoattractants. Chemokines produced within the gastrointestinal mucosa are critical players in directing the balance between physiological and pathophysiological inflammation in health, inflammatory bowel disease (IBD), and the progression to colon cancer. In addition to the well-characterized role of chemokines in directed trafficking of immune cells to the gut mucosa, the expression of chemokine receptors on the cells of the epithelium makes them active participants in the chemokine signaling network. Recent findings demonstrate an important role for chemokines and chemokine receptors in epithelial barrier repair and maintenance as well as an intricate involvement in limiting metastasis of colonic carcinoma. Increased recognition of the association between barrier defects and inflammation and the subsequent progression to cancer in IBD thus implicates chemokines as key regulators of mucosal homeostasis and disease pathogenesis. PMID:18452220

  16. Selective release of cytokines, chemokines, and growth factors by minced skin in vitro supports the effectiveness of autologous minced micrografts technique for chronic ulcer repair.

    Science.gov (United States)

    Pertusi, Ginevra; Tiberio, Rossana; Graziola, Francesca; Boggio, Paolo; Colombo, Enrico; Bozzo, Chiarella

    2012-01-01

    A new effective surgical procedure to repair chronic ulcers called minced micrografts technique has been recently reported. The technique consists in spreading a finely minced skin sample upon the wound bed. In this study, we investigate the in vitro release of cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1α, and granulocyte-colony stimulating factor), chemokines (monocyte chemoattractant protein-1 and growth-related oncogene-α), and growth factors (platelet-derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor) by minced (referred to as the minced sample) vs. not minced (referred to as the whole sample) human skin biopsy samples from the same donor. Factor release in the culture medium at different time points was detected using a multiplexed protein assay. The minced sample, which could behave like the skin fragments used in vivo in the autologous minced micrografts technique, expressed higher levels of tumor necrosis factor-α, interleukin-1α, platelet-derived growth factor, and basic fibroblast growth factor, and lower levels of interleukin-6, monocyte chemoattractant protein-1, growth related oncogene-α, and vascular endothelial growth factor compared with the whole sample. In conclusion, mincing of healthy skin may allow appropriate regulation of the inflammatory phase of wound healing and could induce overexpression of some growth factors, which facilitates the proliferative phase of healing. PMID:22304391

  17. Diverse sensitivity thresholds in dynamic signaling responses by social amoebae.

    Science.gov (United States)

    Wang, C Joanne; Bergmann, Adriel; Lin, Benjamin; Kim, Kyuri; Levchenko, Andre

    2012-02-28

    The complex transition from a single-cell to a multicellular life form during the formation of a fruiting body by the amoeba Dictyostelium discoideum is accompanied by a pulsatile collective signaling process that instigates chemotaxis of the constituent cells. Although the cells used for the analysis of this phenomenon are normally genetically identical (isogenic), it is not clear whether they are equally responsive to the waves of the signaling stimulus, nor is it clear how responses across the population influence collective cell behavior. Here, we found that isogenic Dictyostelium cells displayed differing sensitivities to the chemoattractant cyclic adenosine monophosphate (cAMP). Furthermore, the resulting signaling responses could be explained by a model in which cells are refractory to further stimulation for 5 to 6 min after the initial input and the signaling output is amplified, with the amplification threshold varying across the cells in the population. This pathway structure could explain intracellular amplification of the chemoattractant gradient during cell migration. The new model predicts that diverse cell responsiveness can facilitate collective cell behavior, specifically due to the presence of a small number of cells in the population with increased responsiveness that aid in propagating the initial cAMP signaling wave across the cell population. PMID:22375055

  18. Expression of Interferon γ by Decidual Cells and Natural Killer Cells at the Human Implantation Site: Implications for Preeclampsia, Spontaneous Abortion, and Intrauterine Growth Restriction.

    Science.gov (United States)

    Chen, Chie-Pein; Piao, Longzhu; Chen, Xilin; Yu, Jianhua; Masch, Rachel; Schatz, Frederick; Lockwood, Charles J; Huang, S Joseph

    2015-11-01

    Human first-trimester decidual cells (FTDCs) chemoattract CXCR3-expressing circulating CD56(bright)CD16(-) natural killer (NK) cells, which increase uteroplacental blood flow by remodeling spiral arteries and arterioles. This recruitment reflects elevated FTDC expression of NK cell-recruiting induced protein 10 and interferon (IFN)-inducible T-cell-α chemoattractant produced in response to the synergistic effects of tumor necrosis factor α (TNF-α) and IFN-γ stimulation. Decidual macrophages express TNF-α, whereas the cellular origin of IFN-γ is unclear. Therefore, this study aims to identify the cell source(s) of IFN-γ in human first trimester decidua. Immunostaining of decidual sections revealed that both FTDCs and decidual NK (dNK) cells express IFN-γ. Although individual dNK cells express higher IFN-γ levels, the more numerous FTDCs account for greater proportion of total IFN-γ immunostaining. Freshly isolated FTDCs express greater IFN-γ staining than dNK cells as measured by flow cytometry, whereas incubation of dNK cells with documented NK cell activators significantly increases IFN-γ above FTDC levels. Confluent FTDCs intrinsically produce, but paradoxically respond to, exogenous IFN-γ. PMID:25963913

  19. The therapeutic detoxification of chlorogenic acid against acetaminophen-induced liver injury by ameliorating hepatic inflammation.

    Science.gov (United States)

    Zheng, Zhiyong; Sheng, Yuchen; Lu, Bing; Ji, Lili

    2015-08-01

    Chlorogenic acid (CGA) has been reported to prevent acetaminophen (AP)-induced hepatotoxicity when mice were pre-administered orally with CGA for consecutive 7days before AP intoxication in our previous study. This study investigated the therapeutic detoxification of CGA against AP-induced hepatotoxicity and the engaged mechanism. The mice were orally administered with CGA (10, 20, 40mg/kg) at 1h after given AP (400mg/kg), and another 3h later the mice were killed for the following experiments. Results of serum transaminases analysis and histological evaluation demonstrated the detoxification of CGA against AP-induced hepatotoxicity. CGA reduced AP-induced the increased myeloperoxidase (MPO) enzymatic activity and its expression. CGA reduced AP-induced the increased liver expression of toll-like receptor (TLR)-3/4 and MyD88, and the increased phosphorylation of inhibitor of kappa B (IκB) and p65 subunit of nuclear factor κB (NFκB). CGA reduced AP-induced the increased NFκBp65 expression in nucleus. In addition, CGA reduced AP-induced the increased serum levels and liver mRNA expression of tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1), and keratinocyte chemoattractant (KC). Taken together, our results demonstrate the therapeutic detoxification of CGA against AP-induced liver injury, and TLR3/4 and NFκB signaling pathway are involved in such process. PMID:26079055

  20. The Migration of Cancer Cells in Gradually Varying Chemical Gradients and Mechanical Constraints

    Directory of Open Access Journals (Sweden)

    Smitha M. N. Rao

    2014-01-01

    Full Text Available We report a novel approach to study cell migration under physical stresses by utilizing established growth factor chemotaxis. This was achieved by studying cell migration in response to epidermal growth factor (EGF chemoattraction in a gradually tapered space, imposing mechanical stresses. The device consisted of two 5-mm-diameter chambers connected by ten 600 µm-long and 10 µm-high tapered microchannels. The taper region gradually changes the width of the channel. The channels tapered from 20 µm to 5 µm over a transition length of 50 µm at a distance of 250 µm from one of the chambers. The chemoattractant drove cell migration into the narrow confines of the tapered channels, while the mechanical gradient clearly altered the migration of cells. Cells traversing the channels from the wider to narrow-end and vice versa were observed using time-lapsed imaging. Our results indicated that the impact of physical stress on cell migration patterns may be cell type specific.

  1. Neurotensin Decreases the Proinflammatory Status of Human Skin Fibroblasts and Increases Epidermal Growth Factor Expression

    Directory of Open Access Journals (Sweden)

    Lucília Pereira da Silva

    2014-01-01

    Full Text Available Fibroblasts colonization into injured areas during wound healing (WH is responsible for skin remodelling and is also involved in the modulation of inflammation, as fibroblasts are immunologically active. Herein, we aimed to determine neurotensin effect on the immunomodulatory profile of fibroblasts, both in homeostatic and inflammatory conditions. Neurotensin mediated responses occurred through NTR1 or NTR3 receptors, while under inflammatory conditions NTR1 expression increase seemed to modulate neurotensin responses. Among different immunomodulatory genes, CCL11, IL-8, and IL-6 were the most expressed genes, while CCL4 and EGF were the less expressed genes. After neurotensin exposure, IL-8 mRNA expression was increased while CCL11 was decreased, suggesting a proinflammatory upregulation and chemoattractant ability downregulation of fibroblasts. Under inflammatory conditions, gene expression was significantly increased. After neurotensin exposure, CCL4 and IL-6 mRNA expression were decreased while CCL11 was increased, suggesting again a decrease in the chemoattractant capacity of fibroblasts and in their proinflammatory status. Furthermore, the expression of EGF, a crucial growth factor for skin cells proliferation and WH, was increased in all conditions. Overall, neurotensin, released by nerve fibers or skin cells, may be involved in the decrease of the chemotaxis and the proinflammatory status in the proliferation and remodelling phases of WH.

  2. Denitrification and chemotaxis of Pseudomonas stutzeri KC in porous media.

    Science.gov (United States)

    Roush, Caroline J; Lastoskie, Christian M; Worden, R Mark

    2006-01-01

    Chemotaxis is an important mechanism by which microorganisms are dispersed in porous media. A vigorous chemotactic response to concentration gradients formed by microbial consumption of chemoattractants can accelerate transport of bacteria to highly contaminated regions of soils and sediments, enhancing the efficiency of in situ bioremediation operations. Although chemotaxis plays a key role in establishment of biodegradation zones in the subsurface, the effects of physical heterogeneity on bacterial motility are poorly understood. To investigate the influence of porous media heterogeneity on microbial chemotaxis, swarm plate migration experiments were conducted using Pseudomonas stutzeri strain KC, a denitrifying bacterium used for in situ biodegradation of carbon tetrachloride in groundwater. Swarm plate measurements indicate that strain KC is strongly chemotactic toward both acetate and nitrate. A three-component mathematical model was developed to describe the migration of strain KC. Estimates of chemotactic sensitivity were obtained in the homogeneous (agar) phase and in a heterogeneous medium of aquifer solids extracted from the Schoolcraft bioremediation field site in western Michigan. Interestingly, the motility of strain KC is significantly larger in the porous medium than in the aqueous phase. We hypothesize that chemotactic response is enhanced within the heterogeneous medium because chemoattractant gradients formed by nitrate consumption are larger in the confined spaces of the porous medium than in unconfined agar solution. PMID:16760079

  3. Chemotaxis of large granular lymphocytes

    International Nuclear Information System (INIS)

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-β and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1+ cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 μm nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML(3H)P, suggesting that LGL bear receptors for the chemotactic peptide

  4. A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia.

    Science.gov (United States)

    Kaneko, Kazuhiro; Yonemitsu, Yoshikazu; Fujii, Takaaki; Onimaru, Mitsuho; Jin, Chen-Hao; Inoue, Makoto; Hasegawa, Mamoru; Onohara, Toshihiro; Maehara, Yoshihiko; Sueishi, Katsuo

    2006-04-01

    The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed. PMID:16301206

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility and progre.......9), viral load (P=0.9), or CCL3 protein levels (P=1.0). Survival among the HIV infected individuals did not differ according to CCL3L copy number. In this cohort, CCL3L CNV did not affect HIV status, pathogenesis, or survival.......The C-C motif chemokine ligand 3-like (CCL3L) protein is a potent chemoattractant which by binding to C-C chemokine receptor type 5 (CCR5) inhibits human immunodeficiency virus (HIV) entry. Copy number variation (CNV) of the CCL3L has been shown to be associated with HIV susceptibility and...... progression to AIDS, but these results have been inconsistent. We examined a Zimbabwean study population for an association of CCL3L CNV with HIV status, progression (CD4 T-cells and viral load), and survival. Another aim was to investigate the possible effects of CCL3L CNV on CCL3 protein concentration. A...

  6. Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Bolanle Famakin

    2012-07-01

    Full Text Available Abstract Background Deletion of some Toll-like receptors (TLRs affords protection against cerebral ischemia, but disruption of their known major downstream adaptors does not. To determine whether compensation in the production of downstream effectors by one pathway when the other is disrupted can explain these findings, we examined cytokine/chemokine expression and inflammatory infiltrates in wild-type (WT, MyD88−/− and TRIF-mutant mice following permanent middle cerebral artery occlusion (pMCAO. Methods Cytokine/chemokine expression was measured with a 25-plex bead array in the serum and brains of all three groups of mice at baseline (no surgery/naïve and at 3 hours and 24 hours following pMCAO. Brain inflammatory and neutrophil infiltrates were examined 24 hours following pMCAO. Results IL-6, keratinocyte chemoattractant (KC, granulocyte colony-stimulating factor (G-CSF and IL-10 were significantly decreased in MyD88−/− mice compared to WT mice following pMCAO. Significantly, decreased levels of the neutrophil chemoattractants KC and G-CSF corresponded with a trend toward fewer neutrophils in the brains of MyD88−/− mice. IP-10 was significantly decreased when either pathway was disrupted. MIP-1α was significantly decreased in TRIF-mutant mice, consistent with TRIF-dependent production. MyD88−/− mice showed elevations of a number of Th2 cytokines, such as IL-13, at baseline, which became significantly decreased following pMCAO. Conclusions Both MyD88 and TRIF mediate pathway-specific cytokine production following focal cerebral ischemia. Our results also suggest a compensatory Th2-type skew at baseline in MyD88−/− mice and a paradoxical switch to a Th1 phenotype following focal cerebral ischemia. The MyD88 pathway directs the expression of neutrophil chemoattractants following cerebral ischemia.

  7. Identification of colorectal cancer metastasis markers by an angiogenesis-related cytokine-antibody array

    Institute of Scientific and Technical Information of China (English)

    Ana Abajo; Nerea Bitarte; Ruth Zarate; Valentina Boni; Ines Lopez; Marisol Gonzalez-Huarriz; Javier Rodriguez; Eva Bandres; Jesus Garcia-Foncillas

    2012-01-01

    AIM:To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer (mCRC) with the aim of identifying prognostic markers.METHODS:The expression of 44 angiogenesissecreted factors was measured by a novel cytokine antibody array methodology.The study evaluated vascular endothelial growth factor (VEGF) and its soluble vascular endothelial growth factor receptor (sVEGFR)-1 protein levels by enzyme immunoassay (EIA) in a panel of 16 CRC cell lines.mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) and vascular endothelial growth factor receptor (VEGFR)-2 expression was analyzed by flow cytometry.RESULTS:Metastasis-derived CRC cell lines expressed a distinctive molecular profile as compared with those isolated from a primary tumor site.Metastatic CRC cell lines were characterized by higher expression of angiogenin-2 (Ang-2),macrophage chemoattractant proteins-3/4 (MCP-3/4),matrix metalloproteinase-1 (MMP-1),and the chemokines interferon γ inducible T cell α chemoattractant protein (I-TAC),monocyte chemoattractant protein 1-309,and interleukins interleukin (IL)-2 and IL-1α,as compared to primary tumor cell lines.In contrast,primary CRC cell lines expressed higher levels of interferon γ (IFN-γ),insulin-like growth factor-1 (IGF-1),IL-6,leptin,epidermal growth factor (EGF),placental growth factor (PIGF),thrombopoietin,transforming growth factor β1 (TGF-β1) and VEGF-D,as compared with the metastatic cell lines.VEGF expression does not significantly differ according to the CRC cellular origin in normoxia.Severe hypoxia induced VEGF expression up-regulation but contrary to expectations,metastatic CRC cell lines did not respond as much as primary cell lines to the hypoxic stimulus.In CRC primary-derived cell lines,we observed a twofold increase in VEGF expression between normoxia and hypoxia as compared to metastatic cell lines.CRC cell lines express a

  8. Polarization of migrating monocytic cells is independent of PI 3-kinase activity.

    Directory of Open Access Journals (Sweden)

    Silvia Volpe

    Full Text Available BACKGROUND: Migration of mammalian cells is a complex cell type and environment specific process. Migrating hematopoietic cells assume a rapid amoeboid like movement when exposed to gradients of chemoattractants. The underlying signaling mechanisms remain controversial with respect to localization and distribution of chemotactic receptors within the plasma membrane and the role of PI 3-kinase activity in cell polarization. METHODOLOGY/PRINCIPAL FINDINGS: We present a novel model for the investigation of human leukocyte migration. Monocytic THP-1 cells transfected with the alpha(2A-adrenoceptor (alpha(2AAR display comparable signal transduction responses, such as calcium mobilization, MAP-kinase activation and chemotaxis, to the noradrenaline homologue UK 14'304 as when stimulated with CCL2, which binds to the endogenous chemokine receptor CCR2. Time-lapse video microscopy reveals that chemotactic receptors remain evenly distributed over the plasma membrane and that their internalization is not required for migration. Measurements of intramolecular fluorescence resonance energy transfer (FRET of alpha(2AAR-YFP/CFP suggest a uniform activation of the receptors over the entire plasma membrane. Nevertheless, PI 3-kinase activation is confined to the leading edge. When reverting the gradient of chemoattractant by moving the dispensing micropipette, polarized monocytes--in contrast to neutrophils--rapidly flip their polarization axis by developing a new leading edge at the previous posterior side. Flipping of the polarization axis is accompanied by re-localization of PI-3-kinase activity to the new leading edge. However, reversal of the polarization axis occurs in the absence of PI 3-kinase activation. CONCLUSIONS/SIGNIFICANCE: Accumulation and internalization of chemotactic receptors at the leading edge is dispensable for cell migration. Furthermore, uniformly distributed receptors allow the cells to rapidly reorient and adapt to changes in the

  9. Eosinophilic inflammation in allergic asthma

    Directory of Open Access Journals (Sweden)

    Samantha Souza Possa

    2013-04-01

    Full Text Available Eosinophils are circulating granulocytes involved in pathogenesis of asthma. A cascade of processes directed by Th2 cytokine producing T-cells influence the recruitment of eosinophils into the lungs. Furthermore, multiple elements including interleukin (IL-5, IL-13, chemoattractants such as eotaxin, Clara cells, and CC chemokine receptor (CCR3 are already directly involved in recruiting eosinophils to the lung during allergic inflammation. Once recruited, eosinophils participate in the modulation of immune response, induction of airway hyperresponsiveness and remodeling, characteristic features of asthma. Various types of promising treatments for reducing asthmatic response are related to reduction in eosinophil counts both in human and experimental models of pulmonary allergic inflammation, showing that the recruitment of these cells really plays an important role in the pathophysiology of allergic diseases such asthma.

  10. Genomic organization, complete sequence, and chromosomal location of the gene for human eotaxin (SCYA11), an eosinophil-specific CC chemokine

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Zepeda, E.A.; Sarafi, M.N.; Luster, A.D. [Massachusetts General Hospital, Charlestown, MA (United States)]|[Harvard Medical School, Boston, MA (United States)] [and others

    1997-05-01

    Eotaxin is a CC chemokine that is a specific chemoattractant for eosinophils and is implicated in the pathogenesis of eosinophilic inflammatory diseases, such as asthma. We describe the genomic organization, complete sequence, including 1354 bp 5{prime} of the RNA initiation site, and chromosomal localization of the human eotaxin gene. Fluorescence in situ hybridization analysis localized eotaxin to human chromosome 17, in the region q21.1-q21.2, and the human gene name SCYA11 was assigned. We also present the 5{prime} flanking sequence of the mouse eotaxin gene and have identified several regulatory elements that are conserved between the murine and the human promoters. In particular, the presence of elements such as NF-{Kappa}B, interferon-{gamma} response element, and glucocorticoid response element may explain the observed regulation of the eotaxin gene by cytokines and glucocorticoids. 17 refs., 4 figs., 1 tab.

  11. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts

    Science.gov (United States)

    Eckes, B.; Dogic, D.; Colucci-Guyon, E.; Wang, N.; Maniotis, A.; Ingber, D.; Merckling, A.; Langa, F.; Aumailley, M.; Delouvee, A.; Koteliansky, V.; Babinet, C.; Krieg, T.

    1998-01-01

    Loss of a vimentin network due to gene disruption created viable mice that did not differ overtly from wild-type littermates. Here, primary fibroblasts derived from vimentin-deficient (-/-) and wild-type (+/+) mouse embryos were cultured, and biological functions were studied in in vitro systems resembling stress situations. Stiffness of -/- fibroblasts was reduced by 40% in comparison to wild-type cells. Vimentin-deficient cells also displayed reduced mechanical stability, motility and directional migration towards different chemo-attractive stimuli. Reorganization of collagen fibrils and contraction of collagen lattices were severely impaired. The spatial organization of focal contact proteins, as well as actin microfilament organization was disturbed. Thus, absence of a vimentin filament network does not impair basic cellular functions needed for growth in culture, but cells are mechanically less stable, and we propose that therefore they are impaired in all functions depending upon mechanical stability.

  12. Chemotaxis of crawling and swimming Caenorhabditis Elegans

    Science.gov (United States)

    Patel, Amar; Bilbao, Alejandro; Padmanabhan, Venkat; Khan, Zeina; Armstrong, Andrew; Rumbaugh, Kendra; Vanapalli, Siva; Blawzdziewicz, Jerzy

    2012-11-01

    A soil-dwelling nematode Caenorhabditis Elegans efficiently navigates through complex environments, responding to chemical signals to find food or avoid danger. According to previous studies, the nematode uses both gradual-turn and run-and-tumble strategies to move in the direction of the increasing concentration of chemical attractants. We show that both these chemotaxis strategies can be described using our kinematic model [PLoS ONE, 7: e40121 (2012)] in which harmonic-curvature modes represent elementary nematode movements. In our chemotaxis model, the statistics of mode changes is governed by the time history of the chemoattractant concentration at the position of the nematode head. We present results for both nematodes crawling without transverse slip and for swimming nematodes. This work was supported by NSF grant No. CBET 1059745.

  13. Blunted activation of NF-κB and NF-κB-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response

    International Nuclear Information System (INIS)

    Geranylgeranylacetone (GGA), an anti-ulcer agent, has anti-inflammatory potential against experimental colitis and ischemia-induced renal inflammation. However, molecular mechanisms involved in its anti-inflammatory effects are largely unknown. We found that, in glomerular mesangial cells, GGA blocked activation of nuclear factor-κB and consequent induction of monocyte chemoattractant protein 1 (MCP-1) by inflammatory cytokines. It was inversely correlated with induction of unfolded protein response (UPR) evidenced by expression of 78 kDa glucose-regulated protein (GRP78) and suppression of endoplasmic reticulum stress-responsive alkaline phosphatase. Various inducers of UPR including tunicamycin, thapsigargin, A23187, 2-deoxyglucose, dithiothreitol, and AB5 subtilase cytotoxin reproduced the suppressive effects of GGA. Furthermore, attenuation of UPR by stable transfection with GRP78 diminished the anti-inflammatory effects of GGA. These results disclosed a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of GGA

  14. Modeling cellular deformations using the level set formalism

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    Yang Liu

    2008-07-01

    Full Text Available Abstract Background Many cellular processes involve substantial shape changes. Traditional simulations of these cell shape changes require that grids and boundaries be moved as the cell's shape evolves. Here we demonstrate that accurate cell shape changes can be recreated using level set methods (LSM, in which the cellular shape is defined implicitly, thereby eschewing the need for updating boundaries. Results We obtain a viscoelastic model of Dictyostelium cells using micropipette aspiration and show how this viscoelastic model can be incorporated into LSM simulations to recreate the observed protrusion of cells into the micropipette faithfully. We also demonstrate the use of our techniques by simulating the cell shape changes elicited by the chemotactic response to an external chemoattractant gradient. Conclusion Our results provide a simple but effective means of incorporating cellular deformations into mathematical simulations of cell signaling. Such methods will be useful for simulating important cellular events such as chemotaxis and cytokinesis.

  15. Enzymes and Genes Involved in Aerobic Alkane Degradation

    Directory of Open Access Journals (Sweden)

    ZongzeShao

    2013-05-01

    Full Text Available Alkanes are major constituents of crude oil. They are also present at low concentrations in diverse non-contaminated because many living organisms produce them as chemo-attractants or as protecting agents against water loss. Alkane degradation is a widespread phenomenon in nature. The numerous microorganisms, both prokaryotic and eukaryotic, capable of utilizing alkanes as a carbon and energy source, have been isolated and characterized. This review summarizes the current knowledge of how bacteria metabolize alkanes aerobically, with a particular emphasis on the oxidation of long-chain alkanes, including factors that are responsible for chemotaxis to alkanes , transport across cell membrane of alkanes , the regulation of alkane degradation gene and initial oxidation.

  16. Selective suppression of leukocyte recruitment in allergic inflammation

    Directory of Open Access Journals (Sweden)

    CL Weller

    2005-03-01

    Full Text Available Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.

  17. Ratchetaxis: Long-Range Directed Cell Migration by Local Cues.

    Science.gov (United States)

    Caballero, David; Comelles, Jordi; Piel, Matthieu; Voituriez, Raphaël; Riveline, Daniel

    2015-12-01

    Directed cell migration is usually thought to depend on the presence of long-range gradients of either chemoattractants or physical properties such as stiffness or adhesion. However, in vivo, chemical or mechanical gradients have not systematically been observed. Here we review recent in vitro experiments, which show that other types of spatial guidance cues can bias cell motility. Introducing local geometrical or mechanical anisotropy in the cell environment, such as adhesive/topographical microratchets or tilted micropillars, show that local and periodic external cues can direct cell motion. Together with modeling, these experiments suggest that cell motility can be viewed as a stochastic phenomenon, which can be biased by various types of local cues, leading to directional migration. PMID:26615123

  18. Innate immune properties of the immortalized macrophage cell line I-9.5.

    Science.gov (United States)

    Chang, W; Yeh, S H; Drath, D B

    1995-01-01

    A colony stimulating factor-1-dependent macrophage cell line, I-9.5, originally derived from a BALB/c splenic macrophage colony, was maintained in culture and examined for the expression of certain properties key to its innate immune function. Chemotaxis, phagocytosis, and superoxide release were assessed in this cell line and compared to either freshly isolated elicited murine peritoneal or splenic macrophages from BALB/c mice. Three separate experiments indicated that I-9.5 displayed comparable phagocytosis of 14C-radio-labeled Staphylococcus aureus and similar levels of superoxide release in response to opsonized zymosan. I-9.5, however, demonstrated impaired chemotaxis toward the chemoattractant, N-formyl-methionyl-leucyl-phenylalanine, and displayed impaired random migration in response to a balanced salt solution. This observation suggests that I-9.5 may serve as an important model for elucidating the structural and molecular correlates of chemotaxis. PMID:7704335

  19. Gene expression in epithelial cells in response to pneumovirus infection

    Directory of Open Access Journals (Sweden)

    Rosenberg Helene F

    2001-05-01

    Full Text Available Abstract Respiratory syncytial virus (RSV and pneumonia virus of mice (PVM are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner.

  20. Emergent collective chemotaxis without single-cell gradient sensing

    CERN Document Server

    Camley, Brian A; Levine, Herbert; Rappel, Wouter-Jan

    2015-01-01

    Many eukaryotic cells chemotax, sensing and following chemical gradients. However, even if single cells do not chemotax significantly, small clusters may still follow a gradient; this behavior is observed in neural crest cells and during border cell migration in Drosophila, but its origin remains puzzling. Here, we study this "collective guidance" analytically and computationally. We show collective chemotaxis can exist without single-cell chemotaxis if contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. We present explicit formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. Pairs of cells will have velocities that are strongly dependent on the cell pair's orientation: this provides a simple test for the presence of collective guidance in neural crest cells and other systems. We also study cluster-level adaptation, amplification, and cohesion via co-attraction.

  1. Slime mold uses an externalized spatial "memory" to navigate in complex environments.

    Science.gov (United States)

    Reid, Chris R; Latty, Tanya; Dussutour, Audrey; Beekman, Madeleine

    2012-10-23

    Spatial memory enhances an organism's navigational ability. Memory typically resides within the brain, but what if an organism has no brain? We show that the brainless slime mold Physarum polycephalum constructs a form of spatial memory by avoiding areas it has previously explored. This mechanism allows the slime mold to solve the U-shaped trap problem--a classic test of autonomous navigational ability commonly used in robotics--requiring the slime mold to reach a chemoattractive goal behind a U-shaped barrier. Drawn into the trap, the organism must rely on other methods than gradient-following to escape and reach the goal. Our data show that spatial memory enhances the organism's ability to navigate in complex environments. We provide a unique demonstration of a spatial memory system in a nonneuronal organism, supporting the theory that an externalized spatial memory may be the functional precursor to the internal memory of higher organisms. PMID:23045640

  2. Giant cell tumor of the uterus: case report and response to chemotherapy

    International Nuclear Information System (INIS)

    Giant cell tumor (GCT) is usually a benign but locally aggressive primary bone neoplasm in which monocytic macrophage/osteoclast precursor cells and multinucleated osteoclast-like giant cells infiltrate the tumor. The etiology of GCT is unknown, however the tumor cells of GCT have been reported to produce chemoattractants that can attract osteoclasts and osteoclast precursors. Rarely, GCT can originate at extraosseous sites. More rarely, GCT may exhibit a much more aggressive phenotype. The role of chemotherapy in metastatic GCT is not well defined. We report a case of an aggressive GCT of the uterus with rapidly growing lung metastases, and its response to chemotherapy with pegylated-liposomal doxorubicin, ifosfamide, and bevacizumab, along with a review of the literature. Aggressive metastasizing GCT may arise in the uterus, and may respond to combination chemotherapy

  3. Growth Patterns of Microscopic Brain Tumors

    CERN Document Server

    Sander, L M; Sander, Leonard M.; Deisboeck, Thomas S.

    2002-01-01

    Highly malignant brain tumors such as Glioblastoma Multiforme (GBM) form complex growth patterns in vitro in which invasive cells organize in tenuous branches. Here, we formulate a chemotaxis model for this sort of growth. A key element controlling the pattern is homotype attraction, i.e., the tendency for invasive cells to follow pathways previously explored. We investigate this in two ways: we show that there is an intrinsic instability in the model, which leads to branch formation. We also give a discrete description for the expansion of the invasive zone, and a continuum model for the nutrient supply. The results indicate that both, strong heterotype chemotaxis and strong homotype chemo-attraction are required for branch formation within the invasive zone. Our model thus can give a way to assess the importance of the various processes, and a way to explore and analyze transitions between different growth regimes.

  4. Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects

    DEFF Research Database (Denmark)

    Bruun, Jens M; Helge, Jørn W; Richelsen, Bjørn;

    2006-01-01

    Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle...... insulin sensitivity (homeostasis model assessment; P < 0.05). Plasma adiponectin (P < 0.001) increased, and C-reactive protein (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.05), and monocyte chemoattractant protein-1 (P < 0.01) decreased. AT inflammation was reduced, determined from an increased m...... found in SM. The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM. Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low-grade inflammation. Markers of inflammation were particularly reduced in AT, whereas SM does not contribute to...

  5. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue

    DEFF Research Database (Denmark)

    Nielsen, Ninna Bo; Højbjerre, Lise; Sonne, Mette P;

    2009-01-01

    Adipokines play important regulatory roles in the pathophysiology of obesity and insulin resistance. We measured plasma and interstitial concentrations of the adipokines adiponectin, resistin, leptin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) in...... subcutaneous, abdominal and femoral adipose tissue using calibrated, large-pore microdialysis technique in 8 healthy, lean men on 2 experimental days. The interstitial leptin concentration was 2.5-fold higher in subcutaneous, femoral than abdominal adipose tissue (P<0.05), but no regional differences were...... found for the remaining adipokines (P>0.05). Adiponectin and leptin concentrations were higher in plasma than subcutaneous adipose tissue (approximately 25-fold and approximately 2-fold, respectively, P<0.05), whereas MCP-1, IL-6 and IL-8 concentrations were higher in subcutaneous adipose tissue than...

  6. Chemotaxis: new role for Ras revealed

    Institute of Scientific and Technical Information of China (English)

    Jianshe Yan; Dale Hereld; Tian Jin

    2010-01-01

    @@ A recent study of chemotaxis revealed a new role for the proto-oncogene Ras in the social ameba Dictyostelium discoideum.Chemotaxis,the directional movement of cells toward chemokines and other chemoattractants,plays critical roles in diverse physiological processes,such as mobilization of immune cells to fight invading microorganisms,targeting of metastatic cancer cells to specific tissues,and guidance of sperm cells to ova during fertilization.This work,published in the July 26 issue of The Journal of Cell Biology,was conducted in Dr.Devreotes' lab at John Hopkins University and Dr.Parent's lab at National Cancer Institute.This research team demonstrated that RasC functions as an upstream regulator of TORC2 and thereby governs the effects of TORC2-PKB signaling on the cytoskeleton and cell migration.

  7. Antileishmanial and immunomodulatory activity of Xylopia discreta.

    Science.gov (United States)

    López, R; Cuca, L E; Delgado, G

    2009-10-01

    This study aimed at determining the in vitro antileishmanial activity of the essential oil and eight extracts obtained from Xylopia discreta. J774 and U937 macrophages were exposed to the different substances to establish the median lethal concentration (LC(50)). The median effective concentration (EC(50)) was obtained by determining the reduction of Leishmania panamensis-infected cells. A selectivity index (SI) (LC(50)/EC(50)) >or= 20 defined a specific activity for one Xylopia discreta leaf extracts and for the essential oil, being these the two that showed the highest activity (SI = 64.8 and 110, respectively in J774 cells). To assess the substances' immunomodulatory activity, pro- and anti-inflammatory soluble mediators produced after treating infected macrophages were quantified by flow cytometry. The leaf methanol extract and the essential oil induced a differential production of monocyte chemoattractant protein-1, a chemokine associated with a Leishmania-resistant phenotype (Th1). PMID:19751474

  8. Citrus auraptene acts as an agonist for PPARs and enhances adiponectin production and MCP-1 reduction in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Citrus fruit compounds have many health-enhancing effects. In this study, using a luciferase ligand assay system, we showed that citrus auraptene activates peroxisome proliferator-activated receptor (PPAR)-α and PPARγ. Auraptene induced up-regulation of adiponectin expression and increased the ratio of the amount of high-molecular-weight multimers of adiponectin to the total adiponectin. In contrast, auraptene suppressed monocyte chemoattractant protein (MCP)-1 expression in 3T3-L1 adipocytes. Experiments using PPARγ antagonist demonstrated that these effects on regulation of adiponectin and MCP-1 expression were caused by PPARγ activations. The results indicate that auraptene activates PPARγ in adipocytes to control adipocytekines such as adiponectin and MCP-1 and suggest that the consumption of citrus fruits, which contain auraptene can lead to a partial prevention of lipid and glucose metabolism abnormalities

  9. Emergent Collective Chemotaxis without Single-Cell Gradient Sensing

    Science.gov (United States)

    Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan

    2016-03-01

    Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments show that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior is observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this "collective guidance," and study a model based on this mechanism both analytically and computationally. Our approach posits that contact inhibition of locomotion, where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how the cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance.

  10. Spontaneous hepatitis C viral clearance and hepatitis C chronic infection are associated with distinct cytokine profiles in Mexican patients

    Directory of Open Access Journals (Sweden)

    Nora A Fierro

    2015-04-01

    Full Text Available The mechanisms related to the spontaneous clearance of hepatitis C virus (HCV have been primarily studied in regions where the infection is endemic. Results of prior studies have been extrapolated to populations with low endemicity, such as Mexico. Herein, we determined the cytokine profiles in serum samples from Mexican patients who spontaneously cleared HCV and patients chronically infected with HCV genotype 1a. Chronic HCV-infected patients displayed increased interleukin (IL-8 and regulated upon activation, normal T-cell expressed and secreted (CCL-5 secretion, whereas patients who spontaneously cleared HCV showed augmented levels of IL-1 alpha, tumour necrosis factor-alpha, transforming growth factor-beta, monocyte chemoattractant protein-2 (CCL-8, IL-13 and IL-15. Our study suggeststhat cytokine profiles may predict disease outcome during HCV infection.

  11. Tp17 membrane protein of Treponema pallidum activates endothelial cells in vitro.

    Science.gov (United States)

    Zhang, Rui-Li; Wang, Qian-Qiu; Zhang, Jing-Ping; Yang, Li-Jia

    2015-04-01

    Tp17, a membrane immunogen of Treponema pallidum subsp. pallidum, was initially recognized as an inflammatory mediator of syphilis. Because the histopathology of syphilis is characterized by endothelial cell abnormalities, we investigated the effects of recombinant Tp17 (rTp17) on endothelial cell activation in vitro. Using real-time reverse transcription-PCR and whole-cell ELISA, we found that rTp17 activated endothelial cells, as demonstrated by the up-regulated expression and increased gene transcription of intercellular adhesion molecule 1 (ICAM-1), E-selectin, and monocyte chemoattractant protein-1 (MCP-1). rTp17 also enhanced the migration and subsequent adhesion of monocytes to endothelial cells as well as increased transendothelial migration of monocytes. These data suggest that the ability of Tp17 to activate endothelial cells may play an important role in the immunopathogenesis of syphilis. PMID:25744604

  12. Simulating individual-based models of bacterial chemotaxis with asymptotic variance reduction

    CERN Document Server

    Rousset, Mathias

    2011-01-01

    We discuss variance reduced simulations for an individual-based model of chemotaxis of bacteria with internal dynamics. The variance reduction is achieved via a coupling of this model with a simpler process in which the internal dynamics has been replaced by a direct gradient sensing of the chemoattractants concentrations. In the companion paper \\cite{limits}, we have rigorously shown, using a pathwise probabilistic technique, that both processes converge towards the same advection-diffusion process in the diffusive asymptotics. In this work, a direct coupling is achieved between paths of individual bacteria simulated by both models, by using the same sets of random numbers in both simulations. This coupling is used to construct a hybrid scheme with reduced variance. We first compute a deterministic solution of the kinetic density description of the direct gradient sensing model; the deviations due to the presence of internal dynamics are then evaluated via the coupled individual-based simulations. We show th...

  13. Increased migration of monocytes in essential hypertension is associated with increased transient receptor potential channel canonical type 3 channels

    DEFF Research Database (Denmark)

    Zhao, Zhigang; Ni, Yinxing; Chen, Jing; Zhong, Jian; Yu, Hao; Xu, Xingsen; He, Hongbo; Yan, Zhencheng; Scholze, Alexandra; Liu, Daoyan; Zhu, Zhiming; Tepel, Martin

    2012-01-01

    in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2-aminoethoxydiphenylborane (2-APB) and small...... interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246 ± 14% vs 151 ± 10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also...... significantly increased compared to normotensive control subjects (221 ± 20% vs 138 ± 18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from...

  14. Mast Cell-Mediated Mechanisms of Nociception

    Science.gov (United States)

    Aich, Anupam; Afrin, Lawrence B.; Gupta, Kalpna

    2015-01-01

    Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner. PMID:26690128

  15. Cannabinoid CB1 receptor inhibition decreases vascular smooth muscle migration and proliferation

    International Nuclear Information System (INIS)

    Vascular smooth muscle proliferation and migration triggered by inflammatory stimuli and chemoattractants such as platelet-derived growth factor (PDGF) are key events in the development and progression of atherosclerosis and restenosis. Cannabinoids may modulate cell proliferation and migration in various cell types through cannabinoid receptors. Here we investigated the effects of CB1 receptor antagonist rimonabant (SR141716A), which has recently been shown to have anti-atherosclerotic effects both in mice and humans, on PDGF-induced proliferation, migration, and signal transduction of human coronary artery smooth muscle cells (HCASMCs). PDGF induced Ras and ERK 1/2 activation, while increasing proliferation and migration of HCASMCs, which were dose dependently attenuated by CB1 antagonist, rimonabant. These findings suggest that in addition to improving plasma lipid alterations and decreasing inflammatory cell migration and inflammatory response, CB1 antagonists may exert beneficial effects in atherosclerosis and restenosis by decreasing vascular smooth muscle proliferation and migration.

  16. Ovarian fluid allows directional cryptic female choice despite external fertilization.

    Science.gov (United States)

    Alonzo, Suzanne H; Stiver, Kelly A; Marsh-Rollo, Susan E

    2016-01-01

    In species with internal fertilization, females can favour certain males over others, not only before mating but also within the female's reproductive tract after mating. Here, we ask whether such directional post-mating (that is, cryptic) female mate choice can also occur in species with external fertilization. Using an in vitro sperm competition experiment, we demonstrate that female ovarian fluid (ovarian fluid) changes the outcome of sperm competition by decreasing the importance of sperm number thereby increasing the relative importance of sperm velocity. We further show that ovarian fluid does not differentially affect sperm from alternative male phenotypes, but generally enhances sperm velocity, motility, straightness and chemoattraction. Under natural conditions, female ovarian fluid likely increases the paternity of the preferred parental male phenotype, as these males release fewer but faster sperm. These results imply females have greater control over fertilization and potential to exert selection on males in species with external fertilization than previously thought possible. PMID:27529581

  17. A possible role of chemotaxis in germinal center formation

    CERN Document Server

    Beyer, T; Soff, G; Beyer, Tilo; Meyer-Hermann, Michael; Soff, Gerhard

    2002-01-01

    During the germinal center reaction a characteristic morphology is developed. In the framework of a recently developed space-time-model for the germinal center a mechanism for the formation of dark and light zones has been proposed. The mechanism is based on a diffusing differentiation signal which is secerned by follicular dendritic cells. Here, we investigate a possible influence of recently found chemokines for the germinal center formation in the framework of a single-cell-based stochastic and discrete three-dimensional model. We will also consider alternative possible chemotactic pathways that may play a role for the development of both zones. Our results suggest that the centrocyte motility resulting from a follicular dendritic cell-derived chemokine has to exceed a lower limit to allow the separation of centroblasts and centrocytes. In contrast to light microscopy the dark zone is ring shaped. This suggests that FDC-derived chemoattractants alone cannot explain the typical germinal center morphology.

  18. Oxidative stress in tumor microenvironment——Its role in angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Armando ROJAS; Raúl SILVA; Héctor FIGUEROA; Miguel A MORALES

    2008-01-01

    The tumor angiogenesis process is believed to be dependent on an "angiogenic switch" formed by a cascade of biologic events as a consequence of the "cross-talk" between tumor cells and several components of local microenvironment including endothelial cells, macrophages, mast cells and stromal components. Oxidative stress represents an important stimulus that widely contributes to this angiogenic switch, which is particularly relevant in lungs,where oxidative stress is originated from different sources including the incomplete reduction of oxygen during respiration,exposure to hypoxia/reoxygenation, stimulated resident or chemoattracted immune ceils to lung tissues, as well as by a variety of chemicals compounds. In the present review we highlight the role of oxidative stress in tumor angiogenesis as a key signal linked to other relevant actors in this complex process.

  19. A Computational Model of Cell Migration in Response to Biochemical Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Dexter, Nicholas C [ORNL; Kruse, Kara L [ORNL; Nutaro, James J [ORNL; Ward, Richard C [ORNL

    2009-01-01

    The Computational Sciences and Engineering Division of the Oak Ridge National Laboratory is partnering with the University of Tennessee Graduate School of Medicine to design a computational model describing various factors related to the development of intimal hyperplasia (IH) in response to arterial injury. This research focuses on modeling the chemotactic and haptotactic processes that stimulate vascular smooth muscle cell migration into the intima. A hybrid discrete-continuous mathematical model of cell migration in response to biochemical diffusion was developed in C++. Chemoattractant diffusion is modeled as a continuous partial differential equation, whereas migration of the cells is modeled as a series of discrete events. Results obtained from the discrete state model for cell migration agree with those obtained from Boyden chamber experiments.

  20. The expression and role of CXC chemokines in colorectal cancer.

    Science.gov (United States)

    Verbeke, Hannelien; Struyf, Sofie; Laureys, Geneviève; Van Damme, Jo

    2011-01-01

    Cancer is a life-threatening disease world-wide and colorectal cancer is the second common cause of cancer mortality. The interaction between tumor cells and stromal cells plays a crucial role in tumor initiation and progression and is partially mediated by chemokines. Chemokines predominantly participate in the chemoattraction of leukocytes to inflammatory sites. Nowadays, it is clear that CXC chemokines and their receptors (CXCR) may also modulate tumor behavior by several important mechanisms: regulation of angiogenesis, activation of a tumor-specific immune response by attracting leukocytes, stimulation of tumor cell proliferation and metastasis. Here, we review the expression and complex roles of CXC chemokines (CXCL1 to CXCL16) and their receptors (CXCR1 to CXCR6) in colorectal cancer. Overall, increased expression levels of CXC chemokines correlate with poor prognosis. PMID:22000992

  1. Application of Coarse Integration to Bacterial Chemotaxis

    CERN Document Server

    Setayeshgar, S; Othmer, H G; Kevrekidis, Yu G

    2003-01-01

    We have developed and implemented a numerical evolution scheme for a class of stochastic problems in which the temporal evolution occurs on widely-separated time scales, and for which the slow evolution can be described in terms of a small number of moments of an underlying probability distribution. We demonstrate this method via a numerical simulation of chemotaxis in a population of motile, independent bacteria swimming in a prescribed gradient of a chemoattractant. The microscopic stochastic model, which is simulated using a Monte Carlo method, uses a simplified deterministic model for excitation/adaptation in signal transduction, coupled to a realistic, stochastic description of the flagellar motor. We show that projective time integration of ``coarse'' variables can be carried out on time scales long compared to that of the microscopic dynamics. Our coarse description is based on the spatial cell density distribution. Thus we are assuming that the system ``closes'' on this variable so that it can be desc...

  2. Traveling plateaus for a hyperbolic Keller-Segel system with attraction and repulsion: existence and branching instabilities

    CERN Document Server

    Perthame, Benoit; Tang, Min; Vauchelet, Nicolas

    2010-01-01

    How can repulsive and attractive forces, acting on a conservative system, create stable traveling patterns or branching instabilities? We have proposed to study this question in the framework of the hyperbolic Keller-Segel system with logistic sensitivity. This is a model system motivated by experiments on cell communities auto-organization, a field which is also called socio-biology. We continue earlier modeling work, where we have shown numerically that branching patterns arise for this system and we have analyzed this instability by formal asymptotics for small diffusivity of the chemo-repellent. Here we are interested in the more general situation, where the diffusivities of both the chemo-attractant and the chemo-repellent are positive. To do so, we develop an appropriate functional analysis framework. We apply our method to two cases. Firstly we analyze steady states. Secondly we analyze traveling waves when neglecting the degradation coefficient of the chemo-repellent; the unique wave speed appears thr...

  3. Microfluidic device to study cell transmigration under physiological shear stress conditions

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Kiilerich-Pedersen, Katrine; Moresco, Jacob Lange;

    2011-01-01

    the membrane under flow conditions. The 3D environment of migrating cells is imitated by injecting cell adhesion proteins to coat the membrane in the device. We tested the developed device with Jurkat cells migration towards medium supplemented with serum, and with chemokine induced lymphocytes...... natural migration process. Here we describe a novel in vitro cell transmigration microfluidic assay, which mimicks physiological shear flow conditions in blood vessels. The device was designed to incorporate the principles of both the Boyden chamber and the shear flow chamber assay, i.e. migration through...... migration. The applied continuous flow of cell suspension and chemoattractant ensures that the concentration gradient is maintained in time and space. The cell adhesion proteins used to enhance cell migration in the device were fibronectin and VCAM-1. We successfully observed a multistep transmigration...

  4. Travelling waves in hybrid chemotaxis models

    CERN Document Server

    Franz, Benjamin; Painter, Kevin J; Erban, Radek

    2013-01-01

    Hybrid models of chemotaxis combine agent-based models of cells with partial differential equation models of extracellular chemical signals. In this paper, travelling wave properties of hybrid models of bacterial chemotaxis are investigated. Bacteria are modelled using an agent-based (individual-based) approach with internal dynamics describing signal transduction. In addition to the chemotactic behaviour of the bacteria, the individual-based model also includes cell proliferation and death. Cells consume the extracellular nutrient field (chemoattractant) which is modelled using a partial differential equation. Mesoscopic and macroscopic equations representing the behaviour of the hybrid model are derived and the existence of travelling wave solutions for these models is established. It is shown that cell proliferation is necessary for the existence of non-transient (stationary) travelling waves in hybrid models. Additionally, a numerical comparison between the wave speeds of the continuum models and the hybr...

  5. Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Frøkiær, Hanne; Andersen, Anders D.; Lauritzen, Lotte

    2008-01-01

    , fibrinogen, C-reactive protein, interleukin-6, vascular cell adhesion molecule-1, P-selectin, oxidized LDL, cluster of differentiation antigen 40 ligand (CD40L), adiponectin, or fasting or postprandial BP or HR after adjustment for body weight changes. In conclusion, neither fish oil supplementation nor the...... intake in the S/B groups than in the R/K groups. Diet, (n-3) LCPUFA in peripheral blood mononuclear cells, blood pressure (BP), heart rate (HR), and plasma CVD risk markers were measured before and after the intervention. FO lowered fasting plasma triacylglycerol (TAG) (P <0.001) by 51% and 19% in the FO......+R/K-group and FO+S/B-group, respectively, which was also reflected in postprandial TAG measured after the intervention (P <0.01). Although a fat x FO interaction was found for monocyte chemoattractant protein-1, neither the FO nor fat intervention affected fasting plasma cholesterol, glucose, insulin...

  6. Targeted reduction of advanced glycation improves renal function in obesity

    DEFF Research Database (Denmark)

    Harcourt, Brooke E; Sourris, Karly C; Coughlan, Melinda T;

    2011-01-01

    Obesity is highly prevalent in Western populations and is considered a risk factor for the development of renal impairment. Interventions that reduce the tissue burden of advanced glycation end-products (AGEs) have shown promise in stemming the progression of chronic disease. Here we tested if...... function and an inflammatory profile (monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF)) were improved following the low-AGE diet. Mechanisms of advanced glycation-related renal damage were investigated in a mouse model of obesity using the AGE......, and renal oxidative stress. Alagebrium treatment, however, resulted in decreased weight gain and improved glycemic control compared with wild-type mice on a high-fat Western diet. Thus, targeted reduction of the advanced glycation pathway improved renal function in obesity....

  7. Stability and dynamics of anisotropically-tumbling chemotactic swimmers

    CERN Document Server

    Lushi, Enkeleida

    2016-01-01

    Micro-swimmers such as bacteria E. coli are known to perform random walks known as run-and-tumbles to move up chemo-attractant gradients and as a result aggregate. It is also known that such micro-swimmers can self-organize into macroscopic patterns due to interactions with neighboring cells through the fluidic environment they live in. While the pattern formation resulting from chemotactic and hydrodynamic interactions separately and together have been previously investigated, the effect of the tumbling anisotropy in micro-swimmers has been unexplored. Here we show through linear analysis and full nonlinear simulations that the slight anisotropy in the individual swimmer tumbles can alter the collective pattern formation in non-trivial ways. We show that the tumbling anisotropy diminishes the magnitude of the chemotactic aggregates but may result in more such aggregation peaks.

  8. A comparison of mathematical models for polarization of single eukaryotic cells in response to guided cues.

    Directory of Open Access Journals (Sweden)

    Alexandra Jilkine

    2011-04-01

    Full Text Available Polarization, a primary step in the response of an individual eukaryotic cell to a spatial stimulus, has attracted numerous theoretical treatments complementing experimental studies in a variety of cell types. While the phenomenon itself is universal, details differ across cell types, and across classes of models that have been proposed. Most models address how symmetry breaking leads to polarization, some in abstract settings, others based on specific biochemistry. Here, we compare polarization in response to a stimulus (e.g., a chemoattractant in cells typically used in experiments (yeast, amoebae, leukocytes, keratocytes, fibroblasts, and neurons, and, in parallel, responses of several prototypical models to typical stimulation protocols. We find that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness.

  9. Dicty_cDB: Contig-U05613-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 64_1( AY964064 |pid:none) Cavia porcellus chemoattractant re... 35 0.84 DQ216731_1( DQ216731 |pid:none) Taeniopygia guttat...|pid:none) Aspergillus niger contig An02c009... 39 0.076 CU928176_689( CU928176 |pid:none) Zygosaccharomyces rouxii strain...g-U13884-1Q.Seq.d Length = 1710 Score = 36.2 bits (18), Expect = 0.026 Identities = 18/18 (100%) Strand = Plus / Min...abase: nrp_A 3,268,448 sequences; 1,061,185,681 total letters Searching..................................................done Scor... CBS7... 41 0.015 CR382125_179( CR382125 |pid:none) Kluyveromyces lactis strain NRRL... 39

  10. Mast Cell-Mediated Mechanisms of Nociception

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    Anupam Aich

    2015-12-01

    Full Text Available Mast cells are tissue-resident immune cells that release immuno-modulators, chemo-attractants, vasoactive compounds, neuropeptides and growth factors in response to allergens and pathogens constituting a first line of host defense. The neuroimmune interface of immune cells modulating synaptic responses has been of increasing interest, and mast cells have been proposed as key players in orchestrating inflammation-associated pain pathobiology due to their proximity to both vasculature and nerve fibers. Molecular underpinnings of mast cell-mediated pain can be disease-specific. Understanding such mechanisms is critical for developing disease-specific targeted therapeutics to improve analgesic outcomes. We review molecular mechanisms that may contribute to nociception in a disease-specific manner.

  11. Innate Immunity Derived Factors as External Modulators of the CXCL12 - CXCR4 Axis and Their Role in Stem Cell Homing and Mobilization

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    Mariusz Z. Ratajczak, Karol Serwin, Gabriela Schneider

    2013-01-01

    Full Text Available The α-chemokine CXCL12 (stromal derived factor-1; SDF-1 and its corresponding GαI protein-coupled CXCR4 receptor axis play an important role in retention of hematopoietic stem progenitor cells (HSPCs in bone marrow (BM stem cell niches. CXCL12 has also been identified as a strong chemoattractant for HSPCs and implicated both in homing of HSPCs to BM after transplantation and in egress of these cells from BM into peripheral blood (PB. However, since CXCL12, as a peptide, is highly susceptible to degradation by proteolytic enzymes, its real biological availability in biological fluids may be somewhat limited. In this review, we will present data demonstrating that the CXCL12-CXCR4 axis is positively modulated by innate immunity-derived several external factors, ensuring that even low (near threshold doses of CXCL12 still exert a robust chemotactic influence on HSPCs.

  12. mRNA Transfection to Improve NK Cell Homing to Tumors.

    Science.gov (United States)

    Levy, Emily R; Carlsten, Mattias; Childs, Richard W

    2016-01-01

    The ability of natural killer (NK) cells to mediate antitumor effects following adoptive transfer is dependent on their capacity to traffic to the microenvironment where tumors reside. Recent studies have shown that cytokine-activated and ex vivo-expanded NK cells lack or express at low levels homing receptors required to achieve tissue-specific tumor targeting by cells administered intravenously. In this chapter, we describe a method to enhance NK cell homing toward specific chemoattractants expressed in secondary lymphoid tissues through genetic modification of NK cells using mRNA electroporation. The method described here is scalable, cGMP-compliant, and offers a strategy to bolster the efficacy of adoptive NK cell immunotherapy for the treatment of hematological malignancies in the clinic. PMID:27177670

  13. Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1alpha or its CCR5 receptor

    DEFF Research Database (Denmark)

    Tran, E H; Kuziel, W A; Owens, T

    2000-01-01

    Macrophage inflammatory protein (MIP)-1alpha is a chemokine that is associated with Th1 cytokine responses. Expression and antibody blocking studies have implicated MIP-1alpha in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). We examined the role of MIP-1alpha and...... its CCR5 receptor in the induction of EAE by immunizing C57BL / 6 mice deficient in either MIP-1alpha or CCR5 with myelin oligodendrocyte glycoprotein (MOG). We found that MIP-1alpha-deficient mice were fully susceptible to MOG-induced EAE. These knockout animals were indistinguishable from wild...... chemoattractant protein-1, MIP-1beta, MIP-2, lymphotactin and T cell activation gene-3 during the course of the disease. CCR5-deficient mice were also susceptible to disease induction by MOG. The dispensability of MIP-1alpha and CCR5 for MOG-induced EAE in C57BL / 6 mice supports the idea that differential...

  14. A PKC-dependent recruitment of MMP-2 controls semaphorin-3A growth-promoting effect in cortical dendrites.

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    Bertrand Gonthier

    Full Text Available There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3. Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved.

  15. Lung-homing of endothelial progenitor cells and airway vascularization is only partially dependant on eosinophils in a house dust mite-exposed mouse model of allergic asthma.

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    Nirooya Sivapalan

    Full Text Available Asthmatic responses involve a systemic component where activation of the bone marrow leads to mobilization and lung-homing of progenitor cells. This traffic may be driven by stromal cell derived factor-1 (SDF-1, a potent progenitor chemoattractant. We have previously shown that airway angiogenesis, an early remodeling event, can be inhibited by preventing the migration of endothelial progenitor cells (EPC to the lungs. Given intranasally, AMD3100, a CXCR4 antagonist that inhibits SDF-1 mediated effects, attenuated allergen-induced lung-homing of EPC, vascularization of pulmonary tissue, airway eosinophilia and development of airway hyperresponsiveness. Since SDF-1 is also an eosinophil chemoattractant, we investigated, using a transgenic eosinophil deficient mouse strain (PHIL whether EPC lung accumulation and lung vascularization in allergic airway responses is dependent on eosinophilic inflammation.Wild-type (WT BALB/c and eosinophil deficient (PHIL mice were sensitized to house dust mite (HDM using a chronic exposure protocol and treated with AMD3100 to modulate SDF-1 stimulated progenitor traffic. Following HDM challenge, lung-extracted EPCs were enumerated along with airway inflammation, microvessel density (MVD and airway methacholine responsiveness (AHR.Following Ag sensitization, both WT and PHIL mice exhibited HDM-induced increase in airway inflammation, EPC lung-accumulation, lung angiogenesis and AHR. Treatment with AMD3100 significantly attenuated outcome measures in both groups of mice. Significantly lower levels of EPC and a trend for lower vascularization were detected in PHIL versus WT mice.This study shows that while allergen-induced lung-homing of endothelial progenitor cells, increased tissue vascularization and development lung dysfunction can occur in the absence of eosinophils, the presence of these cells worsens the pathology of the allergic response.

  16. Response coefficient analysis of E. coli chemotaxis to parametric perturbations under the influence of noise

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    Pratap R Patnaik

    2012-08-01

    Full Text Available Escherichia coli and other bacteria navigating through ‘open’ environments are under the impact of noise from the environment and from within the cells. This generates fluctuations in the kinetic parameters that characterize the intra-cellular reactions of the chemosensory network, thus affecting the chemotaxis of the cells. This aspect has been studied here for E. coli synthesizing recombinant glucoamylase in a continuous-flow microreactor. Response coefficient analysis (RCA was applied to a new four-parameter model of the chemotaxis of E. coli. The model considered two types of responses of the cells – linear and adaptive – and two rates of movement of the chemoattractant – slow and fast. Some cells at each position in the microreactor were considered to be moving to the left, some to the right and others in a tumbling state. Striking similarities and differences were observed between the different types of cells, between linear and adaptive responses, and between the kinetic responses to a slow-moving and a fast-moving chemoattractant distribution. One salient observation was that the response coefficients of the left-moving and right-moving sub-populations were mirror images of each other. Tumbling cells either had intermediate characteristics in some situations, as might be expected, or, in other circumstances, resembled the left-moving cells more than they corresponded to the right-moving bacteria. Under certain conditions, cells with normal linear responses exhibited pseudo-adaptive kinetic behavior. Such unexpected observations have been explained. The results offer new insights into possible quantitative effects of environmental noise on the chemotaxis of E. coli and other bacteria.

  17. The parity-associated microenvironmental niche in the omental fat band is refractory to ovarian cancer metastasis.

    Science.gov (United States)

    Cohen, Courtney A; Shea, Amanda A; Heffron, C Lynn; Schmelz, Eva M; Roberts, Paul C

    2013-11-01

    Ovarian cancer is an insidious and aggressive disease of older women, typically undiscovered before peritoneal metastasis due to its asymptomatic nature and lack of early detection tools. Epidemiologic studies suggest that child-bearing (parity) is associated with decreased ovarian cancer risk, although the molecular mechanisms responsible for this phenomenon have not been delineated. Ovarian cancer preferentially metastasizes to the omental fat band (OFB), a secondary lymphoid organ that aids in filtration of the peritoneal serous fluid (PSF) and helps combat peritoneal infections. In the present study, we assessed how parity and age impact the immune compositional profile in the OFB of mice, both in the homeostatic state and as a consequence of peritoneal implantation of ovarian cancer. Using fluorescence-activated cell sorting analysis and quantitative real-time PCR, we found that parity was associated with a significant reduction in omental monocytic subsets and B1-B lymphocytes, correlating with reduced homeostatic expression levels of key chemoattractants and polarization factors (Ccl1, Ccl2, Arg1, and Cxcl13). Of note, parous animals exhibited significantly reduced tumor burden following intraperitoneal implantation compared with nulliparous animals. This was associated with a reduction in tumor-associated neutrophils and macrophages, as well as in the expression levels of their chemoattractants (Cxcl1 and Cxcl5) in the OFB and PSF. These findings define a preexisting "parity-associated microenvironmental niche" in the OFB that is refractory to metastatic tumor seeding and outgrowth. Future studies designed to manipulate this niche may provide a novel means to mitigate peritoneal dissemination of ovarian cancer. PMID:24022590

  18. Role of platelet-derived growth factor/platelet-derived growth factor receptor axis in the trafficking of circulating fibrocytes in pulmonary fibrosis.

    Science.gov (United States)

    Aono, Yoshinori; Kishi, Masami; Yokota, Yuki; Azuma, Momoyo; Kinoshita, Katsuhiro; Takezaki, Akio; Sato, Seidai; Kawano, Hiroshi; Kishi, Jun; Goto, Hisatsugu; Uehara, Hisanori; Izumi, Keisuke; Nishioka, Yasuhiko

    2014-12-01

    Circulating fibrocytes have been reported to migrate into the injured lungs, and contribute to fibrogenesis via CXCL12-CXCR4 axis. In contrast, we report that imatinib mesylate prevented bleomycin (BLM)-induced pulmonary fibrosis in mice by inhibiting platelet-derived growth factor receptor (PDGFR), even when it was administered only in the early phase. The goal of this study was to test the hypothesis that platelet-derived growth factor (PDGF) might directly contribute to the migration of fibrocytes to the injured lungs. PDGFR expression in fibrocytes was examined by flow cytometry and RT-PCR. The migration of fibrocytes was evaluated by using a chemotaxis assay for human fibrocytes isolated from peripheral blood. The numbers of fibrocytes triple-stained for CD45, collagen-1, and CXCR4 were also examined in lung digests of BLM-treated mice. PDGFR mRNA levels in fibrocytes isolated from patients with idiopathic pulmonary fibrosis were investigated by real-time PCR. Fibrocytes expressed both PDGFR-α and -β, and migrated in response to PDGFs. PDGFR inhibitors (imatinib, PDGFR-blocking antibodies) suppressed fibrocyte migration in vitro, and reduced the number of fibrocytes in the lungs of BLM-treated mice. PDGF-BB was a stronger chemoattractant than the other PDGFs in vitro, and anti-PDGFR-β-blocking antibody decreased the numbers of fibrocytes in the lungs compared with anti-PDGFR-α antibody in vivo. Marked expression of PDGFR-β was observed in fibrocytes from patients with idiopathic pulmonary fibrosis compared with healthy subjects. These results suggest that PDGF directly functions as a strong chemoattractant for fibrocytes. In particular, the PDGF-BB-PDGFR-β biological axis might play a critical role in fibrocyte migration into the fibrotic lungs. PMID:24885373

  19. Pericytes: brain-immune interface modulators

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    Gabriela eHurtado-Alvarado

    2014-01-01

    Full Text Available The premise that the central nervous system is immune-privileged arose from the fact that direct contact between immune and nervous cells is hindered by the blood-brain barrier. However, the blood-brain barrier also comprises the interface between the immune and nervous systems by secreting chemo-attractant molecules and by modulating immune cell entry into the brain. The majority of published studies on the blood-brain barrier focus on endothelial cells, which are a critical component, but not the only one; other cellular components include astroglia, microglia, and pericytes. Pericytes are poorly studied in comparison with astrocytes or endothelial cells; they are mesenchymal cells that can modify their ultrastructure and gene expression in response to changes in the central nervous system microenvironment. Pericytes have a unique synergistic relationship with brain endothelial cells in the regulation of capillary permeability through secretion of cytokines, chemokines, nitric oxide, matrix metallo-proteinases, and by means of capillary contraction. Those pericyte manifestations are related to changes in blood-brain barrier permeability by an increase in endocytosis-mediated transport and by tight junction disruption. In addition, recent reports demonstrate that pericytes control the migration of leukocytes in response to inflammatory mediators by up-regulating the expression of adhesion molecules and releasing chemo-attractants; however, under physiological conditions they appear to be immune-suppressors. Better understanding of the immune properties of pericytes and their participation in the effects of brain infections, neurodegenerative diseases, and sleep loss will be achieved by analyzing pericyte ultrastructure, capillary coverage, and protein expression. That knowledge may provide a mechanism by which pericytes participate in the maintenance of the proper function of the brain-immune interface.

  20. Imaging neutrophil migration dynamics using micro-optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Chu, Kengyeh K.; Yonker, Lael; Som, Avira; Pazos, Michael; Kusek, Mark E.; Hurley, Bryan P.; Tearney, Guillermo J.

    2016-03-01

    Neutrophils are immune cells that undergo chemotaxis, detecting and migrating towards a chemical signal gradient. Neutrophils actively migrate across epithelial boundaries, interacting with the epithelium to selectively permit passage without compromising the epithelial barrier. In many inflammatory disorders, excessive neutrophil migration can cause damage to the epithelium itself. The signaling pathways and mechanisms that facilitate trans-epithelial migration are not fully characterized. Our laboratory has developed micro-optical coherence tomography (μOCT), which has 2 μm lateral resolution and 1 μm axial resolution. As a high-resolution native contrast modality, μOCT can directly visualize individual neutrophils as they interact with a cell layer cultured on a transwell filter. A chemoattractant can be applied to the apical side of inverted monolayer, and human neutrophils placed in the basolateral compartment, while μOCT captures 3D images of the chemotaxis. μOCT images can also generate quantitative metrics of migration volume to study the dependence of chemotaxis on monolayer cell type, chemoattractant type, and disease state of the neutrophils. For example, a disease known as leukocyte adhesion deficiency (LAD) can be simulated by treating neutrophils with antibodies that interfere with the CD18 receptor, a facilitator of trans-epithelial migration. We conducted a migration study of anti-CD18 treated and control neutrophils using T84 intestinal epithelium as a barrier. After one hour, μOCT time-lapse imaging indicated a strong difference in the fraction of neutrophils that remain attached to the epithelium after migration (0.67 +/- 0.12 attached anti-CD18 neutrophils, 0.23 +/- 0.08 attached control neutrophils, n = 6, p immune diseases.

  1. 4-hydroxy-2, 3-nonenal activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Kikuta; Atsushi Masamune; Masahiro Satoh; Noriaki Suzuki; Tooru Shimosegawa

    2004-01-01

    AIM: Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis,where oxidative stress is thought to play a key role. 4-hydroxy2,3-nonenal (HNE) is generated endogenously during the process of lipid peroxidation, and has been accepted as a mediator of oxidative stress. The aim of this study was to clarify the effects of HNE on the activation of signal transduction pathways and cellular functions in PSCs.METHODS: PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase P, and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. PSCs were treated with physiologically relevant and non-cytotoxic concentrations (up to 5 μmol/L)of HNE. Activation of transcription factors was examined by electrophoretic mobility shift assay and luciferase assay.Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Production of type Ⅰ collagen and monocyte chemoattractant protein-1was determined by enzyme-linked immunosorbent assay.The effect of HNE on the transformation of freshly isolated PSCs in culture was also assessed.RESULTS: HNE activated activator protein-1, but not nuclear factor κB. In addition, HNE activated three classes of MAP kinases: extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAP kinase. HNE increased type Ⅰ collagen production through the activation of p38 MAP kinase and c-Jun N-terminal kinase. HNE did not alter the proliferation,or monocyte chemoattractant protein-1 production. HNE did not initiate the transformation of freshly isolated PSCs to myofibroblast-like phenotype.CONCLUSION: Specific activation of these signal transduction pathways and altered cell functions such as collagen production by HNE may play a role in the pathogenesis of pancreatic

  2. Macrophages clear refrigerator storage-damaged RBCs and subsequently secrete cytokines in vivo, but not in vitro, in a murine model

    Science.gov (United States)

    Wojczyk, Boguslaw S.; Kim, Nina; Bandyopadhyay, Sheila; Francis, Richard O.; Zimring, James C.; Hod, Eldad A.; Spitalnik, Steven L.

    2014-01-01

    BACKGROUND In mice, refrigerator-stored red blood cells (RBCs) are cleared by extravascular hemolysis and induce cytokine production. To enhance understanding of this phenomenon, we sought to model it in vitro. STUDY DESIGN AND METHODS Ingestion of refrigerator-stored murine RBCs and subsequent cytokine production were studied using J774A.1 mouse macrophage cells and primary murine splenic macrophages. Wild-type and Ccl2-GFP-reporter mice were used for RBC clearance in vivo. RESULTS Although J774A.1 cells and primary macrophages preferentially ingested refrigerator-stored RBCs in vitro, as compared to freshly-isolated RBCs, neither produced increased cytokines following erythrophagocytosis. In contrast, phagocytosis of refrigerator-stored RBCs in vivo induced increases in circulating monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC), and correspondingly increased mRNA levels in mouse spleen and liver. In the spleen, these were predominantly expressed by CD11b+ cells. Using Ccl2-GFP-reporter mice, the predominant splenic population responsible for MCP-1 mRNA production were tissue-resident macrophages (i.e., CD45+, CD11b+, F4/80+, Ly6c+, CD11clow cells). CONCLUSION J774A.1 cells and primary macrophages selectively ingested refrigerator-stored RBCs by phagocytosis. Although cytokine expression was not enhanced, this approach could be used to identify the relevant receptor-ligand combination(s). In contrast, cytokine levels increased following phagocytosis of refrigerator-stored RBCs in vivo. These were primarily cleared in the liver and spleen, which demonstrated increased MCP-1 and KC mRNA expression. Finally, in mouse spleen, tissue-resident macrophages were predominantly involved in MCP-1 mRNA production. The differences between cytokine production in vitro and in vivo are not yet well understood. PMID:25041478

  3. Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice

    Science.gov (United States)

    Hong, Fashui; Wang, Ling; Yu, Xiaohong; Zhou, Yingjun; Hong, Jie; Sheng, Lei

    2015-08-01

    Currently, impacts of exposure to TiO2 nanoparticles (NPs) on the cardiovascular system are not well understood. The aim of this study was to investigate whether TiO2 NPs induce myocarditis and its underlying molecular mechanism in the cardiac inflammation in mice. Mice were exposed to TiO2 NPs for 6 months; biochemical parameters of serum and expression of Th1-related and Th2-related cytokines in the heart were investigated. The results showed that TiO2 NP exposure resulted in cardiac lesions coupling with pulmonary inflammation; increases of aspartate aminotransferase (AST), creatine kinase (CK), C-reaction protein (CRP), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels; and a reduction of nitric oxide (NOx) level in the serum. These were associated with increases of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, transforming growth factor-β (TGF-β), creatine kinase, CRP, adhesion molecule-1, and monocyte chemoattractant protein-1, interferon-γ (IFN-γ), signal transducers and activators of transcription (STAT)1, STAT3, or STAT6, GATA-binding domain-3, GATA-binding domain-4, endothelin-1 expression levels, and T-box expressed in T cells expression level that is the master regulator of pro-inflammatory cytokines and transcription factors in the heart. These findings imply that TiO2 NP exposure may increase the occurrence and development of cardiovascular diseases.

  4. The Effect Of Chemotaxis On The Swarming Ability Of Bacillus Subtilis Critical Effect Of Glutamic Acid And Lysine

    Directory of Open Access Journals (Sweden)

    Lina Hamouche

    2015-08-01

    Full Text Available Abstract Bacterial cells differentiation constitutes an appropriate and efficient way to respond to an ever-changing environment. Bacillus subtilis are no different where in some conditions planktonic cells differentiate into highly motile swarmer cells. The hyperflagellated swarmer cells located usually at the colony edge move in a cooperative manner in order to reconnoiter new sites for colonization this movement is called swarming. The chemotaxis proteins take a part of several factors playing an essential role in swarmer differentiation hence migration therefore we assumed a connection between chemotaxis and swarming profile of B. subtilis. To this end we examined the effect of amino acids chemoattractants glutamic acid and lysine deprivation on the capability of swarming. Here we show that deprivation of synthetic B-media from glutamic acid result on attenuated defective and random swarming pattern deprivation of lysine lead to an almost normal swarming pattern meanwhile double deprivation of both amino acids result in important reduction of swarming capability. Moreover we developed a method to screen the chemotaxis clearly using swarm plates with concentration gradient. Using this approach we found that B. subtilis manage to swarm completely toward glutamic acid and didnt swarm toward medium lacking this amino acid meanwhile the bacteria manage to swarm in all sides of plates with concentration gradient of lysine. Furthermore our results indicate that these two chemoattractants can reduce the motility by modulating the expression of hag gene. The absence of glutamic acid and lysine decrease the expression of hag during swarming respectively for 36 and 15.

  5. The connection of monocytes and reactive oxygen species in pain.

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    Dagmar Hackel

    Full Text Available The interplay of specific leukocyte subpopulations, resident cells and proalgesic mediators results in pain in inflammation. Proalgesic mediators like reactive oxygen species (ROS and downstream products elicit pain by stimulation of transient receptor potential (TRP channels. The contribution of leukocyte subpopulations however is less clear. Local injection of neutrophilic chemokines elicits neutrophil recruitment but no hyperalgesia in rats. In meta-analyses the monocytic chemoattractant, CCL2 (monocyte chemoattractant protein-1; MCP-1, was identified as an important factor in the pathophysiology of human and animal pain. In this study, intraplantar injection of CCL2 elicited thermal and mechanical pain in Wistar but not in Dark Agouti (DA rats, which lack p47(phox, a part of the NADPH oxidase complex. Inflammatory hyperalgesia after complete Freund's adjuvant (CFA as well as capsaicin-induced hyperalgesia and capsaicin-induced current flow in dorsal root ganglion neurons in DA were comparable to Wistar rats. Macrophages from DA expressed lower levels of CCR2 and thereby migrated less towards CCL2 and formed limited amounts of ROS in vitro and 4-hydroxynonenal (4-HNE in the tissue in response to CCL2 compared to Wistar rats. Local adoptive transfer of peritoneal macrophages from Wistar but not from DA rats reconstituted CCL2-triggered hyperalgesia in leukocyte-depleted DA and Wistar rats. A pharmacological stimulator of ROS production (phytol restored CCL2-induced hyperalgesia in vivo in DA rats. In Wistar rats, CCL2-induced hyperalgesia was completely blocked by superoxide dismutase (SOD, catalase or tempol. Likewise, inhibition of NADPH oxidase by apocynin reduced CCL2-elicited hyperalgesia but not CFA-induced inflammatory hyperalgesia. In summary, we provide a link between CCL2, CCR2 expression on macrophages, NADPH oxidase, ROS and the development CCL2-triggered hyperalgesia, which is different from CFA-induced hyperalgesia. The study

  6. Elevated bronchoalveolar concentrations of MCP-1 in patients with pulmonary alveolar proteinosis.

    Science.gov (United States)

    Iyonaga, K; Suga, M; Yamamoto, T; Ichiyasu, H; Miyakawa, H; Ando, M

    1999-08-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown aetiology characterized by accumulations of lipoproteinaceous material within the alveoli. The alveolar macrophages become increasingly foamy, and are thought to have a role in the pathogenesis of PAP. However, the mechanisms of macrophage recruitment are unclear. In the bronchoalveolar lavage fluid (BALF) of four patients with PAP and 20 normal control subjects, the following were examined: the monocyte chemotactic activity due to the chemokine monocyte chemoattractant protein (MCP)-1 with the use of a chemotactic chamber assay, the levels of MCP-1 by enzyme-linked immunosorbent assay, and the MCP-1 expression on lavage cells by immunocytochemistry and in situ hybridization. The monocyte chemotactic activity in the BALF of the PAP patients was markedly elevated, and the activity was completely absorbed by treatment with anti-MCP-1. The MCP-1 levels in the BALF were surprisingly high in the PAP group (25,100+/-472 pg x mL(-1)), whereas low levels of MCP-1 were detected in the normal control subjects (mean: never smokers 4.8; smokers 10.4 pg x mL(-1)). MCP-1 protein and messenger ribonucleic acid were expressed by macrophages from the PAP patients, and the expression was reduced according to foaming of the cells; there were monocyte-like macrophages with strong expression, small foamy cells with moderate expression, large foamy cells with a faint expression of MCP-1, and ghost cells with no expression. However, the increase of macrophage number in the PAP BALF was relatively small. These data suggest that monocyte chemoattractant protein(-1) expression by alveolar macrophages represents an amplification mechanism for the recruitment of additional macrophages to the alveoli in pulmonary alveolar proteinosis. It is possible that an ingestion of an excess of alveolar materials in pulmonary alveolar proteinosis may impair the macrophage function and the survival, resulting in the lack of a prominent

  7. Sensitivity of the rate of nutrient uptake by chemotactic bacteria to physical and biological parameters in a turbulent environment.

    Science.gov (United States)

    Watteaux, Romain; Stocker, Roman; Taylor, John R

    2015-12-21

    In this study, we use direct numerical simulations (DNS) to investigate the response of chemotactic bacteria to an isolated patch of chemoattractant in a turbulent environment. Previous work has shown that by stirring nutrients that are chemoattractants into a network of thin, elongated filaments, turbulence directly influences the rate at which chemotactic bacteria consume nutrients. However, the quantitative outcome of this process is influenced by a host of physical and biological factors, and many of these remain unexplored. Here, we analyse the sensitivity of nutrient uptake by chemotactic bacteria on a wide range of physical and biological parameters using a series of controlled DNS. Starting with uniformly distributed populations of motile and non-motile bacteria in a fully developed homogeneous, isotropic turbulent flow, we inject a patch of dissolved nutrients. We then assess the chemotactic advantage, defined as the difference between the nutrients consumed by motile and non-motile bacteria over the lifetime of the patch. We find that the chemotaxis can enhance the total uptake rate by a factor of 1.6 and allows the population of chemotactic bacteria to absorb nutrients 2.2 times faster than non-motile bacteria Results show that chemotactic bacteria are subject to a trade-off between swimming to leave regions devoid of nutrients and, once a nutrient gradient is detected, staying in regions of large nutrient concentration. These findings could help explain how the physical characteristics of turbulent marine ecosystems influence the optimal biological traits of bacteria through the competition for limited resources. PMID:26392215

  8. Chemical basis of prey recognition in thamnophiine snakes: the unexpected new roles of parvalbumins.

    Directory of Open Access Journals (Sweden)

    Maïté Smargiassi

    Full Text Available Detecting and locating prey are key to predatory success within trophic chains. Predators use various signals through specialized visual, olfactory, auditory or tactile sensory systems to pinpoint their prey. Snakes chemically sense their prey through a highly developed auxiliary olfactory sense organ, the vomeronasal organ (VNO. In natricine snakes that are able to feed on land and water, the VNO plays a critical role in predatory behavior by detecting cues, known as vomodors, which are produced by their potential prey. However, the chemical nature of these cues remains unclear. Recently, we demonstrated that specific proteins-parvalbumins-present in the cutaneous mucus of the common frog (Rana temporaria may be natural chemoattractive proteins for these snakes. Here, we show that parvalbumins and parvalbumin-like proteins, which are mainly intracellular, are physiologically present in the epidermal mucous cells and mucus of several frog and fish genera from both fresh and salt water. These proteins are located in many tissues and function as Ca(2+ buffers. In addition, we clarified the intrinsic role of parvalbumins present in the cutaneous mucus of amphibians and fishes. We demonstrate that these Ca(2+-binding proteins participate in innate bacterial defense mechanisms by means of calcium chelation. We show that these parvalbumins are chemoattractive for three different thamnophiine snakes, suggesting that these chemicals play a key role in their prey-recognition mechanism. Therefore, we suggest that recognition of parvalbumin-like proteins or other calcium-binding proteins by the VNO could be a generalized prey-recognition process in snakes. Detecting innate prey defense mechanism compounds may have driven the evolution of this predator-prey interaction.

  9. Protective effects of ghrelin on cisplatin-induced nephrotoxicity in mice.

    Science.gov (United States)

    Nojiri, Takashi; Hosoda, Hiroshi; Kimura, Toru; Tokudome, Takeshi; Miura, Koichi; Takabatake, Hiroyuki; Miyazato, Mikiya; Okumura, Meinoshin; Kangawa, Kenji

    2016-08-01

    Cisplatin is a potent chemotherapeutic agent that has activity against malignant tumors. However, cisplatin causes various adverse effects, such as nephrotoxicity, which are associated with high morbidity and mortality. Recent studies have revealed that the mechanism of cisplatin nephrotoxicity includes a robust inflammatory response. Since ghrelin has been shown to have anti-inflammatory properties, we hypothesized that ghrelin might have protective effects against cisplatin nephrotoxicity. Mice were randomly divided into three groups: control, cisplatin with vehicle, and cisplatin with ghrelin. Ghrelin (0.8μg/kg/min via osmotic-pump, subcutaneously) or vehicle administration was started one day before cisplatin injection. At 72h after cisplatin administration (20mg/kg, intraperitoneally), we measured serum blood urea nitrogen and creatinine, urine albumin/creatinine, renal mRNA levels of monocyte chemoattractant protein-1, interleukin-6, tumor necrosis factor-α, interleukin-1β, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin by real-time polymerase chain reaction, and histological changes. Ghrelin significantly attenuated the increase in serum blood urea nitrogen and creatinine induced by cisplatin. Ghrelin tended to attenuate the increase in urine albumin/creatinine, although not significantly. Cisplatin-induced renal tubular injury and apoptosis were significantly attenuated by ghrelin pretreatment. Consequently, ghrelin significantly attenuated renal mRNA levels of monocyte chemoattractant protein-1, interleukin-6, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin. In conclusion, ghrelin produces protective effects in cisplatin-induced nephrotoxicity through inhibition of inflammatory reactions. Pretreatment with ghrelin may become a new prophylactic candidate for cisplatin-induced nephrotoxicity. PMID:27298204

  10. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers.

    Science.gov (United States)

    Kjell, Jacob; Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew; Olson, Lars

    2015-11-01

    With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines--monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)--to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  11. Matrix metalloproteinases and chemokines in the gingival crevicular fluid during orthodontic tooth movement.

    Science.gov (United States)

    Capelli, Jonas; Kantarci, Alpdogan; Haffajee, Anne; Teles, Ricardo Palmier; Fidel, Rivail; Figueredo, Carlos Marcelo

    2011-12-01

    Matrix metalloproteinases (MMPs) and monocyte chemoattractants are key modulators of the biological mechanisms triggered in the periodontium by mechanical forces. The gingival crevicular fluid (GCF) provides a non-invasive method to assess longitudinally the release of inflammatory mediators during orthodontic tooth movement. The goal of this study was to examine the GCF levels of MMP-3, MMP-9, and MMP-13 and of the chemokines macrophage inflammatory protein (MIP)-1β, monocyte chemoattractant protein (MCP)-1, and regulated on activation normal T cells expressed and secreted (RANTES) at different time points during orthodontic tooth movement. Fourteen subjects (three males and 11 females, 18.8 ± 4.8 years of age; range from 12 to 28 years) had their maxillary canines retracted. Thirty-second GCF samples were collected from the tension and pressure sides 7 days prior to the activation of the orthodontic appliance, on the day of activation, and after 1 and 24 hours, and 14, 21, and 80 days of constant force application. The volume of GCF was measured and samples analysed using a multiplexed bead immunoassay for the content of the six target molecules. Differences in the mean GFC volumes and mean level for each analyte over time were assessed using the Friedman test, and differences between the tension and pressure sides at each time point with the Mann-Whitney test. The mean levels of the three MMPs changed significantly over time but only at the compression side (P < 0.05, Friedman test). The GCF levels of the three chemokines were not affected by the application of mechanical stress. The levels of MMPs in GCF at the pressure side are modulated by the application of orthodontic force. PMID:21389074

  12. Contact-inhibited chemotaxis in de novo and sprouting blood-vessel growth.

    Directory of Open Access Journals (Sweden)

    Roeland M H Merks

    Full Text Available Blood vessels form either when dispersed endothelial cells (the cells lining the inner walls of fully formed blood vessels organize into a vessel network (vasculogenesis, or by sprouting or splitting of existing blood vessels (angiogenesis. Although they are closely related biologically, no current model explains both phenomena with a single biophysical mechanism. Most computational models describe sprouting at the level of the blood vessel, ignoring how cell behavior drives branch splitting during sprouting. We present a cell-based, Glazier-Graner-Hogeweg model (also called Cellular Potts Model simulation of the initial patterning before the vascular cords form lumens, based on plausible behaviors of endothelial cells. The endothelial cells secrete a chemoattractant, which attracts other endothelial cells. As in the classic Keller-Segel model, chemotaxis by itself causes cells to aggregate into isolated clusters. However, including experimentally observed VE-cadherin-mediated contact inhibition of chemotaxis in the simulation causes randomly distributed cells to organize into networks and cell aggregates to sprout, reproducing aspects of both de novo and sprouting blood-vessel growth. We discuss two branching instabilities responsible for our results. Cells at the surfaces of cell clusters attempting to migrate to the centers of the clusters produce a buckling instability. In a model variant that eliminates the surface-normal force, a dissipative mechanism drives sprouting, with the secreted chemical acting both as a chemoattractant and as an inhibitor of pseudopod extension. Both mechanisms would also apply if force transmission through the extracellular matrix rather than chemical signaling mediated cell-cell interactions. The branching instabilities responsible for our results, which result from contact inhibition of chemotaxis, are both generic developmental mechanisms and interesting examples of unusual patterning instabilities.

  13. Trehalose is a chemical attractant in the establishment of coral symbiosis.

    Directory of Open Access Journals (Sweden)

    Mary Hagedorn

    Full Text Available Coral reefs have evolved with a crucial symbiosis between photosynthetic dinoflagellates (genus Symbiodinium and their cnidarian hosts (Scleractinians. Most coral larvae take up Symbiodinium from their environment; however, the earliest steps in this process have been elusive. Here we demonstrate that the disaccharide trehalose may be an important signal from the symbiont to potential larval hosts. Symbiodinium freshly isolated from Fungia scutaria corals constantly released trehalose (but not sucrose, maltose or glucose into seawater, and released glycerol only in the presence of coral tissue. Spawning Fungia adults increased symbiont number in their immediate area by excreting pellets of Symbiodinium, and when these naturally discharged Symbiodinium were cultured, they also released trehalose. In Y-maze experiments, coral larvae demonstrated chemoattractant and feeding behaviors only towards a chamber with trehalose or glycerol. Concomitantly, coral larvae and adult tissue, but not symbionts, had significant trehalase enzymatic activities, suggesting the capacity to utilize trehalose. Trehalase activity was developmentally regulated in F. scutaria larvae, rising as the time for symbiont uptake occurs. Consistent with the enzymatic assays, gene finding demonstrated the presence of a trehalase enzyme in the genome of a related coral, Acropora digitifera, and a likely trehalase in the transcriptome of F. scutaria. Taken together, these data suggest that adult F. scutaria seed the reef with Symbiodinium during spawning and the exuded Symbiodinium release trehalose into the environment, which acts as a chemoattractant for F. scutaria larvae and as an initiator of feeding behavior- the first stages toward establishing the coral-Symbiodinium relationship. Because trehalose is a fixed carbon compound, this cue would accurately demonstrate to the cnidarian larvae the photosynthetic ability of the potential symbiont in the ambient environment. To our

  14. FTY720 Attenuates Acute Pancreatitis in Hypertriglyceridemic Apolipoprotein CIII Transgenic Mice.

    Science.gov (United States)

    Liu, Jinjiao; Xu, Pengfei; Zhang, Ling; Kayoumu, Abudurexiti; Wang, Yunan; Wang, Mengyu; Gao, Mingming; Zhang, Xiaohong; Wang, Yuhui; Liu, George

    2015-09-01

    Hypertriglyceridemic pancreatitis (HTGP) is often encountered clinically as a common form of recurrent acute pancreatitis (AP). It is important to evaluate the management of severe hypertriglyceridemia (HTG) or anti-inflammation in the prophylaxis of HTGP in the clinic. FTY720 (2-amino-2[2-(4-octylphenyl) ethyl]-1, 3-propanediol) is a new anti-inflammatory agent with low toxicity and reported to ameliorate lung injury with pancreatitis in rat. We evaluated its protective affection on AP induced by seven hourly intraperitoneal injection of cerulein in apolipoprotein CIII transgenic mice with severe HTG. FTY720 at 1.5 mg/kg was administered by gastric lavage daily for 3 days before induction of AP. The effects of FTY720 to protect against HTGP were assessed by serum amylase, pancreatic pathological scores, immunostaining, and the expression of inflammatory cytokine genes. As a result, injection of cerulein resulted in more severe pathological changes of AP and higher monocyte chemoattractant protein 1 expression in the pancreas in transgenic than in nontransgenic mice. FTY720 pretreatment improved the pathological severity of AP and decreased the expression of monocyte chemoattractant protein 1 in the pancreas significantly, especially near fourfold reduction in transgenic mice. However, FTY720 did not affect plasma triglyceride levels, and other inflammatory factors and plasma amylase were not correlated with the extent of pancreatic damage in AP with or without FTY720 administration. In summary, our study in a new model, apolipoprotein CIII transgenic mice, demonstrated that HTG mice are susceptible to induction of AP. Prophylactic treatment of FTY720 can significantly attenuate cerulein-induced AP and hence warrant further investigation of sphingosine-1-phosphate receptors agonist for potential clinical application in recurrent attacks of HTGP. PMID:25944794

  15. Size effects of latex nanomaterials on lung inflammation in mice

    International Nuclear Information System (INIS)

    Effects of nano-sized materials (nanomaterials) on sensitive population have not been well elucidated. This study examined the effects of pulmonary exposure to (latex) nanomaterials on lung inflammation related to lipopolysaccharide (LPS) or allergen in mice, especially in terms of their size-dependency. In protocol 1, ICR male mice were divided into 8 experimental groups that intratracheally received a single exposure to vehicle, latex nanomaterials (250 μg/animal) with three sizes (25, 50, and 100 nm), LPS (75 μg/animal), or LPS plus latex nanomaterials. In protocol 2, ICR male mice were divided into 8 experimental groups that intratracheally received repeated exposure to vehicle, latex nanomaterials (100 μg/animal), allergen (ovalbumin: OVA; 1 μg/animal), or allergen plus latex nanomaterials. In protocol 1, latex nanomaterials with all sizes exacerbated lung inflammation elicited by LPS, showing an overall trend of amplified lung expressions of proinflammatory cytokines. Furthermore, LPS plus nanomaterials, especially with size less than 50 nm, significantly elevated circulatory levels of fibrinogen, macrophage chemoattractant protein-1, and keratinocyte-derived chemoattractant, and von Willebrand factor as compared with LPS alone. The enhancement tended overall to be greater with the smaller nanomaterials than with the larger ones. In protocol 2, latex nanomaterials with all sizes did not significantly enhance the pathophysiology of allergic asthma, characterized by eosinophilic lung inflammation and Igs production, although latex nanomaterials with less than 50 nm significantly induced/enhanced neutrophilic lung inflammation. These results suggest that latex nanomaterials differentially affect two types of (innate and adaptive immunity-dominant) lung inflammation

  16. CCL21/IL21-armed oncolytic adenovirus enhances antitumor activity against TERT-positive tumor cells.

    Science.gov (United States)

    Li, Yang; Li, Yi-Fei; Si, Chong-Zhan; Zhu, Yu-Hui; Jin, Yan; Zhu, Tong-Tong; Liu, Ming-Yuan; Liu, Guang-Yao

    2016-07-15

    Multigene-armed oncolytic adenoviruses are capable of efficiently generating a productive antitumor immune response. The chemokine (C-C motif) ligand 21 (CCL21) binds to CCR7 on naïve T cells and dendritic cells (DCs) to promote their chemoattraction to the tumor and resultant antitumor activity. Interleukin 21 (IL21) promotes survival of naïve T cells while maintaining their CCR7 surface expression, which increases their capacity to transmigrate in response to CCL21 chemoattraction. IL21 is also involved in NK cell differentiation and B cell activation and proliferation. The generation of effective antitumor immune responses is a complex process dependent upon coordinated interactions of various subsets of effector cells. Using the AdEasy system, we aimed to construct an oncolytic adenovirus co-expressing CCL21 and IL21 that could selectively replicate in TERTp-positive tumor cells (Ad-CCL21-IL21 virus). The E1A promoter of these oncolytic adenoviruses was replaced by telomerase reverse transcriptase promoter (TERTp). Ad-CCL21-IL21 was constructed from three plasmids, pGTE-IL21, pShuttle-CMV-CCL21 and AdEasy-1 and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Our results showed that our targeted and armed oncolytic adenoviruses Ad-CCL21-IL21 can induce apoptosis in TERTp-positive tumor cells to give rise to viral propagation, in a dose-dependent manner. Importantly, we confirm that these modified oncolytic adenoviruses do not replicate efficiently in normal cells even under high viral loads. Additionally, we investigate the role of Ad-CCL21-IL21 in inducing antitumor activity and tumor specific cytotoxicity of CTLs in vitro. This study suggests that Ad-CCL21-IL21 is a promising targeted tumor-specific oncolytic adenovirus. PMID:27157859

  17. Inverse association of plasma IL-13 and inflammatory chemokines with lung function impairment in stable COPD: a cross-sectional cohort study

    Directory of Open Access Journals (Sweden)

    Choi Augustine MK

    2007-09-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is a heterogeneous syndrome characterized by varying degrees of airflow limitation and diffusion impairment. There is increasing evidence to suggest that COPD is also characterized by systemic inflammation. The primary goal of this study was to identify soluble proteins in plasma that associate with the severity of airflow limitation in a COPD cohort with stable disease. A secondary goal was to assess whether unique markers associate with diffusion impairment, based on diffusion capacity of carbon monoxide (DLCO, independent of the forced expiratory volume in 1 second (FEV1. Methods A cross sectional study of 73 COPD subjects was performed in order to examine the association of 25 different plasma proteins with the severity of lung function impairment, as defined by the baseline measurements of the % predicted FEV1 and the % predicted DLCO. Plasma protein concentrations were assayed using multiplexed immunobead-based cytokine profiling. Associations between lung function and protein concentrations were adjusted for age, gender, pack years smoking history, current smoking, inhaled corticosteroid use, systemic corticosteroid use and statin use. Results Plasma concentrations of CCL2/monocyte chemoattractant protein-1 (CCL2/MCP-1, CCL4/macrophage inflammatory protein-1β (CCL4/MIP -1β, CCL11/eotaxin, and interleukin-13 (IL-13 were inversely associated with the % FEV1. Plasma concentrations of soluble Fas were associated with the % DLCO, whereas CXCL9/monokine induced by interferon-γ (CXCL9/Mig, granulocyte- colony stimulating factor (G-CSF and IL-13 showed inverse relationships with the % DLCO. Conclusion Systemic inflammation in a COPD cohort is characterized by cytokines implicated in inflammatory cell recruitment and airway remodeling. Plasma concentrations of IL-13 and chemoattractants for monocytes, T lymphocytes, and eosinophils show associations with increasing severity of

  18. Aspirin's Active Metabolite Salicylic Acid Targets High Mobility Group Box 1 to Modulate Inflammatory Responses.

    Science.gov (United States)

    Choi, Hyong Woo; Tian, Miaoying; Song, Fei; Venereau, Emilie; Preti, Alessandro; Park, Sang-Wook; Hamilton, Keith; Swapna, G V T; Manohar, Murli; Moreau, Magali; Agresti, Alessandra; Gorzanelli, Andrea; De Marchis, Francesco; Wang, Huang; Antonyak, Marc; Micikas, Robert J; Gentile, Daniel R; Cerione, Richard A; Schroeder, Frank C; Montelione, Gaetano T; Bianchi, Marco E; Klessig, Daniel F

    2015-01-01

    Salicylic acid (SA) and its derivatives have been used for millennia to reduce pain, fever and inflammation. In addition, prophylactic use of acetylsalicylic acid, commonly known as aspirin, reduces the risk of heart attack, stroke and certain cancers. Because aspirin is rapidly de-acetylated by esterases in human plasma, much of aspirin's bioactivity can be attributed to its primary metabolite, SA. Here we demonstrate that human high mobility group box 1 (HMGB1) is a novel SA-binding protein. SA-binding sites on HMGB1 were identified in the HMG-box domains by nuclear magnetic resonance (NMR) spectroscopic studies and confirmed by mutational analysis. Extracellular HMGB1 is a damage-associated molecular pattern molecule (DAMP), with multiple redox states. SA suppresses both the chemoattractant activity of fully reduced HMGB1 and the increased expression of proinflammatory cytokine genes and cyclooxygenase 2 (COX-2) induced by disulfide HMGB1. Natural and synthetic SA derivatives with greater potency for inhibition of HMGB1 were identified, providing proof-of-concept that new molecules with high efficacy against sterile inflammation are attainable. An HMGB1 protein mutated in one of the SA-binding sites identified by NMR chemical shift perturbation studies retained chemoattractant activity, but lost binding of and inhibition by SA and its derivatives, thereby firmly establishing that SA binding to HMGB1 directly suppresses its proinflammatory activities. Identification of HMGB1 as a pharmacological target of SA/aspirin provides new insights into the mechanisms of action of one of the world's longest and most used natural and synthetic drugs. It may also provide an explanation for the protective effects of low-dose aspirin usage. PMID:26101955

  19. Imaging neutrophil migration dynamics using micro-optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Chu, Kengyeh K.; Yonker, Lael; Som, Avira; Pazos, Michael; Kusek, Mark E.; Hurley, Bryan P.; Tearney, Guillermo J.

    2016-03-01

    Neutrophils are immune cells that undergo chemotaxis, detecting and migrating towards a chemical signal gradient. Neutrophils actively migrate across epithelial boundaries, interacting with the epithelium to selectively permit passage without compromising the epithelial barrier. In many inflammatory disorders, excessive neutrophil migration can cause damage to the epithelium itself. The signaling pathways and mechanisms that facilitate trans-epithelial migration are not fully characterized. Our laboratory has developed micro-optical coherence tomography (μOCT), which has 2 μm lateral resolution and 1 μm axial resolution. As a high-resolution native contrast modality, μOCT can directly visualize individual neutrophils as they interact with a cell layer cultured on a transwell filter. A chemoattractant can be applied to the apical side of inverted monolayer, and human neutrophils placed in the basolateral compartment, while μOCT captures 3D images of the chemotaxis. μOCT images can also generate quantitative metrics of migration volume to study the dependence of chemotaxis on monolayer cell type, chemoattractant type, and disease state of the neutrophils. For example, a disease known as leukocyte adhesion deficiency (LAD) can be simulated by treating neutrophils with antibodies that interfere with the CD18 receptor, a facilitator of trans-epithelial migration. We conducted a migration study of anti-CD18 treated and control neutrophils using T84 intestinal epithelium as a barrier. After one hour, μOCT time-lapse imaging indicated a strong difference in the fraction of neutrophils that remain attached to the epithelium after migration (0.67 +/- 0.12 attached anti-CD18 neutrophils, 0.23 +/- 0.08 attached control neutrophils, n = 6, p metrics with simultaneously acquired measurements of transepithelial electrical resistance (TEER), a measure of membrane integrity that decreases when neutrophils create openings in the epithelium to permit migration. Preliminary

  20. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    Directory of Open Access Journals (Sweden)

    Jaiswal Pundrik

    2012-01-01

    Full Text Available Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factors affecting aggregate size are modulated by adenosine and caffeine. Result Adenosine and caffeine induced the formation of large and small aggregates respectively, in evolutionarily distinct slime molds known to use diverse chemoattractants for their aggregation. Due to its genetic tractability, we chose D. discoideum to further investigate the factors affecting aggregate size. The changes in aggregate size are caused by the effect of the compounds on several parameters such as cell number and size, cell-cell adhesion, cAMP signal relay and cell counting mechanisms. While some of the effects of these two compounds are opposite to each other, interestingly, both compounds increase the intracellular glucose level and strengthen cell-cell adhesion. These compounds also inhibit the synthesis of cAMP phosphodiesterase (PdsA, weakening the relay of extracellular cAMP signal. Adenosine as well as caffeine rescue mutants impaired in stream formation (pde4- and pdiA- and colony size (smlA- and ctnA- and restore their parental aggregate size. Conclusion Adenosine increased the cell division timings thereby making large number of cells available for aggregation and also it marginally increased the cell size contributing to large aggregate size. Reduced cell division rates and decreased cell size in the presence of caffeine makes the aggregates smaller than controls. Both the compounds altered the speed of the chemotactic amoebae causing a variation in aggregate size

  1. The effects of second-hand smoke on biological processes important in atherogenesis

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    Schneider Matthias

    2007-01-01

    Full Text Available Abstract Background Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis. Methods To perform these studies, a smoking system that closely simulates exposure of humans to second-hand smoke was developed and a mouse model system transgenic for human apoB100 was used. These mice have moderate lipid levels that closely mimic human conditions that lead to atherosclerotic plaque formation. Results "Second-hand" cigarette smoke decreases plasma high density lipoprotein levels in the blood and also decreases the ratios between high density lipoprotein and low density lipoprotein, high density lipoprotein and triglyceride, and high density lipoprotein and total cholesterol. This change in lipid profiles causes not only more lipid accumulation in the aorta but also lipid deposition in many of the smaller vessels of the heart and in hepatocytes. In addition, mice exposed to smoke have increased levels of Monocyte Chemoattractant Protein–1 in circulation and in the heart/aorta tissue, have increased macrophages in the arterial walls, and have decreased levels of adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice exposed to smoke do not undergo the switch from the pro-inflammatory cytokine profile (that develops when the mice are initially exposed to second-hand smoke to the adaptive response. Furthermore, triglyceride levels increase significantly in the liver of smoke-exposed mice. Conclusion Long-term exposure to "second-hand" smoke creates a state of permanent inflammation and an imbalance in the lipid profile that

  2. Fracture initiates systemic inflammatory response syndrome through recruiting polymorphonuclear leucocytes.

    Science.gov (United States)

    Li, Haipeng; Liu, Jia; Yao, Jianhua; Zhong, Jianfeng; Guo, Lei; Sun, Tiansheng

    2016-08-01

    Fracture, a common type injury in trauma patients, often results in the development of the systemic inflammatory response syndrome (SIRS). Though the mechanism of the fracture-initiated SIRS still remains not well characterized, it is well documented that the polymorphonuclear leucocytes (PMN) play an important role in the inflammatory process. We hypothesize that fractures recruit PMN to the local tissue, which is followed by an increase in the number of peripheral PMN and initiation of SIRS. In the current study, we established a closed femoral fracture rat model. We evaluated the levels of MPO, IL-1β and CINC-1 in fractured tissue homogenate, and we measured the levels of IL-6 and IL-10, the biomarkers for systemic inflammatory response, in the rat sera. In clinical part of the study, we collected blood from patients with isolated closed femoral fractures and evaluated PMN-related chemoattractants (IL-8, IL-1β and G-CSF) and the number of peripheral PMN. We further evaluated the level of mitochondrial DNA in the local haematoma of fracture and the circulating plasma of the patients with fracture. In the animal model of closed femoral fracture, we found a significant recruitment of PMN to the local tissue after fracture, which correlates with the elevated MPO level. We also showed that the concentration of IL-1β and CINC-1 in local tissue is significantly increased and might be responsible for the PMN recruitment. Recruitment of PMN to the local tissue was accompanied with a significant increase in the systemic levels of IL-6 and IL-10 in serum. In the patients with closed femoral fracture, we observed an increase in the number of peripheral PMN and PMN-related chemoattractants, including IL-8, IL-1β and G-CSF. The level of mitochondrial DNA in the local haematoma of fracture and the circulating plasma of patients were significantly higher compared to the healthy volunteers. Our data suggest that fracture released mitochondrial DNA into the local haematoma of

  3. 系统性红斑狼疮靶向治疗药物研究进展%Development of targeted therapeutic agents for systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    石平荣

    2013-01-01

    近十年来,随着免疫及分子生物学的发展,针对SLE免疫病理机制或相关靶点的生物靶向治疗药物取得了重大进展,以贝利单抗为标志的生物靶向治疗药物为SLE的治疗开辟了新的途径.目前有近20种SLE靶向治疗药物在进行临床前期或临床研究,根据其作用靶位的不同主要分为以下7类:B细胞特异性靶点药物、T细胞供刺激分子特异性靶点药物、细胞因子抑制剂、天然免疫靶位、耐受原、细胞表面受体抑制剂以及单核细胞趋化蛋白-1/单核细胞趋化因子CC配体2抑制剂、N-乙酰半胱氨酸等其他靶点药物.%With the development of immunology and molecular-biology,great advances have been made in biological therapies targeted at the immunopathological mechanisms or directed against some targets in systemic lupus erythematosus (SLE) in the past decade.These biological agents,with belimumab as a representative,have offered a new approach to the treatment of SLE.At present,there are nearly 20 targeteddrugs for SLE that undergo preclinical research or clinical trials.According to the difference in action targets,they are mainly divided into seven categories:B-cell-targeted drugs,T-cell/costimulatory molecule-targeteddrugs,cytokine inhibitors,innate immunity-targeted drugs,tolerogens,inhibitors of cell surface receptors,and other targeted agents including monocyte chemoattractant protein 1/monocyte chemoattractant CC chemokineligand 2 inhibitors,N-acetyl cysteine,etc.

  4. Phlorizin Supplementation Attenuates Obesity, Inflammation, and Hyperglycemia in Diet-Induced Obese Mice Fed a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Su-Kyung Shin

    2016-02-01

    Full Text Available Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w, high-fat diet (HFD, 20% fat, w/w, or HFD supplemented with phlorizin (PH, 0.02%, w/w. The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon-γ, and interleukin-6, and prevented HFD-induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance.

  5. Wogonin, a plant flavone from Scutellariae radix, attenuated ovalbumin-induced airway inflammation in mouse model of asthma via the suppression of IL-4/STAT6 signaling.

    Science.gov (United States)

    Ryu, Eun Kyung; Kim, Tae-Hyun; Jang, Eun Jeong; Choi, Yoon Suk; Kim, Seon Tae; Hahm, Ki Baik; Lee, Ho-Jae

    2015-09-01

    Bronchial asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of eosinophils at the site of inflammation. Eotaxins are potent chemoattractants for eosinophils and play important roles in pathogenesis of asthma. In the course of screening for eotaxin-3 inhibitors, we found that wogonin showed potent inhibitory activity of interleukin-4 (IL-4)-induced eotaxin-3 expression in BEAS-2B cells. In this study, we examined the effects of wogonin on IL-4/STAT6 signaling pathway and biological implication in a mouse model of asthma. Wogonin inhibited IL-4-induced activation and nuclear translocation of STAT6 which plays a key role in either the transcription of STAT6-response genes or Th2 cytokine-mediated inflammation. Oral administration of wogonin significantly reduced activation of STAT6 in the lung and the expression of eotaxin and RANTES in bronchoalveolar lavage fluids. Histological examination of lung tissue demonstrated that wogonin significantly inhibited allergen-induced eosinophilic inflammation. Administration of wogonin reduced the total IgE and ovalbumin-specific IgE levels compared with the ovalbumin-challenged group. All of these data demonstrated that wogonin could alleviate airway inflammation through inhibition of STAT6 activation induced by Th2 cytokines. Our finding implicates a potential therapeutic value of wogonin in the treatment of asthma through regulation of IL-4/STAT6 signaling pathway. PMID:26388667

  6. Eotaxin-Rich Proangiogenic Hematopoietic Progenitor Cells and CCR3+ Endothelium in the Atopic Asthmatic Response.

    Science.gov (United States)

    Asosingh, Kewal; Vasanji, Amit; Tipton, Aaron; Queisser, Kimberly; Wanner, Nicholas; Janocha, Allison; Grandon, Deepa; Anand-Apte, Bela; Rothenberg, Marc E; Dweik, Raed; Erzurum, Serpil C

    2016-03-01

    Angiogenesis is closely linked to and precedes eosinophilic infiltration in asthma. Eosinophils are recruited into the airway by chemoattractant eotaxins, which are expressed by endothelial cells, smooth muscles cells, epithelial cells, and hematopoietic cells. We hypothesized that bone marrow-derived proangiogenic progenitor cells that contain eotaxins contribute to the initiation of angiogenesis and inflammation in asthma. Whole-lung allergen challenge of atopic asthma patients revealed vascular activation occurs within hours of challenge and before airway inflammation. The eotaxin receptor CCR3 was expressed at high levels on submucosal endothelial cells in patients and a murine model of asthma. Ex vivo exposure of murine endothelial cells to eotaxins induced migration and angiogenesis. In mechanistic studies, wild-type mice transplanted with eotaxin-1/2-deficient bone marrow had markedly less angiogenesis and inflammation in an atopic asthma model, whereas adoptive transfer of proangiogenic progenitor cells from wild-type mice in an atopic asthma model into the eotaxin-1/2-deficient mice led to angiogenesis and airway inflammation. The findings indicate that Th2-promoting hematopoietic progenitor cells are rapidly recruited to the lung upon allergen exposure and release eotaxins that coordinately activate endothelial cells, angiogenesis, and airway inflammation. PMID:26810221

  7. Modeling of chemotactic steering of bacteria-based microrobot using a population-scale approach.

    Science.gov (United States)

    Cho, Sunghoon; Choi, Young Jin; Zheng, Shaohui; Han, Jiwon; Ko, Seong Young; Park, Jong-Oh; Park, Sukho

    2015-09-01

    The bacteria-based microrobot (Bacteriobot) is one of the most effective vehicles for drug delivery systems. The bacteriobot consists of a microbead containing therapeutic drugs and bacteria as a sensor and an actuator that can target and guide the bacteriobot to its destination. Many researchers are developing bacteria-based microrobots and establishing the model. In spite of these efforts, a motility model for bacteriobots steered by chemotaxis remains elusive. Because bacterial movement is random and should be described using a stochastic model, bacterial response to the chemo-attractant is difficult to anticipate. In this research, we used a population-scale approach to overcome the main obstacle to the stochastic motion of single bacterium. Also known as Keller-Segel's equation in chemotaxis research, the population-scale approach is not new. It is a well-designed model derived from transport theory and adaptable to any chemotaxis experiment. In addition, we have considered the self-propelled Brownian motion of the bacteriobot in order to represent its stochastic properties. From this perspective, we have proposed a new numerical modelling method combining chemotaxis and Brownian motion to create a bacteriobot model steered by chemotaxis. To obtain modeling parameters, we executed motility analyses of microbeads and bacteriobots without chemotactic steering as well as chemotactic steering analysis of the bacteriobots. The resulting proposed model shows sound agreement with experimental data with a confidence level <0.01. PMID:26487902

  8. 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 concentra......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......-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......, the compound suppressed lipopolysaccharide-mediated inflammation by reducing the release of the pro-inflammatory cytokines IL-6 and tumor necrosis factor-α....

  9. Neuroprotective effects of (-)-linalool against oxygen-glucose deprivation-induced neuronal injury.

    Science.gov (United States)

    Park, Hyeon; Seol, Geun Hee; Ryu, Sangwoo; Choi, In-Young

    2016-04-01

    (-)-Linalool, a major component of many essential oils, is widely used in cosmetics and flavoring ingredients as well as in traditional medicines. Although various in vitro and in vivo studies have shown that (-)-linalool has anti-convulsant, anti-nociceptive, anti-inflammatory and anti-oxidative properties, its anti-ischemic/hypoxic effects have yet to be determined. This study assessed the neuroprotective effects of (-)-linalool against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cortical neuronal injury, an in vitro model of ischemic stroke. (-)-Linalool significantly attenuated OGD/R-evoked cortical neuronal injury/death, although it did not inhibit N-methyl-D-aspartate (NMDA)-induced excitotoxicity. (-)-Linalool significantly reduced intracellular oxidative stress during OGD/R-induced injury, as well as scavenging peroxyl radicals (Trolox equivalents or TE = 3.8). This anti-oxidant effect was found to correlate with the restoration of OGD/R-induced decreases in the activities of SOD and catalase. In addition, (-)-linalool inhibited microglial migration induced by monocyte-chemoattractant protein-1 (MCP-1), a chemokine released by OGD/R. These findings show that (-)-linalool has neuroprotective effects against OGD/R-induced neuronal injury, which may be due to its anti-oxidant and anti-inflammatory activities. Detailed examination of the anti-ischemic mechanisms of (-)-linalool may indicate strategies for the development of drugs to treat cerebral ischemic injury. PMID:26832326

  10. Interleukin-8 and eicosanoid production in the lung during moderate to severe Pneumocystis carinii pneumonia in AIDS: a role of interleukin-8 in the pathogenesis of P. carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; van Steenwijk, R; Nielsen, T L;

    1995-01-01

    Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins ...... suggests a role of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear....... (PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A2 (PLA2) and have been implicated in the host response to micro-organisms. Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant...... the corticosteroid-treated patients from days 0-10, whereas no change was detected in the placebo group. No change in levels of LTB4, LTC4, PGE2, PGF2a and PLA2 were detected cover time in either treatment group. This study establishes a correlation between IL-8, BAL neutrophilia and P(A-a)O2, and...

  11. A transgenic probiotic secreting a parasite immunomodulator for site-directed treatment of gut inflammation.

    Science.gov (United States)

    Whelan, Rose A; Rausch, Sebastian; Ebner, Friederike; Günzel, Dorothee; Richter, Jan F; Hering, Nina A; Schulzke, Jörg-Dieter; Kühl, Anja A; Keles, Ahmed; Janczyk, Pawel; Nöckler, Karsten; Wieler, Lothar H; Hartmann, Susanne

    2014-10-01

    New treatment strategies for inflammatory bowel disease are needed and parasitic nematode infections or application of helminth components improve clinical and experimental gut inflammation. We genetically modified the probiotic bacterium Escherichia coli Nissle 1917 to secrete the powerful nematode immunomodulator cystatin in the gut. This treatment was tested in a murine colitis model and on post-weaning intestinal inflammation in pigs, an outbred model with a gastrointestinal system similar to humans. Application of the transgenic probiotic significantly decreased intestinal inflammation in murine acute colitis, associated with increased frequencies of Foxp3(+) Tregs, suppressed local interleukin (IL)-6 and IL-17A production, decreased macrophage inflammatory protein-1α/β, monocyte chemoattractant protein -1/3, and regulated upon activation, normal T-cell expressed, and secreted expression and fewer inflammatory macrophages in the colon. High dosages of the transgenic probiotic were well tolerated by post-weaning piglets. Despite being recognized by T cells, secreted cystatin did not lead to changes in cytokine expression or macrophage activation in the colon. However, colon transepithelial resistance and barrier function were significantly improved in pigs receiving the transgenic probotic and post-weaning colon inflammation was reduced. Thus, the anti-inflammatory efficiency of a probiotic can be improved by a nematode-derived immunoregulatory transgene. This treatment regimen should be further investigated as a potential therapeutic option for inflammatory bowel disease. PMID:24985163

  12. Anti-Oxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Resveratrol in Ocular Diseases

    Directory of Open Access Journals (Sweden)

    Allan Lançon

    2016-03-01

    Full Text Available Resveratrol (3,4′,5 trihydroxy-trans-stilbene is one of the best known phytophenols with pleiotropic properties. It is a phytoalexin produced by vine and it leads to the stimulation of natural plant defenses but also exhibits many beneficial effects in animals and humans by acting on a wide range of organs and tissues. These include the prevention of cardiovascular diseases, anti-cancer potential, neuroprotective effects, homeostasia maintenance, aging delay and a decrease in inflammation. Age-related macular degeneration (AMD is one of the main causes of deterioration of vision in adults in developed countries This review deals with resveratrol and ophthalmology by focusing on the antioxidant, anti-inflammatory, and anti-angiogenic effects of this molecule. The literature reports that resveratrol is able to act on various cell types of the eye by increasing the level of natural antioxidant enzymatic and molecular defenses. Resveratrol anti-inflammatory effects are due to its capacity to limit the expression of pro-inflammatory factors, such as interleukins and prostaglandins, and also to decrease the chemo-attraction and recruitment of immune cells to the inflammatory site. In addition to this, resveratrol was shown to possess anti-VEGF effects and to inhibit the proliferation and migration of vascular endothelial cells. Resveratrol has the potential to be used in a range of human ocular diseases and conditions, based on animal models and in vitro experiments.

  13. Prolonged Helium Postconditioning Protocols during Early Reperfusion Do Not Induce Cardioprotection in the Rat Heart In Vivo: Role of Inflammatory Cytokines

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    Gezina Tanya Mei Ling Oei

    2015-01-01

    Full Text Available Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg and diazepam (1.5 mg/kg. Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3 and interleukin-1 beta (IL-1β were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6, and tumor necrosis factor alpha (TNF-α in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

  14. Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury.

    Science.gov (United States)

    Hansen, Christopher N; Norden, Diana M; Faw, Timothy D; Deibert, Rochelle; Wohleb, Eric S; Sheridan, John F; Godbout, Jonathan P; Basso, D Michele

    2016-08-01

    Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24h and 7days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24h after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9. PMID:27191729

  15. Treatment of autoimmune inflammation by a TLR7 ligand regulating the innate immune system.

    Directory of Open Access Journals (Sweden)

    Tomoko Hayashi

    Full Text Available The Toll-like receptors (TLR have been advocated as attractive therapeutic targets because TLR signaling plays dual roles in initiating adaptive immune responses and perpetuating inflammation. Paradoxically, repeated stimulation of bone marrow mononuclear cells with a synthetic TLR7 ligand 9-benzyl-8-hydroxy-2-(2-methoxyethoxy adenine (called 1V136 leads to subsequent TLR hyporesponsiveness. Further studies on the mechanism of action of this pharmacologic agent demonstrated that the TLR7 ligand treatment depressed dendritic cell activation, but did not directly affect T cell function. To verify this mechanism, we utilized experimental allergic encephalitis (EAE as an in vivo T cell dependent autoimmune model. Drug treated SJL/J mice immunized with proteolipid protein (PLP(139-151 peptide had attenuated disease severity, reduced accumulation of mononuclear cells in the central nervous system (CNS, and limited demyelination, without any apparent systemic toxicity. Splenic T cells from treated mice produced less cytokines upon antigenic rechallenge. In the spinal cords of 1V136-treated EAE mice, the expression of chemoattractants was also reduced, suggesting innate immune cell hyposensitization in the CNS. Indeed, systemic 1V136 did penetrate the CNS. These experiments indicated that repeated doses of a TLR7 ligand may desensitize dendritic cells in lymphoid organs, leading to diminished T cell responses. This treatment strategy might be a new modality to treat T cell mediated autoimmune diseases.

  16. Production of Fibronectin by the Human Alveolar Macrophage: Mechanism for the Recruitment of Fibroblasts to Sites of Tissue Injury in Interstitial Lung Diseases

    Science.gov (United States)

    Rennard, Stephen I.; Hunninghake, Gary W.; Bitterman, Peter B.; Crystal, Ronald G.

    1981-11-01

    Because cells of the mononuclear phagocyte system are known to produce fibronectin and because alveolar macrophages are activated in many interstitial lung diseases, the present study was designed to evaluate a role for the alveolar macrophage as a source of the increased levels of fibronectin found in the lower respiratory tract in interstitial lung diseases and to determine if such fibronectin might contribute to the development of the fibrosis found in these disorders by being a chemoattractant for human lung fibroblasts. Production of fibronectin by human alveolar macrophages obtained by bronchoalveolar lavage and maintained in short-term culture in serum-free conditions was demonstrated; de novo synthesis was confirmed by the incorporation of [14C]proline. This fibronectin had a monomer molecular weight of 220,000 and was antigenically similar to plasma fibronectin. Macrophages from patients with idiopathic pulmonary fibrosis produced fibronectin at a rate 20 times higher than did normal macrophages; macrophages from patients with pulmonary sarcoidosis produced fibronectin at 10 times the normal rate. Macrophages from 6 of 10 patients with various other interstitial disorders produced fibronectin at rates greater than the rate of highest normal control. Human alveolar macrophage fibronectin was chemotactic for human lung fibroblasts, suggesting a functional role for this fibronectin in the derangement of the alveolar structures that is characteristic of these disorders.

  17. The in vivo fibrotic role of FIZZ1 in pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Tianju Liu

    Full Text Available FIZZ (found in inflammatory zone 1, a member of a cysteine-rich secreted protein family, is highly induced in lung allergic inflammation and bleomycin induced lung fibrosis, and primarily expressed by airway and type II alveolar epithelial cells. This novel mediator is known to stimulate α-smooth muscle actin and collagen expression in lung fibroblasts. The objective of this study was to investigate the in vivo effects of FIZZ1 on the development of lung fibrosis by evaluating bleomycin-induced pulmonary fibrosis in FIZZ1 deficient mice. FIZZ1 knockout mice exhibited no detectable abnormality. When these mice were treated with bleomycin they exhibited significantly impaired pulmonary fibrosis relative to wild type mice, along with impaired proinflammatory cytokine/chemokine expression. Deficient lung fibroblast activation was also noted in the FIZZ1 knockout mice. Moreover, recruitment of bone marrow-derived cells to injured lung was deficient in FIZZ1 knockout mice. Interestingly in vitro FIZZ1 was shown to have chemoattractant activity for bone marrow cells, including bone marrow-derived dendritic cells. Finally, overexpression of FIZZ1 exacerbated fibrosis. These findings suggested that FIZZ1 exhibited profibrogenic properties essential for bleomycin induced pulmonary fibrosis, as reflected by its ability to induce myofibroblast differentiation and recruit bone marrow-derived cells.

  18. Cryoglobulins as Potential Triggers of Inflammation in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Andranik Chavushyan

    2013-01-01

    Full Text Available This case study aimed to investigate effects of type III cryoglobulins isolated from the blood of patients with schizophrenia on the production of proinflammatory cytokines interleukin(IL-1β, IL-6 and tumor necrosis factor-α (TNF-α, anti-inflammatory cytokine IL-10, and chemotactic cytokines IL-8 and monocyte chemoattractant protein-1 (MCP-1 by peripheral blood mononuclear cells (PBMCs. The experiments were performed in vitro using PBMCs healthy subjects and the blood of patients whit schizoprenia. The enzyme-linked immunosorbent assay and 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay were used upon study. The results obtained indicated significant increase (P<0.05 in IL-1β, IL-6, TNF-α, IL-8, and MCP-1 production by cultured PBMCs when incubating for 24 hours with cryoglobulins, beginning from 0.4 mg/mL. The gender difference does not affect the cryoglobulins-induced production of these cytokines by PBMCs. No influence of cryoglobulins on production of IL-10 by PBMCs was observed. Also, it was shown that cryoglobulins in concentration ≤4 mg/mL possessed no cytotoxic effect towards cultured PBMCs. Based upon the results obtained, we concluded that type III cryoglobulins are implicated in schizophrenia-associated alterations in the immune response through induction of the expression of proinflammatory and chemotactic cytokines by PBMCs.

  19. Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in angiotensin II-salt hypertension.

    Science.gov (United States)

    Bakri, Mahinur; Yi, Yang; Chen, Ling-Dan; Aisa, Haji Akber; Wang, Mong-Heng

    2014-04-01

    In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg·kg(-1)·d(-1), i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers. PMID:24863351

  20. Anti-Inflammatory Activity of Bioaccessible Fraction from Eryngium foetidum Leaves

    Directory of Open Access Journals (Sweden)

    Suwitcha Dawilai

    2013-01-01

    Full Text Available Eryngium foetidum (EF has long been used as a medicinal plant and culinary spice in tropical regions. Phytochemicals in its leaves have been proposed to be responsible for the anti-inflammatory and antioxidant activities. The present study used in vitro digestion coupled with Caco-2 cells to assess such activities. Caco-2 cells were incubated with aqueous fraction from simulated digestion (bioaccessible fraction of EF leaves with/without bile extract prior to stimulation with interleukin-1 beta (IL-1β. Monocyte chemoattractant protein-1 (MCP-1 and IL-8 in culture media and the intracellular reactive oxygen species (ROS were measured. Approximately 24% β-carotene and 35% lutein of leaves were present in the aqueous fraction. The transfer of caffeic and chlorogenic acids to the aqueous fraction was 76%–81%, while that of kaempferol was 48%. Prior incubation of Caco-2 cells with the bioaccessible fraction suppressed IL-1β activated IL-8 and MCP-1 by 33%, but the fraction lacking mixed micelles decreased IL-8 and MCP-1 levels only by 11%. The pretreatment of Caco-2 cells with the bioaccessible fraction of EF reduced ROS by 34%; the fraction lacking mixed micelles decreased ROS by 28%. These data suggest that bioactive compounds partitioning in mixed micelles play a significant role to suppress the proinflammatory insult but with a modest antioxidant effect.

  1. Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

    Directory of Open Access Journals (Sweden)

    Loft Steffen

    2006-02-01

    Full Text Available Abstract Background Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs. Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6 and the chemokines, monocyte chemoattractant protein (Mcp-1, macrophage inflammatory protein-2 (Mip-2 and keratinocyte derived chemokine (Kc in the lung tissue at different time points after exposure. Results Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. Conclusion Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1.

  2. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipopolysaccharide-Induced Renal Inflammation Mice.

    Science.gov (United States)

    Ye, Jian-Hong; Liu, Meng-Hua; Zhang, Xu-Lin; He, Jing-Yu

    2015-01-01

    Protective effect of Hedyotis diffusa (H. diffusa) Willd against lipopolysaccharide (LPS)-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography-diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight) obviously protected renal tissues, significantly suppressed the productions of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1, as well as significantly promoted the production of IL-10 in serum and renal tissues. According the chemical profiles of H. diffusa, flavonoids, iridoid glycosides and anthraquinones were greatly detected in serum from H. diffusa extract treatment mice. Two main chemotypes, including eight flavonoids and four iridoid glycosides were found in renal tissues from H. diffusa extract treatment mice. The results demonstrated that water extract of H. diffusa had protective effect on renal inflammation, which possibly resulted from the bioactive constituents consisting of flavonoids, iridoids and anthraquinones. PMID:26580602

  3. Chemical Profiles and Protective Effect of Hedyotis diffusa Willd in Lipopolysaccharide-Induced Renal Inflammation Mice

    Directory of Open Access Journals (Sweden)

    Jian-Hong Ye

    2015-11-01

    Full Text Available Protective effect of Hedyotis diffusa (H. diffusa Willd against lipopolysaccharide (LPS-induced renal inflammation was evaluated by the productions of cytokines and chemokine, and the bioactive constituents of H. diffusa were detected by the ultra-fast liquid chromatography -diode array detector-quadrupole-time of flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS method. As the results showed, water extract of H. diffusa (equal to 5.0 g/kg body weight obviously protected renal tissues, significantly suppressed the productions of tumor necrosis factor-α (TNF-α, interleukin (IL-1β, IL-6, and monocyte chemoattractant protein (MCP-1, as well as significantly promoted the production of IL-10 in serum and renal tissues. According the chemical profiles of H. diffusa, flavonoids, iridoid glycosides and anthraquinones were greatly detected in serum from H. diffusa extract treatment mice. Two main chemotypes, including eight flavonoids and four iridoid glycosides were found in renal tissues from H. diffusa extract treatment mice. The results demonstrated that water extract of H. diffusa had protective effect on renal inflammation, which possibly resulted from the bioactive constituents consisting of flavonoids, iridoids and anthraquinones.

  4. Tunable chemokine production by antigen presenting dendritic cells in response to changes in regulatory T cell frequency in mouse reactive lymph nodes.

    Directory of Open Access Journals (Sweden)

    Valentina Dal Secco

    Full Text Available BACKGROUND: Although evidence exists that regulatory T cells (Tregs can suppress the effector phase of immune responses, it is clear that their major role is in suppressing T cell priming in secondary lymphoid organs. Recent experiments using two photon laser microscopy indicate that dendritic cells (DCs are central to Treg cell function and that the in vivo mechanisms of T cell regulation are more complex than those described in vitro. PRINCIPAL FINDINGS: Here we have sought to determine whether and how modulation of Treg numbers modifies the lymph node (LN microenvironment. We found that pro-inflammatory chemokines -- CCL2 (MCP-1 and CCL3 (MIP-la -- are secreted in the LN early (24 h after T cell activation, that this secretion is dependent on antigen-specific DC-T cell interactions, and that it was inversely related to the frequency of Tregs specific for the same antigen. Furthermore, we demonstrate that Tregs modify the chemoattractant properties of antigen-presenting DCs, which, as the frequency of Tregs increases, fail to produce CCL2 and CCL3 and to attract antigen-specific T cells. CONCLUSIONS: These results substantiate a major role of Tregs in LN patterning during antigen-specific immune responses.

  5. Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping.

    Science.gov (United States)

    Ghoneim, H M; Maher, Sara; Abdel-Aty, Asmaa; Saad, A; Kazem, A; Demian, S R

    2009-01-01

    Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand-2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings. PMID:22059352

  6. PDGF stimulation of Mueller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway

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    Moon, Sang Woong [Department of Ophthalmology, Seoul Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of); Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation, Ilsan Hospital, Gyounggi-do (Korea, Republic of); Jung, Sun-Ah [Myunggok Eye Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Myunggok Eye Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

    2009-10-09

    Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Mueller cells and the intracellular signaling pathway mediating these changes. PDGF induced Mueller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Mueller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Mueller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Mueller cells in the development of proliferative vitreoretinopathy.

  7. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10

    Directory of Open Access Journals (Sweden)

    Soojin Park

    2016-01-01

    Full Text Available Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of <10 μM (PM10. PM10 stimulates the production of reactive oxygen species (ROS and inflammatory mediators. Thus, we assumed that natural antioxidants might provide health benefits attenuating hazardous effects of PM10. In the present study, we examined the effects of pomegranate peel extract (PPE on THP-1 monocytic cells exposed to PM10. PM10 induced cytotoxicity and the production of ROS. It also increased the expression and secretion of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and monocyte chemoattractant protein-1 (MCP-1, and cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1. PPE at 10–100 μg mL−1 attenuated the production of ROS and the expression of TNF-α, IL-1β, MCP-1, and ICAM-1, but not VCAM-1, in THP-1 cells stimulated by PM10 (100 μg mL−1. PPE also attenuated the adhesion of PM10-stimulated THP-1 cells to EA.hy926 endothelial cells. PPE constituents, punicalagin and ellagic acid, attenuated PM10-induced monocyte adhesion to endothelial cells, and punicalagin was less cytotoxic compared to ellagic acid. The present study suggests that PPE and punicalagin may be useful in alleviating inflammatory reactions due to particulate matter.

  8. Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine.

    Science.gov (United States)

    Bozzi, Yuri; Caleo, Matteo

    2016-06-01

    Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Several lines of evidence demonstrate that inflammatory processes within the brain parenchyma contribute to recurrence and precipitation of seizures. In both epileptic patients and animal models, seizures upregulate inflammatory mediators, which in turn may enhance brain excitability. We recently showed that the C-C motif ligand 2 (CCL2) chemokine (also known as monocyte chemoattractant protein-1 [MCP-1]) mediates the seizure-promoting effects of inflammation. Systemic inflammatory challenge in chronically epileptic mice markedly enhanced seizure frequency and upregulated CCL2 expression in the brain. Selective pharmacological blockade of CCL2 synthesis or C-C chemokine receptor type 2 (CCR2) significantly suppressed inflammation-induced seizures. These results have important implications for the development of novel anticonvulsant therapies: drugs interfering with CCL2 signaling are used clinically for several human disorders and might be redirected for use in pharmacoresistant epilepsy. Here we review the role of CCL2/CCR2 signaling in linking systemic inflammation with seizure susceptibility and discuss some open questions that arise from our recent studies. PMID:27167681

  9. Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma.

    Science.gov (United States)

    Xie, Yuran; Kim, Na Hyung; Nadithe, Venkatareddy; Schalk, Dana; Thakur, Archana; Kılıç, Ayşe; Lum, Lawrence G; Bassett, David J P; Merkel, Olivia M

    2016-05-10

    Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy. PMID:27001893

  10. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.

    Science.gov (United States)

    Bindels, Laure B; Beck, Raphaël; Schakman, Olivier; Martin, Jennifer C; De Backer, Fabienne; Sohet, Florence M; Dewulf, Evelyne M; Pachikian, Barbara D; Neyrinck, Audrey M; Thissen, Jean-Paul; Verrax, Julien; Calderon, Pedro Buc; Pot, Bruno; Grangette, Corinne; Cani, Patrice D; Scott, Karen P; Delzenne, Nathalie M

    2012-01-01

    The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis) in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L) in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay). These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle. PMID:22761662

  11. Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review.

    Science.gov (United States)

    Nevius, Erin; Gomes, Ana Cordeiro; Pereira, João P

    2016-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Self-reactive B and T lymphocytes cooperate to promote antibody responses against self proteins and are major drivers of disease. T lymphocytes also promote RA independently of B lymphocytes mainly through the production of key inflammatory cytokines, such as IL-17, that promote pathology. While the innate signals that initiate self-reactive adaptive immune responses are poorly understood, the disease is predominantly caused by inflammatory cellular infiltration and accumulation in articular tissues, and by bone erosions driven by bone-resorbing osteoclasts. Osteoclasts are giant multinucleated cells formed by the fusion of multiple myeloid cells that require short-range signals, such as the cytokines MCSF and RANKL, for undergoing differentiation. The recruitment and positioning of osteoclast precursors to sites of osteoclast differentiation by chemoattractants is an important point of control for osteoclastogenesis and bone resorption. Recently, the GPCR EBI2 and its oxysterol ligand 7a, 25 dihydroxycholesterol, were identified as important regulators of osteoclast precursor positioning in proximity to bone surfaces and of osteoclast differentiation under homeostasis. In chronic inflammatory diseases like RA, osteoclast differentiation is also driven by inflammatory cytokines such as TNFa and IL-1, and can occur independently of RANKL. Finally, there is growing evidence that the chemotactic signals guiding osteoclast precursors to inflamed articular sites contribute to disease and are of great interest. Furthering our understanding of the complex osteoimmune cell interactions should provide new avenues of therapeutic intervention for RA. PMID:26511861

  12. Bacterial Chemotaxis with a Moving Target

    Science.gov (United States)

    Dominick, Corey

    2015-03-01

    Most chemotaxis studies so far have been conducted in a quiescent fluid with a well-defined chemical gradient. Such experiments may be appropriate for studying enteric bacteria, such as Escherichia coli, but the environment it provides is very different from that typically encountered by marine bacteria. Herein we describe an experiment in which marine bacterium Vibrio alginolyticusis subject to stimulation by a small moving target. A micropipette of the tip size <1 ?m is used to slowly release a chemoattractant, serine, at different concentrations. The pipette is made to move with different patterns and speeds, ranging from 0 to 100 ?m/s; the latter is about twice the bacterial swimming speed. We found that if the pipette is moved slowly, with 1/4 of bacterial swimming speed, cells accumulate near the tip region but when it is moved with speed greater than 1/2 the bacterial swimming speed, cells trail behind the pipette over a large distance. The behaviors observed in V. alginolyticusare significantly different from E. coli, suggesting that the former is a better chemotaxer in a changing environment.

  13. Changing paradigms in cranio-facial regeneration: current and new strategies for the activation of endogenous stem cells

    Directory of Open Access Journals (Sweden)

    Luigi eMele

    2016-02-01

    Full Text Available Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients’ quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients’ own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet–Rich-Plasma and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue.

  14. Identification of peripheral inflammatory markers between normal control and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Jo Sangmee

    2011-05-01

    Full Text Available Abstract Background Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD. Peripheral blood markers have been used to assess biochemical changes associated with AD and mild cognitive impairment (MCI and involved in their pathophysiology. Methods Plasma samples and clinical data were obtained from participants in the Ansan Geriatric Study (AGE study. Plasma concentrations of four candidate biomarkers were measured in the normal control (NC, MCI, and AD group: interleukin-8 (IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1, and tumor necrosis factor-α (TNF-α. Body mass index (BMI, MMSE (Mini Mental State Examination, CDR(Clinical Dementia Rating score and homocystein level were recorded with social and demographic information. Results Total of 59 subjects were randomly selected for this analysis [NC (n = 21, MCI(n = 20 and AD(n = 18]. In demographic data, educational year was correlated with the diagnosis states (p p Conclusions Our study suggests the existence of an independent and negative relationship between plasma IL-8 levels and functional status in MCI and AD patients.

  15. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10

    Science.gov (United States)

    Park, Soojin; Seok, Jin Kyung; Kwak, Jun Yup; Suh, Hwa-Jin; Kim, Young Mi; Boo, Yong Chool

    2016-01-01

    Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of pomegranate peel extract (PPE) on THP-1 monocytic cells exposed to PM10. PM10 induced cytotoxicity and the production of ROS. It also increased the expression and secretion of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), and cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). PPE at 10–100 μg mL−1 attenuated the production of ROS and the expression of TNF-α, IL-1β, MCP-1, and ICAM-1, but not VCAM-1, in THP-1 cells stimulated by PM10 (100 μg mL−1). PPE also attenuated the adhesion of PM10-stimulated THP-1 cells to EA.hy926 endothelial cells. PPE constituents, punicalagin and ellagic acid, attenuated PM10-induced monocyte adhesion to endothelial cells, and punicalagin was less cytotoxic compared to ellagic acid. The present study suggests that PPE and punicalagin may be useful in alleviating inflammatory reactions due to particulate matter. PMID:27247608

  16. Tanshinone IIA Attenuates Renal Fibrosis after Acute Kidney Injury in a Mouse Model through Inhibition of Fibrocytes Recruitment

    Science.gov (United States)

    Jiang, Chunming; Shao, Qiuyuan; Jin, Bo; Zhang, Miao

    2015-01-01

    Acute kidney injury (AKI) is associated with an increased risk of developing advanced chronic kidney disease (CKD). Yet, effective interventions to prevent this conversion are unavailable for clinical practice. In this study, we examined the beneficial effects of Tanshinone IIA on renal fibrosis in a mouse model of folic acid induced AKI. We found that Tanshinone IIA treatment significantly attenuated the folic acid elicited kidney dysfunction on days 3, 14, and 28. This effect was concomitant with a much lessened accumulation of fibronectin and collagen in tubulointerstitium 28 days after folic acid injury, denoting an ameliorated renal fibrosis. The kidney protective and antifibrotic effect of Tanshinone IIA was likely attributable to an early inhibition of renal recruitment of fibrocytes positive for both CD45 and collagen I. Mechanistically, Tanshinone IIA treatment not only markedly diminished renal expression of chemoattractants for fibrocytes such as TGFβ1 and MCP-1, but also significantly reduced circulating fibrocytes at the acute phase of kidney injury. These data suggested that Tanshinone IIA might be a novel therapy for preventing progression of CKD after AKI. PMID:26885500

  17. C-reactive protein, cytokines and inflammation in cardiovascular diseases.

    Science.gov (United States)

    Bucova, M; Bernadic, M; Buckingham, T

    2008-01-01

    Inflammation of vascular cell wall is the key problem and proinflammatory cytokines and chemokines play a great role in it. These molecules, togheter with C-reactive protein (CRP) can predict risk of coronary events. It is questionable to what extend are CRP and pro-inflammatory cytokines purely acute phase markers and to what extend are they active inflammatory participants. Besides inflammation, other prominent mechanism in the pathogenesis of atherosclerosis and atherothrombosis--underlying causes of coronary events, is genetics. Gene polymorphisms including polymorphisms of inflammatory markers are studied and one of them, polymorphism of monocyte chemoattractant protein (MCP-1/CCL2) and its receptor CCR2 (key components of atherosclerosis) belong to most studied one. MCP-1/CCL2 and CCR2 polymorphisms have been implicated as susceptibility factors for chronic stable angina pectoris and myocardial infarction by several independent investigators. It seems that CCL2/CCR2 axis plays an important role both in post-ischemic and post-reperfusion inflammation and could become a new therapeutic goal in selected cardiovascular diseases as well as in stroke in future. Inhibition of this axis disrupts ischemic-reperfusion injury by decreasing edema, leucocyte infiltration and expression of inflammatory mediators. One can suppose that identifying genes influencing inflammatory biomarkers might improve understanding of genetic determinants of cardiovascular disease our management and prevention (Tab. 2, Fig. 1, Ref. 105). Full Text (Free, PDF) www.bmj.sk. PMID:18837239

  18. Axicon-based annular laser trap for studies on sperm activity

    Science.gov (United States)

    Shao, Bing; Vinson, Jaclyn M.; Botvinick, Elliot L.; Esener, Sadik C.; Berns, Michael W.

    2005-08-01

    As a powerful and noninvasive tool, laser trapping has been widely applied for the confinement and physiological study of biological cells and organelles. Researchers have used the single spot laser trap to hold individual sperm and quantitatively evaluated the motile force generated by a sperm. Early studies revealed the relationship between sperm motility and swimming behavior and helped the investigations in medical aspects of sperm activity. As sperm chemotaxis draws more and more interest in fertilization research, the studies on sperm-egg communication may help to explain male or female infertility and provide exciting new approaches to contraception. However, single spot laser trapping can only be used to investigate an individual target, which has limits in efficiency and throughput. To study the chemotactic response of sperm to eggs and to characterize sperm motility, an annular laser trap with a diameter of several hundred microns is designed, simulated with ray tracing tool, and implemented. An axicon transforms the wavefront such that the laser beam is incident on the microscope objective from all directions while filling the back aperture completely for high efficiency trapping. A trapping experiment with microspheres is carried out to evaluate the system performance. The power requirement for annular sperm trapping is determined experimentally and compared with theoretical calculations. With a chemo-attractant located in the center and sperm approaching from all directions, the annular laser trapping could serve as a speed bump for sperm so that motility characterization and fertility sorting can be performed efficiently.

  19. Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

    Science.gov (United States)

    Xie, Jieshi; Yang, Le; Tian, Lei; Li, Weiyang; Yang, Lin; Li, Liying

    2016-01-01

    Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation. PMID:27273604

  20. Supragingival biofilm control and systemic inflammation in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hilana Paula Carillo ARTESE

    2015-01-01

    Full Text Available The objective of this study was to evaluate the effect of strict supragingival biofilm control on serum inflammatory markers and on periodontal clinical parameters in type 2 diabetes mellitus (T2DM patients with chronic severe periodontitis. Twenty-four individuals with T2DM and periodontitis were randomly allocated to two treatment groups. The supragingival therapy group (ST, n = 12 received supragingival scaling, whereas the intensive therapy group (IT, n = 12 underwent supra- and subgingival scaling, as well as root planing. Patients from both groups received professional oral hygiene instructions every month. Data regarding visible plaque index (VPI, gingival bleeding index (GBI, bleeding on probing (BOP, probing pocket depth (PPD, clinical attachment level (CAL, serum levels of interleukin (IL-6, IL-17A, IL-8, tumor necrosis factor α (TNF-α, monocyte chemoattractant protein (MCP-1 enzyme-linked immunosorbent assay (ELISA, and glycated hemoglobin (HbA1c levels were obtained at baseline and at 6 months post-therapy. Both therapies resulted in the improvement of almost all clinical periodontal parameters (p 0.05, between the two periods. However, MCP-1 levels were significantly reduced in both the ST (p = 0.034 and the IT (p = 0.016 groups, whereas the serum IL-6 levels were significantly reduced only in the IT group (p = 0.001. Strict control of supragingival biofilm has a limited effect on systemic inflammatory markers, and a moderate effect on periodontal clinical parameters.

  1. Opposing Effects of Zac1 and Curcumin on AP-1-Regulated Expressions of S100A7

    Science.gov (United States)

    Chu, Yu-Wen; Liu, Shu-Ting; Cheng, Hsiao-Chun; Huang, Shih-Ming; Chang, Yung-Lung; Chiang, Chien-Ping; Liu, Ying-Chun; Wang, Wei-Ming

    2015-01-01

    ZAC, an encoding gene mapped at chromosome 6q24-q25 within PSORS1, was previously found over-expressed in the lower compartment of the hyperplastic epidermis in psoriatic lesions. Cytokines produced in the inflammatory dermatoses may drive AP-1 transcription factor to induce responsive gene expressions. We demonstrated that mZac1 can enhance AP-1-responsive S100A7 expression of which the encoding gene was located in PSORS4 with HaCaT keratinocytes. However, the mZac1-enhanced AP-1 transcriptional activity was suppressed by curcumin, indicating the anti-inflammatory property of this botanical agent and is exhibited by blocking the AP-1-mediated cross-talk between PSORS1 and PSORS4. Two putative AP-1-binding sites were found and demonstrated to be functionally important in the regulation of S100A7 promoter activity. Moreover, we found curcumin reduced the DNA-binding activity of AP-1 to the recognition element located in the S100A7 promoter. The S100A7 expression was found to be upregulated in the lesioned epidermis of atopic dermatitis and psoriasis, which is where this keratinocyte-derived chemoattractant engaged in the pro-inflammatory feedback loop. Understanding the regulatory mechanism of S100A7 expression will be helpful to develop therapeutic strategies for chronic inflammatory dermatoses via blocking the reciprocal stimuli between the inflammatory cells and keratinocytes. PMID:26633653

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

    International Nuclear Information System (INIS)

    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.

  3. Role of Kupffer cells in the pathogenesis of liver disease

    Institute of Scientific and Technical Information of China (English)

    George Kolios; Vassilis Valatas; Elias Kouroumalis

    2006-01-01

    Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by producing harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.

  4. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Michael Wolf

    2014-01-01

    Full Text Available High mobility group box protein-1 (HMGB1 is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

  5. Observing Chemotaxis in Vibrio fischeri Using Soft Agar Assays in an Undergraduate Microbiology Laboratory

    Directory of Open Access Journals (Sweden)

    Cindy R. DeLoney-Marino

    2013-08-01

    Full Text Available Chemotaxis, the directed movement of cells towards or away from a chemical, is both an exciting and complicated behavior observed in many bacterial species. Attempting to adequately visualize or demonstrate the chemotaxic response of bacteria in the classroom is difficult at best, with good models to illustrate the concept lacking. The BSL-1 marine bacterium Vibrio fischeri (a.k.a. Aliivibrio fischeri is easy to culture, making it an ideal candidate for experiments in an undergraduate microbiology course. A number of chemoattractants for V. fischeri have been identified, including a variety of sugars, nucleosides, and amino acids (1, 2. Below presents how the soft agar-based chemotaxis assay can be implemented in the undergraduate laboratory. As bacterial cells migrate towards one or more attractants in soft agar, students can directly observe the chemotaxic behavior of V. fischeri without the need to learn complicated techniques or use specialized equipment. Once the bands of bacterial cells are observed, the migration can then be disrupted by the addition of excess attractant to the soft agar, thereby visualizing what happens once cells are no longer in a gradient of attractant. In addition, soft agar plates lacking attractants can be used to visualize the random movements of bacterial cells that are non-chemotaxing. These exercises can be used in the microbiology laboratory to help students understand the complex behavior of bacterial chemotaxis.

  6. Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts.

    Science.gov (United States)

    Villa, Oscar; Brookes, Steven J; Thiede, Bernd; Heijl, Lars; Lyngstadaas, Staale P; Reseland, Janne E

    2015-01-01

    Enamel matrix derivative is used to promote periodontal regeneration during the corrective phase of the treatment of periodontal defects. Our main goal was to analyze the bioactivity of different molecular weight fractions of enamel matrix derivative. Enamel matrix derivative, a complex mixture of proteins, was separated into 13 fractions using size-exclusion chromatography and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-electrospray ionization-tandem mass spectrometry. Human periodontal ligament fibroblasts were treated with either enamel matrix derivative or the different fractions. Proliferation and cytokine secretion to the cell culture medium were measured and compared to untreated cells. The liquid chromatography-electrospray ionization-tandem mass spectrometry analyses revealed that the most abundant peptides were amelogenin and leucine-rich amelogenin peptide related. The fractions containing proteins above 20 kDa induced an increase in vascular endothelial growth factor and interleukin-6 secretion, whereas lower molecular weight fractions enhanced proliferation and secretion of interleukin-8 and monocyte chemoattractant protein-1 and reduced interleukin-4 release. The various molecular components in the enamel matrix derivative formulation might contribute to reported effects on tissue regeneration through their influence on vascularization, the immune response, and chemotaxis. PMID:26090085

  7. Global Existence and Finite Time Blow-Up for Critical Patlak-Keller-Segel Models with Inhomogeneous Diffusion

    CERN Document Server

    Bedrossian, Jacob

    2011-01-01

    The $L^1$-critical parabolic-elliptic Patlak-Keller-Segel system is a classical model of chemotactic aggregation in micro-organisms well-known to have critical mass phenomena. In this paper we study this critical mass phenomenon in the context of Patlak-Keller-Segel models with spatially varying diffusivity and decay rate of the chemo-attractant. The primary tool for the proof of global existence below the critical mass is the use of pseudo-differential operators to precisely evaluate the leading order quadratic portion of the potential energy (interaction energy). Under the assumption of radial symmetry, blow-up is proved above critical mass using a maximum-principle type argument based on comparing the mass distribution of solutions to a barrier consisting of the unique stationary solutions of the scale-invariant PKS. Although effective where standard Virial methods do not apply, this method seems to be dependent on the assumption of radial symmetry. For technical reasons we work in dimensions three and hig...

  8. MET is required for the recruitment of anti-tumoural neutrophils.

    Science.gov (United States)

    Finisguerra, Veronica; Di Conza, Giusy; Di Matteo, Mario; Serneels, Jens; Costa, Sandra; Thompson, A A Roger; Wauters, Els; Walmsley, Sarah; Prenen, Hans; Granot, Zvi; Casazza, Andrea; Mazzone, Massimiliano

    2015-06-18

    Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-α or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases. PMID:25985180

  9. [The effects of PEMF on the activation of human monocytes].

    Science.gov (United States)

    Chen, Xiaoying; Han, Xiaoyu; Wang, Qian; Wu, Wenchao; Liu, Xiaojing

    2012-08-01

    The aim of the present study is to investigate the effect of pulsed electromagnetic field (PEMF) on the activation of human monocytes (THP-1). Cultured THP-1 cells were exposed to PEMF stimulation with radiation of 32Hz or 64Hz respectively, using sinusoidal wave, and 1mT, twice a day, 30 minutes each time, with an interval of 8 hours, for 3 days. Those with 0Hz stimulation served as the controls. Monocytes activation was monitored by measuring both the release of monocyte chemoattractant protein-1 (MCP-1) from monocytes and their adhesion to monolayers of human umbilical vein endothelial cells (HUVECs). The adhesion of THP-1 cells to HUVECs was evaluated by cell counting method. The secretion of MCP-1 from THP-1 cells was detected by ELISA and MCP-1 mRNA expression was assessed by real time quantitative RT-PCR. The data showed that exposure to PEMF with above parameters could significantly inhibit the adhesion of THP-1 cells to HUVECs and decrease the MCP-1 mRNA and protein expression. The results demonstrated that exposure to PEMF of 1mT, 32Hz or 64Hz for 3 days could significantly inhibit the activation of THP-1 cells. PMID:23016400

  10. [The interrelation of the "local" and the "general" in inflammation].

    Science.gov (United States)

    Paukov, V S; Kaufman, O Ia

    1988-01-01

    The relationships between the local and the general in inflammation are analysed basing on the literature and original data. Local chemoattraction is postulated to be an underlying factor initiating primary local cooperation of cells relevant to inflammation. Being essential in this cooperation, macrophage seems to warrant both the local developments and triggering of general mechanisms of regulation which are relevant to control over subsequent secondary cell cooperation. The latter is biologically aimed at localization of the inflammation focus and separation of its pathogenic factors from intact internal medium. General mechanisms of inflammation control are provided by neuroendocrine, immune, vascular, coagulative, fibrinolytic and other systems, and operate through the products of the acute phase, by immune defence factors and rearrangement of nervous regulation of homeostasis in intact organs and tissues. The result of the regulation manifests with sequential presentation of the inflammation stages in time, correlation of local and general responses intensity. Eventually, local inflammation and lesion involve stress and intoxication which are not considered direct attributes of inflammation, nevertheless can influence general regulatory systems concerned with the course of local inflammation. It is concluded that inflammation implies dialectic unity of local and systemic responses of the body outlined to resolve inflammation and restore homeostasis. PMID:3056343

  11. Anti-Inflammatory Action of Keratinocyte-Derived Vaspin: Relevance for the Pathogenesis of Psoriasis.

    Science.gov (United States)

    Saalbach, Anja; Tremel, Jenny; Herbert, Diana; Schwede, Katharina; Wandel, Elke; Schirmer, Christine; Anderegg, Ulf; Beck-Sickinger, Annette G; Heiker, John T; Schultz, Stephan; Magin, Thomas; Simon, Jan C

    2016-03-01

    Impaired cross talk between keratinocytes (KCs) and immune cells is believed to contribute to the pathogenesis of chronic inflammatory skin diseases, such as psoriasis. We have previously identified KCs as a rich source of the serpin protease inhibitor vaspin (serpinA12), originally described as an adipokine in adipose tissue. Herein, we studied whether dysregulated vaspin expression in KCs contributes to the pathogenesis of psoriasis. We found vaspin expression to be closely associated to epidermal differentiation, with low levels in proliferating KCs and high levels in differentiated cells. Consistently, in human psoriasis and in a mouse model of a psoriasis-like skin inflammation, epidermal vaspin expression was significantly down-regulated. Down-regulation of vaspin in KCs resulted in decreased expression of differentiation-associated genes and up-regulation of interferon-inducible and inflammation-associated psoriasis signature genes. Vaspin was also shown to modulate the communication between KCs and inflammatory cells under co-culture conditions. A decrease in vaspin expression in KCs stimulated the secretion of tumor necrosis factor-α, IL-1β, IL-6, IL-8, and monocyte chemoattractant protein-1 by co-cultured dendritic cells, macrophages, monocytes, and neutrophils. Consequently, the application of vaspin inhibited myeloid cell infiltration in a mouse model of a psoriasis-like skin inflammation. In conclusion, vaspin expression by maturing KCs modulates cutaneous immune responses and may be involved in the pathogenesis of psoriasis. PMID:26783881

  12. Detection of Chemerin and It’s Clinical Significance in Peripheral Blood of Patients with Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaohan QU

    2009-11-01

    Full Text Available Background and objective Chemerin was recently found a chemoattractant just like a chemotatic factor. It can induce immune chemotaxis to dendritic cells and macrophages by binding to its receptor ChemR23. It has been known that the activation of Chemerin could enhance the phagocytosis and antigen presentation of APC. Along with this observation, the contribution of Chemerin in the genesis and development of a tumor attracts more attention. We explored the relation between Chemerin and lung cancer through detecting the expression of Chemerin in peripheral blood of patients. Methods The experiment selected samples of lung cancer patients and normal people. The concentration of Chemerin in peripheral blood was detected by ELISA method. T test was used to compare the statistic difference. We compared the concentration of Chemerin in peripheral blood with age, sex, pathological type, degree of differentiation, metastasis of lymphonode, UICC staging and other clinicopathological index, and analyzed by t test and one-way ANOVA. Results The concentration of Chemerin in peripheral blood of 42 patients with lung cancer (1 965.81 pg/mL±374.03 pg/mL were significantly higher than the concentration of 31 healthy examination (1 111.44 pg/mL±250.72 pg/mL(P < 0.001. The concentration of Chemerin in peripheral blood of patients with lung cancer had no relationship with clinicopathological factors. Conclusion Chemerin has the potential to lung cancer diagnosis as a marker.

  13. Biofunctionalization of nonwoven complex oriented scaffolds with distinct differentiation molecules for the directed tissue regeneration

    Science.gov (United States)

    Antonova, L. V.; Krivkina, E. O.; Sergeeva, E. A.; Sevostyanova, V. V.; Burago, A. Yu.; Burkov, N. N.; Hryachkova, O. N.; Velikanova, E. A.; Matveeva, V. G.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S.

    2016-08-01

    In our research we tested electrospun scaffolds prepared from poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/polycaprolactone (PCL) with and without the vascular endothelial growth factor (VEGF) and the stromal-derived growth factor-lα (SDF-lα). Chemoattractant activity of VEGF and SDF-lα was evaluated on an endothelial cell line EA.hy 926 using in vitro migration assay. Biocompatibility of the scaffolds was assessed by implanting them into the rat pericardial sac. After 4 days of culturing, we found that the number of cells migrated to the PHBV/PCL/VEGF and PHBV/PCL/SDF-lα scaffolds was 1.4 and 1.35-fold higher, respectively, compared to the PHBV/PCL scaffolds (p < 0.05). Implantation of the scaffolds for 3 months did not cause any local or systemic inflammatory reaction. Histological examination revealed active neoangiogenesis in the PHBV/PCL/VEGF scaffolds and adjacent tissues. In addition, we detected active cell infiltration and production of extracellular matrix in the PHBV/PCL/SDF-lα scaffolds. Therefore, VEGF and SDF-lα retained their bioactivity after being incorporated into the PHBV/PCL scaffolds. We suggest biofunctionalization of the PHBV/PCL scaffolds with VEGF and SDF-lα as an appropriate approach for regenerative medicine.

  14. The histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates human astrocyte neurotoxicity induced by interferon-γ

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    Hashioka Sadayuki

    2012-05-01

    Full Text Available Abstract Backgrounds Increasing evidence shows that the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA possesses potent anti-inflammatory and immunomodulatory properties. It is tempting to evaluate the potential of SAHA as a therapeutic agent in various neuroinflammatory and neurodegenerative disorders. Methods We examined the effects of SAHA on interferon (IFN-γ-induced neurotoxicity of human astrocytes and on IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT 3 in human astrocytes. We also studied the effects of SAHA on the astrocytic production of two representative IFN-γ-inducible inflammatory molecules, namely IFN-γ-inducible T cell α chemoattractant (I-TAC and intercellular adhesion molecule-1 (ICAM-1. Results SAHA significantly attenuated the toxicity of astrocytes activated by IFN-γ towards SH-SY5Y human neuronal cells. In the IFN-γ-activated astrocytes, SAHA reduced the STAT3 phosphorylation. SAHA also inhibited the IFN-γ-induced astrocytic production of I-TAC, but not ICAM-1. These results indicate that SAHA suppresses IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway. Conclusion Due to its anti-neurotoxic and anti-inflammatory properties, SAHA appears to have the therapeutic or preventive potential for a wide range of neuroinflammatory disorders associated with activated astrocytes.

  15. Characterization of buffalo interleukin 8 (IL-8 and its expression in endometritis

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    Ahlam A. Abou Mossallam

    2015-06-01

    Full Text Available River buffalo (Bubalus bubalis bubalis with a population over 135 million heads is an important livestock. Interleukin 8 (IL-8 is a member of the chemokine family and is an important chemoattractant for neutrophils associated with a wide variety of inflammatory diseases such as endometritis. Tissue samples from the mammary gland, uterus and ovary were obtained from river buffalo (Mediterranean type with and without endometritis. Bacteriological examination showed the presence of both gram positive and negative in all buffalo with endometritis. RNA extraction and complementary DNA (cDNA synthesis were conducted from all tissues. Specific primer for IL8 full coding regions was designed using known cDNA sequences of Bubalus bubalis, Genbank accession number AY952930.1. IL-8 gene expression was investigated in buffalo tissues. Expression of IL-8 in buffalo with endometritis was found to increase significantly over buffalo without endometritis only in the uterus (P = 0.0159. PCR products from uterus tissues (target organs of buffalo with and without endometritis, were purified and sequenced. No polymorphic sites were detected in the investigated samples. IL-8 cDNA nucleotide sequences of buffalo with and without endometritis were 100% identical (accession number JX413057. Buffalo IL8 cDNAs were compared with corresponding sequences of member of subfamily Bovinae (buffalo and cattle and subfamily Caprinae (sheep and goat. IL-8 species specific differences were identified.

  16. Erythropoietin Levels Increase during Cerebral Malaria and Correlate with Heme, Interleukin-10 and Tumor Necrosis Factor-Alpha in India

    Science.gov (United States)

    Dalko, Esther; Tchitchek, Nicolas; Pays, Laurent; Herbert, Fabien; Cazenave, Pierre-André; Ravindran, Balachandran; Sharma, Shobhona; Nataf, Serge; Das, Bidyut; Pied, Sylviane

    2016-01-01

    Cerebral malaria (CM) caused by Plasmodium falciparum parasites often leads to the death of infected patients or to persisting neurological sequelae despite anti-parasitic treatments. Erythropoietin (EPO) was recently suggested as a potential adjunctive treatment for CM. However diverging results were obtained in patients from Sub-Saharan countries infected with P. falciparum. In this study, we measured EPO levels in the plasma of well-defined groups of P. falciparum-infected patients, from the state of Odisha in India, with mild malaria (MM), CM, or severe non-CM (NCM). EPO levels were then correlated with biological parameters, including parasite biomass, heme, tumor necrosis factor (TNF)-α, interleukin (IL)-10, interferon gamma-induced protein (IP)-10, and monocyte chemoattractant protein (MCP)-1 plasma concentrations by Spearman’s rank and multiple correlation analyses. We found a significant increase in EPO levels with malaria severity degree, and more specifically during fatal CM. In addition, EPO levels were also found correlated positively with heme, TNF-α, IL-10, IP-10 and MCP-1 during CM. We also found a significant multivariate correlation between EPO, TNF-α, IL-10, IP-10 MCP-1 and heme, suggesting an association of EPO with a network of immune factors in CM patients. The contradictory levels of circulating EPO reported in CM patients in India when compared to Africa highlights the need for the optimization of adjunctive treatments according to the targeted population. PMID:27441662

  17. Smoking-induced expression of the GPR15 gene indicates its potential role in chronic inflammatory pathologies.

    Science.gov (United States)

    Kõks, Gea; Uudelepp, Mari-Liis; Limbach, Maia; Peterson, Pärt; Reimann, Ene; Kõks, Sulev

    2015-11-01

    Despite the described clear epigenetic effects of smoking, the effect of smoking on genome-wide gene expression in the blood is obscure. We therefore studied the smoking-induced changes in the gene-expression profile of the peripheral blood. RNA was extracted from the whole blood of 48 individuals with a detailed smoking history (24 never-smokers, 16 smokers, and 8 ex-smokers). Gene-expression profiles were evaluated with RNA sequencing, and results were analyzed separately in 24 men and 24 women. In the male smokers, 13 genes were statistically significantly (false-discovery rate <0.1) differentially expressed; in female smokers, 5 genes. Although most of the differentially expressed genes were different between the male and female smokers, the G-protein-coupled receptor 15 gene (GPR15) was differentially expressed in both male and female smokers compared with never-smokers. Analysis of GPR15 methylation identified significantly greater hypomethylation in smokers compared with that in never-smokers. GPR15 is the chemoattractant receptor that regulates T-cell migration and immunity. Up-regulation of GPR15 could explain to some extent the health hazards of smoking with regard to chronic inflammatory diseases. PMID:26348578

  18. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

    International Nuclear Information System (INIS)

    Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis

  19. FLIM FRET Visualization of Cdc42 Activation by Netrin-1 in Embryonic Spinal Commissural Neuron Growth Cones

    Science.gov (United States)

    Rappaz, Benjamin; Lai Wing Sun, Karen; Correia, James P.; Wiseman, Paul W.; Kennedy, Timothy E.

    2016-01-01

    Netrin-1 is an essential extracellular chemoattractant that signals through its receptor DCC to guide commissural axon extension in the embryonic spinal cord. DCC directs the organization of F-actin in growth cones by activating an intracellular protein complex that includes the Rho GTPase Cdc42, a critical regulator of cell polarity and directional migration. To address the spatial distribution of signaling events downstream of netrin-1, we expressed the FRET biosensor Raichu-Cdc42 in cultured embryonic rat spinal commissural neurons. Using FLIM-FRET imaging we detected rapid activation of Cdc42 in neuronal growth cones following application of netrin-1. Investigating the signaling mechanisms that control Cdc42 activation by netrin-1, we demonstrate that netrin-1 rapidly enriches DCC at the leading edge of commissural neuron growth cones and that netrin-1 induced activation of Cdc42 in the growth cone is blocked by inhibiting src family kinase signaling. These findings reveal the activation of Cdc42 in embryonic spinal commissural axon growth cones and support the conclusion that src family kinase activation downstream of DCC is required for Cdc42 activation by netrin-1. PMID:27482713

  20. Saturated Fatty Acid Induces Insulin Resistance Partially Through Nucleotide-binding Oligomerization Domain 1 Signaling Pathway in Adipocytes

    Institute of Scientific and Technical Information of China (English)

    Yi-jun Zhou; Yin-si Tang; Yu-ling Song; Ai Li; Hui Zhou; Yan Li

    2013-01-01

    Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.

  1. Tomato extract suppresses the production of proinflammatory mediators induced by interaction between adipocytes and macrophages.

    Science.gov (United States)

    Kim, Young-il; Mohri, Shinsuke; Hirai, Shizuka; Lin, Shan; Goto, Tsuyoshi; Ohyane, Chie; Sakamoto, Tomoya; Takahashi, Haruya; Shibata, Daisuke; Takahashi, Nobuyuki; Kawada, Teruo

    2015-01-01

    Obese adipose tissue is characterized by enhanced macrophage infiltration. A loop involving monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNFα) between adipocytes and macrophages establishes a vicious cycle that augments inflammatory changes and insulin resistance in obese adipose tissue. Tomatoes, one of the most popular crops worldwide, contain many beneficial phytochemicals that improve obesity-related diseases such as diabetes. Some of them have also been reported to have anti-inflammatory properties. In this study, we focused on the potential protective effects of phytochemicals in tomatoes on inflammation. We screened fractions of tomato extract using nitric oxide (NO) assay in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. One fraction, RF52, significantly inhibited NO production in LPS-stimulated RAW264 macrophages. Furthermore, RF52 significantly decreased MCP-1 and TNFα productions. The coculture of 3T3-L1 adipocytes and RAW264 macrophages markedly enhanced MCP-1, TNFα, and NO productions compared with the control cultures; however, the treatment with RF52 inhibited the production of these proinflammatory mediators. These results suggest that RF52 from tomatoes may have the potential to suppress inflammation by inhibiting the production of NO or proinflammatory cytokines during the interaction between adipocytes and macrophages. PMID:25603813

  2. Sensory axon guidance with semaphorin 6A and nerve growth factor in a biomimetic choice point model

    International Nuclear Information System (INIS)

    The direct effect of guidance cues on developing and regenerating axons in vivo is not fully understood, as the process involves a multiplicity of attractive and repulsive signals, presented both as soluble and membrane-bound ligands. A better understanding of axon guidance is critical to functional recovery following injury to the nervous system through improved outgrowth and mapping of damaged nerves. Due to their implications as inhibitors to central nervous system regeneration, we investigated the repulsive properties of semaphorin 6A and ephrin-B3 on E15 rat dorsal root ganglion explants, as well as possible interactions with soluble gradients of chemoattractive nerve growth factor (NGF). We employed a 3D biomimetic in vitro choice point model, which enabled the simple and rapid preparation of patterned gel growth matrices with quantifiable presentation of guidance cues in a specifiable manner that resembles the in vivo presentation of soluble and/or immobilized ligands. Neurites demonstrated an inhibitory response to immobilized Sema6A by lumbosacral dorsal root ganglion explants, while no such repulsion was observed for immobilized ephrin-B3 by explants at any spinal level. Interestingly, Sema6A inhibition could be partially attenuated in a concentration-dependent manner through the simultaneous presentation of soluble NGF gradients. The in vitro model described herein represents a versatile and valuable investigative tool in the quest for understanding developmental processes and improving regeneration following nervous system injury. (paper)

  3. 2007 E. Mead Johnson award: scientific pursuit of the allergy problem.

    Science.gov (United States)

    Rothenberg, Marc E

    2008-07-01

    My research has focused on elucidating the allergy problem over the past two decades. The primary approach has been to uncover critical mechanisms of allergic inflammation, with particular focus on eosinophils, a hallmark cellular constituent of allergic responses. Molecular processes that bridge T helper cell type 2 (TH2) immunity with eosinophilia and key checkpoints for regulating eosinophilia have been uncovered. Notably, interleukin (IL)-5 (derived from TH2 cells) has been identified as the chief hematopoietin responsible for eosinophil expansion in the circulation. Pathways for selective eosinophil mobilization from the blood stream to the tissue have been uncovered by defining the role of the eotaxin subfamily of chemokines in eosinophil chemoattraction and activation. Finally, TH2 cell derived IL-4 and IL-13 have been defined as chief inducers of the eotaxins, and upstream orchestrators of eosinophilic inflammation. These translational studies have formulated novel therapeutic strategies (currently being tested) for a variety of eosinophilic conditions, with particular attention on hypereosinophilic syndromes and eosinophil-associated gastrointestinal disorders such as eosinophilic esophagitis. PMID:18414146

  4. CXCL12 chemokine and GABA neurotransmitter systems crosstalk and their putative roles

    Directory of Open Access Journals (Sweden)

    Guyon eAlice

    2014-04-01

    Full Text Available Since CXCL12 and its receptors, CXCR4 and CXCR7, have been found in the brain, the role of this chemokine has been expanded from chemoattractant in the immune system to neuromodulatory in the brain. Several pieces of evidence suggest that this chemokine system could crosstalk with the GABAergic system, known to be the main inhibitory neurotransmitter system in the brain. Indeed, GABA and CXCL12 as well as their receptors are colocalized in many cell types including neurons and there are several examples in which these two systems interact. Several mechanisms can be proposed to explain how these systems interact, including receptor-receptor interactions, crosstalk at the level of second messenger cascades, or direct pharmacological interactions, as GABA and GABAB receptor agonists/antagonists have been shown to be allosteric modulators of CXCR4.The interplay between CXCL12/CXCR4-CXCR7 and GABA/GABAA-GABAB receptors systems could have many physiological implications in neurotransmission, cancer and inflammation. In addition, the GABAB agonist baclofen is currently used in medicine to treat spasticity in patients with spinal cord injury, cerebral palsy, traumatic brain injury, multiple sclerosis and other disorders. More recently it has also been used in the treatment of alcohol dependence and withdrawal. The allosteric effects of this agent on CXCR4 could contribute to these beneficial effects or at the opposite, to its side effects.

  5. Plasticity in Tumor-Promoting Inflammation: Impairment of Macrophage Recruitment Evokes a Compensatory Neutrophil Response

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    Jessica C. Pahler

    2008-04-01

    Full Text Available Previous studies in the K14-HPV/E2 mouse model of cervical carcinogenesis demonstrated that infiltrating macrophages are the major source of matrix metalloproteinase 9 (MMP-9, a metalloprotease important for tumor angiogenesis and progression. We observed increased expression of the macrophage chemoattractant, CCL2, and its receptor, CCR2, concomitant with macrophage influx and MMP-9 expression. To study the role of CCL2-CCR2 signaling in cervical tumorigenesis, we generated CCR2-deficient K14-HPV/E2 mice. Cervixes of CCR2-null mice contained significantly fewer macrophages. Surprisingly, there was only a modest delay in time to progression from dysplasia to carcinoma in the CCR2-deficient mice, and no difference in end-stage tumor incidence or burden. Moreover, there was an unexpected persistence of MMP-9 activity, associated with increased abundance of MMP-9+ neutrophils in tumors from CCR2-null mice. In vitro bioassays revealed that macrophages produce soluble factor(s that can suppress neutrophil dynamics, as evidenced by reduced chemotaxis in response to CXCL8, and impaired invasion into three-dimensional tumor masses grown in vitro. Our data suggest a mechanism whereby CCL2 attracts proangiogenic CCR2+ macrophages with the ancillary capability to limit infiltration by neutrophils. If such tumor-promoting macrophages are suppressed, MMP-9+ neutrophils are then recruited, providing alternative paracrine support for tumor angiogenesis and progression.

  6. Inflammatory Markers and Obstructive Sleep Apnea in Obese Children: The NANOS Study

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    Alex Gileles-Hillel

    2014-01-01

    Full Text Available Introduction. Obesity and obstructive sleep apnea syndrome (OSA are common coexisting conditions associated with a chronic low-grade inflammatory state underlying some of the cognitive, metabolic, and cardiovascular morbidities. Aim. To examine the levels of inflammatory markers in obese community-dwelling children with OSA, as compared to no-OSA, and their association with clinical and polysomnographic (PSG variables. Methods. In this cross-sectional, prospective multicenter study, healthy obese Spanish children (ages 4–15 years were randomly selected and underwent nocturnal PSG followed by a morning fasting blood draw. Plasma samples were assayed for multiple inflammatory markers. Results. 204 children were enrolled in the study; 75 had OSA, defined by an obstructive respiratory disturbance index (RDI of 3 events/hour total sleep time (TST. BMI, gender, and age were similar in OSA and no-OSA children. Monocyte chemoattractant protein-1 (MCP-1 and plasminogen activator inhibitor-1 (PAI-1 levels were significantly higher in OSA children, with interleukin-6 concentrations being higher in moderate-severe OSA (i.e., AHI > 5/hrTST; P<0.01, while MCP-1 levels were associated with more prolonged nocturnal hypercapnia (P<0.001. Conclusion. IL-6, MCP-1, and PAI-1 are altered in the context of OSA among community-based obese children further reinforcing the proinflammatory effects of sleep disorders such as OSA. This trial is registered with ClinicalTrials.gov NCT01322763.

  7. EPOXYEICOSATRIENOIC ACID ANALOG ATTENUATES ANGIOTENSIN II HYPERTENSION AND KIDNEY INJURY

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    Md. Abdul Hye Khan

    2014-09-01

    Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  8. Foxc1 dependent mesenchymal signalling drives embryonic cerebellar growth

    Science.gov (United States)

    Haldipur, Parthiv; Gillies, Gwendolyn S; Janson, Olivia K; Chizhikov, Victor V; Mithal, Divakar S; Miller, Richard J; Millen, Kathleen J

    2014-01-01

    Loss of Foxc1 is associated with Dandy-Walker malformation, the most common human cerebellar malformation characterized by cerebellar hypoplasia and an enlarged posterior fossa and fourth ventricle. Although expressed in the mouse posterior fossa mesenchyme, loss of Foxc1 non-autonomously induces a rapid and devastating decrease in embryonic cerebellar ventricular zone radial glial proliferation and concurrent increase in cerebellar neuronal differentiation. Subsequent migration of cerebellar neurons is disrupted, associated with disordered radial glial morphology. In vitro, SDF1α, a direct Foxc1 target also expressed in the head mesenchyme, acts as a cerebellar radial glial mitogen and a chemoattractant for nascent Purkinje cells. Its receptor, Cxcr4, is expressed in cerebellar radial glial cells and conditional Cxcr4 ablation with Nes-Cre mimics the Foxc1−/− cerebellar phenotype. SDF1α also rescues the Foxc1−/− phenotype. Our data emphasizes that the head mesenchyme exerts a considerable influence on early embryonic brain development and its disruption contributes to neurodevelopmental disorders in humans. DOI: http://dx.doi.org/10.7554/eLife.03962.001 PMID:25513817

  9. The human tri-peptide GHK and tissue remodeling.

    Science.gov (United States)

    Pickart, Loren

    2008-01-01

    Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing superoxide dismutase, vessel vasodilation, blocking ultraviolet damage to skin keratinocytes and improving fibroblast recovery after X-ray treatments); (3) increases protein synthesis of collagen, elastin, metalloproteinases, anti-proteases, vascular endothelial growth factor, fibroblast growth factor 2, nerve growth factor, neutrotropins 3 and 4, and erythropoietin; (4) increases the proliferation of fibroblasts and keratinocytes; nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu stimulates wound healing in numerous models and in humans. Controlled studies on aged skin demonstrated that it tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage and hyperpigmentation. GHK-Cu also improves hair transplant success, protects hepatic tissue from tetrachloromethane poisoning, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue. These results are beginning to define the complex biochemical processes that regulate tissue remodeling. PMID:18644225

  10. Chemotactic response of plant-growth-promoting bacteria towards roots of vesicular-arbuscular mycorrhizal tomato plants.

    Science.gov (United States)

    Gupta Sood, Sushma

    2003-08-01

    The chemotactic responses of the plant-growth-promoting rhizobacteria Azotobacter chroococcum and Pseudomonas fluorescens to roots of vesicular-arbuscular mycorrhizal (Glomus fasciculatum) tomato plants were determined. A significantly (P=0.05) greater number of bacterial cells of wild strains were attracted towards vesicular-arbuscular mycorrhizal tomato roots compared to non-vesicular-arbuscular mycorrhizal tomato roots. Substances exuded by roots served as chemoattractants for these bacteria. P. fluorescens was strongly attracted towards citric and malic acids, which were predominant constituents in root exudates of tomato plants. A. chroococcum showed a stronger response towards sugars than amino acids, but the response was weakest towards organic acids. The effects of temperature, pH, and soil water matric potential on bacterial chemotaxis towards roots were also investigated. In general, significantly (P=0.05) greater chemotactic responses of bacteria were observed at higher water matric potentials (0, -1, and -5 kPa), slightly acidic to neutral pH (6, 6.5 and 7), and at 20-30 degrees C (depending on the bacterium) than in other environmental conditions. It is suggested that chemotaxis of P. fluorescens and A. chroococcum towards roots and their exudates is one of the several steps in the interaction process between bacteria and vesicular-arbuscular mycorrhizal roots. PMID:19719591

  11. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis.

    Science.gov (United States)

    Hatano, Yutaka; Man, Mao-Qiang; Uchida, Yoshikazu; Crumrine, Debra; Scharschmidt, Tiffany C; Kim, Esther G; Mauro, Theodora M; Feingold, Kenneth R; Elias, Peter M; Holleran, Walter M

    2009-07-01

    Neutralization of stratum corneum (SC) adversely impacts key epidermal functions, including permeability barrier homeostasis and SC integrity. Conversely, acidification of SC improves these functions in developmentally impaired (neonatal or aged) skin, and enhances function in normal skin. Hence, we hypothesized that acidification could alter the course of inflammatory dermatoses, which invariably exhibit an increased SC pH. Maintenance of a low pH by topical applications of the polyhydroxyl acid, lactobionic acid, during the repeated-challenge phase inhibited the development of oxazolone-induced atopic dermatitis (AD). Neither gross/histological dermatitis nor altered barrier function developed, and emergence of epidermal hyperplasia was prevented; however, cytokine generation decreased. Acidification also largely normalized the development of hapten-induced changes in eosinophil/mast cell densities, density of chemoattractant receptor-homologous molecule expressed on TH2-positive lymphocytes, and serum IgE levels. The pH-induced improvement in barrier function most likely accounts for the anti-inflammatory activity, which could be further attributed to normalization of both lamellar body secretion and lamellar bilayer formation. Acidification of SC alone substantially prevents development of barrier abnormalities and downstream immune abnormalities during the elicitation phase of murine AD. These results provide direct evidence for the "outside-inside" pathogenesis of AD and further suggest that maintenance of an acidic SC pH could prevent the emergence of AD in humans. PMID:19177139

  12. Regulation of human cytokines by Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Yong Sun

    2014-12-01

    Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

  13. Probing the impact of sex steroids and menopause-related sex steroid deprivation on modulation of immune senescence.

    Science.gov (United States)

    Vrachnis, Nikolaos; Zygouris, Dimitrios; Iliodromiti, Zoe; Daniilidis, Angelos; Valsamakis, Georgios; Kalantaridou, Sophia

    2014-07-01

    Immune senescence denotes the general decline in immune system function, characterized by a reduced immune response and an increased inflammatory state. Menopause is a natural change in a women's life, the menopause-related low estrogen levels affecting many body functions, among them the immune system. Numerous human studies with menopausal women and animal models with surgically induced menopause show a clear impact of sex steroids in immune responses. Female superiority in vaccination response and predisposition to infections are eliminated after menopause, while during menopause inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukins-1β, 6, 8 and 13 (IL-1β, IL-6, IL-8, IL-13) and Monocyte Chemoattractant Protein-1 (MCP-1) are increased, implying a molecular connection of sex steroid loss with immune senescence. Moreover, immune cells modify their number and function after the menopausal transition, this offering another explanation for immune senescence. Until now most of the existing studies have concluded that menopause plays an additional role to aging in immune senescence. While it is clear that we are as yet far from thoroughly understanding the molecular pathways connecting sex steroids and menopause with immune senescence, such knowledge is highly likely to enable future targeted interventions in treatment and prevention of age-related diseases in women. PMID:24852404

  14. Angiostatin overexpression is associated with an improvement in chronic kidney injury by an anti-inflammatory mechanism.

    Science.gov (United States)

    Mu, Wei; Long, David A; Ouyang, Xiaosen; Agarwal, Anupam; Cruz, Pedro E; Roncal, Carlos A; Nakagawa, Takahiko; Yu, Xueqing; Hauswirth, William W; Johnson, Richard J

    2009-01-01

    Angiostatin, a proteolytic fragment of plasminogen, is a potent anti-angiogenic factor recently shown also to have an inhibitory effect on leukocyte recruitment and macrophage migration. Because both angiogenesis and inflammation play key roles in the progression of chronic kidney disease, we evaluated the effect of angiostatin treatment in the rat remnant kidney model. Rats were pretreated for 4 wk with recombinant adeno-associated viruses expressing either angiostatin or green fluorescence protein. Chronic renal disease was then induced by a subtotal nephrectomy, and rats were killed 8 wk later for analysis. Angiostatin treatment was associated with significantly less proteinuria but no alterations in serum creatinine, creatinine clearance, and blood urea nitrogen levels. Treatment with angiostatin reduced renal peritubular capillary number and decreased urinary nitric oxide levels. Despite reducing capillary density, angiostatin diminished interstitial fibrosis in association with reduced macrophage and T-cell infiltration and renal monocyte chemoattractant protein-1 mRNA levels. In conclusion, angiostatin overexpression was associated with attenuated renal disease progression in a model of chronic kidney injury, likely because of its anti-inflammatory actions. However, its anti-angiogenic actions suggest countering effects that could partially offset its benefit in chronic kidney diseases. PMID:18971211

  15. Study of lung-metastasized prostate cancer cell line chemotaxis to epidermal growth factor with a BIOMEMS device

    International Nuclear Information System (INIS)

    Understanding the effects of different growth factors on cancer metastasis will enable researchers to develop effective post-surgery therapeutic strategies to stop the spread of cancer. Conventional Boyden chamber assays to evaluate cell motility in metastasis studies require high volumes of reagents and are impractical for high-throughput analysis. A microfluidic device was designed for arrayed assaying of prostate cancer cell migration towards different growth factors. The device was created with polydimethylsiloxane (PDMS) and featured two wells connected by 10 micro channels. One well was for cell seeding and the other well for specific growth factors. Each channel has a width of 20 μm, a length of 1 mm and a depth of 10 μm. The device was placed on a culture dish and primed with growth media. Lung-metastasized cells in suspension of RPMI 1640 media supplemented with 2% of fetal bovine serum (FBS) were seeded in the cell wells. Cell culture media with epidermal growth factor (EGF) of 25, 50, 75, 100 and 125 ng ml−1 concentrations were individually added in the respective growth factor wells. A 5-day time-lapsed study of cell migration towards the chemoattractant was performed. The average numbers of cells per device in the microchannels were obtained for each attractant condition. The results indicated migration of cells increased from 50 to 100 ng ml−1 of EGF and significantly decreased at 125 ng ml−1 of EGF, as compared to control. (paper)

  16. Inhibitory effect of Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts on lipopolysaccharide-stimulated inflammatory response in RAW 264.7 cells.

    Science.gov (United States)

    Xu, Wei; Zhou, Qing; Yao, Yong; Li, Xing; Zhang, Jiu-Liang; Su, Guan-Hua; Deng, Ai-Ping

    2016-06-01

    Blueberries are a rich source of anthocyanins, which are associated with health benefits contributing to a reduced risk for many diseases. The present study identified the functional Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts (GBBAEs) and evaluated their capacity and underlying mechanisms in protecting murine RAW 264.7 cells from lipopolysaccharide (LPS)-stimulated inflammation in vitro. Enzyme-linked immunosorbent assay (ELISA) kit results showed that GBBAEs significantly inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-1β, and interferon-γ (INF-γ). Real-time polymerase chain reaction (PCR) analysis indicated that the mRNA expression levels of IL-6, IL-1β, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and cyclooxygenase 2 (COX-2) were suppressed in LPS-stimulated RAW 264.7 cells. Additionally, Western blot analysis was used to evaluate the relative protein expression levels of COX-2 and nuclear factor-κB p65 (NF-κBp65). All these results suggested the potential use of GBBAEs as a functional food for the treatment of inflammatory diseases. PMID:27256676

  17. Changing Paradigms in Cranio-Facial Regeneration: Current and New Strategies for the Activation of Endogenous Stem Cells.

    Science.gov (United States)

    Mele, Luigi; Vitiello, Pietro Paolo; Tirino, Virginia; Paino, Francesca; De Rosa, Alfredo; Liccardo, Davide; Papaccio, Gianpaolo; Desiderio, Vincenzo

    2016-01-01

    Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight, and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients' quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless, both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment, and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients' own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet-Rich-Plasma, and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue. PMID:26941656

  18. Three-Dimensional Blood-Brain Barrier Model for in vitro Studies of Neurovascular Pathology

    Science.gov (United States)

    Cho, Hansang; Seo, Ji Hae; Wong, Keith H. K.; Terasaki, Yasukazu; Park, Joseph; Bong, Kiwan; Arai, Ken; Lo, Eng H.; Irimia, Daniel

    2015-10-01

    Blood-brain barrier (BBB) pathology leads to neurovascular disorders and is an important target for therapies. However, the study of BBB pathology is difficult in the absence of models that are simple and relevant. In vivo animal models are highly relevant, however they are hampered by complex, multi-cellular interactions that are difficult to decouple. In vitro models of BBB are simpler, however they have limited functionality and relevance to disease processes. To address these limitations, we developed a 3-dimensional (3D) model of BBB on a microfluidic platform. We verified the tightness of the BBB by showing its ability to reduce the leakage of dyes and to block the transmigration of immune cells towards chemoattractants. Moreover, we verified the localization at endothelial cell boundaries of ZO-1 and VE-Cadherin, two components of tight and adherens junctions. To validate the functionality of the BBB model, we probed its disruption by neuro-inflammation mediators and ischemic conditions and measured the protective function of antioxidant and ROCK-inhibitor treatments. Overall, our 3D BBB model provides a robust platform, adequate for detailed functional studies of BBB and for the screening of BBB-targeting drugs in neurological diseases.

  19. Role of Dickeya dadantii 3937 chemoreceptors in the entry to Arabidopsis leaves through wounds.

    Science.gov (United States)

    Río-Álvarez, Isabel; Muñoz-Gómez, Cristina; Navas-Vásquez, Mariela; Martínez-García, Pedro M; Antúnez-Lamas, María; Rodríguez-Palenzuela, Pablo; López-Solanilla, Emilia

    2015-09-01

    Chemotaxis enables bacteria to move towards an optimal environment in response to chemical signals. In the case of plant-pathogenic bacteria, chemotaxis allows pathogens to explore the plant surface for potential entry sites with the ultimate aim to prosper inside plant tissues and to cause disease. Chemoreceptors, which constitute the sensory core of the chemotaxis system, are usually transmembrane proteins which change their conformation when sensing chemicals in the periplasm and transduce the signal through a kinase pathway to the flagellar motor. In the particular case of the soft-rot pathogen Dickeya dadantii 3937, jasmonic acid released in a plant wound has been found to be a strong chemoattractant which drives pathogen entry into the plant apoplast. In order to identify candidate chemoreceptors sensing wound-derived plant compounds, we carried out a bioinformatics search of candidate chemoreceptors in the genome of Dickeya dadantii 3937. The study of the chemotactic response to several compounds and the analysis of the entry process to Arabidopsis leaves of 10 selected mutants in chemoreceptors allowed us to determine the implications of at least two of them (ABF-0020167 and ABF-0046680) in the chemotaxis-driven entry process through plant wounds. Our data suggest that ABF-0020167 and ABF-0046680 may be candidate receptors of jasmonic acid and xylose, respectively. PMID:25487519

  20. Hyperresistinemia and metabolic dysregulation: a risky crosstalk in obese breast cancer.

    Science.gov (United States)

    Crisóstomo, Joana; Matafome, Paulo; Santos-Silva, Daniela; Gomes, Ana L; Gomes, Manuel; Patrício, Miguel; Letra, Liliana; Sarmento-Ribeiro, Ana B; Santos, Lelita; Seiça, Raquel

    2016-08-01

    Breast cancer is the most common malignancy among women worldwide. There is extensive literature on the relationship between body weight and breast cancer risk but some doubts still remain about the role of adipokines per se, the role of insulin and glucose regardless of obesity, as well as the crosstalk between these players. Thus, in this study, we intend to determine the relation between body mass index (BMI), glycaemia, insulinemia, insulin-resistance, blood adipokine levels and tumour characteristics in a Portuguese group of pre- and postmenopausal overweight/obese women with breast cancer. We evaluated clinical and biochemical data in 154 participants, divided in 4 groups: (1) control with BMI 25 kg/m(2), n = 48 (CTOb); (3) breast cancer with BMI 25 kg/m(2), n = 47 (BCOb). In women with breast cancer, we also performed tumour characterization. We found that BCOb present increased fasting blood glucose, insulin, resistin and monocyte chemoattractant protein 1, insulin resistance and more aggressive tumours. Notably, this profile is not correlated with BMI, proposing the involvement of other processes than adiposity. Altogether, our results suggest that glucose dysmetabolism, insulin resistance and changes in adipokine secretion, in particular resistin, may be involved in the development and progression of breast cancer in overweight/obese pre- and postmenopausal women. PMID:26892376

  1. Mallotus philippinensis bark extracts promote preferential migration of mesenchymal stem cells and improve wound healing in mice.

    Science.gov (United States)

    Furumoto, Tadashi; Ozawa, Noriyasu; Inami, Yuta; Toyoshima, Misaki; Fujita, Kosuke; Zaiki, Kaori; Sahara, Shunya; Akita, Mariko; Kitamura, Keiko; Nakaoji, Koichi; Hamada, Kazuhiko; Tamai, Katsuto; Kaneda, Yasufumi; Maeda, Akito

    2014-02-15

    In the present study, we report the effects of the ethanol extract from Mallotus philippinensis bark (EMPB) on mesenchymal stem cell (MSC) proliferation, migration, and wound healing in vitro and in a mouse model. Chemotaxis assays demonstrated that EMPB acted an MSC chemoattractant and that the main chemotactic activity of EMPB may be due to the effects of cinnamtannin B-1. Flow cytometric analysis of peripheral blood mononuclear cells in EMPB-injected mice indicated that EMPB enhanced the mobilization of endogenous MSCs into blood circulation. Bioluminescent whole-animal imaging of luciferase-expressing MSCs revealed that EMPB augmented the homing of MSCs to wounds. In addition, the efficacy of EMPB on migration of MSCs was higher than that of other skin cell types, and EMPB treatment improved of wound healing in a diabetic mouse model. The histopathological characteristics demonstrated that the effects of EMPB treatment resembled MSC-induced tissue repair. Taken together, these results suggested that EMPB activated the mobilization and homing of MSCs to wounds and that enhancement of MSC migration may improve wound healing. PMID:24182990

  2. Modern therapy of chronic wounds with respect to radiation

    International Nuclear Information System (INIS)

    Background: Descriptions of wound care techniques have been found in some of the oldest archeological findings and chronic wounds have been threading man thousands of years. However, only in the last few decades substantial progress has been made in understanding the cellular and biochemical processes relevant in normal healing. Pathophysiology: Wound healing is a complex process involving a variety of different cells, proteins, chemoattractants, proteinases and growth factors. The normal repair process is a coordinated cellular and biochemical event and can be characterized by 3 different healing phases (inflammatory, proliferative, and remodeling phase). Certain pathophysiologic conditions and metabolic disorders alter this preprogrammed course, leading to delayed healing or chronic nonhealing wounds. Disturbance of wound healing after radiation: Especially irradiation can complicate tissue repair and surgical wound healing. Therefore this article will review the basic understanding of the wound healing process and the knowledge of modern surgical and conservative wound therapy from a surgical point of view, which is essential to surpass pathophysiological situations and avoid chronic wounds. (orig.)

  3. Disruption of Stromal-Derived Factor-1/Chemokine Receptor 4 by Simvastatin

    Directory of Open Access Journals (Sweden)

    A Jalili

    2010-03-01

    Full Text Available Background: The alpha chemokine, stromal-derived factor (SDF-1 is produced by bone marrow stromal cells and other cells, especially damaged tissues. SDF-1 receptor, a chemokine receptor 4 (CXCR4, is expressed on inflammatory cells and that SDF-1/CXCR4 axis plays a critical role in migration of inflammatory cells. In cardiovascular diseases, SDF-1 is produced by endothelial cells and plaques and that SDF-1 chemoattracts monocytes to the endothelial cells resulting in a local inflammation. Simvastatin, a cholesterol-lowering agent, is a general drug for treatment of cardiovascular diseases. However, its molecular mechanism has not yet been completely elucidated.Method: Herein, we investigated the role of simvastatin on the SDF- 1/CXCR4 axis by employing flow cytometry, RT-PCR, chemotaxis and adhesion assays. Results: Simvastatin (i downregulates CXCR4 expression on monocytic cell line (THP-1 and primary monocyte in a dose-dependent manner, (ii inhibits adhesion of monocytes to endothelial cells and (iii decreases SDF-1 production by endothelial cells. Moreover, preincubation with simvastatin significantly decreased the migration of THP-1 towards the SDF-1 gradient.Conclusion: All together our data indicate that simvastatin inhibits the binding of monocytes to endothelial cells through disrupting of the SDF-1/CXCR4 axis.

  4. Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation

    Directory of Open Access Journals (Sweden)

    Sanz Maria J

    2008-07-01

    Full Text Available Abstract Background Leukotriene B4 (LTB4 is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4 released from microspheres (MS. A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB4-loaded MS. Results In the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emigration besides significant decreases in the leukocyte rolling velocity. LTB4-loaded MS also increase peroxisome proliferator-activated receptor-α (PPARα expression by murine peritoneal macrophages and stimulate them to generate nitrite levels. Monocyte chemoattractant protein-1 (MCP-1 and nitric oxide (NO productions were also increased when human umbilical vein and artery endothelial cells (HUVECs and HUAECs, respectively were stimulated with LTB4-loaded MS. Conclusion LTB4-loaded MS preserve the biological activity of the encapsulated mediator indicating their use as a new strategy to modulate cell activation, especially in the innate immune response.

  5. Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments

    Science.gov (United States)

    Manzardo, Ann M.; Poje, Albert B.; Penick, Elizabeth C.; Butler, Merlin G.

    2016-01-01

    Chronic alcohol use alters adaptive immunity and cytokine activity influencing immunological and hormone responses, inflammation, and wound healing. Brain cytokine disturbances may impact neurological function, mood, cognition and traits related to alcoholism including impulsiveness. We examined the relationship between plasma cytokine levels and self-rated psychiatric symptoms in 40 adult males (mean age 51 ± 6 years; range 33–58 years) with current alcohol dependence and 30 control males (mean age 48 ± 6 years; range 40–58 years) with no history of alcoholism using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Log-transformed cytokine levels were analyzed for their relationship with the Symptom Checklist-90R (SCL-90R), Barratt Impulsivity Scales (BIS) and Alcoholism Severity Scale (ASS). Inflammatory cytokines (interferon γ-induced protein-10 (IP-10); monocyte chemoattractant protein-1 (MCP1); regulated on activation, normal T cell expressed and secreted (RANTES)) were significantly elevated in alcoholism compared to controls while bone marrow-derived hematopoietic cytokines and chemokines (granulocyte-colony stimulating factor (GCSF); soluble CD40 ligand (sCD40L); growth-related oncogene (GRO)) were significantly reduced. GRO and RANTES levels were positively correlated with BIS scales; and macrophage-derived chemokine (MDC) levels were positively correlated with SCL-90R scale scores (p phobia. The novel association between RANTES and GRO and impulsivity phenotype in alcoholism should be further investigated in alcoholism and psychiatric conditions with core impulsivity and anxiety phenotypes lending support for therapeutic intervention. PMID:27043532

  6. Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis

    Directory of Open Access Journals (Sweden)

    Madonna R. Peter

    2014-01-01

    Full Text Available Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng+/− mice subjected to dextran sulfate sodium (DSS developed persistent gut inflammation and pathological angiogenesis. We now report that colitic Eng+/− mice have low colonic levels of active TGF-β1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-β1. We also demonstrate dysregulated expression of BMPER and follistatin, which are extracellular regulators of the TGF-β superfamily that modulate angiogenesis and inflammation. Heightened colonic levels of the neutrophil chemoattractant and proangiogenic factor, CXCL1, were also observed in DSS-treated Eng+/− mice. Interestingly, despite increased macrophage and neutrophil infiltration, a gut-specific reduction in expression of the key phagocytic respiratory burst enzymes, NADPH oxidase 2 (Nox-2 and myeloperoxidase, was seen in Eng+/− mice undergoing persistent inflammation. Taken together, these findings suggest that endoglin is required for TGF-β superfamily mediated resolution of inflammation and fully functional myeloid cells.

  7. Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet.

    Science.gov (United States)

    Ferreira, Paula S; Spolidorio, Luis C; Manthey, John A; Cesar, Thais B

    2016-06-15

    The flavanones hesperidin, eriocitrin and eriodictyol were investigated for their prevention of the oxidative stress and systemic inflammation caused by high-fat diet in C57BL/6J mice. The mice received a standard diet (9.5% kcal from fat), high-fat diet (45% kcal from fat) or high-fat diet supplemented with hesperidin, eriocitrin or eriodictyol for a period of four weeks. Hesperidin, eriocitrin and eriodictyol increased the serum total antioxidant capacity, and restrained the elevation of interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and C-reactive protein (hs-CRP). In addition, the liver TBARS levels and spleen mass (g per kg body weight) were lower for the flavanone-treated mice than in the unsupplemented mice. Eriocitrin and eriodictyol reduced TBARS levels in the blood serum, and hesperidin and eriodictyol also reduced fat accumulation and liver damage. The results showed that hesperidin, eriocitrin and eriodictyol had protective effects against inflammation and oxidative stress caused by high-fat diet in mice, and may therefore prevent metabolic alterations associated with the development of cardiovascular diseases in other animals. PMID:27182608

  8. Microfluidic study of the chemotactic response of Escherichia coli to amino acids, signaling molecules and secondary metabolites.

    Science.gov (United States)

    Nagy, Krisztina; Sipos, Orsolya; Valkai, Sándor; Gombai, Éva; Hodula, Orsolya; Kerényi, Ádám; Ormos, Pál; Galajda, Péter

    2015-07-01

    Quorum sensing and chemotaxis both affect bacterial behavior on the population level. Chemotaxis shapes the spatial distribution of cells, while quorum sensing realizes a cell-density dependent gene regulation. An interesting question is if these mechanisms interact on some level: Does quorum sensing, a density dependent process, affect cell density itself via chemotaxis? Since quorum sensing often spans across species, such a feedback mechanism may also exist between multiple species. We constructed a microfluidic platform to study these questions. A flow-free, stable linear chemical gradient is formed in our device within a few minutes that makes it suitable for sensitive testing of chemoeffectors: we showed that the amino acid lysine is a weak chemoattractant for Escherichia coli, while arginine is neutral. We studied the effect of quorum sensing signal molecules of Pseudomonas aeruginosa on E. coli chemotaxis. Our results show that N-(3-oxododecanoyl)-homoserine lactone (oxo-C12-HSL) and N-(butryl)-homoserine lactone (C4-HSL) are attractants. Furthermore, we tested the chemoeffector potential of pyocyanin and pyoverdine, secondary metabolites under a quorum sensing control. Pyocyanin is proved to be a weak attractant while pyoverdine are repellent. We demonstrated the usability of the device in co-culturing experiments, where we showed that various factors released by P. aeruginosa affect the dynamic spatial rearrangement of a neighboring E. coli population, while surface adhesion of the cells is also modulated. PMID:26339306

  9. Rosmarinic Acid Methyl Ester Inhibits LPS-Induced NO Production via Suppression of MyD88- Dependent and -Independent Pathways and Induction of HO-1 in RAW 264.7 Cells.

    Science.gov (United States)

    So, Yangkang; Lee, Seung Young; Han, Ah-Reum; Kim, Jin-Baek; Jeong, Hye Gwang; Jin, Chang Hyun

    2016-01-01

    In this study, we investigated the anti-inflammatory effect of rosmarinic acid methyl ester (RAME) isolated from a mutant cultivar of Perilla frutescens (L.) Britton. We found that RAME inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with an IC50 of 14.25 µM, in RAW 264.7 cells. RAME inhibited the LPS-induced expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, interferon-β, and inducible nitric oxide synthase (iNOS). Moreover, RAME suppressed the activation of nuclear factor kappa B. These results suggest that the downregulation of iNOS expression by RAME was due to myeloid differentiation primary response gene 88 (MyD88)-dependent and -independent pathways. Furthermore, RAME induced the expression of heme oxygenase-1 (HO-1) through activation of nuclear factor-erythroid 2-related factor 2. Treatment with tin protoporphyrin, an inhibitor of HO-1, reversed the RAME-induced suppression of NO production. Taken together, RAME isolated from P. frutescens inhibited NO production in LPS-treated RAW 264.7 cells through simultaneous induction of HO-1 and inhibition of MyD88-dependent and -independent pathways. PMID:27548124

  10. Inducing of Angiogenesis is the Net Effect of the Amniotic Membrane Without Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Hassan Niknejad

    2011-01-01

    Full Text Available Amniotic membrane (AM, the nearest layer of placenta to the fetus, has some biological properties important for the experimental and clinical applications including anti-microbial, anti-fibrosis, anti-scarring, as well as low immunogenicity. The basement membrane of the AM contains several extracellular matrix components such as types І, III, IV, V collagen, laminin, fibronectin and perlecan which can induce proliferation of endothelial cells. The stormal side of the AM consists of mesenchymal cells which have capability to differentiate into endothelial cells. Moreover, several angiogenic factors such as interleukin (IL-6, IL-8, growth-related oncogene (GRO, monocyte chemoattractant protein-1 (MCP-1 and intravascular adhesion molecule (ICAM are secreted by the amniotic mesenchymal cells. Since the majority of anti-angiogenic factors are released by amniotic epithelial cells and due to the advantages of basement membrane and stromal side for inducing of angiogenesis, we have suggested here that the AM without epithelial layer would promote angiogenesis, an effect that would be a beneficial therapeutic approach for ischemic vascular diseases. To evaluate the hypothesis, the AM with or without epithelial cells will be implanted onto the striated muscle tissue of rats. The dorsal skinfold chamber model will be employed for intravital microscopic observation of the angiogenic host tissue response to implanted biomaterials throughout a time period of 7-14 days.

  11. Neurturin influences inflammatory responses and airway remodeling in different mouse asthma models.

    Science.gov (United States)

    Mauffray, Marion; Domingues, Olivia; Hentges, François; Zimmer, Jacques; Hanau, Daniel; Michel, Tatiana

    2015-02-15

    Neurturin (NTN) was previously described for its neuronal activities, but recently, we have shown that this factor is also involved in asthma physiopathology. However, the underlying mechanisms of NTN are unclear. The aim of this study was to investigate NTN involvement in acute bronchial Th2 responses, to analyze its interaction with airway structural cells, and to study its implication in remodeling during acute and chronic bronchial inflammation in C57BL/6 mice. We analyzed the features of allergic airway inflammation in wild-type and NTN(-/-) mice after sensitization with two different allergens, OVA and house dust mite. We showed that NTN(-/-) dendritic cells and T cells had a stronger tendency to activate the Th2 pathway in vitro than similar wild-type cells. Furthermore, NTN(-/-) mice had significantly increased markers of airway remodeling like collagen deposition. NTN(-/-) lung tissues showed higher levels of neutrophils, cytokine-induced neutrophil chemoattractant, matrix metalloproteinase 9, TNF-α, and IL-6. Finally, NTN had the capacity to decrease IL-6 and TNF-α production by immune and epithelial cells, showing a direct anti-inflammatory activity on these cells. Our findings support the hypothesis that NTN could modulate the allergic inflammation in different mouse asthma models. PMID:25595789

  12. Noise-Induced Increase of Sensitivity in Bacterial Chemotaxis.

    Science.gov (United States)

    He, Rui; Zhang, Rongjing; Yuan, Junhua

    2016-07-26

    Flagellated bacteria, like Escherichia coli, can swim toward beneficial environments by modulating the rotational direction of their flagellar motors through a chemotaxis signal transduction network. The noise of this network, the random fluctuation of the intracellular concentration of the signal protein CheY-P with time, has been identified in studies of single cell behavioral variability, and found to be important in coordination of multiple motors in a bacterium and in enhancement of bacterial drift velocity in chemical gradients. Here, by comparing the behavioral difference between motors of wild-type E. coli and mutants without signal noise, we measured the magnitude of this noise in wild-type cells, and found that the noise increases the sensitivity of the bacterial chemotaxis network downstream at the level of the flagellar motor. This provided a simple mechanism for the noise-induced enhancement of chemotactic drift, which we confirmed by simulating the E. coli chemotactic motion in various spatial profiles of chemo-attractant concentration. PMID:27463144

  13. Fitness Cost of Litomosoides sigmodontis Filarial Infection in Mite Vectors; Implications of Infected Haematophagous Arthropod Excretory Products in Host-Vector Interactions

    Directory of Open Access Journals (Sweden)

    Adélaïde Nieguitsila

    2013-01-01

    Full Text Available Filariae are a leading cause of infections which are responsible for serious dermatological, ocular, and vascular lesions. Infective third stage larvae (L3 are transmitted through the bite of a haematophagous vector. Litomosoides sigmodontis is a well-established model of filariasis in the mouse, with the vector being the mite Ornithonyssus bacoti. The aim of the study was to analyse the filarial infection in mites to determine the consequences of filarial infection in the blood-feeding and the reproduction of mites as well as in the regulation of vector-induced inflammation in the mouse skin. Firstly, L3 are unevenly distributed throughout the host population and the majority of the population harbours a moderate infection (1 to 6 L3. Filarial infection does not significantly affect the probing delay for blood feeding. The number of released protonymphs is lower in infected mites but is not correlated with the L3 burden. Finally, induced excreted proteins from infected mites but not from uninfected mites stimulate TNF-α and the neutrophil-chemoattractant KC production by antigen-presenting cells (APCs. Altogether, these results describe the modification of the mite behavior under filarial infection and suggest that the immunomodulatory capacity of the mite may be modified by the presence of the parasite, hindering its defensive ability towards the vertebrate host.

  14. Marangoni-driven chemotaxis, chemotactic collapse, and the Keller-Segel equation

    Science.gov (United States)

    Shelley, Michael; Masoud, Hassan

    2013-11-01

    Almost by definition, chemotaxis involves the biased motion of motile particles along gradients of a chemical concentration field. Perhaps the most famous model for collective chemotaxis in mathematical biology is the Keller-Segel model, conceived to describe collective aggregation of slime mold colonies in response to an intrinsically produced, and diffusing, chemo-attractant. Heavily studied, particularly in 2D where the system is ``super-critical'', it has been proved that the KS model can develop finite-time singularities - so-called chemotactic collapse - of delta-function type. Here, we study the collective dynamics of immotile particles bound to a 2D interface above a 3D fluid. These particles are chemically active and produce a diffusing field that creates surface-tension gradients along the surface. The resultant Marangoni stresses create flows that carry the particles, possibly concentrating them. Remarkably, we show that this system involving 3D diffusion and fluid dynamics, exactly yields the 2D Keller-Segel model for the surface-flow of active particles. We discuss the consequences of collapse on the 3D fluid dynamics, and generalizations of the fluid-dynamical model.

  15. A stochastic model for early placental development.

    KAUST Repository

    Cotter, Simon L

    2014-08-01

    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.

  16. Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor-2 and ICAM-1 Dependent Mechanism

    Science.gov (United States)

    Liu, Xin; Wang, Junling; Zhang, Huiyun; Zhan, Mengmeng; Chen, Hanqiu; Fang, Zeman; Xu, Chiyan; Chen, Huifang; He, Shaoheng

    2016-01-01

    Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2 and tc-LIGRLO-NH2 provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cells in vitro indicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions. PMID:27378825

  17. Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

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    Pramod Nehete

    2014-01-01

    Full Text Available Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1β and anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γ by PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

  18. Nucleotide-binding Oligomerization Domain-1 Ligand Induces Inflammation and Attenuates Glucose Uptake in Human Adipocytes

    Institute of Scientific and Technical Information of China (English)

    Yi-jun Zhou; Ai Li; Yu-ling Song; Yan Li; Hui Zhou

    2012-01-01

    Objective To investigate the effects of stimulant for nucleotide-binding oligomerization domain 1 (NOD1) on secretion of proinflammatory chemokine/cytokines and insulin-dependent glucose uptake in human differentiated adipocytes.Methods Adipose tissues were obtained from patients undergoing liposuction.Stromal vascular cells were extracted and differentiated into adipocytes.A specific ligand for NOD1,was administered to human adipocytes in culture.Nuclear factor-κB transcriptional activity and proinflammatory chemokine/cytokines production were determined by reporter plasmid assay and enzyme-linked immunosorbent assay,respectively.Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H]glucose uptake assay.Furthermore,chemokine/cytokine secretion and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon stimulation of NOD1 ligand were analyzed.Results Nuclear factor-κB transcriptional activity and monocyte chemoattractant protein-1 (MCP-1),interleukin (IL)-6,and IL-8 secretion in human adipocytes were markedly increased stimulated with NOD1 ligand (all P<0.01).Insulin-induced glucose uptake was decreased upon the activation of NOD1 (P<0.05).NOD1 gene silencing by siRNA reduced NOD1 ligand-induced MCP-1,IL-6,and IL-8 release and increased insulin-induced glucose uptake (all P<0.05).Conclusion NOD1 activation in adipocytes might be implicated in the onset of insulin resistance.

  19. Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells.

    Science.gov (United States)

    Prentice-Mott, Harrison V; Meroz, Yasmine; Carlson, Andreas; Levine, Michael A; Davidson, Michael W; Irimia, Daniel; Charras, Guillaume T; Mahadevan, L; Shah, Jagesh V

    2016-02-01

    Chemotaxis, the directional migration of cells in a chemical gradient, is robust to fluctuations associated with low chemical concentrations and dynamically changing gradients as well as high saturating chemical concentrations. Although a number of reports have identified cellular behavior consistent with a directional memory that could account for behavior in these complex environments, the quantitative and molecular details of such a memory process remain unknown. Using microfluidics to confine cellular motion to a 1D channel and control chemoattractant exposure, we observed directional memory in chemotactic neutrophil-like cells. We modeled this directional memory as a long-lived intracellular asymmetry that decays slower than observed membrane phospholipid signaling. Measurements of intracellular dynamics revealed that moesin at the cell rear is a long-lived element that when inhibited, results in a reduction of memory. Inhibition of ROCK (Rho-associated protein kinase), downstream of RhoA (Ras homolog gene family, member A), stabilized moesin and directional memory while depolymerization of microtubules (MTs) disoriented moesin deposition and also reduced directional memory. Our study reveals that long-lived polarized cytoskeletal structures, specifically moesin, actomyosin, and MTs, provide a directional memory in neutrophil-like cells even as they respond on short time scales to external chemical cues. PMID:26764383

  20. Cluster–cluster aggregation with particle replication and chemotaxy: a simple model for the growth of animal cells in culture

    International Nuclear Information System (INIS)

    Aggregation of animal cells in culture comprises a series of motility, collision and adhesion processes of basic relevance for tissue engineering, bioseparations, oncology research and in vitro drug testing. In the present paper, a cluster–cluster aggregation model with stochastic particle replication and chemotactically driven motility is investigated as a model for the growth of animal cells in culture. The focus is on the scaling laws governing the aggregation kinetics. Our simulations reveal that in the absence of chemotaxy the mean cluster size and the total number of clusters scale in time as stretched exponentials dependent on the particle replication rate. Also, the dynamical cluster size distribution functions are represented by a scaling relation in which the scaling function involves a stretched exponential of the time. The introduction of chemoattraction among the particles leads to distribution functions decaying as power laws with exponents that decrease in time. The fractal dimensions and size distributions of the simulated clusters are qualitatively discussed in terms of those determined experimentally for several normal and tumoral cell lines growing in culture. It is shown that particle replication and chemotaxy account for the simplest cluster size distributions of cellular aggregates observed in culture

  1. Disruption of a Regulatory Network Consisting of Neutrophils and Platelets Fosters Persisting Inflammation in Rheumatic Diseases

    Science.gov (United States)

    Maugeri, Norma; Rovere-Querini, Patrizia; Manfredi, Angelo A.

    2016-01-01

    A network of cellular interactions that involve blood leukocytes and platelets maintains vessel homeostasis. It plays a critical role in the response to invading microbes by recruiting intravascular immunity and through the generation of neutrophil extracellular traps (NETs) and immunothrombosis. Moreover, it enables immune cells to respond to remote chemoattractants by crossing the endothelial barrier and reaching sites of infection. Once the network operating under physiological conditions is disrupted, the reciprocal activation of cells in the blood and the vessel walls determines the vascular remodeling via inflammatory signals delivered to stem/progenitor cells. A deregulated leukocyte/mural cell interaction is an early critical event in the natural history of systemic inflammation. Despite intense efforts, the signals that initiate and sustain the immune-mediated vessel injury, or those that enforce the often-prolonged phases of clinical quiescence in patients with vasculitis, have only been partially elucidated. Here, we discuss recent evidence that implicates the prototypic damage-associated molecular pattern/alarmin, the high mobility group box 1 (HMGB1) protein in systemic vasculitis and in the vascular inflammation associated with systemic sclerosis. HMGB1 could represent a player in the pathogenesis of rheumatic diseases and an attractive target for molecular interventions. PMID:27242789

  2. Cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging

    Directory of Open Access Journals (Sweden)

    Luo Jinhua

    2010-10-01

    Full Text Available Abstract Background Most neurodegenerative diseases are age-related disorders; however, how aging predisposes the brain to disease has not been adequately addressed. The objective of this study is to determine whether expression of proteins in the cerebromicrovasculature related to inflammation, oxidative stress and neurotoxicity is altered with aging. Methods Brain microvessels are isolated from Fischer 344 rats at 6, 12, 18 and 24 months of age. Levels of interleukin (IL-1β and IL-6 RNA are determined by RT-PCR and release of cytokines into the media by ELISA. Vessel conditioned media are also screened by ELISA for IL-1α, monocyte chemoattractant protein-1 (MCP-1, tumor necrosis factor-α, (TNFα, and interferon γ (IFNγ. Immunofluorescent analysis of brain sections for IL-1β and IL-6 is performed. Results Expression of IL-1β and IL-6, both at RNA and protein levels, significantly (p Conclusions These data demonstrate that cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging and suggest that the microvasculature may contribute to functional changes in the aging brain.

  3. RORγt modulates macrophage recruitment during a hydrocarbon oil-induced inflammation.

    Science.gov (United States)

    Wu, Qi; Sun, Xin; Chi, Ruo; Xu, Long; Li, Xue; Feng, Jing; Chen, Huaiyong

    2013-01-01

    Hydrocarbon oils are often utilized as adjuvants in vaccines. In response to naturally occurring hydrocarbon oils, inflammation is initiated and persists with the continuous recruitment of immune cells such as macrophages and neutrophils. However, the mechanism underlying the chronic inflammation in response to hydrocarbon oils is not fully defined. In this study, we revealed an essential role of retinoid-related orphan receptor gamma t (RORγt) in sustaining the recruitment of macrophages following pristane treatment. RORγt absence resulted in the incompetent formation of mesenteric oil granulomas which may associate to a reduction in the migration of macrophages into the mesentery during pristane-induced inflammation. This is at least partially dependent on the expression of the monocyte chemoattractant protein-1 (MCP-1) in the mesentery and the decrease in the macrophage reservoir in the spleen. However, the absence of RORγt had no impact on the recruitment of neutrophils to the mesentery after pristane treatment. Our data uncovered an important role of RORγt in the recruitment of macrophages during hydrocarbon oil-induced chronic inflammation. PMID:24260235

  4. Effective Medium Equations for Chemotaxis in Porous Media

    Science.gov (United States)

    Valdes-Parada, F.; Porter, M.; Wood, B. D.; Narayanaswamy, K.; Ford, R.

    2008-12-01

    Biodegradation is an important mechanism for contaminant reduction in groundwater environments; in fact, in-situ bioremediation and bioaugmentation methods represent alternatives to traditional methods such as pump-and-treat. Chemotaxis has been shown to enhance bacterial transport toward or away from concentration gradients of chemical species in laboratory experiments and may signifficantly increase contaminant flux undergoing degradation at the interfaces of low- and high-permeability regions. In this work, the method of volume averaging is used to upscale the microscale description of chemotactic microbial transport in order to obtain the corresponding macroscale equations for bacteria and the chemoattractant. As a first apprach, cellular growth/death and consumption of the attractant by chemical reaction are assumed negligible with respect to convective and diffusive transport, in both levels of scale. For bacteria, two effective coefficients are introduced, namely a total motility tensor and an effective chemotactic sensitivity tensor. Both coefficients are computed by solving the associated closure problems in a capillary tube. Analysis of breakthrough curves resulting from numerical experiments is also presented.

  5. Responses of tumor cell pseudopod protrusion to changes in medium osmolality.

    Science.gov (United States)

    You, J; Aznavoorian, S; Liotta, L A; Dong, C

    1996-04-01

    The potential involvement of osmotically generated force in protrusion of tumor cell pseudopods was examined during a micropipette assay. Experiments were performed on single A2058 melanoma cells activated by a micropipette filled with soluble type IV collagen. Previous observations suggested that tumor cell pseudopod protrusion induced by type IV collagen took place in distinct, separable phases: an initial bleb (first phase) caused by localized Ca2+-activated actin filament severing resulting in an osmotic flux followed by an extension with an irregular shape (second phase) which required G protein-mediated actin polymerization (Dong et al., 1994, Microvasc. Res., 47:55-67). Presently we studied cell pseudopod protrusion in response to the changes in chemoattractant osmolality. Reduction of attractant osmolality by 20-25% from its baseline value (297 mmol/ kg) resulted in an increase in pseudopod length by 50% apparent in the initial phase. Increases in attractant osmolality by 25-30% from the baseline value arrested pseudopod protrusion significantly during both initial and later phases. Using a dual-pipette method, such osmotic influence on the cell pseudopod protrusion was shown to be only a local effect in a small region where the cell surface was stimulated by the micropipette. While forces derived from actin polymerization and osmotic pressure have been proposed to cause protrusion in general, our results suggested that osmotically generated force is more apparent in the initial phase of the pseudopod formation. PMID:8698833

  6. Protective effects of tanshinone ⅡA on endothelial progenitor cells injured by tumor necrosis factor-α.

    Science.gov (United States)

    Wang, Xing-Xiang; Yang, Jin-Xiu; Pan, Yan-Yun; Zhang, Ye-Fei

    2015-09-01

    Tanshinone ⅡA (Tan ⅡA) is a Traditional Chinese Medicine commonly used in Asian and Western countries for the prevention and treatment of cardiovascular disorders, such as atherosclerosis. Endothelial dysfunction and associated inflammatory processes have a critical role in the development of atherosclerosis. Endothelial progenitor cells (EPCs) have been demonstrated to be involved in certain aspects of the endothelial repair process. The present study aimed to investigate the putative protective effects of Tan ⅡA on EPCs injured by tumor necrosis factor‑α (TNF‑α). The potential effects of Tan ⅡA on TNF-α-stimulated EPC proliferation, migration, adhesion, in vitro tube formation ability and paracrine activity were investigated in the current study. The results indicated that TNF‑α impaired EPC proliferation, migration, adhesion capacity and vasculogenesis ability in vitro as well as promoted EPC secretion of inflammatory cytokines, including monocyte chemoattractant protein‑1 (MCP‑1), interleukin‑6 (IL‑6) and soluble CD40 ligand (sCD40L). However, Tan ⅡA was able to reverse these effects. In conclusion, these findings demonstrated that Tan ⅡA may have the potential to protect EPCs against damage induced by TNF‑α. Therefore, these results may provide evidence for the pharmacological basis of Tan ⅡA and its potential use in the prevention and treatment of early atherosclerosis associated with EPC and endothelial damage. PMID:26095681

  7. Tissue- and age-dependent expression of the bovine DEFB103 gene and protein.

    Science.gov (United States)

    Mirabzadeh-Ardakani, Ali; Solie, Jay; Gonzalez-Cano, Patricia; Schmutz, Sheila M; Griebel, Philip J

    2016-02-01

    Beta-defensin 103 (DEFB103) shares little homology with 8 other members of the bovine beta-defensin family and in other species DEFB103 protein has diverse functions, including antimicrobial activity, a chemoattractant for dendritic cells, enhancing epithelial wound repair and regulating hair colour. Expression of the bovine DEFB103 gene was surveyed in 27 tissues and transcript was most abundant in tissues with stratified squamous epithelium. Oral cavity epithelial tissues and nictitating membrane consistently expressed high levels of DEFB103 gene transcript. An age-dependent decrease (P internal organs such as lung, intestine and kidney. Affinity-purified rabbit antisera to bovine DEFB103 was used to identify cells expressing DEFB103 protein within tissues with stratified squamous epitheliums. DEFB103 protein was most abundant in basal epithelial cells and was present in these cells prior to birth. Beta-defensins have been identified as regulators of dendritic cell (DC) chemokine responses and we observed a close association between DCs and epithelial cells expressing DEFB103 in both the fetus and newborn calf. In conclusion, bovine DEFB103 gene expression is most abundant in stratified squamous epithelium with DEFB103 protein localised to basal epithelial cells. These observations are consistent with proposed roles for DEFB103 in DC recruitment and repair of stratified squamous epithelium. PMID:26299200

  8. High Hydrostatic Pressure Extract of Red Ginseng Attenuates Inflammation in Rats with High-fat Diet Induced Obesity.

    Science.gov (United States)

    Jung, Sunyoon; Lee, Mak-Soon; Shin, Yoonjin; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

    2015-12-01

    Chronic low-grade inflammation is associated with obesity. This study investigated effect of high hydrostatic pressure extract of red ginseng (HRG) on inflammation in rats with high-fat (HF) diet induced obesity. Male, Sprague-Dawley rats (80~110 g) were randomly divided into two groups, and fed a 45% HF diet (HF) and a 45% HF diet containing 1.5% HRG (HF+HRG) for 14 weeks. At the end of the experiment, the serum leptin level was reduced by the HRG supplementation. The mRNA expression of genes related to adipogenesis including peroxisome proliferator-activated receptor-gamma and adipocyte protein 2 was down-regulated in the white adipose tissue (WAT). The mRNA levels of major inflammatory cytokines such as tumor necrosis factor-α, monocyte chemoattractant protein 1, and interleukin-6 were remarkably down-regulated by the HRG in WAT. These results suggest that HRG might be beneficial in ameliorating the inflammation-associated health complications by suppressing adipogenic and pro-inflammatory gene expression. PMID:26770912

  9. Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.

    Directory of Open Access Journals (Sweden)

    Akiko Eguchi

    Full Text Available Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity.

  10. Antimicrobial peptides: mediators of innate immunity as templates for the development of novel anti-infective and immune therapeutics.

    Science.gov (United States)

    Hiemstra, P S; Fernie-King, B A; McMichael, J; Lachmann, P J; Sallenave, J-M

    2004-01-01

    Antimicrobial molecules are ancient and essential small cationic molecules of the host defence system which are found in a wide variety of species. They display antimicrobial activity against a wide range of bacteria, fungi and viruses, an activity that has been mostly attributed to the disruption of microbial membranes. In this article, we will review the "classical" functions of 3 classes of antimicrobial molecules, namely defensins, cathelicidins, and the four-disulfide core proteins secretory leukocyte proteinase inhibitor (SLPI) and elafin. In addition to the study of their expression in a variety of cell types and the regulation of their production, we will also describe novel properties of these molecules that have been highlighted by recent studies. These include their ability to chemoattract a variety of inflammatory, immune and other cell types (neutrophils, macrophages, monocytes, lymphocytes, mast cells, epithelial cells) in vitro and in vivo. In addition, we will discuss the potential use of these newly discovered properties for therapeutic or vaccination purposes, using protein- or gene-transfer based methodologies. Finally, we will examine in an extensive fashion the strategies used by microorganisms to circumvent and subvert host defence mechanisms, such as the modifications of cell membranes and walls, the secretion of inactivating proteins and proteases and the down-regulation of expression of antimicrobial molecules. Increased understanding of the mechanisms used by both the host and the microbes to 'win the battle' may ultimately lead to new therapeutic strategies aimed to treat infectious diseases. PMID:15379675

  11. Evaluating the Anti-Neuroinflammatory Capacity of Raw and Steamed Garlic as Well as Five Organosulfur Compounds

    Directory of Open Access Journals (Sweden)

    Su-Chen Ho

    2014-10-01

    Full Text Available The anti-neuroinflammatory capacities of raw and steamed garlic extracts as well as five organosulfur compounds (OSCs were examined in lipopolysaccharide (LPS-stimulated BV2 microglia. According to those results, steaming pretreatment blocked the formation of alliinase-catalyzed OSCs such as allicin and diallyl trisulfide (DATS in crushed garlic. Raw garlic, but not steamed garlic, dose-dependently attenuated the production of LPS-induced nitric oxide (NO, interleukin-1β (IL-1β, tumor necrosis factor (TNF-α, and monocyte chemoattractant protein-1 (MCP-1. DATS and diallyl disulfide at 200 and 400 μM, respectively, displayed significant anti-neuroinflammatory activity. Meanwhile, even at 1 mM, diallyl sulfide, S-allyl cysteine and alliin did not display such activity. Inhibition of nuclear factor-κB activation was the mechanism underlying this protective effect of raw garlic and DATS. Analysis results indicated that the anti-neuroinflammatory capacity of raw garlic is due to the alliin-derived OSCs. Importantly, DATS is a highly promising therapeutic candidate for treating inflammation-related neurodegenerative diseases.

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

    International Nuclear Information System (INIS)

    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

  13. The Multifaceted Functions of CXCL10 in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Pleunie van den Borne

    2014-01-01

    Full Text Available C-X-C motif ligand 10 (CXCL10, or interferon-inducible protein-10, is a small chemokine belonging to the CXC chemokine family. Its members are responsible for leukocyte trafficking and act on tissue cells, like endothelial and vascular smooth muscle cells. CXCL10 is secreted by leukocytes and tissue cells and functions as a chemoattractant, mainly for lymphocytes. After binding to its receptor CXCR3, CXCL10 evokes a range of inflammatory responses: key features in cardiovascular disease (CVD. The role of CXCL10 in CVD has been extensively described, for example for atherosclerosis, aneurysm formation, and myocardial infarction. However, there seems to be a discrepancy between experimental and clinical settings. This discrepancy occurs from differences in biological actions between species (e.g. mice and human, which is dependent on CXCL10 signaling via different CXCR3 isoforms or CXCR3-independent signaling. This makes translation from experimental to clinical settings challenging. Furthermore, the overall consensus on the actions of CXCL10 in specific CVD models is not yet reached. The purpose of this review is to describe the functions of CXCL10 in different CVDs in both experimental and clinical settings and to highlight and discuss the possible discrepancies and translational difficulties. Furthermore, CXCL10 as a possible biomarker in CVD will be discussed.

  14. Integration of chemotaxis, transport and catabolism in Pseudomonas putida and identification of the aromatic acid chemoreceptor PcaY.

    Science.gov (United States)

    Luu, Rita A; Kootstra, Joshua D; Nesteryuk, Vasyl; Brunton, Ceanne N; Parales, Juanito V; Ditty, Jayna L; Parales, Rebecca E

    2015-04-01

    Aromatic and hydroaromatic compounds that are metabolized through the β-ketoadipate catabolic pathway serve as chemoattractants for Pseudomonas putida F1. A screen of P. putida F1 mutants, each lacking one of the genes encoding the 18 putative methyl-accepting chemotaxis proteins (MCPs), revealed that pcaY encodes the MCP required for metabolism-independent chemotaxis to vanillate, vanillin, 4-hydroxybenzoate, benzoate, protocatechuate, quinate, shikimate, as well as 10 substituted benzoates that do not serve as growth substrates for P. putida F1. Chemotaxis was induced during growth on aromatic compounds, and an analysis of a pcaY-lacZ fusion revealed that pcaY is expressed in the presence of β-ketoadipate, a common intermediate in the pathway. pcaY expression also required the transcriptional activator PcaR, indicating that pcaY is a member of the pca regulon, which includes three unlinked gene clusters that encode five enzymes required for the conversion of 4-hydroxybenzoate to tricarboxylic acid cycle intermediates as well as the major facilitator superfamily transport protein PcaK. The 4-hydroxybenzoate permease PcaK was shown to modulate the chemotactic response by facilitating the uptake of 4-hydroxybenzoate, which leads to the accumulation of β-ketoadipate, thereby increasing pcaY expression. The results show that chemotaxis, transport and metabolism of aromatic compounds are intimately linked in P. putida. PMID:25582673

  15. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H Lie; Smit, Jolanda M; Rodenhuis-Zybert, Izabela A

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  16. PDGF stimulation of Mueller cell proliferation: Contributions of c-JNK and the PI3K/Akt pathway

    International Nuclear Information System (INIS)

    Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Mueller cells and the intracellular signaling pathway mediating these changes. PDGF induced Mueller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Mueller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Mueller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Mueller cells in the development of proliferative vitreoretinopathy.

  17. Developing a multiscale, multi-resolution agent-based brain tumor model by graphics processing units

    Directory of Open Access Journals (Sweden)

    Zhang Le

    2011-12-01

    Full Text Available Abstract Multiscale agent-based modeling (MABM has been widely used to simulate Glioblastoma Multiforme (GBM and its progression. At the intracellular level, the MABM approach employs a system of ordinary differential equations to describe quantitatively specific intracellular molecular pathways that determine phenotypic switches among cells (e.g. from migration to proliferation and vice versa. At the intercellular level, MABM describes cell-cell interactions by a discrete module. At the tissue level, partial differential equations are employed to model the diffusion of chemoattractants, which are the input factors of the intracellular molecular pathway. Moreover, multiscale analysis makes it possible to explore the molecules that play important roles in determining the cellular phenotypic switches that in turn drive the whole GBM expansion. However, owing to limited computational resources, MABM is currently a theoretical biological model that uses relatively coarse grids to simulate a few cancer cells in a small slice of brain cancer tissue. In order to improve this theoretical model to simulate and predict actual GBM cancer progression in real time, a graphics processing unit (GPU-based parallel computing algorithm was developed and combined with the multi-resolution design to speed up the MABM. The simulated results demonstrated that the GPU-based, multi-resolution and multiscale approach can accelerate the previous MABM around 30-fold with relatively fine grids in a large extracellular matrix. Therefore, the new model has great potential for simulating and predicting real-time GBM progression, if real experimental data are incorporated.

  18. Pace of macrophage recruitment during different stages of soft tissue infection: Semi-quantitative evaluation by in vivo magnetic resonance imaging

    International Nuclear Information System (INIS)

    We describe the pace of recruitment of iron-oxide-labeled macrophages to the site of different stages of infection by in vivo magnetic resonance (MR) imaging. Peritoneal macrophages were labeled with superparamagnetic iron oxide ex vivo and administered through the tail vein 6 (acute) or 48 (subacute) h after bacterial inoculation. The legs of the mice were imaged sequentially on a 4.7-T MR unit before and 3, 6, 12, 18, 24, 48 and 72 h after macrophage administration. The band-shaped lower signal intensity zone around the abscess on T2*-weighted GRE images became more obvious due to recruited macrophages up until 24 h after injection in the subacute and 48 h after injection in the acute group, indicating that the relative SI of the abscess wall decreased more rapidly and the pace of recruitment of macrophages was faster in the subacute than in the acute group. Chemokine antibody arrays of mouse sera detected increased concentration of granulocyte-colony-stimulating factor and tissue inhibitor of metalloproteinase-1 beginning at 12 h and increased interleukin-13 at 18 h. Monocyte chemoattractant protein-1 and macrophage-colony-stimulating factor began to increase at 96 h after infection. This difference in pace of recruitment may result from the release of chemokines. (orig.)

  19. Toll-Like Receptor 4 Engagement Mediates Prolyl Endopeptidase Release from Airway Epithelia via Exosomes.

    Science.gov (United States)

    Szul, Tomasz; Bratcher, Preston E; Fraser, Kyle B; Kong, Michele; Tirouvanziam, Rabindra; Ingersoll, Sarah; Sztul, Elizabeth; Rangarajan, Sunil; Blalock, J Edwin; Xu, Xin; Gaggar, Amit

    2016-03-01

    Proteases are important regulators of pulmonary remodeling and airway inflammation. Recently, we have characterized the enzyme prolyl endopeptidase (PE), a serine peptidase, as a critical protease in the generation of the neutrophil chemoattractant tripeptide Pro-Gly-Pro (PGP) from collagen. However, PE has been characterized as a cytosolic enzyme, and the mechanism mediating PE release extracellularly remains unknown. We examined the role of exosomes derived from airway epithelia as a mechanism for PE release and the potential extracellular signals that regulate the release of these exosomes. We demonstrate a specific regulatory pathway of exosome release from airway epithelia and identify PE as novel exosome cargo. LPS stimulation of airway epithelial cells induces release of PE-containing exosomes, which is significantly attenuated by small interfering RNA depletion of Toll-like receptor 4 (TLR4). These differences were recapitulated upon intratracheal LPS administration in mice competent versus deficient for TLR4 signaling. Finally, sputum samples from subjects with cystic fibrosis colonized with Pseudomonas aeruginosa demonstrate elevated exosome content and increased PE levels. This TLR4-based mechanism highlights the first report of nonstochastic release of exosomes in the lung and couples TLR4 activation with matrikine generation. The increased quantity of these proteolytic exosomes in the airways of subjects with chronic lung disease highlights a new mechanism of injury and inflammation in the pathogenesis of pulmonary disorders. PMID:26222144

  20. Inhibitory effect of Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts on lipopolysaccharide-stimulated inflammatory response in RAW 264.7 cells*

    Science.gov (United States)

    Xu, Wei; Zhou, Qing; Yao, Yong; Li, Xing; Zhang, Jiu-liang; Su, Guan-hua; Deng, Ai-ping

    2016-01-01

    Blueberries are a rich source of anthocyanins, which are associated with health benefits contributing to a reduced risk for many diseases. The present study identified the functional Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts (GBBAEs) and evaluated their capacity and underlying mechanisms in protecting murine RAW 264.7 cells from lipopolysaccharide (LPS)-stimulated inflammation in vitro. Enzyme-linked immunosorbent assay (ELISA) kit results showed that GBBAEs significantly inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-1β, and interferon-γ (INF-γ). Real-time polymerase chain reaction (PCR) analysis indicated that the mRNA expression levels of IL-6, IL-1β, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and cyclooxygenase 2 (COX-2) were suppressed in LPS-stimulated RAW 264.7 cells. Additionally, Western blot analysis was used to evaluate the relative protein expression levels of COX-2 and nuclear factor-κB p65 (NF-κBp65). All these results suggested the potential use of GBBAEs as a functional food for the treatment of inflammatory diseases. PMID:27256676

  1. Lectin staining and flow cytometry reveals female-induced sperm acrosome reaction and surface carbohydrate reorganization

    Science.gov (United States)

    Kekäläinen, Jukka; Larma, Irma; Linden, Matthew; Evans, Jonathan P.

    2015-01-01

    All cells are covered by glycans, an individually unique layer of oligo- and polysaccharides that are critical moderators of self-recognition and other cellular-level interactions (e.g. fertilization). The functional similarity between these processes suggests that gamete surface glycans may also have an important, but currently overlooked, role in sexual selection. Here we develop a user-friendly methodological approach designed to facilitate future tests of this possibility. Our proposed method is based on flow cytometric quantification of female-induced sperm acrosome reaction and sperm surface glycan modifications in the Mediterranean mussel Mytilus galloprovincialis. In this species, as with many other taxa, eggs release water-soluble factors that attract conspecific sperm (chemoattraction) and promote potentially measurable changes in sperm behavior and physiology. We demonstrate that flow cytometry is able to identify sperm from other seawater particles as well as accurately measure both acrosome reaction and structural modifications in sperm glycans. This methodological approach can increase our understanding of chemically-moderated gamete-level interactions and individual-specific gamete recognition in Mytilus sp. and other taxa with similar, easily identifiable acrosome structure. Our approach is also likely to be applicable to several other species, since carbohydrate-mediated cellular-level interactions between gametes are universal among externally and internally fertilizing species. PMID:26470849

  2. Hyperexcitable neurons and altered non-neuronal cells in the compressed spinal ganglion

    Institute of Scientific and Technical Information of China (English)

    Robert H. LaMotte; Chao MA

    2008-01-01

    The cell body or soma in the dosal root ganglion (DRG) is normally excitable and this excitability can increase and persist after an injury of peripheral sensory neurons. In a rat model of radicular pain, an intraforaminal implantation of a rod that chronically compressed the lumbar DRG ("CCD" model) resulted in neuronal somal hyperexcitability and spontaneous activity that was accom-panied by hyperalgesia in the ipsilateral hind paw. By the 5th day after onset of CCD, there was a novel upregulation in neuronal expression of the chemokine, monocyte chemoattractant protein-1 (MCP- 1 or CCL2) and also its receptor, CCR2. The neurons developed, in response to topically applied MCP-1, an excitatory response that they normally do not have. CCD also activated non-neuronal cells including, for example, the endothelial cells as evidenced by angiogenesis in the form of an increased number of capillaries in the DRG after 7 days. A working hypothesis is that the CCD induced changes in neurons and non-neuronal cells that may act together to promote the survival of the injured tissue. The release of ligands such as CCL2, in addition to possibly activating nociceptive neurons (maintaining the pain), may also act to preserve injured cells in the face of ischemia and hypoxia, for example, by promoting angiogenesis. Thus, somal hyperexcitability, as often said of inflammation, may represent a double edged sword.

  3. Curcuma longa polyphenols improve insulin-mediated lipid accumulation and attenuate proinflammatory response of 3T3-L1 adipose cells during oxidative stress through regulation of key adipokines and antioxidant enzymes.

    Science.gov (United States)

    Septembre-Malaterre, Axelle; Le Sage, Fanny; Hatia, Sarah; Catan, Aurélie; Janci, Laurent; Gonthier, Marie-Paule

    2016-07-01

    Plant polyphenols may exert beneficial action against obesity-related oxidative stress and inflammation which promote insulin resistance. This study evaluated the effect of polyphenols extracted from French Curcuma longa on 3T3-L1 adipose cells exposed to H2 O2 -mediated oxidative stress. We found that Curcuma longa extract exhibited high amounts of curcuminoids identified as curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which exerted free radical-scavenging activities. Curcuma longa polyphenols improved insulin-mediated lipid accumulation and upregulated peroxisome proliferator-activated receptor-gamma gene expression and adiponectin secretion which decreased in H2 O2 -treated cells. Curcuminoids attenuated H2 O2 -enhanced production of pro-inflammatory molecules such as interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and nuclear factor κappa B. Moreover, they reduced intracellular levels of reactive oxygen species elevated by H2 O2 and modulated the expression of genes encoding superoxide dismutase and catalase antioxidant enzymes. Collectively, these findings highlight that Curcuma longa polyphenols protect adipose cells against oxidative stress and may improve obesity-related metabolic disorders. © 2016 BioFactors, 42(4):418-430, 2016. PMID:27094023

  4. Photodynamic therapy mediates innate immune responses via fibroblast-macrophage interactions.

    Science.gov (United States)

    Zulaziz, N; Azhim, A; Himeno, N; Tanaka, M; Satoh, Y; Kinoshita, M; Miyazaki, H; Saitoh, D; Shinomiya, N; Morimoto, Y

    2015-10-01

    Antibacterial photodynamic therapy (PDT) has come to attract attention as an alternative therapy for drug-resistant bacteria. Recent reports revealed that antibacterial PDT induces innate immune response and stimulates abundant cytokine secretion as a part of inflammatory responses. However, the underlying mechanism how antibacterial PDT interacts with immune cells responsible for cytokine secretion has not been well outlined. In this study, we aimed to clarify the difference in gene expression and cytokine secretion between combined culture of fibroblasts and macrophages and their independent cultures. SCRC-1008, mouse fibroblast cell line and J774, mouse macrophage-like cell line were co-cultured and PDT treatments with different parameters were carried out. After various incubation periods (1-24 h), cells and culture medium were collected, and mRNA and protein levels for cytokines were measured using real-time PCR and ELISA, respectively. Our results showed that fibroblasts and macrophages interact with each other to mediate the immune response. We propose that fibroblasts initially respond to PDT by expressing Hspa1b, which regulates the NF-κB pathway via Tlr2 and Tlr4. Activation of the NF-κB pathway then results in an enhanced secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and neutrophil chemoattractant MIP-2 and KC from macrophages. PMID:25997703

  5. Eugenol alters the integrity of cell membrane and acts against the nosocomial pathogen Proteus mirabilis.

    Science.gov (United States)

    Devi, K Pandima; Sakthivel, R; Nisha, S Arif; Suganthy, N; Pandian, S Karutha

    2013-03-01

    Eugenol, a member of the phenylpropanoids class of chemical compounds, is a clear to pale yellow oily liquid extracted from certain essential oils especially from clove oil, nutmeg, cinnamon, and bay leaf. The antibacterial activity of eugenol and its mechanism of bactericidal action against Proteus mirabilis were evaluated. Treatment with eugenol at their minimum inhibitory concentration [0.125 % (v/v)] and minimum bactericidal concentration [0.25 % (v/v)] reduced the viability and resulted in complete inhibition of P. mirabilis. A strong bactericidal effect on P. mirabilis was also evident, as eugenol inactivated the bacterial population within 30 min exposure. Chemo-attractant property and the observance of highest antibacterial activity at alkaline pH suggest that eugenol can work more effectively when given in vivo. Eugenol inhibits the virulence factors produced by P. mirabilis as observed by swimming motility, swarming behavior and urease activity. It interacts with cellular membrane of P. mirabilis and makes it highly permeable, forming nonspecific pores on plasma membrane, which in turn directs the release of 260 nm absorbing materials and uptake of more crystal violet from the medium into the cells. SDS-polyacrylamide gel, scanning electron microscopy and Fourier transform infrared analysis further proves the disruptive action of eugenol on the plasma membrane of P. mirabilis. The findings reveal that eugenol shows an excellent bactericidal activity against P. mirabilis by altering the integrity of cell membrane. PMID:23444040

  6. The HPV16 E7 Oncoprotein Disrupts Dendritic Cell Function and Induces the Systemic Expansion of CD11b+Gr1+ Cells in a Transgenic Mouse Model

    Science.gov (United States)

    Damian-Morales, Gabriela; Serafín-Higuera, Nicolás; Moreno-Eutimio, Mario Adán; Cortés-Malagón, Enoc M.; Bonilla-Delgado, José; Rodríguez-Uribe, Genaro; Ocadiz-Delgado, Rodolfo; Lambert, Paul F.

    2016-01-01

    Objective. The aim of this study was to analyze the effects of the HPV16 E7 oncoprotein on dendritic cells (DCs) and CD11b+Gr1+ cells using the K14E7 transgenic mouse model. Materials and Methods. The morphology of DCs was analyzed in male mouse skin on epidermal sheets using immunofluorescence and confocal microscopy. Flow cytometry was used to determine the percentages of DCs and CD11b+Gr1+ cells in different tissues and to evaluate the migration of DCs. Results. In the K14E7 mouse model, the morphology of Langerhans cells and the migratory activity of dendritic cells were abnormal. An increase in CD11b+Gr1+ cells was observed in the blood and skin of K14E7 mice, and molecules related to CD11b+Gr1+ chemoattraction (MCP1 and S100A9) were upregulated. Conclusions. These data suggest that the HPV16 E7 oncoprotein impairs the function and morphology of DCs and induces the systemic accumulation of CD11b+Gr1+ cells. PMID:27478837

  7. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

    Science.gov (United States)

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H. Lie; Smit, Jolanda M.; Rodenhuis-Zybert, Izabela A.

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  8. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPAR-γ). Although nifedipine did not affect expression levels of PPAR-γ, it increased the PPAR-γ transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-γ activation.

  9. Enhancement of Chemotactic Cell Aggregation by Haptotactic Cell-To-Cell Interaction.

    Directory of Open Access Journals (Sweden)

    Tae-Goo Kwon

    Full Text Available The crawling of biological cell is a complex phenomenon involving various biochemical and mechanical processes. Some of these processes are intrinsic to individual cells, while others pertain to cell-to-cell interactions and to their responses to extrinsically imposed cues. Here, we report an interesting aggregation dynamics of mathematical model cells, when they perform chemotaxis in response to an externally imposed global chemical gradient while they influence each other through a haptotaxis-mediated social interaction, which confers intriguing trail patterns. In the absence of the cell-to-cell interaction, the equilibrium population density profile fits well to that of a simple Keller-Segal population dynamic model, in which a chemotactic current density [Formula: see text] competes with a normal diffusive current density [Formula: see text], where p and ρ refer to the concentration of chemoattractant and population density, respectively. We find that the cell-to-cell interaction confers a far more compact aggregation resulting in a much higher peak equilibrium cell density. The mathematical model system is applicable to many biological systems such as swarming microglia and neutrophils or accumulating ants towards a localized food source.

  10. Lack of association of recipient MCP-1 gene promoter polymorphism with acute graft rejection after orthotopic liver transplantation.

    Science.gov (United States)

    Franco-López, E; González-Escribano, M F; Aguilera, I; Pascasio, J M; Pareja, F; Bernardos, A; Núñez-Roldán, A

    2005-04-01

    Acute graft rejection after orthotopic liver transplantation (OLT) is associated with leukocyte infiltration of the graft. Monocyte chemoattractant protein-1 (MCP-1) is a beta-chemokine involved in the attraction and accumulation of mononuclear granulocytes toward sites of inflammation. A biallelic polymorphism (G/A) at position -2518 of the MCP-1 gene has been described. Cells obtained from individuals with the GG or AG genotypes have been found to produce more MCP-1 than those obtained from individuals with the AA genotype. The goal of this study was to assess the possible association between this polymorphism and susceptibility to acute graft rejection after OLT. One hundred fifty Caucasian liver transplant recipients from the South of Spain underwent genotyping using a polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP). No significant differences were observed when patients with versus without acute rejection episodes were compared for the distribution of -2518 MCP-1 genotypes. The present study supports the lack of involvement of polymorphism at position -2518 (A/G) of the MCP-1 gene on the susceptibility to acute allograft rejection among OLT recipients. PMID:15866653

  11. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    Directory of Open Access Journals (Sweden)

    Aimee L. Dordevic

    2015-07-01

    Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

  12. Proinflammatory cytokine production and insulin sensitivity regulated by overexpression of resistin in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Garvey W Timothy

    2006-07-01

    Full Text Available Abstract Resistin is secreted from adipocytes, and high circulating levels have been associated with obesity and insulin resistance. To investigate whether resistin could exert autocrine effects in adipocytes, we expressed resistin gene in 3T3-L1 fibroblasts using a lentiviral vector, and selected several stably-transduced cell lines under blasticidin selection. We observed that 3T3-L1 adipocytes expressing resistin have a decreased gene expression for related transcriptional factors (CCAAT/enhancer binding protein α(C/EBPα , peroxisome proliferator-activated receptor gamma (PPARγ, and adipocyte lipid binding protein (ALBP/aP2 which is one of target genes for the PPARγ during adipocyte differentiation,. Overexpression of resistin increased the levels of three proinflammatory cytokines, tumor necrosis factor alpha (TNFα, interleukin 6 (IL-6 and monocyte chemoattractant protein-1 (MCP-1, which play important roles for insulin resistance, glucose and lipid metabolisms during adipogenesis. Furthermore, overexpressing resistin in adipocytes inhibits glucose transport 4 (GLUT4 activity and its gene expression, reducing insulin's ability for glucose uptake by 30 %. In conclusion, resistin overexpression in stably transduced 3T3-L1 cells resulted in: 1 Attenuation of programmed gene expression responsible for adipogenesis; 2 Increase in expression of proinflammatory cytokines; 3 Decrease in insulin responsiveness of the glucose transport system. These data suggest a new role for resistin as an autocrine/paracrine factor affecting inflammation and insulin sensitivity in adipose tissue.

  13. Combination of macrophage inflammatory protein 1 alpha with existing therapies to enhance the antitumor effects on murine hepatoma

    International Nuclear Information System (INIS)

    Existing therapies such as irradiation or sorafenib have limited success in the treatment of hepatocellular carcinoma (HCC) due to tumor recurrence and metastasis. Therefore, combination with other therapeutics is often considered. Macrophage inflammatory protein-1 alpha (MIP-1α) is a member of a family of chemo-attractant cytokines that can induce the migration of monocytes, which in turn can play a role in fighting tumors. This study investigated whether intravenous injection of MIP-1α in conjunction with irradiation or sorafenib could enhance the antitumor effects on murine hepatoma. An HCa-I tumor was grown on the right thigh of each C3H/HeN mouse. Mice were then treated with 10 Gy of irradiation, sorafenib, or a combination of MIP-1α with either irradiation or sorafenib, and antitumor and antimetastatic effects were then investigated. To understand the mechanisms, changes in the level of immunological markers were also evaluated. Combination treatment of MIP-1α with irradiation or sorafenib resulted in a significant enhancement of antitumor effects, prevention of lung metastasis and increase in host survival. This was achieved by significantly increasing the levels of the immunological markers: Cluster Differentiation (CD) 8, CD107A and CD11C. We conclude that a combination treatment of MIP-1α with irradiation or sorafenib would be a useful strategy for management of hepatoma. (author)

  14. Atherosclerosis: a chronic inflammatory disease mediated by mast cells.

    Science.gov (United States)

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  15. Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members

    International Nuclear Information System (INIS)

    We evaluated 17 clinically unaffected members of three families with an autosomal dominant form of idiopathic pulmonary fibrosis for evidence of alveolar inflammation. Each person in the study was examined by gallium-67 scanning for a general estimate of pulmonary inflammation, and by bronchoalveolar lavage for characterization of the types of recovered cells and their state of activation. Eight of the 17 subjects had evidence of alveolar inflammation on the lavage studies. Supporting data included increased numbers of neutrophils and activated macrophages that released one or more neutrophil chemoattractants, and growth factors for lung fibroblasts--findings similar to those observed in patients with overt idiopathic pulmonary fibrosis. Four of these eight also had a positive gallium scan; in all the other clinically unaffected subjects the scan was normal. During a follow-up of two to four years in seven of the eight subjects who had evidence of inflammation, no clinical evidence of pulmonary fibrosis has appeared. These results indicate that alveolar inflammation occurs in approximately half the clinically unaffected family members at risk of inheriting autosomal dominant idiopathic pulmonary fibrosis. Whether these persons with evidence of pulmonary inflammation but no fibrosis will proceed to have clinically evident pulmonary fibrosis is not yet known

  16. Canonical and noncanonical g-protein signaling helps coordinate actin dynamics to promote macrophage phagocytosis of zymosan.

    Science.gov (United States)

    Huang, Ning-Na; Becker, Steven; Boularan, Cedric; Kamenyeva, Olena; Vural, Ali; Hwang, Il-Young; Shi, Chong-Shan; Kehrl, John H

    2014-11-15

    Both chemotaxis and phagocytosis depend upon actin-driven cell protrusions and cell membrane remodeling. While chemoattractant receptors rely upon canonical G-protein signaling to activate downstream effectors, whether such signaling pathways affect phagocytosis is contentious. Here, we report that Gαi nucleotide exchange and signaling helps macrophages coordinate the recognition, capture, and engulfment of zymosan bioparticles. We show that zymosan exposure recruits F-actin, Gαi proteins, and Elmo1 to phagocytic cups and early phagosomes. Zymosan triggered an increase in intracellular Ca(2+) that was partially sensitive to Gαi nucleotide exchange inhibition and expression of GTP-bound Gαi recruited Elmo1 to the plasma membrane. Reducing GDP-Gαi nucleotide exchange, decreasing Gαi expression, pharmacologically interrupting Gβγ signaling, or reducing Elmo1 expression all impaired phagocytosis, while favoring the duration that Gαi remained GTP bound promoted it. Our studies demonstrate that targeting heterotrimeric G-protein signaling offers opportunities to enhance or retard macrophage engulfment of phagocytic targets such as zymosan. PMID:25225330

  17. Construction and identification of recombinant plasmid pUIS3-BLC+

    Institute of Scientific and Technical Information of China (English)

    Yingzi Lin; Shixiang Bao; Guanghong Tan; Fengying Huang; Huiqin Huang

    2010-01-01

    Objective:To construct and identify recombinant plasmid pUIS3-BLC+.Methods:The cDNA of B-lymphocyte chemoattractant(BLC)was amplified from the totalRNA of spleen tissues byPCR method, and were inserted into plasmid ofPlasmodium berghei withUIS3knockout by digestion of restrictive endonuclease andT7 ligation. The recombinant plasmids were screened, and then underwent restriction enzymatic digestion andDNA sequencing. Then the confirmed plasmid was further transfected intoCOS-1 cells by lipofectamine and theBLCexpression was tested byRT-PCRand Western blotting.Results:The cDNA ofBLC gene was correctively amplified byRT-PCR and the recombinant plasmid pUIS3-BLC+ was constructed successfully, which was confirmed by restriction enzymatic digestion andDNA sequencing. RT-PCR and Western blotting also showed theBLC gene expression inCOS-1cells.Conclusions:The recombinant plasmid pUIS3-BLC+ hasBLC expression in COS-1cells, and is useful for further study onBLC transgene andUIS3 gene knockout inPlasmodium berghei.

  18. Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis.

    Science.gov (United States)

    Bhuiyan, Md Saruar; Ellett, Felix; Murray, Gerald L; Kostoulias, Xenia; Cerqueira, Gustavo M; Schulze, Keith E; Mahamad Maifiah, Mohd Hafidz; Li, Jian; Creek, Darren J; Lieschke, Graham J; Peleg, Anton Y

    2016-08-23

    Innate cellular immune responses are a critical first-line defense against invading bacterial pathogens. Leukocyte migration from the bloodstream to a site of infection is mediated by chemotactic factors that are often host-derived. More recently, there has been a greater appreciation of the importance of bacterial factors driving neutrophil movement during infection. Here, we describe the development of a zebrafish infection model to study Acinetobacter baumannii pathogenesis. By using isogenic A. baumannii mutants lacking expression of virulence effector proteins, we demonstrated that bacterial drivers of disease severity are conserved between zebrafish and mammals. By using transgenic zebrafish with fluorescent phagocytes, we showed that a mutation of an established A. baumannii global virulence regulator led to marked changes in neutrophil behavior involving rapid neutrophil influx to a localized site of infection, followed by prolonged neutrophil dwelling. This neutrophilic response augmented bacterial clearance and was secondary to an impaired A. baumannii phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate. Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These data identify a previously unknown mechanism of bacterial-guided neutrophil chemotaxis in vivo, providing insight into the role of bacterial metabolism in host innate immune evasion. Furthermore, the work provides a potentially new therapeutic paradigm of targeting a bacterial metabolic pathway to augment host innate immune responses and attenuate disease. PMID:27506797

  19. Fluid flow and particle dynamics inside an evaporating droplet containing live bacteria displaying chemotaxis.

    Science.gov (United States)

    Thokchom, Ashish Kumar; Swaminathan, Rajaram; Singh, Anugrah

    2014-10-21

    Evaporation-induced particle deposition patterns like coffee rings provide easy visual identification that is beneficial for developing inexpensive and simple diagnostic devices for detecting pathogens. In this study, the effect of chemotaxis on such pattern formation has been realized experimentally in drying droplets of bacterial suspensions. We have investigated the velocity field, concentration profile, and deposition pattern in the evaporating droplet of Escherichia coli suspension in the presence and absence of nutrients. Flow visualization experiments using particle image velocimetry (PIV) were carried out with E. coli bacteria as biological tracer particles. Experiments were conducted for suspensions of motile (live) as well as nonmotile (dead) bacteria. In the absence of any nutrient gradient like sugar on the substrate, both types of bacterial suspension showed two symmetric convection cells and a ring like deposition of particles after complete evaporation. Interestingly, the droplet containing live bacterial suspension showed a different velocity field when the sugar was placed at the base of the droplet. This can be attributed to the chemoattractant nature of the sugar, which induced chemotaxis among live bacteria targeted toward the nutrient site. Deposition of the suspended bacteria was also displaced toward the nutrient site as the evaporation proceeded. Our experiments demonstrate that both velocity fields and concentration patterns can be altered by chemotaxis to modify the pattern formation in evaporating droplet containing live bacteria. These results highlight the role of bacterial chemotaxis in modifying coffee ring patterns. PMID:25229613

  20. A chemotactic inhibitor in synovial fluid.

    Science.gov (United States)

    Matzner, Y; Partridge, R E; Babior, B M

    1983-01-01

    Synovial fluid was found to contain an inhibitor of neutrophil chemotaxis. The activity of this inhibitor was masked in native synovial fluid, but could be detected in fluid in which complement had been deactivated by mild heating. The inhibitor was most effective against the chemotactic activity of zymosan-activated serum (C5ades arg). It had little effect when N-formyl-methionyl-leucyl-phenylalanine served as chemoattractant. Inhibition was not the result of a direct effect on the neutrophils, since incubation of cells with synovial fluid did not alter their chemotactic response. The inhibitory activity was destroyed by boiling the synovial fluid or treating it with trypsin, suggesting that it is a protein (or proteins); it was not affected by hyaluronidase treatment. Gel filtration revealed that the inhibitor was present in native as well as decomplemented synovial fluid, and that its molecular weight was in the vicinity of 25,000. It is proposed that this inhibitory activity plays a role in the regulation of the inflammatory response in joints. PMID:6840801

  1. Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

    Science.gov (United States)

    Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

    2006-06-01

    Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts. PMID:16740479

  2. Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal Epithelial Cell Lines in vitro.

    Science.gov (United States)

    Asarat, M; Vasiljevic, T; Apostolopoulos, V; Donkor, O

    2015-01-01

    Short-chain fatty acids (SCFAs) including acetate, propionate and butyrate play an important role in the physiological functions of epithelial cells and colonocytes, such as immune response regulation. Human intestinal epithelial cells (IECs) contribute in intestinal immune response via different ways, such as production of different immune factors including Interleukin (IL) IL-8, which act as chemoattractant for neutrophils, and subsequently enhance inflammation. Therefore, we aimed to evaluate the effects of SCFAs on IECs viability and production of IL-8 in vitro. SCFAs were co-cultured with either normal intestinal epithelial (T4056) or adenocarcinoma derived (HT-29) cell lines for 24-96 h in the presence of E.coli lipopolysaccharides (LPS). Cell viability, proliferation, production of IL-8 and expression of IL-8 mRNA were determined in the cell cultures. The result showed that 20 mM of SCFAs was non-cytotoxic to T4056 and enhanced their growth, whereas the growth of HT-29 was inhibited. The SCFAs down regulated LPS-stimulated IL-8 secretion with different response patterns, but no obvious effects on the release of IL-8 from non LPS- stimulated cells. In conclusion, SCFAs showed regulatory effect on release of LPS-stimulated IL-8 as well as the expression of mRNA of IL-8; these might explain the anti-inflammatory and anti-carcinogenic mechanism of SCFAs. PMID:26436853

  3. New Insights into Eosinophilic Otitis Media.

    Science.gov (United States)

    Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

    2015-12-01

    Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM. PMID:26546407

  4. Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes.

    Science.gov (United States)

    Barnes, Peter J

    2015-09-01

    The recognition that there are some patients with features of asthma and chronic obstructive pulmonary disease (COPD) has highlighted the need to develop more specific treatments for these clinical phenotypes. Some patients with COPD have predominantly eosinophilic inflammation and might respond to high doses of inhaled corticosteroids and newly developed specific antieosinophil therapies, including blocking antibodies against IL-5, IL-13, IL-33, and thymic stromal lymphopoietin, as well as oral chemoattractant receptor-homologous molecule expressed on TH2 cells antagonists. Other patients have severe asthma or are asthmatic patients who smoke with features of COPD-induced inflammation and might benefit from treatments targeting neutrophils, including macrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies against IL-1 and IL-17. Other patients appear to have largely fixed obstruction with little inflammation and might respond to long-acting bronchodilators, including long-acting muscarinic antagonists, to reduce hyperinflation. Highly selected patients with severe asthma might benefit from bronchial thermoplasty. Some patients with overlap syndromes can be conveniently treated with triple fixed-dose combination inhaler therapy with an inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist, several of which are now in development. Corticosteroid resistance is a feature of asthma-COPD overlap syndrome, and understanding the various molecular mechanisms of this resistance has identified novel therapeutic targets and presented the prospect of therapies that can restore corticosteroid responsiveness. PMID:26343937

  5. Waves of ratcheting cancer cells in growing tumor tissue layer

    Science.gov (United States)

    Yang, Taeseok; Kwon, Tae; Kim, Hyun; Lee, Kyoung; CenterCell Dynamics Team

    2015-03-01

    Over many years researchers have shown that the mechanical forces generated by, and acting on, tissues influence the way they grow, develop and migrate. As for cancer research goes, understanding the role of these forces may even be as influential as deciphering the relevant genetic and molecular basis. Often the key issues in the field of cancer mechanics are to understand the interplay of mechanics and chemistry. In this study, we discuss very intriguing population density waves observed in slowly proliferating of tumor cell layers. The temporal periods are around 4 hr and their wavelength is in the order of 1 mm. Tumor cell layer, which is initially plated in a small disk area, expands as a band of tumor cells is ``ratcheting'' in concert in radially outward direction. By adding Cytochalasin D and Latrunculin B, an inhibitor of actin polymerization, or Mytomycin, a chemotherapeutic agent, we could halt and modulate the wave activities reversibly. The observed waves are visually quite similar to those of chemotaxing dictyostelium discodium amoeba population, which are driven by nonlinear chemical reaction-diffusion waves of cAMP. So far, we have not been able to show any relevant chemo-attractants inducing the collective behavior of these tumor cells. Researchers have been investigating how forces from both within and outside developing cancer cells interact in intricate feedback loops. This work reports the example of periodic density waves of tumor cells with an explanation purely based on nonlinear mechanics.

  6. Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils.

    Directory of Open Access Journals (Sweden)

    Zvi G Fridlender

    Full Text Available The role of myeloid cells in supporting cancer growth is well established. Most work has focused on myeloid-derived suppressor cells (MDSC that accumulate in tumor-bearing animals, but tumor-associated neutrophils (TAN are also known to be capable of augmenting tumor growth. However, little is known about their evolution, phenotype, and relationship to naïve neutrophils (NN and to the granulocytic fraction of MDSC (G-MDSC.In the current study, a transcriptomics approach was used in mice to compare these cell types. Our data show that the three populations of neutrophils are significantly different in their mRNA profiles with NN and G-MDSC being more closely related to each other than to TAN. Structural genes and genes related to cell-cytotoxicity (i.e. respiratory burst were significantly down-regulated in TAN. In contrast, many immune-related genes and pathways, including genes related to the antigen presenting complex (e.g. all six MHC-II complex genes, and cytokines (e.g. TNF-α, IL-1-α/β, were up-regulated in G-MDSC, and further up-regulated in TAN. Thirteen of the 25 chemokines tested were markedly up-regulated in TAN compared to NN, including striking up-regulation of chemoattractants for T/B-cells, neutrophils and macrophages.This study characterizes different populations of neutrophils related to cancer, pointing out the major differences between TAN and the other neutrophil populations.

  7. Distinct molecular phenotypes in male and female schizophrenia patients.

    Directory of Open Access Journals (Sweden)

    Jordan M Ramsey

    Full Text Available BACKGROUND: In schizophrenia, sex specific dimorphisms related to age of onset, course of illness and response to antipsychotic treatment may be mirrored by sex-related differences in the underlying molecular pathways. METHODOLOGY/PRINCIPAL FINDINGS: Here, we have carried out multiplex immunoassay profiling of sera from 4 independent cohorts of first episode antipsychotic naive schizophrenia patients (n = 133 and controls (n = 133 to identify such sex-specific illness processes in the periphery. The concentrations of 16 molecules associated with hormonal, inflammation and growth factor pathways showed significant sex differences in schizophrenia patients compared with controls. In female patients, the inflammation-related analytes alpha-1-antitrypsin, B lymphocyte chemoattractant BLC and interleukin-15 showed negative associations with positive and negative syndrome scale (PANSS scores. In male patients, the hormones prolactin and testosterone were negatively associated with PANSS ratings. In addition, we investigated molecular changes in a subset of 33 patients before and after 6 weeks of treatment with antipsychotics and found that treatment induced sex-specific changes in the levels of testosterone, serum glutamic oxaloacetic transaminase, follicle stimulating hormone, interleukin-13 and macrophage-derived chemokine. Finally, we evaluated overlapping and distinct biomarkers in the sex-specific molecular signatures in schizophrenia, major depressive disorder and bipolar disorder. CONCLUSIONS/SIGNIFICANCE: We propose that future studies should investigate the common and sex-specific aetiologies of schizophrenia, as the current findings suggest that different therapeutic strategies may be required for male and female patients.

  8. Intracellular photoactivation of caged cGMP induces myosin II and actin responses in motile cells.

    Science.gov (United States)

    Pfannes, Eva K B; Anielski, Alexander; Gerhardt, Matthias; Beta, Carsten

    2013-12-01

    Cyclic GMP (cGMP) is a ubiquitous second messenger in eukaryotic cells. It is assumed to regulate the association of myosin II with the cytoskeleton of motile cells. When cells of the social amoeba Dictyostelium discoideum are exposed to chemoattractants or to increased osmotic stress, intracellular cGMP levels rise, preceding the accumulation of myosin II in the cell cortex. To directly investigate the impact of intracellular cGMP on cytoskeletal dynamics in a living cell, we released cGMP inside the cell by laser-induced photo-cleavage of a caged precursor. With this approach, we could directly show in a live cell experiment that an increase in intracellular cGMP indeed induces myosin II to accumulate in the cortex. Unexpectedly, we observed for the first time that also the amount of filamentous actin in the cell cortex increases upon a rise in the cGMP concentration, independently of cAMP receptor activation and signaling. We discuss our results in the light of recent work on the cGMP signaling pathway and suggest possible links between cGMP signaling and the actin system. PMID:24136144

  9. Ca2+ spikes in the flagellum control chemotactic behavior of sperm.

    Science.gov (United States)

    Böhmer, Martin; Van, Qui; Weyand, Ingo; Hagen, Volker; Beyermann, Michael; Matsumoto, Midori; Hoshi, Motonori; Hildebrand, Eilo; Kaupp, Ulrich Benjamin

    2005-08-01

    The events that occur during chemotaxis of sperm are only partly known. As an essential step toward determining the underlying mechanism, we have recorded Ca2+ dynamics in swimming sperm of marine invertebrates. Stimulation of the sea urchin Arbacia punctulata by the chemoattractant or by intracellular cGMP evokes Ca2+ spikes in the flagellum. A Ca2+ spike elicits a turn in the trajectory followed by a period of straight swimming ('turn-and-run'). The train of Ca2+ spikes gives rise to repetitive loop-like movements. When sperm swim in a concentration gradient of the attractant, the Ca2+ spikes and the stimulus function are synchronized, suggesting that precise timing of Ca2+ spikes controls navigation. We identified the peptide asterosap as a chemotactic factor of the starfish Asterias amurensis. The Ca2+ spikes and swimming behavior of sperm from starfish and sea urchin are similar, implying that the signaling pathway of chemotaxis has been conserved for almost 500 million years. PMID:16001082

  10. Chemomodulation of cellular movement, collective formation of vortices by swarming bacteria, and colonial development

    Science.gov (United States)

    Ben-Jacob, Eshel; Cohen, Inon; Czirók, András; Vicsek, Tamás; Gutnick, David L.

    1997-02-01

    Bacterial colonies have developed sophisticated modes of cooperative behavior which enable them to respond to adverse growth conditions. It has been shown that such behavior can be manifested in formation of complex colonial patterns. Certain Bacillus species exhibit collective migration, “turbulent like” flow and emergence of whirlpools during colonial development. Here we present experimental observations of collective behavior and a generic model to explain such behavior. The model incorporates self-propelled and interacting “particles” (swarmers). We show that velocity interaction between the particles can lead to a synchronized movement. To explain vortices formation, we propose a plausible mechanism involving a special chemotactic response (rotational chemotaxis) which is based on speed modulations according to the concentration of a chemoattractant. This mechanism differs from that exhibited by swimming bacteria. We show that the chemomodulation of swarmers' speed together with the velocity interactions impose a torque on the collective motion and can lead to formation of vortices. The inclusion of both attractive and repulsive rotational chemotaxis in the model captures the salient features of the observed growth patterns.

  11. A novel role for adipose ephrin-B1 in inflammatory response.

    Directory of Open Access Journals (Sweden)

    Takuya Mori

    Full Text Available AIMS: Ephrin-B1 (EfnB1 was selected among genes of unknown function in adipocytes or adipose tissue and subjected to thorough analysis to understand its role in the development of obesity. METHODS AND RESULTS: EfnB1 mRNA and protein levels were significantly decreased in adipose tissues of obese mice and such reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes to tumor necrosis factor-α (TNF-α and their culture with RAW264.7 cells reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte chemoattractant protein-1 (Mcp-1 mRNA level and augmented the TNF-α-mediated THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1-overexpression significantly reduced the increase in Mcp-1 mRNA level induced by coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay showed that adipose EfnB1-overexpression significantly decreased the increase of monocyte adhesion by coculture with RAW264.7 cells. TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2 was reduced by EFNB1-overexpression. CONCLUSIONS: EFNB1 contributes to the suppression of adipose inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the vicious cycle involved in adipose tissue inflammation.

  12. CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment.

    Science.gov (United States)

    Zhang, Tao; Tseng, Chieh; Zhang, Yan; Sirin, Olga; Corn, Paul G; Li-Ning-Tapia, Elsa M; Troncoso, Patricia; Davis, John; Pettaway, Curtis; Ward, John; Frazier, Marsha L; Logothetis, Christopher; Kolonin, Mikhail G

    2016-01-01

    White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression. PMID:27241286

  13. Planar Gradient Diffusion System to Investigate Chemotaxis in a 3D Collagen Matrix.

    Science.gov (United States)

    Stout, David A; Toyjanova, Jennet; Franck, Christian

    2015-01-01

    The importance of cell migration can be seen through the development of human life. When cells migrate, they generate forces and transfer these forces to their surrounding area, leading to cell movement and migration. In order to understand the mechanisms that can alter and/or affect cell migration, one can study these forces. In theory, understanding the fundamental mechanisms and forces underlying cell migration holds the promise of effective approaches for treating diseases and promoting cellular transplantation. Unfortunately, modern chemotaxis chambers that have been developed are usually restricted to two dimensions (2D) and have complex diffusion gradients that make the experiment difficult to interpret. To this end, we have developed, and describe in this paper, a direct-viewing chamber for chemotaxis studies, which allows one to overcome modern chemotaxis chamber obstacles able to measure cell forces and specific concentration within the chamber in a 3D environment to study cell 3D migration. More compelling, this approach allows one to successfully model diffusion through 3D collagen matrices and calculate the coefficient of diffusion of a chemoattractant through multiple different concentrations of collagen, while keeping the system simple and user friendly for traction force microscopy (TFM) and digital volume correlation (DVC) analysis. PMID:26131645

  14. Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression.

    Science.gov (United States)

    Bonfield, Tracey L; John, Nejimol; Malur, Anagha; Barna, Barbara P; Culver, Daniel A; Kavuru, Mani S; Thomassen, Mary Jane

    2005-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare autoimmune lung disease characterized by abnormal surfactant accumulation within alveolar macrophages, and circulating auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) resulting in functional GM-CSF deficiency. Monocyte/macrophage chemotactic protein-1 (MCP-1) is elevated in PAP, suggesting association with the pathophysiology. Because PAP has been associated with inflammatory pulmonary changes, we hypothesized that other MCP family chemokines would be present and that Chemokine Chemotaxis Receptor 2 (CCR2) would be elevated on PAP mononuclear cells. Here we show for the first time that MCP-2 and MCP-3, like MCP-1, are highly elevated in PAP. We also confirm that PAP alveolar macrophages and not epithelial cells produce MCP-1, and that MCP-1 from PAP lung has functional chemoattractant activity. Surprisingly, CCR2 expression is diminished in PAP lymphocytes and alveolar macrophages compared to controls. Further, MCP-1 from PAP lung suppresses CCR2 expression in vitro, suggesting that in PAP, MCP-1 participates in an autocrine regulatory network in vivo. PMID:15596412

  15. Identification of leads through in silico approaches utilizing benzylthio-1H-benzo[d]imidazol-1-yl acetic acid derivatives: A potent CRTh2 antagonist

    Science.gov (United States)

    Babu, Sathya; Kulkarni, Seema A.; Sohn, Honglae; Madhavan, Thirumurthy

    2015-12-01

    Chemoattractant Receptor-homologous molecule expressed on Th2 cells (CRTh2) is considered as a potential therapeutic target for the treatment of asthma and allergic rhinitis. Herein, we describe the pharmacophore based virtual screening combined with molecular docking and 3D-QSAR methods to identify new potent CRTh2 inhibitors. Several pharmacophore models were generated and validated by Guner-Henry scoring method. The best models were utilized as 3D Pharmacophore query to screen against ZINC database and the retrieved hits were further validated by fitness score, Lipinski's rule of five, Surflex docking and Comparative Molecular Field Analysis (CoMFA) process. The optimum CoMFA model was developed using known inhibitors and the predictive ability of model was examined by statistical parameters like q2 = 0.552 and r2pred = 0.636. The biological activities of the screened compounds were calculated using the generated CoMFA model. Finally nine compounds were found to have good potential and high inhibitory activities and they may act as novel lead compounds for CRTh2 inhibitor designing.

  16. TNF-{alpha} similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Lars, E-mail: lars.mueller@uksh-kiel.de [Department of General and Thoracic Surgery, University Hospital of Schleswig-Holstein (Germany); Seggern, Lena von [Department of Hepatobiliary Surgery and Solid Organ Transplantation, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Schumacher, Jennifer; Goumas, Freya; Wilms, Christian; Braun, Felix; Broering, Dieter C. [Department of General and Thoracic Surgery, University Hospital of Schleswig-Holstein (Germany)

    2010-07-02

    Cancer-associated fibroblasts (CAFs) represent the predominant cell type of the neoplastic stroma of solid tumors, yet their biology and functional specificity for cancer pathogenesis remain unclear. We show here that primary CAFs from colorectal liver metastases express several inflammatory, tumor-enhancing factors, including interleukin (IL)-6 and monocyte-chemoattractant protein (MCP)-1. Both molecules were intensely induced by TNF-{alpha} on the transcript and protein level, whereas PDGF-BB, TGF-{beta}1 and EGF showed no significant effects. To verify their potential specialization for metastasis progression, CAFs were compared to fibroblasts from non-tumor liver tissue. Interestingly, these liver fibroblasts (LFs) displayed similar functions. Further analyses revealed a comparable up-regulation of intercellular adhesion molecule-1 (ICAM-1) by TNF-{alpha}, and of alpha-smooth muscle actin, by TGF-{beta}1. Moreover, the proliferation of both cell types was induced by PDGF-BB, and CAFs and LFs displayed an equivalent migration towards HT29 colon cancer cells in Boyden chamber assays. In conclusion, colorectal liver metastasis may be supported by CAFs and resident fibroblastic cells competent to generate a prometastatic microenvironment through inflammatory activation of IL-6 and MCP-1.

  17. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Takanori [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Yamagishi, Sho-ichi, E-mail: shoichi@med.kurume-u.ac.jp [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Takeuchi, Masayoshi [Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa (Japan); Ueda, Seiji; Fukami, Kei; Okuda, Seiya [Department of Medicine, Kurume University School of Medicine, Kurume (Japan)

    2009-07-24

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}). Although nifedipine did not affect expression levels of PPAR-{gamma}, it increased the PPAR-{gamma} transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-{gamma} activation.

  18. Impact of Tumor-Derived CCL2 on Macrophage Effector Function

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    Brault M. S.

    2005-01-01

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1, CCL2 is produced by many different types of cells. In the current investigation, the effect of tumor-derived CCL2 on macrophages was evaluated to determine the extent to which this chemokine influenced the innate immune response to cancer. To do this, we used the 4T1 murine mammary carcinoma cell line that constitutively expresses CCL2 and generated 4T1 expressing an antisense CCL2 transcript. The antisense-CCL2-expressing 4T1 produced no detectable CCL2. Macrophages from female BALB/c mice were exposed to supernatants from these tumor cells. The results showed that tumor-derived CCL2 was capable of modulating cytokine gene expression but not protein production in resting, activated, and tumor-associated macrophages. In addition, tumor-derived CCL2 did not affect phagocytic activity, nitric oxide production, or cytolytic activity of the macrophages. Overall, these data suggest that tumor-derived CCL2 does not directly influence macrophage-mediated antitumor activity.

  19. In Patients with Coronary Artery Disease and Type 2 Diabetes, SIRT1 Expression in Circulating Mononuclear Cells Is Associated with Levels of Inflammatory Cytokines but Not with Coronary Lesions

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    Yuanmin Li

    2016-01-01

    Full Text Available While SIRT1 is significantly associated with atherosclerosis and diabetic complications, its relevance to coronary lesions in patients with coronary artery disease and type 2 diabetes has not been specifically investigated. Thus, we assessed SIRT1 expression in peripheral blood mononuclear cells in these patients. We found that SIRT1 expression did not significantly correlate with syntax scores from coronary angiography (p>0.05. Notably, plasma levels of the inflammatory cytokines tumor necrosis factor-α, monocyte chemoattractant protein-1, and high-sensitivity C-reactive protein were markedly higher in diabetic patients (p<0.05. In addition, SIRT1 expression was negatively correlated with levels of these cytokines, as well as that of interleukin-6 (p<0.05. In summary, the data indicate that SIRT1 expression in peripheral blood mononuclear cells is significantly correlated with inflammatory cytokines levels in patients with coronary artery disease and type 2 diabetes but not with the severity of coronary lesions.

  20. Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity.

    Science.gov (United States)

    Anthony Jalin, Angela M A; Lee, Jae-Chul; Cho, Geum-Sil; Kim, Chunsook; Ju, Chung; Pahk, Kisoo; Song, Hwa Young; Kim, Won-Ki

    2015-11-01

    Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1β in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions. PMID:26535078