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Sample records for chemotactic protein-1 mcp-1

  1. Adiponectin-induced secretion of interleukin-6 (IL-6, monocyte chemotactic protein-1 (MCP-1, CCL2 and interleukin-8 (IL-8, CXCL8 is impaired in monocytes from patients with type I diabetes

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    Maier Kevin

    2006-08-01

    Full Text Available Abstract Background Systemic adiponectin is reduced in patients with cardiovascular disease (CVD and low adiponectin may contribute to the pathogenesis of atherosclerosis. However, circulating adiponectin is elevated in type 1 diabetes (T1D patients, who have also a higher incidence to develop CVD. Because monocytes play an important role in atherosclerosis, we analysed the influence of adiponectin on cytokine and chemokine release in monocytes from T1D patients and controls. Methods Systemic adiponectin was determined in the plasma and the high-molecular weight (HMW form of adiponectin was analysed by immunoblot. Monocytes were isolated from T1D patients and controls and the adiponectin-stimulated release of interleukin-6 (IL-6, monocyte chemotactic protein-1 (MCP-1, CCL2 and interleukin-8 (IL-8, CXCL8 was analysed. Results Systemic adiponectin was higher in T1D patients. Immunoblot analysis of the plasma indicate abundance of HMW adiponectin in T1D patients and controls. IL-6, CCL2 and CXCL8 secretion in response to adiponectin were found induced in monocytes from controls whereas only IL-6 was upregulated in T1D cells. The induction of IL-6 by adiponectin was abrogated by an inhibitor of the NFκB pathway. Conclusion These data indicate that adiponectin-mediated induction of IL-6, CCL2 and CXCL8 is disturbed in monocytes from T1D patients and therefore elevated systemic adiponectin in T1D patients may be less protective when compared to controls.

  2. Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis

    OpenAIRE

    Wang, Hong; Zhang, Qiongwen; Kong, Hongyu; Zeng, Yunhui; Hao, Meiqin; Yu, Ting; Peng, Jing; Xu, Zhao; Chen, Jingquan; Shi, Huashan

    2014-01-01

    Purpose: A great deal of studies have been performed on the prognostic value of monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However, no consistent outcomes are reported. Therefore, the prognostic value of MCP-1 still remains controversial in patients with solid tumors. Here we aimed to evaluate the prognostic value of MCP-1 expression for patients with solid tumors. Methods: Comprehensive literature was selected from PUBMED and EMBASE and clinical studies which rep...

  3. 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

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

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    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.

  5. Effect of Monocyte Chemotactic Protein-1 on the Intraperitoneal Adhesion Formation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to study the role of monocyte chemotactic protein-1 (MCP-1) in the intra-peritoneal adhesion formation, 23 infertile patients undergoing laparoscopic operation were divided into two groups: experimental group including 12 patients with intra-peritoneal adhesion and control group including 11 patients without intra-peritoneal adhesion. Peritoneal fluid (PF) and peritoneum were collected from these patients during laparoscopic examination. The expression levels of MCP-l protein and MCP-1 mRNA were detected by using enzyme-linked immunosorbent assay (ELISA) and dot blot analysis method respectively. It was found that the levels of MCP-1 protein in PF of the patients with peritoneal adhesion were significantly higher than in the control group (0. 44±0.11 ng/ml vs 0. 19+0. 09 ng/ml respectively, P<0. 01 ). The level of MCP-1 mRNA in the peritoneum of the patients with peritoneal adhesion was significantly higher than in the control group (48.61±3.72 vs 19. 87±2.54 respectively, P<0. 01). It was suggested that MCP-1 might play a role in the adhesion formation, and chemotactic cytokines expressing in the peritoneal mesothelial cells might be take part in the process.

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

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    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.

  7. Plasma Levels of Monocyte Chemotactic Protein-1 Are Associated with Clinical Features and Angiogenesis in Patients with Multiple Myeloma

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    Toni Valković

    2016-01-01

    Full Text Available The aim of this pilot study was to determine the plasma levels of monocyte chemotactic protein-1 (MCP-1 and possible associations with angiogenesis and the main clinical features of untreated patients with multiple myeloma (MM. ELISA was used to determine plasma MCP-1 levels in 45 newly diagnosed MM patients and 24 healthy controls. The blood vessels were highlighted by immunohistochemical staining, and computer-assisted image analysis was used for more objective and accurate determination of two parameters of angiogenesis: microvessel density (MVD and total vascular area (TVA. The plasma levels of MCP-1 were compared to these parameters and the presence of anemia, renal dysfunction, and bone lesions. A significant positive correlation was found between plasma MCP-1 concentrations and TVA (p=0.02. The MCP-1 levels were significantly higher in MM patients with evident bone lesions (p=0.01, renal dysfunction (p=0.02, or anemia (p=0.04. Therefore, our preliminary results found a positive association between plasma MCP-1 levels, angiogenesis (expressed as TVA, and clinical features in patients with MM. However, additional prospective studies with a respectable number of patients should be performed to authenticate these results and establish MCP-1 as a possible target of active treatment.

  8. Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression.

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    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

  9. Human monocyte-derived dendritic cells expressing both chemotactic cytokines IL-8, MCP-1, RANTES and their receptors,and their selective migration to these chemokines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To characterize the mRNA expression of CXC chemokine IL-8, CC chemokine monocyte chemothractant protein-1 (MCP-1) and regulated on activation,normal T cell expressed and secreted (RANTES), and a newly defined DC chemokine DC- CK1 as well as the expression of IL-8 receptor, MCP-1 receptor and RANTES receptor in human monocyte derived dendritic cells (MoDCs).The migratory responsiveness of MoDC to IL-8, MCP-1 and RANTES was alsso studied. Methods In vitro generated MoDCs were obtained by differentiating monocytes in the presence of GM-CSF and IL-4 for 5 days. The time course of RNA expression was analyzed by RT-PCR and migratoly ability was assessed by a micromultiwell chemotaxis chamber assay. Results IL-8, MCP-1, RANTES and their corres ponding receptors were consistently expressed in MoDCs. DC-CK-1 expression was detectable efter 48 hours of differentiation. MoDC selectively migrated in response to MCP-1 and RANTES but not to IL-8 though transcripts of IL-8 receptor were present. Conclusion Because the capacity of dendritic cells to initiate immune responses depends on their specialized migratory and tissue homing properties, the expression of chemokines and their receptors along with the migratory responsiveness to chemokines of MoDC in our study suggests a potential role of chemokines in the interaction between dendritic cells and T cells and the induction of immune responses.

  10. 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...

  11. Postoperative Changes in Aqueous Monocyte Chemotactic Protein-1 Levels and Bleb Morphology after Trabeculectomy vs. Ex-PRESS Shunt Surgery.

    Directory of Open Access Journals (Sweden)

    Kohei Shobayashi

    Full Text Available To evaluate the postoperative changes in blebs and levels of aqueous monocyte chemotactic protein-1 (MCP-1 after trabeculectomy vs. Ex-PRESS tube shunt surgery.Rabbits were subjected to trabeculectomy or Ex-PRESS tube shunt surgery and observed for up to 3 months. Intraocular pressure (IOP was measured using a rebound tonometer. The MCP-1 level was measured by enzyme-linked immunosorbent assay (ELISA. Bleb morphology was evaluated using photos and anterior-segment optical coherence tomography (OCT.There were no differences in bleb appearance or IOP at any time between the groups. Bleb wall density in the anterior-segment OCT image was significantly lower 1 week after surgery in the Ex-PRESS group than the trabeculectomy group. The MCP-1 level in control eyes was 304.1 ± 45.2 pg/mL. In the trabeculectomy group, the mean aqueous MCP-1 level was 1444.9, 1914.3, 1899.8, 516.4, 398.3, 427.3, 609.5, 1612.7, 386.2, and 167.9 pg/mL at 3, 6, and 12 h, and 1, 2, 5, 7, 14, 30, and 90 days after surgery, respectively. In the Ex-PRESS group, the corresponding values were 1744.0, 1372.0, 932.5, 711.7, 396.1, 487.3, 799.5, 1327.9, 293.6, and 184.0 pg/mL. There were no significant differences in the aqueous MCP-1 level between the groups at any time point.The postoperative changes were similar in the Ex-PRESS and trabeculectomy groups, except for bleb wall density in the anterior-segment OCT image. The postoperative aqueous MCP-1 level had bimodal peaks in both groups.

  12. 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.

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    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

  13. Monocyte chemotactic protein-1 and soluble adhesion molecules as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Anatol Panasiuk; Danuta Prokopowicz; Bozena Panasiuk

    2004-01-01

    AIM: To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV).METHODS: Concentrations of MCP-1, soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1), sPselectin, interleukin (IL) 6, and IL10 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0, 16, 32, 48 wk of the therapy.RESULTS: In chronic hepatitis C, before and during the treatment, the serum levels of MCP-1 and sP-selectin in responders were similar to those of healthy subjects. In nonresponders (NR), MCP-1 increased in the course of IFNα+RBV treatment, differences were statistically significant as compared to responders. MCP-1 correlated statistically with the activity of pedportal inflammation (r = 0.35, P<0.05) but not with staging of liver fibrosis. sICAM-1 positively correlated with inflammatory activity and fibrosis in NR. sP-selectin did not correlate with histological findings in the liver. The MCP-1 correlated with the soluble form of sP-selectin concentrations (r = 6, P<0.001) and with IL-10 level in NR (r = 0.4, P<0.05). There was no correlation observed between the concentration of MCP-1 and sICAM-1, IL-6 during the treatment.CONCLUSION: MCP-1 concentration may be a prognostic marker of the efficacy of IFN+RBV therapy in patients with chronic hepatitis C.

  14. Wound Healing in MIP-1α−/− and MCP-1−/− Mice

    OpenAIRE

    Low, Quentin E. H.; Drugea, Iulia A.; Duffner, Lisa A.; Quinn, Daniel G.; Cook, Donald N.; Rollins, Barrett J.; Kovacs, Elizabeth J.; DiPietro, Luisa A.

    2001-01-01

    A salient feature of normal wound healing is the development and resolution of an acute inflammatory response. Although much is known about the function of inflammatory cells within wounds, little is known about the chemotactic and activation signals that influence this response. As the CC chemokines macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1) are abundant in acute wounds, wound repair was examined in MIP-1α−/− and MCP-1−/− mice. Surprisingly, wound ...

  15. 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

  16. Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment.

    Science.gov (United States)

    Ting, Harold; Deep, Gagan; Kumar, Sushil; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

    2016-06-01

    Tumor microenvironment plays an essential role in prostate carcinogenesis and offers novel opportunities to prevent and treat prostate cancer (PCA). Here, we investigated the ability of cancer-associated fibroblasts (CAFs) to promote PCA progression, and silibinin efficacy to target this response. We collected conditioned media from CAFs treated with vehicle or silibinin, and labeled as control conditioned media (CCM) or silibinin-treatment conditioned media (SBCM), respectively. Next, we characterized the effect of CCM and SBCM treatment in several PCA cell lines (RWPE-1, WPE-1 NA-22, WPE-1 NB-14 and PC3). Result showed that compared with SBCM, CCM significantly reduces E-cadherin expression and increases invasiveness and clonogenicity in PCA cells. Further molecular studies identified monocyte chemotactic protein-1 (MCP-1) as the key component of CCM that promotes PCA invasiveness, whereas silibinin treatment strongly reduced MCP-1 expression in CAFs by inhibiting the DNA-binding activity of MCP-1 transcriptional regulators-nuclear factor-kappaB and AP-1. In vivo, silibinin feeding (200mg/kg body weight) strongly reduced TRAMPC1 allografts growth (by 68%) in syngeneic C57Bl/6 mice. TRAMPC1 tumor analysis showed that silibinin reduced MCP-1 and CAFs' biomarkers (fibroblast activation protein, α-smooth muscle actin, transforming growth factor beta 2, vimentin etc.) and significantly modulated the recruitment of immune cells in the tumor microenvironment. Similar inhibitory effects of silibinin on MCP-1 and immune cells recruitment were also observed in TRAMP PCA tissues with reported silibinin efficacy. Overall, our data suggest that silibinin can target CAF-mediated invasiveness in PCA by inhibiting MCP-1 secretion. This, in turn, was associated with a reduction in immune cell recruitment in vivo along with a marked reduction in tumor growth. PMID:27207648

  17. Quantum dots induced monocyte chemotactic protein-1 expression via MyD88-dependent Toll-like receptor signaling pathways in macrophages

    International Nuclear Information System (INIS)

    Quantum dots (QDs) are nano-sized semiconductors. Previously, intratracheal instillation of QD705s induces persistent inflammation in mouse lungs. In our present study, QD705-COOH and QD705-PEG activated NF-κB and increased monocyte chemotactic protein-1 (MCP-1) expression in macrophages RAW264.7 via MyD88 dependent Toll-like receptor (TLR) signaling pathways. MyD88 is an adapter protein for most TLRs to activate NF-κB. Silencing expression of MyD88 or p65 with siRNA or co-treatment with a NF-κB inhibitor tremendously abolished QD705s-induced NF-κB activity and MCP-1 expression. The involved TLRs might locate either on the cell surface or inside of cells. Co-treatment with a TLR4 inhibitor completely prevented MCP-1 induction by QD705-PEG. Nevertheless, QD705-COOH readily entered cells, and co-treatment with either inhibitors of endocytosis or intracellular TLRs prevented MCP-1 induction. These findings indicate that, depending on their surface modification, OD705s activate MyD88 dependent-TLRs at the surface or inside of the cells, which is an important mechanism for nanoparticles-induced inflammatory responses. But other MyD88-independent pathways may also involve in these responses

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

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    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

  19. Lysophosphatidic Acid Stimulates MCP-1 Secretion from C2C12 Myoblast

    OpenAIRE

    Tamotsu Tsukahara; Hisao Haniu

    2012-01-01

    Chemokines are regulatory proteins that play an important role in muscle cell migration and proliferation. In this study, C2C12 cells treated with lysophosphatidic acid (LPA) showed an increase in endogenous monocyte chemotactic protein-1 (MCP-1) expression and secretion. LPA is a naturally occurring bioactive lysophospholipid with hormone- and growth-factor-like activities. LPA is produced by activated platelets, cytokine-stimulated leukocytes, and possibly by other cell types. However, the ...

  20. Lysophosphatidic Acid Stimulates MCP-1 Secretion from C2C12 Myoblast.

    Science.gov (United States)

    Tsukahara, Tamotsu; Haniu, Hisao

    2012-01-01

    Chemokines are regulatory proteins that play an important role in muscle cell migration and proliferation. In this study, C2C12 cells treated with lysophosphatidic acid (LPA) showed an increase in endogenous monocyte chemotactic protein-1 (MCP-1) expression and secretion. LPA is a naturally occurring bioactive lysophospholipid with hormone- and growth-factor-like activities. LPA is produced by activated platelets, cytokine-stimulated leukocytes, and possibly by other cell types. However, the LPA analog cyclic phosphatidic acid (cPA) had no effect on the expression and secretion of MCP-1. LPA, although similar in structure to cPA, had potent inducing effects on MCP-1 expression in C2C12 cells. In this study, we showed that LPA enhanced MCP-1 mRNA expression and protein secretion in a dose-dependent manner. Taken together, these results suggest that LPA enhances MCP-1 secretion in C2C12 cells and thus may play an important role in cell proliferation. PMID:24049655

  1. 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...

  2. Intelectin is required for IL-13-induced monocyte chemotactic protein-1 and -3 expression in lung epithelial cells and promotes allergic airway inflammation

    OpenAIRE

    Gu, Naibing; Kang, Guannan; Jin, Chang'E; Xu, Yongjian; ZHANG, ZHENXIANG; Erle, David J.; Zhen, Guohua

    2009-01-01

    Asthma is characterized by airway inflammation, mucus overproduction, airway hyperreactivity, and peribronchial fibrosis. Intelectin has been shown to be increased in airway epithelium of asthmatics. However, the role of intelectin in the pathogenesis of asthma is unknown. Airway epithelial cells can secrete chemokines such as monocyte chemotactic protein (MCP)-1 and -3 that play crucial roles in asthmatic airway inflammation. We hypothesized that intelectin plays a role in allergic airway in...

  3. MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration.

    Science.gov (United States)

    Shireman, Paula K; Contreras-Shannon, Verónica; Ochoa, Oscar; Karia, Bijal P; Michalek, Joel E; McManus, Linda M

    2007-03-01

    We examined the role of MCP-1, a potent chemotactic and activating factor for macrophages, in perfusion, inflammation, and skeletal muscle regeneration post-ischemic injury. MCP-1-/- or C57Bl/6J control mice [wild-type (WT)] underwent femoral artery excision (FAE). Muscles were collected for histology, assessment of tissue chemokines, and activity measurements of lactate dehydrogenase (LDH) and myeloperoxidase. In MCP-1-/- mice, restoration of perfusion was delayed, and LDH and fiber size, indicators of muscle regeneration, were decreased. Altered inflammation was observed with increased neutrophil accumulation in MCP-1-/- versus WT mice at Days 1 and 3 (P< or =0.003), whereas fewer macrophages were present in MCP-1-/- mice at Day 3. As necrotic tissue was removed in WT mice, macrophages decreased (Day 7). In contrast, macrophage accumulation in MCP-1-/- was increased in association with residual necrotic tissue and impaired muscle regeneration. Consistent with altered inflammation, neutrophil chemotactic factors (keratinocyte-derived chemokine and macrophage inflammatory protein-2) were increased at Day 1 post-FAE. The macrophage chemotactic factor MCP-5 was increased significantly in WT mice at Day 3 compared with MCP-1-/- mice. However, at post-FAE Day 7, MCP-5 was significantly elevated in MCP-1-/- mice versus WT mice. Addition of exogenous MCP-1 did not induce proliferation in murine myoblasts (C2C12 cells) in vitro. MCP-1 is essential for reperfusion and the successful completion of normal skeletal muscle regeneration after ischemic tissue injury. Impaired muscle regeneration in MCP-1-/- mice suggests an important role for macrophages and MCP-1 in tissue reparative processes. PMID:17135576

  4. FGFR3 promotes angiogenesis-dependent metastasis of hepatocellular carcinoma via facilitating MCP-1-mediated vascular formation.

    Science.gov (United States)

    Liu, Xinyu; Jing, Xiaoqian; Cheng, Xi; Ma, Ding; Jin, Zhijian; Yang, Weiping; Qiu, Weihua

    2016-05-01

    The biological role of fibroblast growth factor receptor 3 (FGFR3) in tumor angiogenesis of hepatocellular carcinoma (HCC) has not been discussed before. Our previous work had indicated FGFR3 was overexpressed in HCC, and silencing FGFR3 in Hu7 cells could regulate tumorigenesis via down-regulating the phosphorylation level of key members of classic signaling pathways including ERK and AKT. In the present work, we explored the role of FGFR3 in angiogenesis-dependent metastasis by using SMMC-7721 and QGY-7703 stable cell lines. Our results indicated FGFR3 could regulate in vitro cell migration ability and in vivo lung metastasis ability of HCC, which was in accordance with increased angiogenesis ability in vitro and in vivo. Using the supernatant from SMMC-7721/FGFR3 cells, we conducted a human angiogenesis protein microarray including 43 angiogenesis factors and found that FGFR3 modulated angiogenesis and metastasis of HCC mainly by promoting the protein level of monocyte chemotactic protein 1 (MCP-1). Silencing FGFR3 by short hairpin RNA (shRNA) could reduce MCP-1 level in lysates and supernatant of QGY-7703 cells and SMMC-7721 cells. Silencing MCP-1 in QGY-7703 or SMMC-7721 cells could induce similar phenotypes compared with silencing FGFR3. Our results suggested FGFR3 promoted metastasis potential of HCC, at least partially if not all, via facilitating MCP-1-mediated angiogenesis, in addition to previously found cell growth and metastasis. MCP-1, a key medium between HCC cells and HUVECs, might be a novel anti-vascular target in HCC. PMID:27044356

  5. 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...

  6. 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.

  7. Cardiac Stem Cell Secretome Protects Cardiomyocytes from Hypoxic Injury Partly via Monocyte Chemotactic Protein-1-Dependent Mechanism.

    Science.gov (United States)

    Park, Chi-Yeon; Choi, Seung-Cheol; Kim, Jong-Ho; Choi, Ji-Hyun; Joo, Hyung Joon; Hong, Soon Jun; Lim, Do-Sun

    2016-01-01

    Cardiac stem cells (CSCs) were known to secrete diverse paracrine factors leading to functional improvement and beneficial left ventricular remodeling via activation of the endogenous pro-survival signaling pathway. However, little is known about the paracrine factors secreted by CSCs and their roles in cardiomyocyte survival during hypoxic condition mimicking the post-myocardial infarction environment. We established Sca-1+/CD31- human telomerase reverse transcriptase-immortalized CSCs (Sca-1+/CD31- CSCs(hTERT)), evaluated their stem cell properties, and paracrine potential in cardiomyocyte survival during hypoxia-induced injury. Sca-1+/CD31- CSCs(hTERT) sustained proliferation ability even after long-term culture exceeding 100 population doublings, and represented multi-differentiation potential into cardiomyogenic, endothelial, adipogenic, and osteogenic lineages. Dominant factors secreted from Sca-1+/CD31- CSCs(hTERT) were EGF, TGF-β1, IGF-1, IGF-2, MCP-1, HGF R, and IL-6. Among these, MCP-1 was the most predominant factor in Sca-1+/CD31- CSCs(hTERT) conditioned medium (CM). Sca-1+/CD31- CSCs(hTERT) CM increased survival and reduced apoptosis of HL-1 cardiomyocytes during hypoxic injury. MCP-1 silencing in Sca-1+/CD31- CSCs(hTERT) CM resulted in a significant reduction in cardiomyocyte apoptosis. We demonstrated that Sca-1+/CD31- CSCs(hTERT) exhibited long-term proliferation capacity and multi-differentiation potential. Sca-1+/CD31- CSCs(hTERT) CM protected cardiomyocytes from hypoxic injury partly via MCP-1-dependent mechanism. Thus, they are valuable sources for in vitro and in vivo studies in the cardiovascular field. PMID:27231894

  8. Effect of propofol pretreatment on hippocampal monocyte chemotactic protein-1 and CC-chemokine receptor type 2 expression following forebrain ischemia-reperfusion in rats%异丙酚预先给药对大鼠前脑缺血再灌注时海马单核细胞趋化因子1及其受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    郭永清; 侯晓来; 刘友章; 张华萍; 郭政

    2011-01-01

    Objective To investigate the effect of propofol pretreatment on hippocampal monocyte chemotactic protein-1 ( MCP-1 ) and CC-chemokine receptor type 2 (CCR2) expression following forebrain ischemiarepcrfusion (I/R) in rats. Methods Twenty-four male SD rats weighing 250-300 g were randomly divided into 3 groups ( n = 8 each): group Ⅰ control; group Ⅱ I/R and group Ⅲ propofol pretreatment. Cerebral I/R was induced by clamping bilateral common carotid arteries for 10 min combined with hypotension ( MAP was maintained at 35-45 mm Hg) induced by exsanguinations in group Ⅱ and Ⅲ. In group Ⅲ propofol 50 mg/kg was injected into femoral vein immediately before cerebral ischemia. The animals were sacrificed at 6 h of reperfusion. Hippocampal tissue was obtained for detection of MCP-1 mRNA and CCR2 mRNA and their protein expression by RT-PCR and Western blot technique. Results I/R significantly increased the expression of MCP-1 and CCR2 in hippoeampal tissue as compared with control group. Propofol pretreatment significantly attenuated cerebral I/R induced increase in MCP-1 and CCR2 expression. Conclusion Propofol pretreatment can significantly inhibit forebrain I/R-induced hippocampal MCP-1 and CCP2 expression.%目的 探讨异丙酚预先给药对大鼠前脑缺血再灌注时海马单核细胞趋化因子1(MCP1)及其受体(CCR2)表达的影响.方法 健康成年雄性SD大鼠24只,体重250~300g,随机分为3组(n=8):假手术组(S组)仅暴露双侧颈总动脉及股动静脉置管,不夹闭;缺血再灌注组(IR组)采用夹闭双侧颈总动脉10 min合并放血降压再回输法制备前脑缺血再灌注损伤模型;异丙酚预先给药组(P组)脑缺血前即刻股静脉注射异丙酚50 mg/kg.于再灌注6 h时处死大鼠取脑,分离海马神经元,采用RT-PCR法测定MCP-1 mRNA和CCR2mRNA的表达,Western blot法测定MCP-1和CCR2蛋白的表达.结果 IR组和P组海马神经元MCP-1及CCR2表达较S组上调(P<0.05);P组海马神经元MCP-1

  9. Autocrine MCP-1/CCR2 signaling stimulates proliferation and migration of renal carcinoma cells

    Science.gov (United States)

    Küper, Christoph; Beck, Franz-Xaver; Neuhofer, Wolfgang

    2016-01-01

    The chemokine monocyte chemoattractant protein-1 [MCP-1; also known as chemokine (C-C motif) ligand 2] is an important mediator of monocyte recruitment during inflammatory processes. Pathologically high expression levels of MCP-1 by tumor cells have been observed in a variety of cancer types. In the majority of cases, high MCP-1 expression is associated with a poor prognosis, as infiltration of the tumor with inflammatory monocytes promotes tumor progression and metastasis. MCP-1 is also expressed in renal cell carcinoma (RCC). In the present study, the function and the regulation of MCP-1 was investigated in two RCC cell lines, CaKi-1 and 786-O. In both cell lines, expression of MCP-1 was significantly enhanced compared with non-cancerous control cells. As expected, secretion of MCP-1 into the medium facilitated the recruitment of peripheral blood monocytes via the chemokine (C-C motif) receptor type 2 (CCR2). As expression of CCR2 was also detected in 786-O and CaKi-1 cells, the effect of autocrine MCP-1/CCR2 signaling was evaluated in these cells. In proliferation assays, administration of an MCP-1 neutralizing antibody or of a CCR2 antagonist to CaKi-1 and 786-O cells significantly decreased cell growth; supplementation of the growth medium with recombinant human MCP-1 had no additional effect on proliferation. The migration ability of RCC cells was impaired by MCP-1 neutralization or pharmacological CCR2 inhibition, while it was stimulated by the addition of recombinant human MCP-1, compared with untreated control cells. Finally, substantial differences in the regulation of MCP-1 expression were observed between RCC cell lines. In CaKi-1 cells, expression of MCP-1 appears to be largely mediated by the transcription factor nuclear factor of activated T cells 5, while in 786-O cells, deletion of the tumor suppressor gene Von-Hippel-Lindau appeared to be responsible for MCP-1 upregulation, as suggested by previous studies. Taken together, the results of the

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

    Directory of Open Access Journals (Sweden)

    C Makena Hightower

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

  11. 球形脂联素抑制高糖环境下肾小管上皮细胞单核趋化蛋白-1的高表达%Global adiponectin suppress the high expression of monocyte chemotactic protein-1 induced by high glucose in NRK52E cells

    Institute of Scientific and Technical Information of China (English)

    姚涛; 吴小燕; 於文丽; 高苹; 吴屹哲

    2015-01-01

    Objective To investigate the effect of globular adiponectin on the high expression of monocyte chemotactic protein-1 (MCP-1) induced by high glucose in rat renal tubular epithelial cells (NRK52E),and its relationship with adiponectin receptors and p38MAPK.Methods NRK52E cells were cultured in vitro and divided into six groups:normal glucose group (NG,5.6 mmol/L glucose),high glucose group(HG,25 mmol/L glucose),gAd groupl (HG+gAd 2 mg/L),gAd group2 (HG+gAd 5 mg/L),gAd group3 (HG+gAd 10 mg/L),p38MAPK antagonist group:(SB,HG+SB203580 10 μmol/L).The protein expression of phosphorylated p38MAPK (p-p38MAPK),total p38MAPK (t-p38MAPK),MCP-1 and AdipoR1/AdipoR2 were examined by western blotting.The mRNA expression of MCP-1 and AdipoR1/AdipoR2 were detected by RT-PCR and real-time PCR respectively.Results Compared with NG group,the mRNA and protein expression of MCP-1 increased significantly in HG group (all P< 0.05).The phosphorylation of p38MAPK increased (P< 0.05) with no change in t-p38MAPK protein.The addition of gAd or SB203580 inhibited the unregulation of MCP-1 and p-p38MAPK induced by HG.Two kinds of adipoR,adipoR1 and adipoR2,were all detectable in NG group,and mRNA and protein expression of adipoR1 was higher than that of adipoR2 (P< 0.01).Compared with NG group,the expression of adipoR decreased in HG group,but the difference had no statistical significance(P > 0.05).Compared to HG group,the mRNA and protein expression of adipoR1 increased in gAd groups (all P < 0.01).Conclusion The gAd can dose-dependently attenuate the overexpression of MCP-1 induced by high glucose,and this protective effect may be mediated by adipoR1 and p38MAPK.%目的 探讨高糖环境下球形脂联素(globular adiponectin,gAd)对大鼠近端肾小管上皮细胞(NRK-52E)单核趋化蛋白-1 (MCP-1)表达的影响以及其与脂联素受体(AdipoR)、p38丝裂原活化蛋白激酶(p38MAPK)的关系.方法 体外培养NRK-52E细胞,分为六组:正常对照组(NG,5.6 mmol

  12. Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract.

    Science.gov (United States)

    Starrett, Warren; Blake, David J

    2011-06-01

    Chronic obstructive pulmonary disease (COPD) is currently the fifth leading cause of death worldwide. Exposure to cigarette smoke (CS) is the primary factor associated with the COPD development. CS activates epithelial cells to secrete chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) that recruit neutrophils and macrophages to the lung. These inflammatory cells then release additional chemokines and cytokines leading to chronic inflammation that initiates apoptosis in epithelial and endothelial cells and destruction of alveolar structure. Pulmonary epithelium responds to oxidative stress mediated by CS through activating NRF2-dependent pathways, leading to an increased expression of antioxidant and cytoprotective enzymes thereby providing a protective response against CS-induced lung injury. We hypothesized that activating NRF2-dependent cytoprotective gene expression with sulforaphane (SFN) affords protection against CS-induced lung damage by inhibiting chemokine production. Results indicate that in the human BEAS-2B epithelial cell line, 5 μM SFN activated NRF2-dependent gene expression by triggering the translocation of NRF2 to the nucleus and significantly increased the expression of NRF2-dependent genes such as NADPH quinone oxidoreductase-1, heme oxygenase-1, and glutamate cysteine ligase modulatory subunit. Cigarette smoke extract (CSE) exposure of BEAS-2B cells significantly increased production of both IL-8 and MCP-1. Production of both chemokines was significantly reduced with SFN given prior to CSE; SFN inhibited IL-8 and MCP-1 gene expression at the transcription level. Our results indicate that activating NRF2 pathways with SFN inhibits CSE-induced chemokine production in human epithelial cells. However, the mechanism by which the production of chemokines is inhibited through SFN still remains to be elucidated. SFN may enhance NRF2 transcriptional activity resulting in the inhibition of proinflammatory pathways such

  13. 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

  14. 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

  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. NFAT5 Contributes to Osmolality-Induced MCP-1 Expression in Mesothelial Cells

    Directory of Open Access Journals (Sweden)

    Christoph Küper

    2012-01-01

    Full Text Available Increased expression of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1 in mesothelial cells in response to high glucose concentrations and/or high osmolality plays a crucial role in the development of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD. Recent studies suggest that in kidney cells osmolality-induced MCP-1 upregulation is mediated by the osmosensitive transcription factor, nuclear factor of activated T cells 5 (NFAT5. The present study addressed the question of whether activation of NFAT5 by hyperosmolality, as present in PD fluids, contributes to MCP-1 expression in the mesothelial cell line Met5A. Hyperosmolality, induced by addition of glucose, NaCl, or mannitol to the growth medium, increased NFAT5 activity and stimulated MCP-1 expression in Met5A cells. siRNA-mediated knockdown of NFAT5 attenuated osmolality-induced MCP-1 upregulation substantially. Hyperosmolality also induced activation of nuclear factor-κB (NF-κB. Accordingly, pharmacological inhibition of NF-κB significantly decreased osmolality-induced MCP-1 expression. Taken together, these results indicate that high osmolalities activate the transcription factor NFAT5 in mesothelial cells. NFAT5 in turn upregulates MCP-1, likely in combination with NF-κB, and thus may participate in the development of peritoneal fibrosis during CAPD.

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

    Directory of Open Access Journals (Sweden)

    Luzia Maria de-Oliveira-Pinto

    2012-02-01

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

  18. Endogenous PGE(2) induces MCP-1 expression via EP4/p38 MAPK signaling in melanoma.

    Science.gov (United States)

    Tang, Mingrui; Wang, Yuxin; Han, Sihuan; Guo, Shu; Xu, Nan; Guo, Jiayan

    2013-02-01

    It has been demonstrated that cyclooxygenase-2 (COX-2) is expressed in melanoma tissues and prostaglandin E(2) (PGE(2)) is produced by melanoma cells in vitro. However, the roles of COX-2/PGE(2) in melanoma are largely unknown. In the present study, we set out to analyze the correlation of endogenous PGE(2) with the expression of macrophage chemoattractant protein-1 (MCP-1) and to identify the signaling pathway involved. It was found that MCP-1 mRNA was heterogeneously expressed in 18 melanoma tissue specimens, and the levels of MCP-1 mRNA were positively correlated with those of COX-2 mRNA. Inhibition of endogenous PGE(2) production by a COX-2 inhibitor, COX-2 siRNA or an NFκB inhibitor suppressed MCP-1 expression, whereas treatment with TNF-α (to stimulate endogenous PGE(2) production) or exogenous PGE(2) enhanced MCP-1 expression in melanoma cells. Both the EP4 antagonist and the p38 MAPK inhibitor reduced MCP-1 production in melanoma cells, and abrogated the increased MCP-1 secretion induced by TNF-α or exogenous PGE(2). Conditioned medium from melanoma cells promoted macrophage migration, which was blocked by inhibitors of the PGE(2)/EP4/p38 MAPK signaling pathway. These results indicate that endogenous PGE(2) induces MCP-1 expression via EP4/p38 MAPK signaling in an autocrinal manner in melanoma, and melanoma cell-derived PGE(2) may be involved in macrophage recruitment in the melanoma microenvironment. PMID:23420676

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

    Directory of Open Access Journals (Sweden)

    Murea Mariana

    2012-11-01

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

  20. 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

  1. Effect of pharmacological intervention on MIP-1α, MIP-1β and MCP-1 expression in patients with psoriasis vulgaris

    Institute of Scientific and Technical Information of China (English)

    Yong-Jiang Dai; Yu-Yang Li; Hui-Ming Zeng; Xiong-An Liang; Zhi-Jie Xie; Zhi-Ang Zheng; Qin-Hui Pan; Yi-Xiong Xing

    2014-01-01

    Objective:To detect the expression level of macrophage inflammatory protein-1(MIP-1)α, MIP-1β and monocyte chemoattractant protein-1(MCP-1) in with psoriasis vulgaris and explore the role in the pathogenesis of psoriasis vulgaris.Methods:The level ofMIP-1α,MIP-1β andMCP-1 in peripheral blood from50 patients with psoriasis vulgaris and50 normal controls were measured by enzyme linked immunosorbent assay.The correlation with psoriasis area and severity index(PASI) was analyzed.The level ofMIP-1α,MIP-1β andMCP-1 was compared between psoriasis vulgaris patients at active stage and resting stage.And the change inMIP-1α, MIP-1β andMCP-1 before and after therapy was also observed.Results:The content ofMIP-1α, MIP-1β andMCP-1 in patients with psoriasis vulgaris was(1342.78±210.30),(175.28±28.18) and (266.86±32.75) ng/L, respectively, significantly higher than those in control group(P<0.05).The expression level ofMIP-1α,MIP-1β andMCP-1 in peripheral blood of patients with psoriasis vulgaris was positively correlated withPASI(P<0.01).After acitretin therapy, expression level ofMIP-1α,MIP-1β andMCP-1 in peripheral blood of patients with psoriasis vulgaris was significantly decreased.Conclusions:Chemokine factorMIP-1α,MIP-1β andMCP-1 may be involved in the pathogenesis of psoriasis vulgaris.

  2. Duality of n-3 Polyunsaturated Fatty Acids on Mcp-1 Expression in Vascular Smooth Muscle: A Potential Role of 4-Hydroxy Hexenal

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    Kohji Nagayama

    2015-09-01

    Full Text Available N-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA have protective effects against atherosclerosis. Monocyte chemotactic protein (MCP-1 is a major inflammatory mediator in the progression of atherosclerosis. However, little is known about the regulation of MCP-1 by DHA and EPA in vessels and vascular smooth muscle cells (VSMCs. In this study, we compared the effect of DHA and EPA on the expression of Mcp-1 in rat arterial strips and rat VSMCs. DHA, but not EPA, suppressed Mcp-1 expression in arterial strips. Furthermore, DHA generated 4-hydroxy hexenal (4-HHE, an end product of n-3 polyunsaturated fatty acids (PUFAs, in arterial strips as measured by liquid chromatography-tandem mass spectrometry. In addition, 4-HHE treatment suppressed Mcp-1 expression in arterial strips, suggesting 4-HHE derived from DHA may be involved in the mechanism of this phenomenon. In contrast, Mcp-1 expression was stimulated by DHA, EPA and 4-HHE through p38 kinase and the Keap1-Nuclear factor erythroid-derived 2-like 2 (Nrf2 pathway in VSMCs. In conclusion, there is a dual effect of n-3 PUFAs on the regulation of Mcp-1 expression. Further study is necessary to elucidate the pathological role of this phenomenon.

  3. MCP-1-Induced Histamine Release from Mast Cells Is Associated with Development of Interstitial Cystitis/Bladder Pain Syndrome in Rat Models

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    Jianwei Lv

    2012-01-01

    Full Text Available Objective. Interstitial cystitis/bladder pain syndrome (IC/BPS is characterized by overexpression of monocyte chemoattractant protein-1 (MCP-1 in bladder tissues and induction of mast cell (MC degranulation. This study was undertaken to explore the mechanism of action of MCP-1 in the development of IC/BPS. Methods. A rat model of IC/BPS was developed by perfusing bladders of nine SPF- grade female Sprague-Dawley rats with protamine sulfate and lipopolysaccharide (PS+LPS. MCP-1 and histamine levels in bladder tissue and urine were detected by immunohistochemistry and ELISA. MC degranulation was measured by immunofluorescence techniques and chemokine (C-C motif receptor 2 (CCR2 was assayed by flow cytometry. Results. Increased MCP-1 expression in bladder tissue and elevated MCP-1 and histamine levels were observed in the urine of LS+LPS-treated rats. This was accompanied by the expression of CCR2 on MC surfaces, suggesting MCP-1 may induce MC degranulation through CCR2. Exposure to LPS stimulated MCP-1 expression in bladder epithelial cells, and exposure to MCP-1 induced histamine release from MCs. Conclusions. MCP-1 upregulation in IC/BPS is one of possible contributing factors inducing histamine release from MCs. CCR2 is involved in the process of mast cell degranulation in bladder tissues. These changes may contribute to the development of symptoms of IC/BPS.

  4. 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 ...

  5. 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...

  6. MCP-1 upregulates amylin expression in murine pancreatic β cells through ERK/JNK-AP1 and NF-κB related signaling pathways independent of CCR2.

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    Kun Cai

    Full Text Available BACKGROUND: Amylin is the most abundant component of islet amyloid implicated in the development of type 2 diabetes. Plasma amylin levels are elevated in individuals with obesity and insulin resistance. Monocyte chemoattractant protein-1 (MCP-1, CCL2 is involved in insulin resistance of obesity and type 2 diabetes. We investigated the effect of MCP-1 on amylin expression and the underlying mechanisms with murine pancreatic β-cell line MIN6 and pancreatic islets. METHODOLOGY/PRINCIPAL FINDINGS: We found that MCP-1 induced amylin expression at transcriptional level and increased proamylin and intermediate forms of amylin at protein level in MIN6 cells and islets. However, MCP-1 had no effect on the expressions of proinsulin 1 and 2, as well as prohormone convertase (PC 1/3 and PC2, suggesting that MCP-1 specifically induces amylin expression in β-cells. Mechanistic studies showed that although there is no detectable CCR2 mRNA in MIN6 cells and islets, pretreatment of MIN6 cells with pertussis toxin inhibited MCP-1 induced amylin expression, suggesting that alternative Gi-coupled receptor(s mediates the inductive effect of MCP-1. MCP-1 rapidly induced ERK1/2 and JNK phosphorylation. Inhibitors for MEK1/2 (PD98059, JNK (SP600125 or AP1 (curcumin significantly inhibited MCP-1-induced amylin mRNA expression. MCP-1 failed to induce amylin expression in pancreatic islets isolated from Fos knockout mice. EMSA showed that JNK and ERK1/2 were involved in MCP-1-induced AP1 activation. These results suggest that MCP-1 induces murine amylin expression through AP1 activation mediated by ERK1/2 or JNK. Further studies showed that treatment of MIN6 cells with NF-κB inhibitor or overexpression of IκBα dominant-negative construct in MIN6 cells significantly inhibited MCP-1-induced amylin expression, suggesting that NF-κB related signaling also participates in MCP-1-induced murine amylin expression. CONCLUSIONS/SIGNIFICANCE: MCP-1 induces amylin expression

  7. MCP-1 Upregulates Amylin Expression in Murine Pancreatic β Cells through ERK/JNK-AP1 and NF-κB Related Signaling Pathways Independent of CCR2

    Science.gov (United States)

    Cai, Kun; Qi, Dongfei; Hou, Xinwei; Wang, Oumei; Chen, Juan; Deng, Bo; Qian, Lihua; Liu, Xiaolong; Le, Yingying

    2011-01-01

    Background Amylin is the most abundant component of islet amyloid implicated in the development of type 2 diabetes. Plasma amylin levels are elevated in individuals with obesity and insulin resistance. Monocyte chemoattractant protein-1 (MCP-1, CCL2) is involved in insulin resistance of obesity and type 2 diabetes. We investigated the effect of MCP-1 on amylin expression and the underlying mechanisms with murine pancreatic β-cell line MIN6 and pancreatic islets. Methodology/Principal Findings We found that MCP-1 induced amylin expression at transcriptional level and increased proamylin and intermediate forms of amylin at protein level in MIN6 cells and islets. However, MCP-1 had no effect on the expressions of proinsulin 1 and 2, as well as prohormone convertase (PC) 1/3 and PC2, suggesting that MCP-1 specifically induces amylin expression in β-cells. Mechanistic studies showed that although there is no detectable CCR2 mRNA in MIN6 cells and islets, pretreatment of MIN6 cells with pertussis toxin inhibited MCP-1 induced amylin expression, suggesting that alternative Gi-coupled receptor(s) mediates the inductive effect of MCP-1. MCP-1 rapidly induced ERK1/2 and JNK phosphorylation. Inhibitors for MEK1/2 (PD98059), JNK (SP600125) or AP1 (curcumin) significantly inhibited MCP-1-induced amylin mRNA expression. MCP-1 failed to induce amylin expression in pancreatic islets isolated from Fos knockout mice. EMSA showed that JNK and ERK1/2 were involved in MCP-1-induced AP1 activation. These results suggest that MCP-1 induces murine amylin expression through AP1 activation mediated by ERK1/2 or JNK. Further studies showed that treatment of MIN6 cells with NF-κB inhibitor or overexpression of IκBα dominant-negative construct in MIN6 cells significantly inhibited MCP-1-induced amylin expression, suggesting that NF-κB related signaling also participates in MCP-1-induced murine amylin expression. Conclusions/Significance MCP-1 induces amylin expression through ERK1/2/JNK

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

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    Garcia-Bueno Borja

    2011-07-01

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

  9. Effects of Shock Waves on Expression of IL-6, IL-8, MCP-1, and TNF-α Expression by Human Periodontal Ligament Fibroblasts: An In Vitro Study

    Science.gov (United States)

    Cai, Zhiyu; Falkensammer, Frank; Andrukhov, Oleh; Chen, Jiang; Mittermayr, Rainer; Rausch-Fan, Xiaohui

    2016-01-01

    Background Extracorporeal shock wave therapy (ESWT) can modulate cell behavior through mechanical information transduction. Human periodontal ligament fibroblasts (hPDLF) are sensible to mechanical stimulus and can express pro-inflammatory molecules in response. The aim of this study was to evaluate the impacts of shock waves on interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) expression by hPDLF. Material/Methods After being treated by shock waves with different parameters (100–500 times, 0.05–0.19 mJ/mm2), cell viability was tested using CCK-8. IL-6, IL-8, MCP-1, and TNF-α gene expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and IL-6 and IL-8 protein was measured by enzyme-linked immunosorbent assay (ELISA) at different time points. Results Shock waves with the parameters used in this study had no significant effects on the viability of hPDLF. A statistical inhibition of IL-6, IL-8, MCP-1, and TNF-α expression during the first few hours was observed (P<0.05). Expression of IL-8 was significantly elevated in the group receiving the most pulses of shock wave (500 times) after 4 h (P<0.05). At 8 h and 24 h, all treated groups demonstrated significantly enhanced IL-6 expression (P<0.05). TNF-α expression in the groups receiving more shock pulses (300, 500 times) or the highest energy shock treatment (0.19 mJ/mm2) was statistically decreased (P<0.05) at 24 h. Conclusions Under the condition of this study, a shock wave with energy density no higher than 0.19 mJ/mm2 and pulses no more than 500 times elicited no negative effects on cell viability of hPDLF. After a uniform initial inhibition impact on expression of inflammatory mediators, a shock wave could cause dose-related up-regulation of IL-6 and IL-8 and down-regulation of TNF-α. PMID:26994898

  10. Regulation of MCP-1 chemokine transcription by p53

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    Wasylyk Bohdan

    2010-04-01

    Full Text Available Abstract Background Our previous studies showed that the expression of the monocyte-chemoattractant protein (MCP-1, a chemokine, which triggers the infiltration and activation of cells of the monocyte-macrophage lineage, is abrogated in human papillomavirus (HPV-positive premalignant and malignant cells. In silico analysis of the MCP-1 upstream region proposed a putative p53 binding side about 2.5 kb upstream of the transcriptional start. The aim of this study is to monitor a physiological role of p53 in this process. Results The proposed p53 binding side could be confirmed in vitro by electrophoretic-mobility-shift assays and in vivo by chromatin immunoprecipitation. Moreover, the availability of p53 is apparently important for chemokine regulation, since TNF-α can induce MCP-1 only in human keratinocytes expressing the viral oncoprotein E7, but not in HPV16 E6 positive cells, where p53 becomes degraded. A general physiological role of p53 in MCP-1 regulation was further substantiated in HPV-negative cells harboring a temperature-sensitive mutant of p53 and in Li-Fraumeni cells, carrying a germ-line mutation of p53. In both cases, non-functional p53 leads to diminished MCP-1 transcription upon TNF-α treatment. In addition, siRNA directed against p53 decreased MCP-1 transcription after TNF-α addition, directly confirming a crosstalk between p53 and MCP-1. Conclusion These data support the concept that p53 inactivation during carcinogenesis also affects immune surveillance by interfering with chemokine expression and in turn communication with cells of the immunological compartment.

  11. CPG寡核苷酸对卵清蛋白致敏幼鼠血清中Th1/Th2细胞因子及肥大细胞趋化蛋白1的影响%Effect of CPG oligodeoxynucleotides on Th1/Th2 and mast cell chemotactic protein1 in serum with OVA induced food allergy in young mice

    Institute of Scientific and Technical Information of China (English)

    王本贞; 郑成中

    2015-01-01

    分;眼球取血,检测血清中OVA-IgE、肥大细胞趋化蛋白1(mast cell chemotactic protein 1,mMCP-1)及Th1/Th2相关细胞因子IFN-γ、IL-4的水平;空肠组织行病理学检测。结果除对照组外,致敏组小鼠均出现不同程度过敏症状,空肠表现为Ⅰ型变态反应病理特点,Th2细胞因子、OVA-IgE、mMCP-1水平升高,20μg、50μg致敏组Th1水平降低,50μg致敏组指标改变最显著;与致敏组相比,干预组小鼠过敏症状及病理改变明显减轻,Th2细胞因子、IgE及mMCP-1水平降低,Th1水平升高。结论用50μg OVA建立的BALB/c幼鼠食物过敏模型致敏效果最好,CPG-ODN通过改善Th1/Th2失衡状态,抑制幼鼠食物过敏反应。mMCP-1在过敏性疾病的发生、发展中起重要作用,有望成为食物过敏临床检测指标之一。

  12. Visfatin promotes production of monocyte chemotactic protein-1 and interleukin-6 in human endothelial cells via insulin receptor%内脏脂肪素促进内皮细胞合成单核细胞趋化蛋白1和白介素6的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘圣文; 乔树宾; 刘东青

    2009-01-01

    Objective Visfatin is a new novel proinflammatory adipoeytokine affecting insulin resistance by binding to insulin receptor.To investigate whether visfatin stimulates monoeyte chemotaetic protein-1 (MCP-1) and interleukin-6 (IL-6) production in human umbilical vein endothelial cells (HUVEC) and mediates insulin receptor (IR) is involved in are not known.Methods Cultured HUVEC was treated with different doses and durations of visfatin.Furthermore,HUVEC was pretreated with hydroxy2-naphthalenylmethylphosphonic acid trisaeetoxymethyl ester (HNMPA-(AM)3),a specific inhibitor of IR followed by visfatin (100 ng/ml) treatment.Enzyme-linked immunosorbent assay (ELISA) were used to measure MCP-1 and IL-6 production in HUVEC.Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) was used for determining MCP-1 and IL-6 mRNA expression.Results Visfatin significantly dose- and time-dependently up-regulated protein production of MCP-1 and IL-6 in HUVEC.We therefore found visfatin-induced MCP-1 and IL-6 production and gene expression in HUVEC were inhibited by HNMPA-(AM)3.Condusion Visfatin induces endothelial MCP-1 and IL-6 production in HUVEC in a dose and time-dependently manner.This action appears to be mediated via insulin receptor pathway.%目的 探讨内脏脂肪素是否能调节内皮细胞单核细胞趋化蛋白1(MCP-1)和白介素6(IL-6)生成以及胰岛素受体(IR)的介导作用.方法 不同剂量和不同干预时间的内脏脂肪素刺激3~5代脐静脉内皮细胞(HUVEC);然后在内脏脂肪素(100 ng/m1)刺激基础上加入IR酪氨酸激酶抑制剂预处理HUVEC,24 h后测定MCP-1和IL-6蛋白和基因表达.酶联免疫吸附法和实时定量聚合酶链反应检测MCP-1和IL-6蛋白和mRNA表达.结果 内脏脂肪素剂量和时间依赖性促进HUVEC合成MCP-1[剂量效应:对照组:(62±10) pg/ml、100 ng/ml:(273±65) pg/ml、500 ng/ml:(1630±103) pg/ml;时间效应:对照组:(37±27) pg/ml、12 h:(184±56) pg/ml、48 h

  13. 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

  14. Detection and clinical significance of MCP-1 in gingival crevicular fluid from patients with chronic periodontitis%慢性牙周炎患者龈沟液中MCP-1的检测及临床意义

    Institute of Scientific and Technical Information of China (English)

    张遵; 孙青; 王晓丽

    2011-01-01

    目的:检测慢性牙周炎患者龈沟液中单核细胞趋化蛋白-1(MCP-1)的浓度,并探讨其与牙周临床指标及碱性磷酸酶分泌的关系.方法:采用常规滤纸条法收集慢性牙周炎患者基础治疗前(T1)、基础治疗后(T2)及正常对照组(C)各位点的龈沟液样本,用ELISA法检测各样本中MCP-1及碱性磷酸酶的浓度.采用SPSS11.0软件包对数据进行t检验和直线相关分析.结果:3组受检者中,慢性牙周炎患者龈沟液中MCP-1平均浓度显著高于正常对照组(P<0.01),基础牙周治疗可使牙周炎患者龈沟液中MCP-1含量显著下降(P<0.01),治疗前后MCP-1的浓度变化与菌斑指数、探诊深度、牙龈指数、临床附着丧失以及碱性磷酸酶的分泌均呈正相关.结论:MCP-1作为一个重要的炎性趋化因子参与了慢性牙周炎的发生、发展过程,龈沟液MCP-1可作为牙周病防治及疗效评估的潜在靶分子.%PURPOSE: To evaluate the concentration of monocyte chemoattractant protein-1 (MCP-1) in the gingival crevicular fluid from patients with chronic periodontitis and its correlation with clinic periodontal parameters as well as alkaline phosphates secretions.METHODS: Gingival crevicular fluid (GCF) was collected with standardized filter strips from healthy control sites as well as periodontitis sites from chronic periodontitis patients before and after initial therapy,and the levels of MCP-1 and alkaline phosphatase were detected by ELISA.The data was analyzed with SPSS 11.0 software package.RESULTS: Concentration of MCP-1 in GCF was significantly higher in chronic periodontitis patients,and decreased significantly after initial therapy, the variation of MCP-1 correlated positively with clinical parameters like plaque index (PLI), probing depth (PD), gingival index (GI), clinic attachment lost (CAL) as well as alkaline phosphatase secretion.CONCLUSIONS: As an inflammatory chemotatic factor, MCP-1 in GCF may play an important role in occurrence

  15. 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-...

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

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    Charo Israel F

    2004-09-01

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

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

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    Kazuko Ino

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

  18. "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...

  19. sPLA2-IIA Augments Oxidized LDL-Induced MCP-1 Expression in Vitro Through Activation of Akt

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    Yongjun Guo

    2015-10-01

    Full Text Available Background/Aims: Group IIA secretory phospholipase A2 (sPLA2-IIA has an important role in atherosclerosis. In this study, we explored whether sPLA2-IIA overexpression could promote atherosclerosis in normal environment alone or with other inflammatory factors. Methods: Human aortic smooth muscle cells (HASMCs were transduced with Lv-GFP-sPLA2-IIA, a plasmid containing sPLA2-IIA coupled with green fluorescent protein (GFP. Cells were incubated in the presence or absence of oxidized low-density lipoprotein (LDL, sPLA2 inhibitor LY315920 or PI3K/Akt inhibitor LY294002. The mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1 were assessed by quantitative real-time polymerase chain reaction (QRT-PCR and enzyme-linked immunosorbent assay (ELISA, respectively. Phosphorylation of Akt was examined by western blotting. Results: Lv-GFP-sPLA2-IIA-transduced HASMCs remained fluorescent during 72 h of the study period with infection ratio of around 80%. The mRNA expression and protein secretion of MCP-1was not altered in groups of HASMCs, Lv-GFP transduced and Lv-GFP-sPLA2-IIA-transduced HASMCs (p>0.05, but was significantly increased in the presence of oxidized LDL especially in Lv-GFP-sPLA2-IIA transduction group (ppConclusions: Overexpression of sPLA2-IIA does not alter MCP-1 level at baseline, but could enhance the atherogenic effect of oxidized LDL in HASMCs, at least partly due to activation of Akt. These findings may provide a strategy for treatment of inflammatory cardiovascular diseases.

  20. MCP-1/CCR2 axis promotes the homing of human umbilical cord mesenchymal stem cells to lung cancer tissues%MCP-1/CCR2轴促进脐带间充质干细胞向肺癌组织归巢

    Institute of Scientific and Technical Information of China (English)

    宋新苗; 颜次慧; 吕梦果; 于文文; 张新伟; 任秀宝

    2016-01-01

    目的:探讨单核细胞趋化蛋白-l(monocyte chemoatractant protein-1,MCP-1)/趋化因子(C-C模体)受体2[chemokine(C-C motif) receptor 2,CCR2)轴在人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,HUMSCs)向肺癌归巢中的作用.方法:采用组织块培养法从健康新生儿脐带组织中分离HUMSCs并鉴定,构建BALB/c裸鼠皮下移植瘤模型.体外应用Transwell趋化实验、体内应用IVIS Xenogen动物活体成像系统检测HUMSCs是否向肺癌归巢,ELISA法检测肺癌细胞A549培养上清中MCP-1分泌水平,转染shRNA敲低肺癌细胞内MCP-1的表达和用抑制剂RS504393抑制HUMSCs细胞表面的MCP-1受体CCR2后,体内外检测HUMSCs向肺癌归巢能力的改变.结果:成功分离得到HUMSCs并完成鉴定,成功建立BALB/c裸鼠皮下肺癌移植瘤模型.HUMSCs在体内外均能向肺癌归巢(P<0.01),肺癌细胞高表达MCP-1.成功构建稳定低表达MCP-1的肺癌A549细胞系,与对照组相比,shRNA1和shRNA2敲低组趋化HUMSCs的数目明显减少[(80.0±33.0)、(94.0±16.0)vs (167.0±41.0)个,均P<0.05],抑制HUMSCs细胞表面MCP-1受体CCR2后,体内外均显著抑制HUMSCs向肺癌的趋化能力(P<0.05).结论:MCP-1/CCR2轴促进HUMSCs向肺癌归巢.

  1. 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

  2. Regulation of MCP-1 gene transcription by Smads and HIV-1 Tat in human glial cells

    International Nuclear Information System (INIS)

    Expression of several cytokines involved in signal transduction such as TGFβ-1 and the inflammatory chemokines including MCP-1 is elevated during the course of AIDS progression. The enhancement of these cellular proteins in astrocytic cells is mediated, at least in part, by HIV-1 Tat protein. Here, we investigate the possible regulation of MCP-1 transcription by Tat and the Smad family of transcription factors whose activities are induced by the TGFβ-1 pathway. Results from transfection studies revealed that Smad-3 stimulates basal and Tat-mediated transcription of MCP-1 in human astrocytic cells. Smad-4, on the other hand, had no effect on the basal activity of the MCP-1 promoter, but showed the ability to decrease both Smad-3 and Tat-induced transcription of the MCP promoter. Results from protein-binding studies revealed the ability of both Smad-3 and Smad-4 to associate with the region of Tat spanning residues 1-40. Examination of the transcriptional activity of the various domains of Smad including MH1, at the N-terminus, and MH2, at the C-terminus of the protein indicated that neither MH1 or MH2 alone positively cooperate with Tat in modulating MCP-1 transcription. However, ectopic expression of MH1 and, more notably, MH2 severely suppressed transcriptional activation of MCP-1 by Tat in astrocytic cells. Binding studies revealed that similar to the full-length Smad protein, both MH1 and MH2 associate with Tat protein and that the residues between 1 and 40 of Tat are important for their interaction. These observations reveal a novel mechanism for Tat-mediated transcriptional activation via TGFβ signaling pathway and provide evidence for regulation of MCP-1 gene transcription by this signaling pathway in human astrocytic cells

  3. 当归芍药散对代谢性炎性反应小鼠血脂和血清炎性反应因子IL-6、MCP-1及 NF-κB、PPARγmRNA 表达的影响%Effect of Dangguishaoyaosan on the blood lipids and the expression of inflammatory factors, such as IL-6, MCP-1, NF-κB and PPAR-γmRNA in the metaflammatory mice

    Institute of Scientific and Technical Information of China (English)

    贾丽超; 周明学; 张蕾; 刘卫红

    2014-01-01

    Objective To study the effect of Dangguishaoyaosan on the blood lipids and the expression of inflammatory factors, such as IL-6, MCP-1, NF-κB and PPAR-γ mRNA in the metaflammatory mice. Methods Sixty male C57 mice were randomly divided into normal group, model group, the lipitor group and Dangguishaoyaosan group(n = 15). High-fat diets joining lipopolysaccharide injection were used to build the metabolic inflammatory model in mice. Five weeks later, all groups in addition to the normal were given a gavage twice a day for five weeks,according to the dose conversed from the clinical equivalent dose. When the test was finished, we collect the blood and liver, test the serum cholesterol( TC), triglyceride( TG) and low density lipoprotein cholesterol( LDL-C) level, using flow cytometry to detect the serum level of IL-6 and MCP-1. Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the expression of NF-κB and PPAR-γ mRNA in liver. Results Compared with the model group, the serum TC and LDL-C level of Dangguishaoyaosan group significantly decreased(P<0. 01), and the expression of NF-κB mRNA in liver tissue decreased significantly(P<0. 01), while the expression of PPAR-γmRNA significantly increased(P<0. 01). Conclusion Dangguishaoyaosan can reduce the blood lipid, IL-6 and MCP-1 level of metabolic inflammation mice, and can influence metabolic inflammation in mice, which might have an intervention effect on the early atherosclerosis through regulating nuclear transcription factor NF-κB and PPAR-γ receptors.%目的:研究当归芍药散对代谢性炎性反应小鼠血脂和血清炎性反应因子白细胞介素-6(interleukin-6,IL-6)、单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)以及核因子κB (nuclear factor kappa B,NF-κB)和活化的过氧化物酶体增生物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)mRNA 表达的影响。方法60只雄性 C57小鼠,采用数字表法将动物随机

  4. Association of sICAM-1 and MCP-1 with coronary artery calcification in families enriched for coronary heart disease or hypertension: the NHLBI Family Heart Study

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    Hopkins Paul N

    2007-10-01

    Full Text Available Abstract Background Data accumulated from mouse studies and in vitro studies of human arteries support the notion that soluble intercellular adhesion molecule-1 (sICAM-1 and monocyte chemoattractant protein-1 (MCP-1 play important roles in the inflammation process involved in atherosclerosis. However, at the population level, the utility of sICAM-1 and MCP-1 as biomarkers for subclinical atherosclerosis is less clear. In the follow-up exam of the NHLBI Family Heart Study, we evaluated whether plasma levels of sICAM-1 and MCP-1 were associated with coronary artery calcification (CAC, a measure of the burden of coronary atherosclerosis. Methods CAC was measured using the Agatston score with multidetector computed tomography. Information on CAC and MCP-1 was obtained in 2246 whites and 470 African Americans (mean age 55 years without a history of coronary heart disease (CHD. Information on sICAM-1 was obtained for white participants only. Results In whites, after adjustment for age and gender, the odds ratios (ORs of CAC (CAC > 0 associated with the second, third, fourth, and fifth quintiles of sICAM-1 compared to the first quintile were 1.22 (95% confidence interval [CI]: 0.91–1.63, 1.15 (0.84–1.58, 1.49 (1.09–2.05, and 1.72 (1.26–2.36 (p = 0.0005 for trend test, respectively. The corresponding ORs for the second to fifth quintiles of MCP-1 were 1.26 (0.92–1.73, 0.99 (0.73–1.34, 1.42 (1.03–1.96, and 2.00 (1.43–2.79 (p Conclusion This study suggests that sICAM-1 and MCP-1 are biomarkers of coronary atherosclerotic burden and their association with CAC was mainly driven by established CHD risk factors.

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

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    Ukena Sya N

    2005-12-01

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

  6. Study on the mechanism of radiation-induced MCP-1 expression in RAW264.7 macrophage cells

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the expression mechanism of MCP-1 in gamma-irradiated RAW 264.7 macrophage cells. MCP-1 plays an important role in attracting monocyte to injured site at the early inflammation stage. However the production mechanism of MCP-1 by gamma-irradiation in RAW 264.7 macrophage cells was almost undiscovered. We found that MCP-1 was produced in RAW 264.7 macrophage cells by irradiation with 5 Gy. And these increases were attenuated by specific inhibitors treatment, such as NF-KB, JNK, ERK, JAK2, and Pyk2. These results indicate that radiation-induced MCP-1 production is mediated by MyD88-and TRIF-dependent pathways in RAW 264.7 macrophage cells. Furthermore, gamma-irradiation induced heme oxygenase-1 (HO-1) expression in RAW 264.7 macrophage cells. However this induction level was reduced before MCP-1 and IFN-β production

  7. Association of MCP-1-2518A/G polymorphism with uveitis susceptibility: a Meta-analysis%MCP-1基因-2518A/G多态性与葡萄膜炎易感性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    张小玲; 冀垒兵; 高晓唯; 肖云; 章玮; 张燕

    2015-01-01

    Background Monocyte chemoattractant protein-1 (MCP-1) polymorphisms are demonstrated to be significantly associated with the susceptibility to uveitis in recent years,while a consistent conclusion for the association of MCP-1-2518A/G polymorphism and uveitis risk is not reached yet.Objective This study was to comprehensively investigate the correlation between MCP-1-2518A/G polymorphism and uveitis susceptibility.Methods General searches of electronic database including PubMed,Embase,Web of Science,CNKI,VIP,Wanfang database and China biomedical literature database (CBD) were performed to retrieve published case-control studies regarding the association between MCP-1-2518A/G polymorphism and uveitis risk.The data were screened according to the inclusion and exclusion criteria and extracted,and the quality of included studies was evaluated.The pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.Publication bias and sensitivity analysis were also assessed.All statistical analyses were conducted with RevMan 5.2 and Stata 12.0 software.Results A total of 8 eligible case-control studies involving 1 197 cases and 1 570 controls were included in the Meta-analysis.The results showed no significant association of MCP-1-2518A/G polymorphism with uveitis susceptibility in the G vs.A,GG vs.AA and GG vs.AG+AA models (all at P>0.05).MCP-1-2518A/G polymorphism was found to be significantly associated with uveitis risk in the GG+AG vs.AA model (P =0.01,OR =1.25,95% CI:1.06-1.48),while no significant association was found by the sensitive analysis (GG + AG vs.AA:P =0.19,OR =1.16,95% CI:0.93-1.45).The subgroup analysis by uveitis types revealed that the individuals carrying allele-G or GG genotype harbored a significantly increased risk for anterior uveitis (G vs.A:P=0.01,OR=1.49,95% CI:1.16-1.90;GG vs.AA:P=0.01,OR=2.09,95% CI:1.21-3.61;GG+AG vs.AA:P=0.01,OR=1.58,95% CI:1.12-2.23;GG vs.AG+AA:P=0.01,OR=1.78,95% CI:1.12-2.83).The individuals with

  8. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model.

    Science.gov (United States)

    Conley, Melissa N; Wong, Carmen P; Duyck, Kyle M; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred to as "inflammaging." While it has been demonstrated that the gut microbiome and immune system interact, the relationship between the gut microbiome and age remains to be clearly defined, particularly in the context of inflammation. The aim of our study was to clarify the associations between age, the gut microbiome, and pro-inflammatory marker serum MCP-1 in a C57BL/6 murine model. Results. We used 16S rRNA gene sequencing to profile the composition of fecal microbiota associated with young and aged mice. Our analysis identified an association between microbiome structure and mouse age and revealed specific groups of taxa whose abundances stratify young and aged mice. This includes the Ruminococcaceae, Clostridiaceae, and Enterobacteriaceae. We also profiled pro-inflammatory serum MCP-1 levels of each mouse and found that aged mice exhibited elevated serum MCP-1, a phenotype consistent with inflammaging. Robust correlation tests identified several taxa whose abundance in the microbiome associates with serum MCP-1 status, indicating that they may interact with the mouse immune system. We find that taxonomically similar organisms can exhibit differing, even opposite, patterns of association with the host immune system. We also find that many of the OTUs that associate with serum MCP-1 stratify individuals by age. Discussion. Our results demonstrate that gut microbiome composition is associated with age and the pro-inflammatory marker, serum MCP-1. The correlation between age

  9. The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy.

    Science.gov (United States)

    Sassa, Y; Yoshida, S; Ishikawa, K; Asato, R; Ishibashi, T; Kono, T

    2016-05-01

    PurposeTo determine whether the concentrations of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP)-1 in the vitreous changed after vitrectomy in patients with proliferative diabetic retinopathy (PDR).ParticipantsTwenty-one eyes of 21 patients who needed a second surgery for PDR were included. The reasons for the second surgery were tractional retinal detachment (TRD), neovascular glaucoma, persistent vitreous hemorrhage, macular pucker, and secondary intraocular lens (IOL) implant.MethodsWe measured the VEGF and MCP-1 levels using sandwich enzyme-linked immunosorbent assays in vitreous samples collected from patients with PDR before pars plana vitrectomy (without IOL implantation), and from the same patients during the second surgery.ResultsThere was not significant change in mean VEGF concentrations when comparing first (0.81±0.88 ng/ml) and second surgeries (1.09±1.51 ng/ml). The MCP-1 level was significantly elevated at the time of second surgery (2.20±2.21 ng/ml) compared with the first vitrectomy (0.72±0.57 ng/ml). The MCP-1 levels of the second surgery cases with TRD (3.18±2.27 ng/ml) increased significantly compared with those with other complications (1.72±2.10 ng/ml).ConclusionsAt the second vitrectomy, VEGF did not change significantly in the vitreous of the patients examined. The MCP-1 concentration was markedly elevated at the second vitrectomy, implying an association between the prolonged inflammation after vitrectomy and complications, especially TRD. PMID:26915745

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

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    Salacz ME

    2016-04-01

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

  11. Secretion of MCP-1 and other paracrine factors in a novel tumor-bone coculture model

    International Nuclear Information System (INIS)

    The bone-tumor microenvironment encompasses unique interactions between the normal cells of the bone and marrow cavity and the malignant cells from a primary or metastasized cancer. A multitude of paracrine factors within this microenvironment such as the growth factor, TGF-β, and the chemokine, MCP-1, are secreted by many of these cell types. These factors can act in concert to modulate normal and malignant cell proliferation, malignant cell migration and invasion and, often, mediate bone cancer pain. Although many valuable in vitro and in vivo models exist, identifying the relevant paracrine factors and deciphering their interactions is still a challenge. The aim of our study is to test an ex vivo coculture model that will allow monitoring of the expression, release and regulation of paracrine factors during interactions of an intact femur explant and tumor cells. Intact or marrow-depleted neonatal mouse femurs and select murine and human sarcoma or carcinoma cell lines were incubated singly or in coculture in specialized well plates. Viability of the bone and cells was determined by immunohistochemical stains, microscopy and marrow cytopreps. Secretion and mRNA expression of paracrine factors was quantitated by ELISA and real-time RT-PCR. Compartments of the bone were optimally viable for up to 48 h in culture and tumor cells for up to 4 days. Bone was the major contributor of TGF-β and MMP2 whereas both bone and sarcoma cells secreted the chemokine MCP-1 in cocultures. Synergistic interaction between the femur and sarcoma resulted in enhanced MCP-1 secretion and expression in cocultures and was dependent on the presence of the hematopoietic component of the bone as well as other bone cells. In contrast, coculturing with breast carcinoma cells resulted in reduction of TGF-β and MCP-1 secretion from the bone. These studies illustrate the feasibility of this model to examine paracrine interactions between intact bone and tumor cells. Further study of unique

  12. 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

  13. 5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability

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    Lee Jee

    2012-02-01

    Full Text Available Abstract Background The peroxisome proliferator-activated receptor (PPAR-α activator, 5,8,11,14-eicosatetraynoic acid (ETYA, is an arachidonic acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes; however, its underlying mechanism of action is largely unknown. In the present study, we focused on the inhibitory action of ETYA on the expression of the chemokine, CCL2/MCP-1, which plays a key role in the initiation and progression of inflammation. Methods To determine the effect of ETYA, primary cultured rat astrocytes and microglia were stimulated with IFN-γ in the presence of ETYA and then, expression of CCL2/MCP-1 and MAPK phosphatase (MKP-1 were determined using RT-PCR and ELISA. MKP-1 mRNA stability was evaluated by treating actinomycin D. The effect of MKP-1 and human antigen R (HuR was analyzed by using specific siRNA transfection system. The localization of HuR was analyzed by immunocytochemistry and subcellular fractionation experiment. Results We found that ETYA suppressed CCL2/MCP-1 transcription and secretion of CCL2/MCP-1 protein through up-regulation of MKP-1mRNA levels, resulting in suppression of c-Jun N-terminal kinase (JNK phosphorylation and activator protein 1 (AP1 activity in IFN-γ-stimulated brain glial cells. Moreover, these effects of ETYA were independent of PPAR-α. Experiments using actinomycin D revealed that the ETYA-induced increase in MKP-1 mRNA levels reflected an increase in transcript stability. Knockdown experiments using small interfering RNA demonstrated that this increase in MKP-1 mRNA stability depended on HuR, an RNA-binding protein known to promote enhanced mRNA stability. Furthermore, ETYA-induced, HuR-mediated mRNA stabilization resulted from HuR-MKP-1 nucleocytoplasmic translocation, which served to protect MKP-1 mRNA from the mRNA degradation machinery. Conclusion ETYA induces MKP-1 through HuR at the post-transcriptional level in a receptor-independent manner. The mechanism

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

    International Nuclear Information System (INIS)

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

  15. 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.)

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

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    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.

  17. Selective inhibition of the MCP-1-CCR2 ligand-receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles

    OpenAIRE

    Gibon, Emmanuel; Ma, Ting; Ren, Pei-Gen; Fritton, Kate; Biswal, Sandip; Yao, Zhenyu; Smith, Lane; Goodman, Stuart B.

    2011-01-01

    The biological mechanisms leading to periprosthetic osteolysis involve both chemokines and the monocyte/macrophage cell lineage. Whether MCP-1 plays a major role in macrophage recruitment in the presence of wear particles is unknown. We tested two hypotheses: (1) that exogenous local delivery of MCP-1 induces systematic macrophage recruitment and (2) that blockade of the MCP-1 ligand-receptor axis decreases macrophage recruitment and osteolysis in the presence of UHMWPE particles. Six groups ...

  18. Signal pathways underlying homocysteine-induced production of MCP-1 and IL-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kun ZENG; You-fei GUAN; Daniel G REMICK; Xian WANG

    2005-01-01

    Aim: To elucidate the mechanisms underlying homocysteine (Hcy)-induced chemokine production. Methods: Human whole blood was pretreated with inhibitors of calmodulin (CaM), protein kinase C (PKC), protein tyrosine kinase(PTK), mitogen-activated protein kinase (MAPK), and NF-κB and activators of PPARγ for 60 min followed by incubation with Hcy 100 μmol/L for 32 h. The levels of mitogen chemokine protein (MCP)-1 and interleukin-8 (IL-8) were determined by enzyme-linked immunosorbant assay (ELISA). Results: Inhibitors of PKC (calphostin C, 50-500 nmol/L and RO-31-8220, 10-100 nmol/L), CaM(W7, 28-280 μmol/L), ERK1/2 MAPK (PD 98059, 2-20 μmol/L), p38 MAPK(SB 203580, 0.6-6 μmol/L), JNK MAPK (curcumin, 2-10 μmol/L), and NF-κB(PDTC, 10-100 nmol/L) markedly reduced Hcy 100 μmol/L-induced production of MCP-1 and IL-8 in human cultured whole blood, but the inhibitors of PTK(genistein, 2.6-26 μmol/L and tyrphostin, 0.5-5 μmol/L) had no obvious effect on MCP-1 and IL-8 production. PPARγ activators (ciglitazone 30 μmol/L and troglitazone 10 μmol/L) depressed the Hcy-induced MCP-1 production but not IL-8 production in the cultured whole blood. Conclusion: Hcy-induced MCP-1 and IL-8 production is mediated by activated signaling pathways such as PKC,CaM, MAPK, and NF-κB. Our results not only provide clues for the signal transduction pathways mediating Hcy-induced chemokine production, but also offer a plausible explanation for a pathogenic role of hyperhomocysteinemia in these diseases.

  19. 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.

  20. 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

  1. Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

    Science.gov (United States)

    Chen, Si; Deng, Chuiwen; Hu, Chaojun; Li, Jing; Wen, Xiaoting; Wu, Ziyan; Li, Yuan; Zhang, Fengchun; Li, Yongzhe

    2016-05-01

    We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR = 1.616, 95 % CI 1.027-2.542, P = 0.038) and AA + AG vs. GG (OR = 1.616, 95 % CI 1.027-2.542, P = 0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR = 1.383, 95 % CI 1.142-1.676, P = 0.022) and AA vs. AG + GG (OR = 1.575, 95 % CI 1.361-1.823, P < 0.001) in European patients with Crohn's disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG + GG (OR = 0.713, 95 % CI 0.545-0.933, P = 0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD. PMID:26318885

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

    Directory of Open Access Journals (Sweden)

    Rogil José de Almeida Torres

    2012-02-01

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

  3. 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.

  4. The expression of chemokine MCP-1 in colorectal carcinoma and its relationship to the infiltration of macrophage%结直肠癌趋化因子MCP-1的表达及其与巨噬细胞浸润的关系

    Institute of Scientific and Technical Information of China (English)

    杨春康; 陈道达; 黄凯

    2006-01-01

    Objective: To study the expression of MCP-1 in colorectal carcinoma and its relationship to the infiltration of the macrophage and to the biological behaviour of infiltration and metastasis of colorectal carcinoma.Methods: The expression of the MCP-1 mRNAwas assessed in colorectal carcinoma collected freshly from surgical specimen by RT-PCR and the expression of the MCP-1 protein was assessed in colorectal carcinoma collected from surgical specimen by immunohistochemistry.The tumor infiltrating cell and macrophage were also investigated by immunohistochemistry.Results: All the 12 specimens of colorectal carcinoma detected by RT-PCR expressed the MCP-1 mRNA; MCP-1 protein was detected in 90% (36/40) cases of the tumor; The expression of the MCP-1 protein in colorectal carcinoma correlated negatively with its state of metastasis and the Dukes' stage.But a postive correlation was found between the expression of MCP-1 and the infiltrated macrophage.The stronger expression of MCP-1,the more number of the infiltrated macrophage.Conclusion: The expression of chemokine MCP-1 in colorectal carcinoma may influence its biological behaviour of infiltration and metastasis,and can attract the immuno-cell to the local of the tumor,such as Macrophage.

  5. Chemotactic Behavior of Azotobacter vinelandii

    OpenAIRE

    Haneline, Stephen; Connelly, Carla J.; Melton, Thoyd

    1991-01-01

    Chemotaxis was exhibited by Azotobacter vinelandii motile cells. Exposure of cells to sudden increases in attractant concentration suppressed the frequency of tumbling and resulted in smooth swimming. Cells responded chemotactically to a chemical gradient produced during metabolism. Motility occurred over a temperature range of 25 to 37°C with an optimum pH range of between pH 7.0 and 8.0. The average speed of motile cells was determined to be 74 μm/s or 37 body lengths per s. The speed of ce...

  6. 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

  7. 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

  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-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.

  9. 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

  10. 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

  11. 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...

  12. 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.

  13. Spiral ligament fibrocyte-derived MCP-1/CCL2 contributes to inner ear inflammation secondary to nontypeable H. influenzae-induced otitis media

    Directory of Open Access Journals (Sweden)

    Lim David J

    2010-10-01

    Full Text Available Abstract Background Otitis media (OM, one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs recognize OM pathogens and up-regulate chemokines. Here, we aim to determine a key molecule derived from SLFs, contributing to OM-induced inner ear inflammation. Methods Live NTHI was injected into the murine middle ear through the tympanic membrane, and histological analysis was performed after harvesting the temporal bones. Migration assays were conducted using the conditioned medium of NTHI-exposed SLFs with and without inhibition of MCP-1/CCL2 and CCR2. qRT-PCR analysis was performed to demonstrate a compensatory up-regulation of alternative genes induced by the targeting of MCP-1/CCL2 or CCR2. Results Transtympanic inoculation of live NTHI developed serous and purulent labyrinthitis after clearance of OM. THP-1 cells actively migrated and invaded the extracellular matrix in response to the conditioned medium of NTHI-exposed SLFs. This migratory activity was markedly inhibited by the viral CC chemokine inhibitor and the deficiency of MCP-1/CCL2, indicating that MCP-1/CCL2 is a main attractant of THP-1 cells among the SLF-derived molecules. We further demonstrated that CCR2 deficiency inhibits migration of monocyte-like cells in response to NTHI-induced SLF-derived molecules. Immunolabeling showed an increase in MCP-1/CCL2 expression in the cochlear lateral wall of the NTHI-inoculated group. Contrary to the in vitro data, deficiency of MCP-1/CCL2 or CCR2 did not inhibit OM-induced inner ear inflammation in vivo. We demonstrated that targeting MCP-1/CCL2 enhances NTHI-induced up-regulation of MCP-2/CCL8 in SLFs and up-regulates the basal expression of CCR2 in the splenocytes. We also found that targeting CCR2 enhances NTHI-induced up-regulation of MCP-1/CCL2 in SLFs. Conclusions Taken together, we suggest that

  14. 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

  15. The relationship of urinary MCP1、 fetuin-A expression and urinary MDA in patients with nephrolithiasis%肾结石患者尿液MCP-1、胎球蛋白-A表达与MDA的关系

    Institute of Scientific and Technical Information of China (English)

    孙春

    2015-01-01

    目的:探讨肾结石患者尿液炎症细胞因子变化以及氧化应激在结石形成中的作用.方法:选择75例草酸钙结石住院患者,随机挑选25例健康人作正常对照组.收集两组人的晨尿,分别运用ELLISA法和TBA法检测尿液中单核细胞趋化蛋白(MCP-1)、胎球蛋白-A (Fetuin-A)及丙二醛(MDA)的含量.结果:MCP-1在结石组含量为212.45 (59.24,673.50)pg/mg cr,在对照组为74.36(22.45,203.57)pg/mg cr,结石组高于对照组(P<0.05);胎球蛋白-A在结石组为320.80(42.28,1819.85)ng/mg cr,在对照组为787.94(187.03,3269.17)ng/mg cr,结石组低于对照组(P<0.05);MDA在结石组高于正常对照组(P<0.05).相关性分析:结石组尿液MCP-1和MDA不相关,r=0.045,P> 0.05;胎球蛋白-A和MDA不相关,r=-0.016,P> 0.05.结论:尿液炎症细胞因子变化和氧化应激损伤可能在肾结石形成中起作用,但是氧化应激损伤可能未参与尿液炎症细胞因子的调节.

  16. Imaging macrophages and the apoptosis of granulocytes in a rodent model of subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V

    Energy Technology Data Exchange (ETDEWEB)

    Blankenberg, F.G. [Div.of Pediatric Radiology, Lucile Salter Packard Children' s Hospital, Stanford, CA (United States); Tait, J.F. [Dept. of Laboratory Medicine, Univ. of Washington, Seattle (United States); Blankenberg, T.A. [Redding Pathology Labs., Redding, CA (United States); Post, A.M.; Strauss, H.W. [Div. of Nuclear Medicine, Dept. of Radiology, Stanford, CA (United States)

    2001-09-01

    Monocytes/macrophages (M{phi}s), the predominant cell types in subacute and chronic inflammation, are attracted to and activated by monocyte chemotactic peptide-1 (MCP-1). M{phi}s promote the resolution of inflammation through the induction of apoptosis and phagocytosis of senescent (spent) and bystander (superfluous) granulocytes. We wished to determine whether MCP-1, which selectively binds to M{phi}s, could be used to image subacute and chronic inflammation. We also sought to image granulocyte apoptosis within these lesions with technetium-99m labeled annexin V, a marker of apoptotic cells. Sterile inflammation was induced in 45 12-week-old male Sprague-Dawley rats by deep intramuscular injection of turpentine into the right thigh. Groups of four to six animals were then imaged 1 h after tail vein injection of 37-148 MBq (1-4 mCi) of {sup 99m}Tc-labeled MCP-1 or annexin V 1-14 days after turpentine treatment. Image analysis showed significantly greater activity of both MCP-1 and annexin V in inflamed thighs than in control thighs (165%-290% and 188%-313%, respectively; P<0.01) on days 1-5 after turpentine injection. Dual autoradiography in animals co-injected with iodine-125 labeled bovine serum albumin on days 1 and 4 showed specific location of MCP-1 to infiltrating M{phi}s while annexin V localized to focal zones of apoptosis within granulocytic infiltrates adjacent to abscess cavities. Scintillation well counting on day 5 demonstrated significantly higher (P<0.005) ratios of abscess to control thigh specific activities for MCP-1 (5.83{+-}2.17) and annexin V (9.24{+-}2.8) as compared to {sup 125}I-labeled bovine serum albumin (3.11{+-}0.65). No significant increases in uptake were noted at imaging or ex vivo analyses on days 13 and 14, when lesions were predominately fibrotic. It is concluded that {sup 99m}Tc-labeled MCP-1 and {sup 99m}Tc-labeled annexin V both localize in zones of subacute inflammation, reflecting the density of M{phi}s and the incidence of

  17. Curcumin Supplementation Lowers TNF-α, IL-6, IL-8, and MCP-1 Secretion in High Glucose-Treated Cultured Monocytes and Blood Levels of TNF-α, IL-6, MCP-1, Glucose, and Glycosylated Hemoglobin in Diabetic Rats

    OpenAIRE

    Jain, Sushil K.; Rains, Justin; Croad, Jennifer; Larson, Bryon; Jones, Kimberly

    2009-01-01

    This study examined the hypothesis that curcumin supplementation decreases blood levels of IL-6, MCP-1, TNF-α, hyperglycemia, and oxidative stress by using a cell-culture model and a diabetic rat model. U937 monocytes were cultured with control (7 mM) and high glucose (35 mM) in the absence or presence of curcumin (0.01–1 μM) at 37°C for 24 h. Diabetes was induced in Sprague–Dawley rats by injection of streptozotocin (STZ) (i.p., 65 mg/kg BW). Control buffer, olive oil, or curcumin (100 mg/kg...

  18. Hydrodynamical random walker with chemotactic memory

    OpenAIRE

    Mohammady, H.; Esckandariun, B.; Najafi, A.

    2014-01-01

    A three-dimensional hydrodynamical model for a micro random walker is combined with the idea of chemotactic signaling network of E. coli. Diffusion exponents, orientational correlation functions and their dependence on the geometrical and dynamical parameters of the system are analyzed numerically. Because of the chemotactic memory, the walker shows superdiffusing displacements in all directions with the largest diffusion exponent for a direction along the food gradient. Mean square displacem...

  19. Effects of long-term exercise training on adipose tissue expression of fractalkine and MCP-1 in patients with type 2 diabetes and stable coronary artery disease: a substudy of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Njerve IU

    2016-03-01

    Full Text Available Ida Unhammer Njerve,1–3 Rune Byrkjeland,1–3 Harald Arnesen,1–3 Sissel Åkra,1,2 Svein Solheim,1,2 Ingebjørg Seljeflot1–3 1Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, 2Center for Heart Failure Research, Oslo University Hospital, 3Faculty of Medicine, University of Oslo, Oslo, Norway Purpose: Adipose tissue inflammation plays a role in atherosclerosis and type 2 diabetes (T2DM. We aimed to investigate whether 12 months of exercise training in patients with both T2DM and coronary artery disease (CAD reduced the genetic expression of the proinflammatory markers fractalkine (CX3CL1 and its receptor (CX3CR1 and monocyte chemoattractant protein-1 (MCP-1 in the subcutaneous adipose tissue. Expression of the genes in the circulating leukocytes and circulating levels of the markers were also investigated. Patients and methods: A total of 137 patients with T2DM and CAD were included to study the effects of exercise on atherosclerosis progression and glucose control. Patients were randomized to exercise training (combined aerobic and strength training or control. At inclusion and after 12 months, fasting blood samples and a subcutaneous adipose tissue sample were taken. RNA was extracted from the adipose tissue and circulating leukocytes, and the expression levels were examined by reverse transcription-polymerase chain reaction. Circulating fractalkine and MCP-1 were determined by enzyme-linked immunosorbent assay. Results: The analyses were performed in 114 patients who completed the study and adhered to the intervention principle. At baseline, gene expression of fractalkine and CX3CR1 in the adipose tissue was similar in the two groups. There were no change within either group and no between-group differences in changes from baseline. Circulating fractalkine increased after 12 months in the exercise group (P=0.044, significantly more compared to controls (P=0.042, however only in the patients

  20. Effect of PKC-β Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products (AGEs

    Directory of Open Access Journals (Sweden)

    Lisienny C. T. Rempel

    2015-05-01

    Full Text Available Advanced glycation end products (AGEs are compounds classified as uremic toxins in patients with chronic kidney disease that have several pro-inflammatory effects and are implicated in the development of cardiovascular diseases. To explore the mechanisms of AGEs–endothelium interactions through the receptor for AGEs (RAGE in the PKC-β pathway, we evaluated the production of MCP-1 and VCAM-1 in human endothelial cells (HUVECs, monocytes, and a coculture of both. AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. The effect of AGEs on cell viability was assessed with an MTT assay. The cells were also treated with AGEs with and without a PKC-β inhibitor. MCP-1 and VCAM-1 in the cell supernatants were estimated by ELISA, and RAGE was evaluated by immunocytochemistry. AGEs exposure did not affect cell viability, but AGEs induced RAGE, MCP-1, and VCAM-1 expression in HUVECs. When HUVECs or monocytes were incubated with AGEs and a PKC-β inhibitor, MCP-1 and VCAM-1 expression significantly decreased. However, in the coculture, exposure to AGEs and a PKC-β inhibitor produced no significant effect. This study demonstrates, in vitro, the regulatory mechanisms involved in MCP-1 production in three cellular models and VCAM-1 production in HUVECs, and thus mimics the endothelial dysfunction caused by AGEs in early atherosclerosis. Such mechanisms could serve as therapeutic targets to reduce the harmful effects of AGEs in patients with chronic kidney disease.

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

    International Nuclear Information System (INIS)

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

  2. 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

  3. 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

  4. Involvement of M3 Cholinergic Receptor Signal Transduction Pathway in Regulation of the Expression of Chemokine MOB-1, MCP-1 Genes in Pancreatic Acinar Cells

    Institute of Scientific and Technical Information of China (English)

    郑海; 陈道达; 张景輝; 田原

    2004-01-01

    Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-κB and the expression of chemokine MOB-1, MCP-1genes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-κB was monitored by using electrophoretic mobility shift assay.The results showed that as compared with control group, M3 cholinergic receptor agonist (103mol/L, 104-4ol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10 -3mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-κB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10-3 mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10-5 mol/L atropine) or NF-κB inhibitor (10-2 mol/L PDTC) could obviously inhibit the activation of NF-κB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P <0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-1genes in pancreatic acinar cells in vitro through the activation of NF-κB.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Bin Yi

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

  7. 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.

  8. 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 ...

  9. Jeans type analysis of chemotactic collapse

    CERN Document Server

    Chavanis, Pierre-Henri

    2007-01-01

    We perform a linear dynamical stability analysis of a general hydrodynamic model of chemotactic aggregation [Chavanis & Sire, Physica A, in press (2007)]. Specifically, we study the stability of an infinite and homogeneous distribution of cells against ``chemotactic collapse''. We discuss the analogy between the chemotactic collapse of biological populations and the gravitational collapse (Jeans instability) of self-gravitating systems. Our hydrodynamic model involves a pressure force which can take into account several effects like anomalous diffusion or the fact that the organisms cannot interpenetrate. We also take into account the degradation of the chemical which leads to a shielding of the interaction like for a Yukawa potential. Finally, our hydrodynamic model involves a friction force which quantifies the importance of inertial effects. In the strong friction limit, we obtain a generalized Keller-Segel model similar to the generalized Smoluchowski-Poisson system describing self-gravitating Langevi...

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

    Directory of Open Access Journals (Sweden)

    Juliano Magalhães Guedes

    2015-08-01

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

  11. 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

    inflammatory protein-1 a (MIP-1 a) and monocyte chemoattractant protein-1 (MCP-1), are direct chemoattractants for monocytes. Thus alteration in the expression of a wide variety of adhesion molecules and/or cytokines during atherogenesish as been proposed to affect monocyte recruitment and hence modulates both plaque development and stability.

  12. 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.

  13. 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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Xinhua Zhang

    2012-12-01

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

  16. Kinetic and hydrodynamic models of chemotactic aggregation

    CERN Document Server

    Chavanis, Pierre-Henri

    2007-01-01

    We derive general kinetic and hydrodynamic models of chemotactic aggregation that describe certain features of the morphogenesis of biological colonies (like bacteria, amoebae, endothelial cells or social insects). Starting from a stochastic model defined in terms of N coupled Langevin equations, we derive a nonlinear mean field Fokker-Planck equation governing the evolution of the distribution function of the system in phase space. By taking the successive moments of this kinetic equation and using a local thermodynamic equilibrium condition, we derive a set of hydrodynamic equations involving a damping term. In the limit of small frictions, we obtain a hyperbolic model describing the formation of network patterns (filaments) and in the limit of strong frictions we obtain a parabolic model which is a generalization of the standard Keller-Segel model describing the formation of clusters (clumps). Our approach connects and generalizes several models introduced in the chemotactic literature. We discuss the anal...

  17. Effect of ARB on Expression of CD68 and MCP-1 in Adipose Tissue of Rats on Long-term High Fat Diet

    Institute of Scientific and Technical Information of China (English)

    Caihong GUO; Li YUAN; Xiaoling LIU; Aimin DU; Yan HUANG; Lili ZHANG

    2008-01-01

    In adipose tissue of rats on long-term high fat diet, the inflammatory changes the roles of angiotensin receptor blocker (ARB) in pimelitis and insulin resistance (IR) were observed. IR rat model was established by feeding high calorie and high fat diet. The change in insulin sensitivity was detected by euglycemic-hyperinsulinemic clamp technique 8 weeks after intervention by valsartan. The expression levels of CD68 and MCP-1 mRNA and proteins in adipose tissue were examined by RT-PCR and immunohistochemistry respectively. The parameters of blood glucose, insulin and blood lipid were analyzed. The results showed that in high fat diet group intra-abdominal obesity developed, the content of visceral fat and the number of inflammatory cells in local adipose tissue were significantly increased (p<0.01), the levels of serum triglyceride, free fatty acids and fasting serum insulin were markedly increased, the insulin sensitivity was significantly lowered (p<0.01), and the expression of CD68 and MCP-1 was significantly increased as compared with control group (P<0.01). In ARB interventional group, the content of visceral fat, the number of inflammatory cells and the expression of CD68 and MCP-1 in local adipose tissue were significantly reduced (all P<0.01), but the insulin sensitivity was significantly enhanced (P<0.01) as compared with high fat diet group. There were pimelitis and IR in rats with obesity induced by long-term high calorie and high fat diet. The ARB can significantly inhibit the infiltration of macrophages and the expression of MCP-1 in adipose tissue, thereby attenuating the inflammation and improving IR in rats.

  18. Jeans type analysis of chemotactic collapse

    Science.gov (United States)

    Chavanis, Pierre-Henri; Sire, Clément

    2008-07-01

    We perform a linear dynamical stability analysis of a general hydrodynamic model of chemotactic aggregation [P.H. Chavanis, C. Sire, Physica A 384 (2007) 199]. Specifically, we study the stability of an infinite and homogeneous distribution of cells against “chemotactic collapse”. We discuss the analogy between the chemotactic collapse of biological populations and the gravitational collapse (Jeans instability) of self-gravitating systems. Our hydrodynamic model involves a pressure force which can take into account several effects like anomalous diffusion or the fact that the organisms cannot interpenetrate. We also take into account the degradation of the chemical which leads to a shielding of the interaction like for a Yukawa potential. Finally, our hydrodynamic model involves a friction force which quantifies the importance of inertial effects. In the strong friction limit, we obtain a generalized Keller-Segel model similar to the generalized Smoluchowski-Poisson system describing self-gravitating Langevin particles. For small frictions, we obtain a hydrodynamic model of chemotaxis similar to the Euler-Poisson system describing a self-gravitating barotropic gas. We show that an infinite and homogeneous distribution of cells is unstable against chemotactic collapse when the “velocity of sound” in the medium is smaller than a critical value. We study in detail the linear development of the instability and determine the range of unstable wavelengths, the growth rate of unstable modes and the damping rate, or the pulsation frequency, of the stable modes as a function of the friction parameter and shielding length. For specific equations of state, we express the stability criterion in terms of cell density.

  19. 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...

  20. Ox-LDL Promotes Migration and Adhesion of Bone Marrow-Derived Mesenchymal Stem Cells via Regulation of MCP-1 Expression

    Directory of Open Access Journals (Sweden)

    Fenxi Zhang

    2013-01-01

    Full Text Available Bone marrow-derived mesenchymal stem cells (bmMSCs are the most important cell source for stem cell transplant therapy. The migration capacity of MSCs is one of the determinants of the efficiency of MSC-based transplant therapy. Our recent study has shown that low concentrations of oxidized low-density lipoprotein (ox-LDL can stimulate proliferation of bmMSCs. In this study, we investigated the effects of ox-LDL on bmMSC migration and adhesion, as well as the related mechanisms. Our results show that transmigration rates of bmMSCs and cell-cell adhesion between bmMSCs and monocytes are significantly increased by treatments with ox-LDL in a dose- and time-dependent manner. Expressions of ICAM-1, PECAM-1, and VCAM-1 as well as the levels of intracellular Ca2+ are also markedly increased by ox-LDL in a dose-dependent manner. Cytoskeleton analysis shows that ox-LDL treatment benefits to spreading of bmMSCs and organization of F-actin fibers after being plated for 6 hours. More interestingly, treatments with ox-LDL also markedly increase expressions of LOX-1, MCP-1, and TGF-β; however, LOX-1 antibody and MCP-1 shRNA markedly inhibit ox-LDL-induced migration and adhesion of bmMSCs, which suggests that ox-LDL-induced bmMSC migration and adhesion are dependent on LOX-1 activation and MCP-1 expression.

  1. 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.

  2. 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.

  3. Monocyte chemotactic protein-1 and other inflammatory parameters in Bernese Mountain dogs with disseminated histiocytic sarcoma

    DEFF Research Database (Denmark)

    Nielsen, Lise Nikolic; Kjelgaard-Hansen, Mads; Kristensen, Annemarie Thuri

    2013-01-01

    The interaction between cancer and the immune system, and the production of cytokines by the tumour itself have been associated with altered levels of cytokines in human cancer patients. Bernese Mountain dogs with disseminated histiocytic sarcoma (DHS) show vague and non-specific clinical signs...

  4. Identification of a chemotactic sensitivity in a coupled system

    CERN Document Server

    Fister, K Renee

    2007-01-01

    Chemotaxis is the process by which cells behave in a way that follows the chemical gradient. Applications to bacteria growth, tissue inflammation, and vascular tumors provide a focus on optimization strategies. Experiments can characterize the form of possible chemotactic sensitivities. This paper addresses the recovery of the chemotactic sensitivity from these experiments while allowing for nonlinear dependence of the parameter on the state variables. The existence of solutions to the forward problem is analyzed. The identification of a chemotactic parameter is determined by inverse problem techniques. Tikhonov regularization is investigated and appropriate convergence results are obtained. Numerical results of concentration dependent chemotactic terms are explored.

  5. 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

  6. 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

  7. Dynamics of Chemotactic Droplets in Salt Concentration Gradients

    DEFF Research Database (Denmark)

    Cejkova, J.; Novak, M.; Stepanek, F.;

    2014-01-01

    The chemotactic movement of decanol droplets in aqueous solutions of sodium decanoate in response to concentration gradients of NaCl has been investigated. Key parameters of the chemotactic response, namely the induction time and the migration velocity, have been evaluated as a function of the so...

  8. 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

  9. 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.

  10. Gradient sensing in defined chemotactic fields.

    Science.gov (United States)

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

    2010-11-01

    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 way 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 initiated development. These eukaryotic cells are known to be able to sense extremely shallow gradients but the processes underlying their exquisite sensitivity are still largely unknown. In this study we determine the responses of developed cells of Dictyostelium discoideum to stable linear gradients of cAMP of varying steepness generated in 2 μm deep gradient chambers of microfluidic devices. The gradients are generated by molecular diffusion between two 80 μm deep flow-through channels, one of which is perfused with a solution of cAMP and the other with buffer, serving as continuously replenished source and sink. These low ceiling gradient chambers constrained the cells in the vertical dimension, facilitating confocal imaging, such that subcellular localization of fluorescently tagged proteins could be followed for up to 30 min without noticeable phototoxicity. Chemotactic cells enter these low ceiling chambers by flattening and elongating and then move almost as rapidly as unconstrained cells. By following the localization of activated Ras (RasGTP) using a Ras Binding Domain fused to Green Fluorescent Protein (RBD-GFP), we observed the rapid appearance of membrane associated patches at the tips of pseudopods. These patches remained associated with pseudopods while they continued to extend but were rapidly disassembled when pseudopods stalled and the cell moved past them. Likewise, fluorescence associated with localized RasGTP rapidly disappeared when the gradient was turned

  11. Maternal immune activation by poly(I:C induces expression of cytokines IL-1β and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain

    Directory of Open Access Journals (Sweden)

    Arrode-Brusés Géraldine

    2012-04-01

    Full Text Available Abstract Background Maternal viral infection during pregnancy is associated with an increase in the incidence of psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The enhanced risk for developing mental illness appears to be caused by deleterious effects of innate immune response-associated factors on the development of the central nervous system, which predispose the offspring to pathological behaviors in adolescence and adulthood. To identify the immune response-associated soluble factors that may affect central nervous system development, we examined the effect of innate immune response activation by polyriboinosinic-polyribocytidylic acid (poly(I:C, a synthetic analogue of viral double-stranded RNA, on the expression levels of pro- and anti-inflammatory cytokines, chemokines and colony stimulating factors in fetal and postnatal mouse brain 6 h and 24 h after treatment. Methods C57BL/6J pregnant mice (gestational day 16 or newborn mice (postnatal day 4 received a single intraperitoneal injection of the synthetic analogue of viral double-stranded RNA poly(I:C (20 mg/kg. Thirty-two immune response-associated soluble factors, including pro- and anti-inflammatory cytokines, chemokines and colony stimulating factors, were assayed 6 h and 24 h after poly(I:C injection using multiplexed bead-based immunoassay (Milliplex Map and processed in a Luminex 100 IS instrument. Results Maternal exposure to poly(I:C at gestational day 16 induced a significant increase in cytokines interleukin (IL-1β, IL-7 and IL-13; chemokines monocyte chemoattractant protein 1 (MCP-1, macrophage inflammatory protein (MIP-1α, interferon gamma-induced protein (IP-10 and monokine induced by IFN-gamma (MIG; and in the colony stimulating factor vascular endothelial growth factor (VEGF in the fetal brain. IL-1β showed the highest concentration levels in fetal brains and was the only cytokine

  12. 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

  13. 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.

  14. 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

  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. 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、

  17. Mast cell heterogeneity in the gastrointestinal tract: variable expression of mouse mast cell protease-1 (mMCP-1) in intraepithelial mucosal mast cells in nematode-infected and normal BALB/c mice.

    OpenAIRE

    Scudamore, C. L.; McMillan, L; Thornton, E. M.; Wright, S H; Newlands, G. F.; Miller, H. R.

    1997-01-01

    Soluble granule chymases in rodent intestinal mucosal mast cells (IMMCs) may play an important role in altering epithelial permeability during immediate hypersensitivity reactions. Using a monoclonal antibody against the chymase mouse mast cell protease-1 (mMCP-1), we have shown that it is constitutively expressed in < or = 20% of esterase-positive (esterase+) IMMCs but not in esterase+ gastric mucosal mast cells (GMMCs) in normal BALB/c mice. Intestinal infection with mouse- or rat-adapted s...

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Chaur-Jong Hu

    2009-01-01

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

  20. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Directory of Open Access Journals (Sweden)

    Gomez-Lopez Nardhy

    2013-01-01

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

  1. Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors.

    Science.gov (United States)

    Roberts, Christian K; Won, Dean; Pruthi, Sandeep; Kurtovic, Silvia; Sindhu, Ram K; Vaziri, Nosratola D; Barnard, R James

    2006-05-01

    The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (n = 31), 15 of whom had metabolic syndrome, were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress-generating enzyme myeloperoxidase and marker 8-isoprostaglandin F2alpha, the inflammatory protein C-reactive protein, soluble ICAM-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1alpha, and total matrix metalloproteinase-9. Using subject sera and human aortic endothelial cell culture systems, we measured VCAM-1 cell surface abundance and monocyte chemotactic protein-1, nitric oxide, superoxide, and hydrogen peroxide production in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotactic activity. After 3 wk, significant reductions (P fasting glucose, insulin, homeostasis model assessment for insulin resistance, myeloperoxidase, 8-isoprostaglandin F2alpha, C-reactive protein, soluble ICAM-1, soluble P-selectin, macrophage inflammatory protein-1alpha, and matrix metalloproteinase-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, monocyte chemotactic protein-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, whereas a concomitant increase in NO production was noted (all P < 0.01). Additionally, both monocyte adhesion (P < 0.05) and MCA (P < 0.01) decreased. Nine of 15 were no longer positive for metabolic syndrome postintervention. Intensive lifestyle modification may

  2. 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

  3. 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.

  4. 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...

  5. Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection.

    Science.gov (United States)

    Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Nagase, Hiroyuki; Nakamura, Hiroyuki; Matsui, Hirotoshi; Hebisawa, Akira; Ohta, Ken

    2016-01-01

    The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg-Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk's lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg-Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI. PMID:27035669

  6. A peptide tetramer Tk-tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll-like receptor 2 signal-promoted activation of the MCP1 gene.

    Science.gov (United States)

    Li, Zuoqing; Yang, Neng; Zhou, Ling; Gu, Peng; Wang, Hui; Zhou, Yun; Zhou, Peijun; Lu, Liming; Chou, Kuang-Yen

    2016-03-01

    The plant protein trichosanthin (Tk) and its derived peptide tetramer Tk-tPN have been shown to stimulate the type 2 immune responses for treating autoimmune disease. This work explores the possibility of using Tk-tPN as a non-toxic immunosuppressant to induce transplantation tolerance using the mechanisms by which T-cell-mediated immune responses are transferred from type 1 to type 2 through innate immunity-related pathways. Immunocytes and cytokine secretions involved in the mouse cardiac allografting model with Tk-tPN treatment were characterized. Identification of critical genes and analysis of their functions through Toll-like receptor (TLR) -initiated signalling and the possible epigenetic changes were performed. Mean survival times of the cardiac allografts were delayed from 7·7 ± 0·3 days (control) to 22·7 ± 3·9 days (P Gata3(+) ), together with a selective expansion of the IL-4/IL-10-producing CD8(+)  CD28(-) regulatory T-cell subset. A TLR2-initiated high expression of chemokine gene MCP1 was detectable simultaneously. Epigenetically Tk/Tk-tPN could also acetylate the histone H3K9 of MCP1 promoter to skew the immunity towards T helper type 2 responses. Tk/Tk-tPN is therefore capable of down-regulating the type 1 response-dominant rejection of cardiac allografts by evoking type 2 immunity through the activation of a TLR2-initiated signalling pathway and MCP1 gene to expand the IL-4/IL-10-secreting CD8(+)  CD28(-) regulatory T cells. Tk-tPN could be a promising novel immunosuppressant to induce tolerance in allotransplantation. PMID:26694804

  7. Adaptation and optimal chemotactic strategy for E. coli

    International Nuclear Information System (INIS)

    Extending the classic works of Berg and Purcell on the biophysics of bacterial chemotaxis, we find the optimal chemotactic strategy for the peritrichous bacterium E. coli in the high and low signal to noise ratio limits. The optimal strategy depends on properties of the environment and properties of the individual bacterium, and is therefore highly adaptive. We review experiments relevant to testing both the form of the proposed strategy and its adaptability, and propose extensions of them which could test the limits of the adaptability in this simplest sensory processing system. copyright 1998 The American Physical Society

  8. Jeans type instability for a chemotactic model of cellular aggregation

    CERN Document Server

    Chavanis, Pierre-Henri

    2008-01-01

    We consider an inertial model of chemotactic aggregation generalizing the Keller-Segel model and we study the linear dynamical stability of an infinite and homogeneous distribution of cells (bacteria, amoebae, endothelial cells,...) when inertial effects are accounted for. These inertial terms model cells directional persistance. We determine the condition of instability and the growth rate of the perturbation as a function of the cell density and the wavelength of the perturbation. We discuss the differences between overdamped (Keller-Segel) and inertial models. Finally, we show the analogy between the instability criterion for biological populations and the Jeans instability criterion in astrophysics.

  9. 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.

  10. DETECTION OF A NEUTROPHIL CHEMOTACTIC FACTOR IN JAPANESE ENCEPHALITIS PATIENTS

    Directory of Open Access Journals (Sweden)

    Aditi Singh

    2012-12-01

    Full Text Available Japanese encephalitis (JE one of the most common cause of acute encephalitis in tropical regions, has generated much public anxiety in India. An early influx of macrophages followed by neutrophils at the site of injury in different organs in humans and mice has previously been reported. It correlated with production of a neutrophil chemotactic protein derived from macrophages. In the present study out of a total of 324 acute encephalitic patients, admitted in Gandhi memorial and associated hospitals, Lucknow, 121 patients with one or more indicators of JE virus infection were included. Significant pleocytosis (mean TLC value of 126+52 cells / mm3 in CSF and leucocytosis (>11,000 cells/mm3 in peripheral blood was observed at the time of admission. The leucocytosis increased significantly during second week in 67% of patients. The peripheral blood mononuclear cells culture done on alternate days was tested for chemotactic activity (hMDF, which was observed to be highest in second week of illness. The direct detection of hMDF in circulation by dot blot was positive in 92% of acute serum samples, with negligible (12.5% reactivity for convalescent sera. A correlation between the hMDF levels and severity of illness has also been observed.

  11. Diversity of chemotactic heterotrophic bacteria associated with arctic cyanobacteria.

    Science.gov (United States)

    Prasad, Sathish; Pratibha, Mambatta Shankaranarayanan; Manasa, Poorna; Buddhi, Sailaja; Begum, Zareena; Shivaji, Sisinthy

    2013-01-01

    The abundance and diversity of chemotactic heterotrophic bacteria associated with Arctic cyanobacteria was determined. The viable numbers ranged between 10(4) and 10(6) cell g(-1) cyanobacterial biomass. A total of 112 morphotypes, representing 22 phylotypes based on their 16S rRNA sequence similarity were isolated from the samples. All the phylotypes were Gram-negative with affiliation to the proteobacterial and bacteroidetes divisions. Among the 22 phylotypes, 14 were chemotactic to glucose. Majority of the phylotypes were psychrotolerant showing growth up to 30 °C. Representatives of Alphaproteobacteria, the genus Flavobacterium and the gammaproteobacterial Alcanivorax sp, were psychrophilic with growth at or below 18 °C. A significant percentage of phylotypes were pigmented (~68 %), rich in unsaturated membrane fatty acids and tolerated pH values and NaCl concentrations between 5.0-8.0 and 0.15-1.0 M, respectively. The percentages of phylotypes producing extracellular cold-active enzymes at 4 °C were amylase (18.18 %), lipase and urease (45.45 %), caseinase (59.09 %) and gelatinase (31.8 %). PMID:23053490

  12. Effects of bezafibrate on MCP-1 level in rabbits with atherosclerosis%苯扎贝特对兔动脉粥样硬化单核细胞趋化因子的影响

    Institute of Scientific and Technical Information of China (English)

    李彦琦; 董秋立; 刘海涛; 何敬堂; 郭水英

    2011-01-01

    目的 探讨苯扎贝特对兔动脉粥样硬化(AS)时单核细胞趋化因子( MCP-1)的影响.方法24只新西兰大白兔随机分为高脂组、苯扎贝特组和正常对照组,每组8只.对照组饲以常规颗粒饲料,高脂组饲以高胆固醇饲料(1%胆同醇+5%猪油的颗粒饲料),苯扎贝特组饲以高胆固醇饲料加苯扎贝特[5 mg/( kg·d)],共饲养4个月.HE染色检测兔胸主动脉AS程度,并用免疫组化检测AS斑块的MCP-1蛋白及RT-PCR检测MCP-1 mRNA的转录水平,同时检测血胆固醇和甘油三酯的浓度.结果与高脂组比较,苯扎贝特显著降低了甘油三酯的浓度[(0.7l±0.11) vs (1.72±0.96 )mmol/L,P< 0.05].在苯扎贝特组动脉粥样硬化的程度明显减轻,动脉内膜面积减少[(2.92±0.54) vs (4.16±0.98) mm2,P< 0.051.苯扎贝特治疗组斑块内的MCP-l蛋白表达减少[(19.8±2.2)%vs( 26.2±3.1)%,P<0.01],RT-PCR结果显示,苯扎贝特组MCP-1 mRNA的水平亦明显减少[(0.61±0.06)vs(1.06±0.06),P<0.05].结论使用苯扎贝特明显减轻了动脉粥样硬化程度,其中MCP-1基因及蛋白表达的下降具有重要的作用.%Objective To observe the influence of bezafibrate on monocyte chemoattractant protein-l(MCP-l) level in rabbits with atherosclerosis(AS). Methods Twenty-four New Zealand white rabbits were randomly assigned into 3 groups: high-lipid group, bezafibrate group, and control group, with 8 in each group. The rats in high-lipid group were given high-lipid diet, in bezafibrate group were given high-lipid diet plus bezafibrate [5 mg/(kg ? D)], and in control group were given routine diet. The animals were fed for 4 months. The ascending aorta were harvested, and the morphology was observed using HE staining. The MCP-1 protein and mRNA expression was analyzed by immunohistochemical staining and RT-PCR respectively. The concentrations of serum total cholesterol and triglyceride were also measured. Results The concentration of serum triglyceride was

  13. 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

  14. Effect and its mechanism of rosiglitazone on MCP-1 secretion of rat thoracic aorta smooth muscle cells induced by high-glucose%罗格列酮对高糖诱导大鼠胸主动脉血管平滑肌细胞分泌单核细胞趋化蛋白1的影响及其机制

    Institute of Scientific and Technical Information of China (English)

    谢赟; 王绵; 赵占胜; 梁江燕; 邓永贵; 张力辉; 姚玉霞; 丛斌; 苏胜偶

    2011-01-01

    观察不同葡萄糖浓度培养的大鼠胸主动脉平滑肌细胞分泌单核细胞趋化蛋白1(MCP-1)的变化,以及罗格列酮(RGZ)对其分泌的影响.用不同浓度的葡萄糖和RGZ单独或联合孵育大鼠胸主动脉平滑肌细胞,用ELISA方法 检测培养基中MCP-1的水平,Western Blot方法 检测各组所收集细胞胞浆中NF-κBp65和IκBα的表达. 结果高葡萄糖浓度培养(11.2,22.4mmol/L)的大鼠胸主动脉平滑肌细胞分泌的MCP-1[分别为(340.87±43.92)pg/ml和(664.87±23.07) pg/ml]明显高于对照组[(132.20±5.81)pg/ml],RGZ抑制了高葡萄糖孵育下大鼠胸主动脉平滑肌细胞MCP-1蛋白表达水平并呈浓度依赖性,RGZ拮抗剂GW9662(10 μmol/L)预处理可部分拮抗其作用.MCP-1水平的变化与细胞浆NF-κB、IκB的表达变化相伴随. 结论 高糖可以诱导大鼠胸主动脉平滑肌细胞分泌MCP-1,并呈现浓度依赖性;RGZ可抑制高糖诱导的大鼠胸主动脉平滑肌细胞分泌MCP-1水平,上述作用在一定浓度范围内呈现剂量依赖性.高糖诱导平滑肌细胞分泌MCP-1很可能是通过NF-κB通路来调控的.%Objective To observe the MCP-1 secretion of rat thoracic aorta VSMCs incubated with different concentration of glucose and effects of rosiglitazone (RGZ). Methods The rat thoracic aorta VSMCs were incubated with different concentration of glucose alone or with different concentration of glucose and rosiglitazone, the concentration of MCP-1 in the supernatant was measured with the method of enzyme linked immunoabsorbent assay(ELISA). The levels of NF-kB and IkB protein in the aliquots of the cell extract were examined by Western blot. Results The supernatant concentration of MCP-1 in high glucose groupdl. 2, 22. 4mmol/L)was significantly higher than in control group (P<0. 01). They were (340. 87±43. 92)pg/ml and (664. 87±23. 07)pg/ml respectively, and the level of control group was only (132. 20±5. 81)pg/ml. Rosiglitazone significantly inhibited

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

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

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

  16. Induction of IL-8(CXCL8) and MCP-1(CCL2) with oxidative stress and its inhibition with N-acetyl cysteine (NAC) in cell culture model using HK-2 cell.

    Science.gov (United States)

    Kumar, Avneesh; Shalmanova, Liliana; Hammad, Abdul; Christmas, Stephen E

    2016-03-01

    Renal transplantation can often be complicated due to delayed graft function, which is a direct sequel of ischaemia reperfusion injury. The adverse outcome of delayed graft function is not only short term but the long-term function of the graft is also affected. Therefore, it is important to understand the mechanisms of ischaemia reperfusion injury. Reactive oxygen species are the key mediators in ischaemia reperfusion injury causing direct cell damage which also initiate inflammation by inducing chemokines. The presence of inflammation is a marker of severe delayed graft function. However, the effect of oxidative stress on the expression of key chemokines has not been fully established yet. Therefore, the aim of this study was to measure the oxidative stress response and the secretion of chemokines in a cell culture model that mimics the effects of ischaemia reperfusion injury in immortalised human renal proximal tubular epithelial cells, HK-2. Cells were treated with varying concentrations of hydrogen peroxide and markers of oxidative stress response and chemokine release were measured. Exposure to hydrogen peroxide induced a significant increase in the activity of the antioxidant enzyme glutathione peroxidase and the levels of the chemokines Interleukin-8 (IL-8; CXCL8) and MCP-1 (CCL2). A dose related increase of chemokine secretion was also observed. The cytokine Interleukin-1β (IL-1β) at 1ng/ml significantly potentiated the expression of both IL-8 (CXCL8) and MCP-1 (CCL2) which showed synergistic response in the presence of hydrogen peroxide. Pre-incubation of the cells with the anti-oxidant N-acetyl cysteine (NAC) strongly suppressed the induction of both IL-8 and MCP-1 when stimulated with hydrogen peroxide and IL-1β. This study demonstrates the potential of anti-oxidants like N-acetyl cysteine in ameliorating the effects of ischaemia reperfusion injury thus suggesting a new therapeutic approach in renal transplantation. These findings can have potential

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

    DEFF Research Database (Denmark)

    Shaker, S.B.; Wachenfeldt, K.A. von; Larsson, S.; Mile, I.; Persdotter, S.; Dahlback, M.; Broberg, P.; Stoel, B.; Bach, K.S.; Hestad, M.; Fehniger, T.E.; Dirksen, A.

    2008-01-01

    smokers and patients with COPD. Methods: We used commercially available enzyme-linked immunosorbent assay kits to measure the plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), tissue inhibitor of...

  18. Excessive Pro-Inflammatory Serum Cytokine Concentrations in Virulent Canine Babesiosis

    DEFF Research Database (Denmark)

    Goddard, Amelia; Leisewitz, Andrew L; Kjelgaard-Hansen, Mads;

    2016-01-01

    admission, prior to any treatment. Cytokine concentrations were assessed using a canine-specific multiplex assay on an automated analyser. Serum concentrations of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-18, granulocyte-macrophage colony stimulating factor (GM-CSF) and monocyte chemotactic protein-1 (MCP-1...

  19. 有氧运动加谷氨酰胺补充对2型糖尿病大鼠骨骼肌炎症因子NF-κB、MPO及MCP-1基因表达的影响%Effect of Aerobic Exercise plus Glutamine Supplement on Expression of Muscle NF-κB,MPO and MCP-1 mRNA of Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    付德荣; 孙小华; 刘承宜; 廖八根; 李鹏博; 田祯祥

    2012-01-01

    目的:观察长期有氧运动联合谷氨酰胺(Gln)补充对2型糖尿病(T2DM)大鼠骨骼肌炎症因子核转录因子-κB(NF-κB)、单核细胞趋化蛋白-1(MCP-1)、髓过氧化物酶(MPO)基因表达及空腹血糖(FBG)、血胰岛素(ISN)及胰高血糖素样肽-1(GLP-1)的影响.方法:将雄性Sprague-Dawley大鼠60只(179.8±19.2 g)随机分为健康对照组(C组,26只)和糖尿病造模组(D组,34只).对照组普通饲料喂养,糖尿病组高脂喂养.4周后糖尿病组大鼠腹腔注射35 mg/kg链脲佐菌素诱导T2DM.成模后两组进一步随机分为:安静组(CQ,DQ)、运动组(CE,DE)、Gln组(CG,DG)、运动加Gln组(CEG,DEG).运动组大鼠进行6周游泳运动.Gln组改用含2%(w/w) L-Gln饲料喂养.腹主动脉取血测FBG、ISN及GLP-1水平,腓肠肌测NF-κB、MPO及MCP-1的mRNA的表达.结果:安静状态下T2DM大鼠(DQ)骨骼肌NF-κB、MCP-1及MPO的mRNA表达量及血FBG值显著高于对照组(CQ),血ISN和GLP-1水平明显低于对照组.6周游泳运动(DE)或Gln补充(DG)可明显降低T2DM大鼠骨骼肌NF-κB、MCP-1及MPO的mRNA表达和血FBG水平,并增加ISN及GLP-1水平.6周游泳运动联合Gln补充(DEG)时,降低T2DM大鼠骨骼肌NF-κB mRNA表达的效应显著高于单纯Gln补充组(DG),但与单纯运动组(DE)相似;对MCP-1 mRNA的抑制与单纯Gln补充组(DG)相似,但明显高于单纯运动组(DE);对MPO mRNA表达的影响与单纯运动组(DE)或单纯Gln补充组(DG)相似;降低FBG水平、增加GLP-1的作用较单纯运动组(DE)或Gln补充组(DG)明显,增加ISN的效应与单纯运动组(DE)或Gln补充组(DG)相似.结论:长期有氧运动或Gln补充明显抑制T2DM大鼠骨骼肌炎症因子NF-κB、MPO及MCP-1的基因表达,增加GLP-1及ISN的分泌量,降低FBG值.当运动联合Gln补充时,降低T2DM骨骼肌炎症因子产生、升高GLP-1及降低FBG的效应较运动或Gln单因素作用时明显,对ISN分泌的影响与单纯运动或Gln补充相似.

  20. Bacterial chemotactic oligopeptides and the intestinal mucosal barrier

    International Nuclear Information System (INIS)

    Intestinal absorption and enterohepatic circulation of N-formyl-methionyl-leucyl-125I-tyrosine, a bioactive synthetic analog of the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine has been investigated in the rat. In ileum and proximal and distal colon, dithiothreitol, which increases mucosal permeability, increased peptide absorption and biliary recovery fourfold, 70-fold, and 20-fold over control values, respectively. When dithiothreitol was combined with d-l-benzyl succinate, a potent inhibitor of intestinal carboxypeptidase, absorption and biliary recovery from ileal loops increased markedly to 40-fold over control, whereas there was no further increase in absorption from colon loops. There was a strong correlation between biliary N-formyl-methionyl-leucyl-125I-tyrosine recovery and intestinal absorption of 51Cr-ethylenediaminetetraacetate, a marker of passive mucosal permeability (r = 0.97). We conclude that in the ileum both enzymic degradation and restricted mucosal permeability contribute to the intestinal barrier to luminal bacterial formyl oligopeptides. In the colon, however, enzymic mechanisms are less active and restricted mucosal permeability is the major factor. Abnormalities of the intestinal mucosal barrier to proinflammatory bacterial peptides could play a role in inflammatory disorders of the gut

  1. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

  2. Human sperm pattern of movement during chemotactic re-orientation towards a progesterone source

    Institute of Scientific and Technical Information of China (English)

    Cecilia Soledad Blengini; Maria Eugenia Teves; Diego Rafael Unates; Hector Alejandro Guidobaldi; Laura Virginia Gatica; Laura Cecilia Giojalas

    2011-01-01

    @@ Human spermatozoa may chemotactically find out the egg by following an increasing gradient of attractant molecules.Although human spermatozoa have been observed to show several of the physiological characteristics of chemotaxis,the chemotactic pattern of movement has not been easy to describe.However,it is apparent that chemotactic cells may be identified while returning to the attractant source.This study characterizes the pattern of movement of human spermatozoa during chemotactic re-orientation towards a progesterone source,which is a physiological attractant candidate.By means of videomicroscopy and image analysis,a chemotactic pattern of movement was identified as the spermatozoon returned towards the source of a chemotactic concentration of progesterone (10 pmol l-1).First,as a continuation of its original path,the spermatozoon swims away from the progesterone source with linear movement and then turns back with a transitional movement that can be characterized by an increased velocity and decreased linearity.This sperm behaviour may help the spermatozoon to re-orient itself towards a progesterone source and may be used to identify the few cells that are undergoing chemotaxis at a given time.

  3. 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

  4. Collective Chemotactic Dynamics in the Presence of Self-Generated Fluid Flows

    CERN Document Server

    Lushi, Enkeleida; Shelley, Michael J

    2012-01-01

    In micro-swimmer suspensions locomotion necessarily generates fluid motion, and it is known that such flows can lead to collective behavior from unbiased swimming. We examine the complementary problem of how chemotaxis is affected by self-generated flows. A kinetic theory coupling run-and-tumble chemotaxis to the flows of collective swimming shows separate branches of chemotactic and hydrodynamic instabilities for isotropic suspensions, the first driving aggregation, the second producing increased orientational order in suspensions of "pushers" and maximal disorder in suspensions of "pullers". Nonlinear simulations show that hydrodynamic interactions can limit and modify chemotactically-driven aggregation dynamics. In puller suspensions the dynamics form aggregates that are mutually-repelling due to the non-trivial flows. In pusher suspensions chemotactic aggregation can lead to destabilizing flows that fragment the regions of aggregation.

  5. 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.

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

    DEFF Research Database (Denmark)

    Benfield, T L; Kharazmi, A; Larsen, C G; Lundgren, J D

    1997-01-01

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

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  8. Draft Genome Sequence of Halomonas sp. KHS3, a Polyaromatic Hydrocarbon-Chemotactic Strain

    OpenAIRE

    Gasperotti, Ana Florencia; Studdert, Claudia Alicia; Revale, Santiago; Herrera Seitz, María Karina

    2015-01-01

    The draft genome sequence of Halomonas sp. KHS3, isolated from seawater from Mar del Plata harbor, is reported. This strain is able to grow using aromatic compounds as a carbon source and shows strong chemotactic response toward these substrates. Genes involved in motility, chemotaxis, and degradation of aromatic hydrocarbons were identified.

  9. RANTES and chemotactic activity in synovial fluids from patients with rheumatoid arthritis and osteoarthritis.

    Science.gov (United States)

    Stanczyk, Joanna; Kowalski, Marek L; Grzegorczyk, Janina; Szkudlinska, Barbara; Jarzebska, Marzanna; Marciniak, Marek; Synder, Marek

    2005-12-14

    A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62 +/- 12 and 24 +/- 6 cells/HPF, resp) as compared to patients with OA (23 +/- 6; P < .05 and 6 +/- 2 cells/HPF; P < 0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145+/- 36 pg/mL), while OA SF was characterised by only trace amount of this chemokine (2 +/- 1 pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA + MoCA; R = 0.61; P < .05). Surprisingly, RANTES correlated also positively with neutrophiles number (R = 0.77; P < 0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. An enzyme immunoassay for detection of Japanese encephalitis virus-induced chemotactic cytokine

    Indian Academy of Sciences (India)

    Aditi Singh; Rajesh Kulshreshtha; Asha Mathur

    2000-03-01

    Japanese encephalitis virus (JEV) induces human peripheral blood monocytes to secrete a chemotactic cytokine [human macrophage-derived factor (hMDF)] which causes chemotaxis of neutrophils. The only known assay for hMDF cannot quantify its level in samples, so an enzyme immunoassay has been standardized for detection of hMDF and hMDF-specific antibodies in test samples. The reported enzyme linked immunosorbent assay (ELISA) was found to be sensitive (89%), specific (91%), accurate (92·2%) and reproducible and was able to detect a minimum concentration of 23 ng hMDF/ml in test samples. The chemotactic factor could be detected in JEV inoculated mouse sera and JEV infected culture fluids. Significant finding of the test was the detection of hMDF in sera of human cases of JE.

  16. Fluorine-18 labeled chemotactic peptides: A potential approach for the PET imaging of bacterial infection

    International Nuclear Information System (INIS)

    A potent chemotactic peptide, formyl-norleucyl-leucyl-phenylalanyl-norleucyl-tyrosyl-lysine was derivatized by reaction with N-succinimidyl 4-fluorobenzoate. This derivatized peptide bound to human polymorphonuclear leukocytes in vitro and exhibited biological activity in a superoxide production assay. Peptide labeling using N-succinimidyl 4-[18F]fluorobenzoate was accomplished in reasonable yields with 10-15 mCi of labeled peptide available per 100 Ci of [18F]fluoride. With the exception of the gastrointestinal tract, clearance of activity from tissues following injection of this peptide in normal mice was rapid. Although preliminary in nature, these results suggest that 18F-labeled chemotactic peptides should be investigated as potential agents for positron emission tomographic imaging of bacterial infections

  17. The interaction between different types of activated RAW 264.7 cells and macrophage inflammatory protein-1 alpha

    International Nuclear Information System (INIS)

    Two major ways of macrophage (MΦ) activation can occur in radiation-induced pulmonary injury (RPI): classical and alternative MΦ activation, which play important roles in the pathogenesis of RPI. MΦ can produce chemokine MΦ inflammatory protein-1α (MIP-1α), while MIP-1α can recruit MΦ. The difference in the chemotactic ability of MIP-1α toward distinct activated MΦ is unclear. We speculated that there has been important interaction of MIP-1α with different activated MΦ, which might contribute to the pathogenesis of RPI. Classically and alternatively activated MΦ were produced by stimulating murine MΦ cell line RAW 264.7 cells with three different stimuli (LPS, IL-4 and IL-13); Then we used recombinant MIP-1α to attract two types of activated MΦ. In addition, we measured the ability of two types of activated MΦ to produce MIP-1α at the protein or mRNA level. Chemotactic ability of recombinant MIP-1α toward IL-13-treated MΦ was the strongest, was moderate for IL-4-treated MΦ, and was weakest for LPS-stimulated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to secrete MIP-1α was significantly stronger than that of IL-4-treated or IL-13-treated MΦ (p < 0.01). The ability of LPS-stimulated MΦ to express MIP-1α mRNA also was stronger than that of IL-4- or IL-13-stimulated MΦ (p < 0.01). The chemotactic ability of MIP-1α toward alternatively activated MΦ (M2) was significantly greater than that for classically activated MΦ (M1). Meanwhile, both at the mRNA and protein level, the capacity of M1 to produce MIP-1α is better than that of M2. Thus, chemokine MIP-1α may play an important role in modulating the transition from radiation pneumonitis to pulmonary fibrosis in vivo, through the different chemotactic affinity for M1 and M2

  18. Fucose-binding Lotus tetragonolobus lectin binds to human polymorphonuclear leukocytes and induces a chemotactic response.

    Science.gov (United States)

    VanEpps, D E; Tung, K S

    1977-09-01

    Fucose-binding L. tetragonolobus lectin to the surface of human polymorphonuclear leukocytes (PMN) and induces a chemotactic response. Both surface binding and chemotaxis are inhibited by free fucose but not by fructose, mannose, or galactose. The lectin-binding sites on PMN are unrelated to the A, B, or O blood group antigen. Utilization of this lectin should be a useful tool in isolating PMN membrane components and in analyzing the mechanism of neutrophil chemotaxis. PMID:330752

  19. Neutrophil Chemotactic Activities In Bronchoalveolar Lavage Fluid From Patients with Bronchial Asthma

    OpenAIRE

    Park, Choon Sik; Cho, Seung Woo; Lee, Sei Young; Park, Tae Eung; Jeong, Seung Whan; Lee, Sang Moo; Kim, Hyeon Tae; Uh, Sootaek; Kim, Young Hoon

    1995-01-01

    Objectives To elucidate the presence of neutrophil chemotactic factor (NCF) and characterize them in the bronchial trees of symptomatic patients with bronchial asthma. Methods Bronchoalveolar lavage (BAL) fluids were concentrated by ultrafiltration. Differential counts of BAL cells was performed upto 500 cells on the cytocentrifuge-prepared slides. NCF activities in concentrated BAL fluids were measured by using microchemotactic chamber. These NCF activities were characterized by heat-stabili...

  20. A chemotactic model for interaction of antagonistic microflora colonies: front asymptotics and numerical simulations.

    OpenAIRE

    Málaga Iguiñiz, Carlos; Minzoni, Antonmaria Alessio; Plaza, Ramón Gabriel; Simeoni, Chiara

    2013-01-01

    International audience This paper studies a two-dimensional chemotactic model for two species in which one of them produces a chemo-repellent for the other. It is shown asymptotically and numerically how the chemical inhibits the invasion of a moving front for the second species and how stable steady states, which depend on the chemical concentration, can be reached. The results qualitatively explain experimental observations by Swain and Ray (Microbiol. Res. 164(2), 2009), where colonies ...

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

    OpenAIRE

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

    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 channe...

  2. Chemotactic model for interaction of antagonistic microflora colonies and numerical simulations

    CERN Document Server

    Malaga, Carlos; Plaza, Ramon G; Simeoni, Chiara

    2011-01-01

    This paper studies a two-dimensional chemotactic model for two species in which one of them produces a chemo-repellent for the other. Under these circumstances, the chemical inhibits the invasion of a moving front for the second species. It is shown asymptotically and numerically how stable steady states, which depend on the chemical concentration, can be reached. The results qualitatively explain experimental observations by Swain and Ray, where colonies of bacteria produce metabolite agents which prevent the invasion of fungi.

  3. Biodegradation of naphthalene and anthracene by chemo-tactically active rhizobacteria of populus deltoides

    OpenAIRE

    Sandeep Bisht; Piyush Pandey; Anchal Sood; Shivesh Sharma; Bisht, N. S.

    2010-01-01

    Several naphthalene and anthracene degrading bacteria were isolated from rhizosphere of Populus deltoides, which were growing in non-contaminated soil. Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans showed positive chemotactic response for naphthalene and anthracene. The mean growth rate constant (K) of isolat...

  4. Automated Chemotactic Sorting and Single-cell Cultivation of Microbes using Droplet Microfluidics

    Science.gov (United States)

    Dong, Libing; Chen, Dong-Wei; Liu, Shuang-Jiang; Du, Wenbin

    2016-04-01

    We report a microfluidic device for automated sorting and cultivation of chemotactic microbes from pure cultures or mixtures. The device consists of two parts: in the first part, a concentration gradient of the chemoeffector was built across the channel for inducing chemotaxis of motile cells; in the second part, chemotactic cells from the sample were separated, and mixed with culture media to form nanoliter droplets for encapsulation, cultivation, enumeration, and recovery of single cells. Chemotactic responses were assessed by imaging and statistical analysis of droplets based on Poisson distribution. An automated procedure was developed for rapid enumeration of droplets with cell growth, following with scale-up cultivation on agar plates. The performance of the device was evaluated by the chemotaxis assays of Escherichia coli (E. coli) RP437 and E. coli RP1616. Moreover, enrichment and isolation of non-labelled Comamonas testosteroni CNB-1 from its 1:10 mixture with E. coli RP437 was demonstrated. The enrichment factor reached 36.7 for CNB-1, based on its distinctive chemotaxis toward 4-hydroxybenzoic acid. We believe that this device can be widely used in chemotaxis studies without necessarily relying on fluorescent labelling, and isolation of functional microbial species from various environments.

  5. 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,

  6. Novel Biochemical Markers of Psychosocial Stress in Women

    OpenAIRE

    Marie Asberg; Ake Nygren; Rosario Leopardi; Gunnar Rylander; Ulla Peterson; Lukas Wilczek; Håkan Källmén; Mirjam Ekstedt; Torbjörn Akerstedt; Mats Lekander; Rolf Ekman

    2009-01-01

    BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (T...

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    Po-Chen Shih

    2010-01-01

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

  10. 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

  11. CONSTRUCTION OF EUKARYOTIC EXPRESSION VECTOR FOR HUMAN CCL21 AND CHARACTERIZATION OF ITS CHEMOTACTIC ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    HOU Li; LIU Qi; JIAO Yu-lian; ZHANG Jie; WANG Lai-cheng; MA Chun-yan; CUI Bin; ZHANG Xue; ZHAO Yue-ran

    2006-01-01

    Objective: To obtain recombinant human CCL21 with biological activity from eukaryotic expression system for further use in cancer gene therapy. Methods: A fragment of human CCL21 gene was obtained from pSK-hCCL21 plasmid digested by Xho I and BamH I, inserted into the responding sites of eukaryotic expression vector pVAX1, and then transfected into COS-7 cells by electroporation method. The expression of hCCL21 protein was detected by western blotting analysis. The in vitro chemotaxis assay was used to test the chemotactic function of the expression product to lymphocytes. Results: Human CCL21 protein was expressed by transfected COS-7 cells with recombinant plasmid containing hCCL21 gene, and was verified by western blotting. The in vitro chemotaxis assay demonstrated that human CCL21 protein had a potent chemotactic function to lymphocytes. Conclusion: Human CCL21 was successfully and transiently expressed in eukaryotic cells, which lays some foundation for the study of CCL21 gene therapy in murine tumor models.

  12. Chemotactic behavior of deep subsurface bacteria toward carbohydrates, amino acids and a chlorinated alkene

    Energy Technology Data Exchange (ETDEWEB)

    Lopez de Victoria, G. (Puerto Rico Univ., Rio Piedras (Puerto Rico). Dept. of Biology)

    1989-02-01

    The chemotactic behavior of deep terrestrial subsurface bacteria toward amino acids, carbohydrates and trichloroethylene was assayed using a modification of the capillary method and bacterial enumeration by acridine orange direct counts. Eleven isolates of bacteria isolated from six different geological formations were investigated. A bimodal response rather than an absolute positive or negative response was observed in most assays. Most of the isolates were positively chemotactic to low concentrations of substrates and were repelled by high concentrations of the same substrate. However, this was not the case for trichloroethylene (TCE) which was mostly an attractant and elicited the highest responses in all the isolates when compared with amino acids and carbohydrates. The movement rates of these isolates in aseptic subsurface sediments in the absence and presence of TCE were also determined using a laboratory model. All of the isolates showed distinct response range, peak, and threshold concentrations when exposed to the same substrates suggesting that they are possibly different species as has been inferred from DNA homology studies. 101 refs., 4 figs., 57 tabs.

  13. 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

  14. A model for cell type localization in the migrating slug of Dictyostelium discoideum based on differential chemotactic sensitivity to cAMP and differential sensitivity to suppression of chemotaxis by ammonia

    Indian Academy of Sciences (India)

    Ira N Feit; Jeffrey Pawlikowski; Caroline Zawilski

    2007-03-01

    The three basic cell types in the migrating slug of Dictyostelium discoideum show differential chemotactic response to cyclic AMP (cAMP) and differential sensitivity to suppression of the chemotaxis by ammonia. The values of these parameters indicate a progressive maturation of chemotactic properties during the transdifferentiation of slug cell types. We present a model that explains the localization of the three cell types within the slug based on these chemotactic differences and on the maturation of their chemotactic properties.

  15. 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

  16. How many consumer levels can survive in a chemotactic food chain?

    Institute of Scientific and Technical Information of China (English)

    Jing LIU; Chunhua OU

    2009-01-01

    We investigate the effect and the impact of predator-prey interactions, diffusivity and chemotaxis on the ability of survival of multiple consumer levels in a predator-prey microbial food chain. We aim at answering the question of how many consumer levels can survive from a dynamical system point of view. To solve this standing issue on food-chain length, first we construct a chemotactic food chain model. A priori bounds of the steady state populations are obtained. Then under certain sufficient conditions combining the effect of conversion efficiency, diffusivity and chemotaxis parameters, we derive the co-survival of all consumer levels, thus obtaining the food chain length of our model. Numerical simulations not only confirm our theoretical results, but also demonstrate the impact of conversion efficiency, diffusivity and chemotaxis behavior on the survival and stability of various consumer levels.

  17. 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.

  18. 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

  19. Biodegradation of naphthalene and anthracene by chemo-tactically active rhizobacteria of populus deltoides

    Directory of Open Access Journals (Sweden)

    Sandeep Bisht

    2010-12-01

    Full Text Available Several naphthalene and anthracene degrading bacteria were isolated from rhizosphere of Populus deltoides, which were growing in non-contaminated soil. Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans showed positive chemotactic response for naphthalene and anthracene. The mean growth rate constant (K of isolates were found to increase with successive increase in substrate concentration (0.5 to 1.0 mg/50ml. B. circulans SBA12 and Kurthia SBA4 degraded 87.5% and 86.6% of anthracene while, Kurthia sp. SBA4, B. circulans SBA12, and M. varians SBA8 degraded 85.3 %, 95.8 % and 86.8 % of naphthalene respectively after 6 days of incubation as determined by HPLC analysis.

  20. Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs

    International Nuclear Information System (INIS)

    Four DTPA-derivatized chemotactic peptide analogs: ForNleLFNleYK-DTPA (P1), ForMLFNH(CH2)6NH-DTPA (P2), ForNleLFK(NH2)-DTPA (P3), and ForNleLFK-DTPA (P4), were synthesized and evaluated for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 111In by transchelation and their biodistribution determined in rats at 5, 30, 60 and 120 min after injection. Localization at sites of infection was determined by scintillation camera imaging in animals with deep-thigh infection due to Escherichia coli. Images were recorded from 5 min to 2 hr after injection. All peptides maintained biologic activity (EC50 for O2-production by human PMN's: 3-150 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMN's (EC50 for binding: 7.5-50 nM); biologic activity and receptor binding were highly correlated (r = 0.99). For all the peptides, blood clearance was rapid (half-lives: 21.5, 33.1, 31.6, and 28.7 min for P1, P2, P3, and P4, respectively). Biodistributions of the individual peptides were similar with low levels of accumulation in the heart, lung, liver, spleen, and gastrointestinal tract. In the kidney, P1 had much greater accumulation than other organs. All peptides yielded high quality images of the infection sites within 1 hr of injection. This study demonstrates that 111In-labeled chemotactic peptide analogs were effective agents for the external imaging of focal sites of infection

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

    International Nuclear Information System (INIS)

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

  2. Loss-of-function mutations in Rab escort protein 1 (REP-1 affect intracellular transport in fibroblasts and monocytes of choroideremia patients.

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    Natalia V Strunnikova

    Full Text Available BACKGROUND: Choroideremia (CHM is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1, an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion in peripheral cells of CHM patients. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations. With the use of pHrodo BioParticles conjugated with E. coli, collagen I coated FluoSpheres beads and fluorescent DQ ovalbumin with BODYPY FL dye, we demonstrated for the first time that lysosomal pH was increased in monocytes of CHM patients and, as a consequence, the rates of proteolytic degradation were slowed. Microarray analysis of gene expression revealed that some genes involved in the immune response, small GTPase regulation, transcription, cell adhesion and the regulation of exocytosis were significantly up and down regulated in cells from CHM patients compared to controls. Finally, CHM fibroblasts secreted significantly lower levels of cytokine/growth factors such as macrophage chemoattractant protein-1 (MCP-1, pigment epithelial derived factor (PEDF, tumor necrosis factor (TNF alpha, fibroblast growth factor (FGF beta and interleukin (lL-8. CONCLUSIONS/SIGNIFICANCE: We demonstrated for the first time that peripheral cells of CHM patients had increased pH levels in lysosomes, reduced rates of proteolytic degradation and altered secretion of cytokines. Peripheral cells from CHM patients expose characteristics that were not previously recognized and could used as an alternative models to study the effects of different

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

    International Nuclear Information System (INIS)

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

  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. Emerging morphologies in round bacterial colonies: comparing volumetric versus chemotactic expansion.

    Science.gov (United States)

    Giverso, Chiara; Verani, Marco; Ciarletta, Pasquale

    2016-06-01

    Biological experiments performed on living bacterial colonies have demonstrated the microbial capability to develop finger-like shapes and highly irregular contours, even starting from an homogeneous inoculum. In this work, we study from the continuum mechanics viewpoint the emergence of such branched morphologies in an initially circular colony expanding on the top of a Petri dish coated with agar. The bacterial colony expansion, based on either a source term, representing volumetric mitotic processes, or a nonconvective mass flux, describing chemotactic expansion, is modeled at the continuum scale. We demonstrate that the front of the colony is always linearly unstable, having similar dispersion curves to the ones characterizing branching instabilities. We also perform finite element simulations, which not only prove the emergence of branching, but also highlight dramatic differences between the two mechanisms of colony expansion in the nonlinear regime. Furthermore, the proposed combination of analytical and numerical analysis allowed studying the influence of different model parameters on the selection of specific patterns. A very good agreement has been found between the resulting simulations and the typical structures observed in biological assays. Finally, this work provides a new interpretation of the emergence of branched patterns in living aggregates, depicted as the results of a complex interplay among chemical, mechanical and size effects. PMID:26296713

  6. Effect of selective phosphodiesterase inhibitors on the rat eosinophil chemotactic response in vitro

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    Alves Alessandra C

    1997-01-01

    Full Text Available In the present study, we have performed a comparative analysis of the effect of selective inhibitors of phosphodiesterase (PDE type III, IV and V on eosinophil chemotaxis triggered by platelet activating factor (PAF and leukotriene B4 (LTB4 in vitro. The effect of the analogues N6-2'-O-dibutyryladenosine 3':5' cyclic monophosphate (Bt2 cyclic AMP and N2-2'-O- dibutyrylguanosine 3':5' cyclic monophosphate (Bt2 cyclic GMP has also been determined. The eosinophils were obtained from the peritoneal cavity of naive Wistar rats and purified in discontinuous Percoll gradients to 85-95% purity. We observed that pre-incubation of eosinophils with the PDE type IV inhibitor rolipram suppressed the chemotactic response triggered by PAF and LTB4, in association with an increase in the intracellular levels of cyclic AMP. In contrast, neither zaprinast (type V inhibitor nor type III inhibitors milrinone and SK&F 94836 affected the eosinophil migration. Only at the highest concentration tested did the analogue Bt2 cyclic AMP suppress the eosinophil chemotaxis, under conditions where Bt2 cyclic GMP was ineffective. We have concluded that inhibition of PDE IV, but not PDE III or V, was able to block the eosinophil chemotaxis in vitro, suggesting that the suppressive activity of selective PDE IV inhibitors on tissue eosinophil accumulation may, at least, be partially dependent on their ability to directly inhibit the eosinophil migration.

  7. 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.

  8. 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

  9. Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques

    International Nuclear Information System (INIS)

    Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor γ (PPARγ). Introduction of an endogenous PPARγ ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARγ. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARγ, which may be further related to the atherogenesis

  10. 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.

  11. Influence of corticosteroids on chemotactic response and collagen metabolism of human skin fibroblasts.

    Science.gov (United States)

    Hein, R; Mauch, C; Hatamochi, A; Krieg, T

    1988-07-15

    Following chronic administration of corticosteroids in vivo, a number of complications occur, which mainly involve the metabolism of connective tissue cells. Therefore, several attempts have been made to develop corticosteroids, which show less pronounced side effects. Fibroblasts were kept in monolayer cultures and were exposed to corticosteroids demonstrating similar anti-inflammatory activity (prednicarbate, desoximetasone). Chemotaxis of fibroblasts was studied over 4 hr, protein and collagen synthesis were estimated using proteinchemical methods and also by dot blot hybridization. Corticosteroids used in a high dosage (10 microM) affected all biosynthetic capacities of the investigated fibroblasts. Protein synthesis and production of collagen types I and III were reduced and a similar decrease of mRNA levels for collagen type I could be found indicating an influence on the pretranslational control. In the same concentrations desoximetasone was much more active than prednicarbate. Fibroblast migration was dosage dependently inhibited from 10(-9) M to 10(-5) M for desoximetasone, while incubation with prednicarbate did not cause a reduction of the chemotactic response at concentrations lower than 10(-7) M. These data suggest that modifications of corticosteroids might result in a dissociation of some of their biological activities and can specifically influence their effects on biosynthetic capacities of fibroblasts. PMID:3395353

  12. 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

  13. A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells

    Science.gov (United States)

    Wong, Elisabeth; Hamza, Bashar; Bae, Albert; Martel, Joseph; Kataria, Rama; Keizer-Gunnink, Ineke; Kortholt, Arjan; Van Haastert, Peter J. M.; Charras, Guillaume; Janetopoulos, Christopher; Irimia, Daniel

    2016-01-01

    Chemotaxis is the ability to migrate towards the source of chemical gradients. It underlies the ability of neutrophils and other immune cells to hone in on their targets and defend against invading pathogens. Given the importance of neutrophil migration to health and disease, it is crucial to understand the basic mechanisms controlling chemotaxis so that strategies can be developed to modulate cell migration in clinical settings. Because of the complexity of human genetics, Dictyostelium and HL60 cells have long served as models system for studying chemotaxis. Since many of our current insights into chemotaxis have been gained from these two model systems, we decided to compare them side by side in a set of winner-take-all races, the Dicty World Races. These worldwide competitions challenge researchers to genetically engineer and pharmacologically enhance the model systems to compete in microfluidic racecourses. These races bring together technological innovations in genetic engineering and precision measurement of cell motility. Fourteen teams participated in the inaugural Dicty World Race 2014 and contributed cell lines, which they tuned for enhanced speed and chemotactic accuracy. The race enabled large-scale analyses of chemotaxis in complex environments and revealed an intriguing balance of speed and accuracy of the model cell lines. The successes of the first race validated the concept of using fun-spirited competition to gain insights into the complex mechanisms controlling chemotaxis, while the challenges of the first race will guide further technological development and planning of future events. PMID:27332963

  14. [Macrophages promote the migration of neural stem cells into mouse spinal cord injury site].

    Science.gov (United States)

    Cheng, Zhijian; Zhu, Wen; Li, Haopeng; He, Xijing

    2016-09-01

    Objective To explore the role of macrophages in the migration of neural stem cells (NSCs) in vivo and in vitro . Methods NSCs with green fluorescent protein (GFP) were isolated from GFP transgenic mice and the immunofluorescence cytochemical staining of nestin was used to identify NSCs. After spinal cord injury was induced, the tissue level of macrophage chemotactic protein-1 (MCP-1) mRNA was detected using quantitative real time PCR. The migration of GFP-NSCs was investigated 1 week after GFP-NSCs were injected into both sides of the damaged area. The effect of macrophage on the migration of NSCs in vitro was tested by Transwell(TM) system and the content of MCP-1 was detected by ELISA. Results NSCs highly expressed nestin. Compared with the control group, the level of MCP-1 mRNA significantly increased in the spinal cord injury group. The NSCs which were injected into the spinal cord migrated into the center of the injured site where F4/80 was highly expressed. Macrophages significantly increased the number of migrating NSCs in vitro and the secretion of MCP-1. Conclusion Macrophages induce NSC migrating into the spinal cord injury site possibly through promoting the secretion of MCP-1. PMID:27609570

  15. 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.

  16. Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis

    International Nuclear Information System (INIS)

    The association of hepatobiliary disorders with colonic inflammation is well recognized. Although the pathophysiology is obscure, increased permeation of toxic bacterial products across the inflamed gut to the portal circulation might be one mechanism. Potentially toxic metabolites include N-formylated chemotactic peptides that are produced by several species of intestinal bacteria and can be detected in colonic fluid in vivo. To investigate the metabolic fate of one of these low molecular weight proinflammatory peptides, N-formyl L-methionine L-leucine 125I-L-tyrosine was introduced into colon loops of healthy rats (n = 10) and rats with experimental colitis (n = 15) induced by rectal instillation of 15% (vol/vol) acetic acid. Gut, liver, and blood radioactivity were monitored by external gamma-counting and radioactivity in bile was measured by biliary catheter drainage into a well counter. Bile was processed by high-performance liquid chromatography to determine the amount of intact, bioactive peptide excreted over 3 h. After colonic instillation of 1 nmol of peptide, the mean (+/- SEM) biliary excretion of intact peptide was 6.4 +/- 2.0 pmol in normal rats and 49.0 +/- 20 pmol in rats with colitis (p less than 0.01). An enterohepatic circulation of synthetic N-formyl L-methionine L-leucine L-tyrosine has been demonstrated in the rat. Experimental colitis was associated with an eightfold increase in biliary excretion of this proinflammatory bacterial peptide. Proinflammatory bacterial peptides synthesized by colonic bacteria could be important in the pathophysiology of colon inflammation and its frequently associated hepatobiliary complications

  17. Chemotactic signal transduction and phosphate metabolism as adaptive strategies during citrus canker induction by Xanthomonas citri.

    Science.gov (United States)

    Moreira, Leandro Marcio; Facincani, Agda Paula; Ferreira, Cristiano Barbalho; Ferreira, Rafael Marine; Ferro, Maria Inês Tiraboshi; Gozzo, Fabio Cesar; de Oliveira, Julio Cezar Franco; Ferro, Jesus Aparecido; Soares, Márcia Regina

    2015-03-01

    The genome of Xanthomonas citri subsp. Citri strain 306 pathotype A (Xac) was completely sequenced more than 10 years; to date, few studies involving functional genomics Xac and its host compatible have been developed, specially related to adaptive events that allow the survival of Xac within the plant. Proteomic analysis of Xac showed that the processes of chemotactic signal transduction and phosphate metabolism are key adaptive strategies during the interaction of a pathogenic bacterium with its plant host. The results also indicate the importance of a group of proteins that may not be directly related to the classical virulence factors, but that are likely fundamental to the success of the initial stages of the infection, such as methyl-accepting chemotaxis protein (Mcp) and phosphate specific transport (Pst). Furthermore, the analysis of the mutant of the gene pstB which codifies to an ABC phosphate transporter subunit revealed a complete absence of citrus canker symptoms when inoculated in compatible hosts. We also conducted an in silico analysis which established the possible network of genes regulated by two-component systems PhoPQ and PhoBR (related to phosphate metabolism), and possible transcriptional factor binding site (TFBS) motifs of regulatory proteins PhoB and PhoP, detaching high degree of conservation of PhoB TFBS in 84 genes of Xac genome. This is the first time that chemotaxis signal transduction and phosphate metabolism were therefore indicated to be fundamental to the process of colonization of plant tissue during the induction of disease associated with Xanthomonas genus bacteria. PMID:25403594

  18. Functional characterization of ferret CCL20 and CCR6 and identification of chemotactic inhibitors.

    Science.gov (United States)

    Qin, Shulin; Klamar, Cynthia R; Fallert Junecko, Beth A; Craigo, Jodi; Fuller, Deborah H; Reinhart, Todd A

    2013-03-01

    CCL20 is currently the only known chemokine ligand for the receptor CCR6, and is a mucosal chemokine involved in normal and pathological immune responses. Although nucleotide sequence data are available for ccl20 and ccr6 sequences from multiple species, the ferret ccl20 and ccr6 sequences have not been determined. To increase our understanding of immune function in ferret models of infection and vaccination, we have used RT-PCR to obtain the ferret ccl20 and ccr6 cDNA sequences and functionally characterize the encoded proteins. The open reading frames of both genes were highly conserved across species and mostly closely related to canine sequences. For functional analyses, single cell clones expressing ferret CCR6 were generated, a ferret CCL20/mouse IgG(2a) fusion protein (fCCL20-mIgG(2a)) was produced, and fCCL20 was chemically synthesized. Cell clones expressing ferret CCR6 responded chemotactically to fCCL20-mIgG2a fusion protein and synthetic ferret CCL20. Chemotaxis inhibition studies identified the polyphenol epigallocatechin-3-gallate and the murine γ-herpesvirus 68 M3 protein as inhibitors of fCCL20. Surface plasmon resonance studies revealed that EGCG bound directly to fCCL20. These results provide molecular characterization of previously unreported ferret immune gene sequences and for the first time identify a broad-spectrum small molecule inhibitor of CCL20 and reveal CCL20 as a target for the herpesviral M3 protein. PMID:23360828

  19. Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure.

    Science.gov (United States)

    Tolosa, Ezequiel J; Fernández-Zapico, Martín E; Battiato, Natalia L; Rovasio, Roberto A

    2016-01-01

    Our aim was to understand the involvement of Sonic hedgehog (Shh) morphogen in the oriented distribution of neural crest cells (NCCs) toward the optic vesicle and to look for potential disorders of this guiding mechanism after ethanol exposure. In vitro directional analysis showed the chemotactic response of NCCs up Shh gradients and to notochord co-cultures (Shh source) or to their conditioned medium, a response inhibited by anti-Shh antibody, receptor inhibitor cyclopamine and anti-Smo morpholino (MO). Expression of the Ptch-Smo receptor complex on in vitro NCCs was also shown. In whole embryos, the expression of Shh mRNA and protein was seen in the ocular region, and of Ptch, Smo and Gli/Sufu system on cephalic NCCs. Anti-Smo MO or Ptch-mutated plasmid (Ptch1(Δloop2)) impaired cephalic NCC migration/distribution, with fewer cells invading the optic region and with higher cell density at the homolateral mesencephalic level. Beads embedded with cyclopamine (Smo-blocking) or Shh (ectopic signal) supported the role of Shh as an in vivo guide molecule for cephalic NCCs. Ethanol exposure perturbed in vitro and in vivo NCC migration. Early stage embryos treated with ethanol, in a model reproducing Fetal Alcohol Syndrome, showed later disruptions of craniofacial development associated with abnormal in situ expression of Shh morphogen. The results show the Shh/Ptch/Smo-dependent migration of NCCs toward the optic vesicle, with the support of specific inactivation with genetic and pharmacological tools. They also help to understand mechanisms of accurate distribution of embryonic cells and of their perturbation by a commonly consumed teratogen, and demonstrate, in addition to its other known developmental functions, a new biological activity of cellular guidance for Shh. PMID:26979762

  20. Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

    Directory of Open Access Journals (Sweden)

    Cheng-Yuk Lee

    Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

  1. Modulation of signalling in neutrophils activated by a chemotactic peptide: calcium regulates diacyl glycerol metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Korchak, H.M.; Vosshall, L.B.; Lundquist, K.F.

    1987-05-01

    Neutrophils activated by ligands such as the chemotactic peptide f-Met-Leu-Phe (FMLP) generate superoxide anion (O/sub 2//sup -/) and release specific and azurophil granule contents. The signalling for this response is thought to involve both elevated cytosolic Ca and protein kinase C activity. Receptor-occupation triggers a phospholipase C to cleave phosphatidyl inositol 4,5 bisphosphate (PIP/sub 2/) yielding inositol 1,4,5 trisphosphate, (IP/sub 3/), a trigger for intracellular Ca release, and diacyl glycerol (DG), which together with Ca activates protein kinase C. The DG can be metabolized to phosphatidic acid (PA). FMLP triggered a rapid increase in cytosolic Ca (fura-2). Loading cells with MAPTAM, and intracellular Ca buffer, suppressed this Ca transient in FMLP activated cells and inhibited O/sub 2//sup -/ generation to 12.5% of control, beta-glucuronidase release to 40.3% of control and lysozyme release to 55.1% of control. FMLP triggered a prompt decrease in PIP/sub 2/ in cells pre-labelled with /sup 32/P or /sup 3/H-inositol and an increase in PA and release of /sup 3/H-IP/sub 3/. A rapid increase in /sup 14/C-DG levels was also observed in /sup 14/C-glycerol pre-loaded cells activated by FMLP. Suppression of the Ca transient by buffering with MAPTAM inhibited elevation of /sup 14/C-DG. Breakdown of PIP/sub 2/ was not inhibited and elevation of /sup 32/P-PA was enhanced in MAPTAM loaded cells. Conversely, 200nM ionomycin which elevated cytosolic Ca to an equivalent level to 10/sup -7/M FMLP, triggered a rise in /sup 14/C-DG but not in PA.

  2. 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.

  3. Amplification of the spleen macrophage population in malaria: possible role of a factor chemotactic for blood mononuclear cells

    International Nuclear Information System (INIS)

    The mechanism of amplification of the splenic macrophages' population was investigated using mice infected with malaria as a model of an obligate intravascular infection. It was observed that these macrophages derived from blood monocytes rather than by local proliferation in the spleen. A factor, chemotactic for blood mononuclear cells, was present in spleen cells shortly after infection and preceded detectable increases in spleen macrophage number by 48 hours. This factor, in concert with spleen derived macrophage migration inhibition factor, may be important in the amplification of splenic macrophage population in intravascular infections

  4. Quantitative modeling of Escherichia coli chemotactic motion in environments varying in space and time.

    Directory of Open Access Journals (Sweden)

    Lili Jiang

    2010-04-01

    Full Text Available Escherichia coli chemotactic motion in spatiotemporally varying environments is studied by using a computational model based on a coarse-grained description of the intracellular signaling pathway dynamics. We find that the cell's chemotaxis drift velocity v(d is a constant in an exponential attractant concentration gradient [L] proportional, variantexp(Gx. v(d depends linearly on the exponential gradient G before it saturates when G is larger than a critical value G(C. We find that G(C is determined by the intracellular adaptation rate k(R with a simple scaling law: G(C infinity k(1/2(R. The linear dependence of v(d on G = d(ln[L]/dx directly demonstrates E. coli's ability in sensing the derivative of the logarithmic attractant concentration. The existence of the limiting gradient G(C and its scaling with k(R are explained by the underlying intracellular adaptation dynamics and the flagellar motor response characteristics. For individual cells, we find that the overall average run length in an exponential gradient is longer than that in a homogeneous environment, which is caused by the constant kinase activity shift (decrease. The forward runs (up the gradient are longer than the backward runs, as expected; and depending on the exact gradient, the (shorter backward runs can be comparable to runs in a spatially homogeneous environment, consistent with previous experiments. In (spatial ligand gradients that also vary in time, the chemotaxis motion is damped as the frequency omega of the time-varying spatial gradient becomes faster than a critical value omega(c, which is controlled by the cell's chemotaxis adaptation rate k(R. Finally, our model, with no adjustable parameters, agrees quantitatively with the classical capillary assay experiments where the attractant concentration changes both in space and time. Our model can thus be used to study E. coli chemotaxis behavior in arbitrary spatiotemporally varying environments. Further experiments are

  5. 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

  6. In vitro inhibitory effects of Moringa oleifera leaf extract and its major components on chemiluminescence and chemotactic activity of phagocytes.

    Science.gov (United States)

    Vongsak, Boonyadist; Gritsanapan, Wandee; Wongkrajang, Yuvadee; Jantan, Ibrahim

    2013-11-01

    The ethanol extract of Moringa oleifera Lam. leaves and its major constituents, crypto-chlorogenic acid, quercetin 3-O-glucoside and kaempferol 3-O-glucoside, were investigated on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using a luminol-based chemiluminescence assay. The chemotactic migration of PMNs was also investigated using the Boyden chamber technique. The ethanol extract demonstrated inhibitory activities on the oxidative burst and the chemotactic migration of PMNs. Quercetin 3-O-glucoside, crypto-chlorogenic acid, and kaempferol 3-O-glucoside, isolated from the extract, expressed relatively strong inhibitory activity on the oxidative burst of PMNs with IC50 values of 4.1, 6.7 and 7.0 microM, respectively, comparable with that of aspirin. They also demonstrated strong inhibition of chemotatic migration of PMNs with IC50 values of 9.5, 15.9 and 18.2 microM, respectively. The results suggest that M. oleifera leaves could modulate the immune response of human phagocytes, linking to its ethnopharmacological use as an anti-inflammatory agent. The immunomodulating activity of the plant was mainly due to its major components. PMID:24427941

  7. 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.

  8. Immunohistochemical localization of dentin matrix protein 1 in human dentin

    OpenAIRE

    G Orsini; Ruggeri, A.; Mazzoni, A.; Nato, F; Falconi, M; Putignano, A; Di Lenarda, R.; A Nanci; Breschi, L.

    2009-01-01

    Dentin matrix protein 1 (DMP1) is a non-collagenous matrix protein with a recognized role in the formation of mineralized tissues such as dentin. The aim of this study was to analyze the distribution of DMP1 in human dentin by means of immunofluorescence and high-resolution immunogold labeling. Fully developed, sound human dentin specimens were submitted to fluorescence labeling and post-embedding immunolabeling techniques with a rabbit polyclonal antihuman DMP1 antibody followed by correspon...

  9. Chronic Alcohol-Induced microRNA-155 Contributes to Neuroinflammation in a TLR4-Dependent Manner in Mice

    OpenAIRE

    Lippai, Dora; Bala, Shashi; Csak, Timea; Evelyn A. Kurt-Jones; Szabo, Gyongyi

    2013-01-01

    Introduction Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-α (TNFα), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1β). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-κB (NF-κB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene e...

  10. Plasma Levels of Monocyte Chemotactic Protein 3 and Beta-Nerve Growth Factor Increase with Amnestic Mild Cognitive Impairment

    Institute of Scientific and Technical Information of China (English)

    Kang Soo Lee; Ji Hyung Chung; Kyung Hye Lee; Min-Jeong Shin; Byoung Hoon Oh; Soo Hyung Lee; Chang Hyung Hong

    2009-01-01

    A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (β-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and β-NGF may be useful in differentiating subtypes of MCI. Cellular & Molecular Immunology.

  11. Multiscale dynamics of biological cells with chemotactic interactions: from a discrete stochastic model to a continuous description

    CERN Document Server

    Alber, M; Glimm, T; Lushnikov, P M; Alber, Mark; Chen, Nan; Glimm, Tilmann; Lushnikov, Pavel M.

    2006-01-01

    The Cellular Potts Model (CPM) has been used for simulating various biological phenomena such as differential adhesion, fruiting body formation of the slime mold Dictyostelium discoideum, angiogenesis, cancer invasion, chondrogenesis in embryonic vertebrate limbs, and many others. In this paper, we derive continuous limit of discrete one dimensional CPM with the chemotactic interactions between cells in the form of a Fokker-Planck equation for the evolution of the cell probability density function. This equation is then reduced to the classical macroscopic Keller-Segel model. In particular, all coefficients of the Keller-Segel model are obtained from parameters of the CPM. Theoretical results are verified numerically by comparing Monte Carlo simulations for the CPM with numerics for the Keller-Segel model.

  12. Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico.

    Science.gov (United States)

    Larsen, Christopher P; Beggs, Marjorie L; Wilson, Jon D; Lathrop, Sarah L

    2016-06-01

    Leukocyte chemotactic factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition. LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanic decedents. It was consistently deposited in the liver, spleen, adrenals, and lungs but did not involve the myocardium or brain. LECT2 amyloidosis is likely not rare among Hispanics in the Southwest United States and could represent an important but under-recognized etiology of chronic kidney disease in this population. PMID:26912093

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

    Directory of Open Access Journals (Sweden)

    Farman Ullah Dawar

    2016-08-01

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

  14. Migration of Chemotactic Bacteria Transverse to Flow in Response to a Benzoate Source Plume Created in a Saturated Sand-Packed Microcosm

    Science.gov (United States)

    Ford, R.; Boser, B.

    2012-12-01

    Bioremediation processes depend on contact between microbial populations and the groundwater contaminants that they biodegrade. Chemotaxis, the ability of bacteria to sense a chemical gradient and swim preferentially toward locations of higher concentration, can enhance the transport of bacteria toward contaminant sources that may not be readily accessible by advection and dispersion alone. A two-dimensional rectangular-shaped microcosm packed with quartz sand was used to quantify the effect of chemotaxis on the migration of bacteria within a saturated model aquifer system. Artificial groundwater was pumped through the microcosm at a rate of approximately 1 m/day. A plume of sodium benzoate was created by continuous injection into an upper port of the microcosm to generate a chemical gradient in the vertical direction transverse to flow. Chemotactic bacteria, Pseudomonas putida F1, or the nonchemotactic mutant, P. putida F1 CheA, were injected with a conservative tracer in a port several centimeters below the benzoate position. As the injectates traversed the one-meter length of the microcosm, samples were collected from a dozen effluent ports to determine vertical concentration distributions for the bacteria, benzoate and tracer. A moment analysis was implemented to estimate the center of mass, variance, and skewness of the concentration profiles. The transverse dispersion coefficient and the transverse dispersivity for chemotactic and nonchemotactic bacteria were also evaluated. Experiments performed with a continuous injection of bacteria showed that the center of mass for chemotactic bacteria was closer to the benzoate source on average than the nonchemotactic control (relative to the conservative tracer). These results demonstrated that chemotaxis can increase bacterial transport toward contaminants, potentially enhancing the effectiveness of in situ bioremediation. Experiments with 2 cm and 3 cm spacing between bacteria and benzoate injection locations were

  15. Nf1+/- monocytes/macrophages induce neointima formation via CCR2 activation.

    Science.gov (United States)

    Bessler, Waylan K; Kim, Grace; Hudson, Farlyn Z; Mund, Julie A; Mali, Raghuveer; Menon, Keshav; Kapur, Reuben; Clapp, D Wade; Ingram, David A; Stansfield, Brian K

    2016-03-15

    Persons with neurofibromatosis type 1 (NF1) have a predisposition for premature and severe arterial stenosis. Mutations in the NF1 gene result in decreased expression of neurofibromin, a negative regulator of p21(Ras), and increases Ras signaling. Heterozygous Nf1 (Nf1(+/-)) mice develop a marked arterial stenosis characterized by proliferating smooth muscle cells (SMCs) and a predominance of infiltrating macrophages, which closely resembles arterial lesions from NF1 patients. Interestingly, lineage-restricted inactivation of a single Nf1 allele in monocytes/macrophages is sufficient to recapitulate the phenotype observed in Nf1(+/-) mice and to mobilize proinflammatory CCR2+ monocytes into the peripheral blood. Therefore, we hypothesized that CCR2 receptor activation by its primary ligand monocyte chemotactic protein-1 (MCP-1) is critical for monocyte infiltration into the arterial wall and neointima formation in Nf1(+/-) mice. MCP-1 induces a dose-responsive increase in Nf1(+/-) macrophage migration and proliferation that corresponds with activation of multiple Ras kinases. In addition, Nf1(+/-) SMCs, which express CCR2, demonstrate an enhanced proliferative response to MCP-1 when compared with WT SMCs. To interrogate the role of CCR2 activation on Nf1(+/-) neointima formation, we induced neointima formation by carotid artery ligation in Nf1(+/-) and WT mice with genetic deletion of either MCP1 or CCR2. Loss of MCP-1 or CCR2 expression effectively inhibited Nf1(+/-) neointima formation and reduced macrophage content in the arterial wall. Finally, administration of a CCR2 antagonist significantly reduced Nf1(+/-) neointima formation. These studies identify MCP-1 as a potent chemokine for Nf1(+/-) monocytes/macrophages and CCR2 as a viable therapeutic target for NF1 arterial stenosis. PMID:26740548

  16. The release of eosinophil chemotactic activity and eosinophil chemokinesis inhibitory activity by mononuclear cells from atopic asthmatic and non-atopic subjects

    Directory of Open Access Journals (Sweden)

    J. Grzegorczyk

    2000-01-01

    Full Text Available The goal of our study was to assess the chemotactic activity for eosinophils (ECA and neutrophils (NCA and histamine releasing activity (HRA in crude supernatants of mononuclear cells in monosensitized atopic asthmatics and healthy controls. Chemotactic activity for ECA and neutrophils was measured in supernatants of cultured mononuclear cells with modified Boyden’s chamber and HRA was assessed on healthy donor basophils. With respect to ECA generation two distinct subgroups of subjects were distinguished: releasers [ECA (+] and non-releasers [ECA (–]. In atopic and non-atopic ECA (+ the mean ECA index was 3.78 ± 0.49 and 2.47 ± 0.27 respectively (P > 0.05. Supernatants from the remaining subjects (seven of 22 atopic and five of 11 non-atopic did not express ECA, but revealed significant inhibitory activity for chemokinesis of eosinophils (mean chemotactic index 0.25 ± 0.16 and 0.48 ± 0.22 for atopic and non-atopic non-releasers respectively. Stimulation with antigen of MNC from atopic and with PHA from non-atopic ECA (– restored cells ability to release ECA. Sephadex gel chromatography revealed that supernatants of MNC contained chemotactic and chemokinesis inhibitory activity in different fractions. The spontaneous productions of NCA and HRA by mononuclear cells was sim ilar in ECA releasers and non-releasers, although the HRA was higher following stimulation with PHA in the non-atopic ECA (+ subgroup. Our study demonstrated, for the first time, that MNC are capable of generating not only chemotactic activity but also chemokinesis inhibitory activity for eosinophils.

  17. Structural studies of human glioma pathogenesis-related protein 1

    International Nuclear Information System (INIS)

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn2+ complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn2+ similarly to snake-venom CRISPs, which are involved in Zn2+-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1

  18. Structural studies of human glioma pathogenesis-related protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  19. Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha.

    OpenAIRE

    Takashiba, S; Takigawa, M; Takahashi, K; Myokai, F; Nishimura, F.; Chihara, T.; Kurihara, H.; Nomura, Y.; Murayama, Y.

    1992-01-01

    Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recom...

  20. Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants.

    Science.gov (United States)

    Jantan, Ibrahim; Harun, Nurul Hikmah; Septama, Abdi Wira; Murad, Shahnaz; Mesaik, M A

    2011-04-01

    The methanol extracts of 20 selected medicinal plants were investigated for their effects on the respiratory burst of human whole blood, isolated human polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the extracts on chemotactic migration of PMNs using the Boyden chamber technique. The extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C. xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to 0.7 μg/ml. For macrophage cells, the extracts which showed strong suppressive activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9 to 1.5 μg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.) Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic migration of cells, with IC(50) values comparable to that of ibuprofen (1.5 μg/ml). The results suggest that some of these plants were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents. PMID:21184195

  1. Characterization of the formyl peptide chemotactic receptor appearing at the phagocytic cell surface after exposure to phorbol myristate acetate

    International Nuclear Information System (INIS)

    The biochemistry and subcellular source of new formyl peptide chemotactic receptor appearing at the human neutrophil and differentiated HL-60 (d-HL-60) cell surface after stimulation with phorbol myristate acetate (PMA) were examined. Formyl peptide receptor was analyzed by affinity labeling with formyl-norleu-leu-phe-norleu- [125I]iodotyr-lys and ethylene glycol bis(succinimidyl succinate) followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and densitometric analysis of autoradiographs. PMA, a specific granule secretagogue, increases affinity labeling of formyl peptide receptors on the neutrophil surface by 100%, and on d-HL-60, which lack specific granule markers, by 20%. Papain treatment markedly reduces surface labeling of formyl peptide receptor in both neutrophils and d-HL-60, and results in the appearance of a lower m.w. membrane-bound receptor fragment. PMA stimulation of papain-treated cells increases uncleaved surface receptor on neutrophils by 400%, and on D-HL-60 by only 45%. This newly appearing receptor is the same apparent m.w. (55,000 to 75,000 for neutrophils; 62,000 to 80,000 for d-HL-60) and yields the same papain cleavage product as receptor on the surface of unstimulated cells. These observations suggest that specific granule membranes contain large amounts of formyl peptide receptor, which is biochemically identical to that found on the cell surface and can be mobilized to the cell surface with appropriate stimulation

  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. MAVS protein is attenuated by rotavirus nonstructural protein 1.

    Directory of Open Access Journals (Sweden)

    Satabdi Nandi

    Full Text Available Rotavirus is the single, most important agent of infantile gastroenteritis in many animal species, including humans. In developing countries, rotavirus infection attributes approximately 500,000 deaths annually. Like other viruses it establishes an intimate and complex interaction with the host cell to counteract the antiviral responses elicited by the cell. Among various pattern recognition receptors (PAMPs of the host, the cytosolic RNA helicases interact with viral RNA to activate the Mitochondrial Antiviral Signaling protein (MAVS, which regulates cellular interferon response. With an aim to identify the role of different PAMPs in rotavirus infected cell, MAVS was found to degrade in a time dependent and strain independent manner. Rotavirus non-structural protein 1 (NSP1 which is a known IFN antagonist, interacted with MAVS and degraded it in a strain independent manner, resulting in a complete loss of RNA sensing machinery in the infected cell. To best of our knowledge, this is the first report on NSP1 functionality where a signaling protein is targeted unanimously in all strains. In addition NSP1 inhibited the formation of detergent resistant MAVS aggregates, thereby averting the antiviral signaling cascade. The present study highlights the multifunctional role of rotavirus NSP1 and reinforces the fact that the virus orchestrates the cellular antiviral response to its own benefit by various back up strategies.

  4. Heterochromatin protein 1 secures survival and transmission of malaria parasites.

    Science.gov (United States)

    Brancucci, Nicolas M B; Bertschi, Nicole L; Zhu, Lei; Niederwieser, Igor; Chin, Wai Hoe; Wampfler, Rahel; Freymond, Céline; Rottmann, Matthias; Felger, Ingrid; Bozdech, Zbynek; Voss, Till S

    2014-08-13

    Clonally variant expression of surface antigens allows the malaria parasite Plasmodium falciparum to evade immune recognition during blood stage infection and secure malaria transmission. We demonstrate that heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, controls expression of numerous P. falciparum virulence genes as well as differentiation into the sexual forms that transmit to mosquitoes. Conditional depletion of P. falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites and disrupts mutually exclusive expression and antigenic variation of the major virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a transcription factor required for gametocyte conversion, controls the switch from asexual proliferation to sexual differentiation, providing insight into the epigenetic mechanisms underlying gametocyte commitment. These findings show that PfHP1 is centrally involved in clonally variant gene expression and sexual differentiation in P. falciparum and have major implications for developing antidisease and transmission-blocking interventions against malaria. PMID:25121746

  5. Cadmium-induced aggregation of iron regulatory protein-1

    International Nuclear Information System (INIS)

    Iron regulatory protein-1 (IRP-1) is central to regulation of iron homeostasis, and has been shown to be sensitive to Cd2+ in vitro. Although Cd2+ induces disulfide-bond formation in many proteins, the critical cysteine residues for iron binding in IRP-1 were shown not to be involved in Cd-induced IRP-1 aggregation in vitro. Here we show that Cd2+ causes polymerization and aggregation of IRP-1 in vitro and in vivo, and decreases in a dose-dependent manner both its RNA-binding and aconitase enzymatic activities, as well as its cytosolic expression. We have used two-dimensional electrophoresis to demonstrate thiol-dependent self-association of purified recombinant IRP-1 treated with Cd2+, as well as self-association in Cd2+-exposed mesangial cells. Circular dichroism spectra confirm significant conformational changes in the purified protein upon Cd2+ exposure. Following Cd2+ treatment, there is increased translocation of inactive IRP-1 to the actin cytoskeletal fraction, and this translocation is diminished by both antioxidant (BHA) treatment and inhibition of CaMK-II. These changes differ from those elicited by manipulation of iron levels. Cadmium-induced translocation of proteins to cellular compartments, and particularly to the cytoskeleton, is becoming a recognized event in Cd2+ toxicity. Polymer-dependent translocation of IRP-1 in Cd2+-exposed cells may underlie effects of Cd2+ on iron homeostasis

  6. Participation of MCP-induced protein 1 in lipopolysaccharide preconditioning-induced ischemic stroke tolerance by regulating the expression of proinflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Liang Jian

    2011-12-01

    Full Text Available Abstract Background Lipopolysaccharide (LPS preconditioning-induced neuroprotection is known to be related to suppression of the inflammatory response in the ischemic area. This study seeks to determine if monocyte chemotactic protein-induced protein 1 (MCPIP1, a recently identified CCCH Zn finger-containing protein, plays a role in focal brain ischemia and to elucidate the mechanisms of LPS-induced ischemic brain tolerance. Methods Transcription and expression of MCPIP1 gene was monitored by qRT-PCR and Western blot. Mouse microglia was prepared from cortices of C57BL/6 mouse brain and primary human microglia was acquired from Clonexpress, Inc. Wild type and MCPIP1 knockout mice were treated with LPS (0.2 mg/kg 24 hours before brain ischemia induced by transient middle cerebral artery occlusion (MCAO. The infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC staining. Results MCPIP1 protein and mRNA levels significantly increased in both mouse and human microglia and mouse brain undergoing LPS preconditioning. MCPIP1 mRNA level significantly increased in mice ipsilateral brain than that of contralateral side after MCAO. The mortality of MCPIP1 knockout mice was significantly higher than that of wild-type after MCAO. MCPIP1 deficiency caused significant increase in the infarct volume compared with wild type mice undergoing LPS preconditioning. MCPIP1 deficiency caused significant upregulation of proinflammatory cytokines in mouse brain. Furthermore, MCPIP1 deficiency increased c-Jun N terminal kinase (JNK activation substantially. Inhibition of JNK signaling decreased the production of proinflammatory cytokines in MCPIP1 knock out mice after MCAO. Conclusions Our data indicate that absence of MCPIP1 exacerbates ischemic brain damage by upregulation of proinflammatory cytokines and that MCPIP1 participates in LPS-induced ischemic stroke tolerance.

  7. Critical chemotactic collapse

    Science.gov (United States)

    Lushnikov, Pavel M.

    2010-04-01

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells as well as dynamics of a gas of self-gravitating Brownian particles. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial (or Brownian particle) density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation or gravitational collapse. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schrödinger equation including critical collapse in two dimensions and supercritical collapse in three dimensions. A self-similar solution near blow up point is studied in the critical two-dimensional case and it has a form of a rescaled steady state solution which contains a critical number of bacteria. Time dependence of scaling of that solution has square root scaling law with logarithmic modification.

  8. Critical chemotactic collapse

    OpenAIRE

    Lushnikov, Pavel M.

    2009-01-01

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schrodinger equation...

  9. Critical chemotactic collapse

    International Nuclear Information System (INIS)

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells as well as dynamics of a gas of self-gravitating Brownian particles. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial (or Brownian particle) density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation or gravitational collapse. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schroedinger equation including critical collapse in two dimensions and supercritical collapse in three dimensions. A self-similar solution near blow up point is studied in the critical two-dimensional case and it has a form of a rescaled steady state solution which contains a critical number of bacteria. Time dependence of scaling of that solution has square root scaling law with logarithmic modification.

  10. Critical chemotactic collapse

    Energy Technology Data Exchange (ETDEWEB)

    Lushnikov, Pavel M., E-mail: plushnik@math.unm.ed [Department of Mathematics and Statistics, University of New Mexico, Albuquerque, NM 87131 (United States)

    2010-04-05

    A Keller-Segel model describes macroscopic dynamics of bacterial colonies and biological cells as well as dynamics of a gas of self-gravitating Brownian particles. Bacteria secret chemical which attracts other bacteria so that they move towards chemical gradient creating nonlocal attraction between bacteria. If bacterial (or Brownian particle) density exceeds a critical value then the density collapses (blows up) in a finite time which corresponds to bacterial aggregation or gravitational collapse. Collapse in the Keller-Segel model has striking qualitative similarities with a nonlinear Schroedinger equation including critical collapse in two dimensions and supercritical collapse in three dimensions. A self-similar solution near blow up point is studied in the critical two-dimensional case and it has a form of a rescaled steady state solution which contains a critical number of bacteria. Time dependence of scaling of that solution has square root scaling law with logarithmic modification.

  11. Effects of bone marrow-derived endothelial progenitor cell transplantation on vein microenvironment in a rat model of chronic thrombosis

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-qiang; MENG Qing-you; WU Hao-rong

    2007-01-01

    Background Endothelial progenitor cells(EPCs) have been used in both experimental studies and clinical treatments of limb ischemia,as well as in the construction of engineered vascular tissue.The objective of this study was to investigate the effects of transplanted bone marrow-derived EPCs on the vein microenvironment in a rat model of chronic vein thrombosis.Methods Mononuclear cells were isolated from the bone marrow of immature rats by density gradient centrifugation,cultured,and then transplanted into experimentally induced thrombi into inferior vena cava through the femoral vein.Vascular endothelial growth factor(VEGF),angiopoietin-1(ANG-1) and monocyte chemotactic protein-1(MCP-1) mRNA and protein expression levels were measured by real-time quantitative polymerase chain reaction and Western blotting of thrombi and adjacent caval walls 28 days post-transplantation.Results Levels of VEGF,ANG-1,and MCP-1 mRNA in EPC-transplanted thrombi were 100%,230.7%,and 212.5% of levels detected in the sham-operated group(P<0.01),and 99.9%,215.4%,and 177.8% of levels detected in the experimental control group(P<0.01).VEGF,ANG-1 and MCP-1 protein levels exhibited a similar trend.Conclusions Transplanted bone marrow-derived EPCs appear to alter the vein microenvironment in experimentally induced chronic vein thrombosis by upregulating cytokines associated with thrombic organization and recanalization.

  12. CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease.

    Science.gov (United States)

    Anderson, Albert M; Fennema-Notestine, Christine; Umlauf, Anya; Taylor, Michael J; Clifford, David B; Marra, Christina M; Collier, Ann C; Gelman, Benjamin B; McArthur, Justin C; McCutchan, J Allen; Simpson, David M; Morgello, Susan; Grant, Igor; Letendre, Scott L

    2015-10-01

    Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R (2) 0.179, p FGM (R (2) 0.224, p < 0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals. PMID:26069183

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

    International Nuclear Information System (INIS)

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

  14. Novel biochemical markers of psychosocial stress in women.

    Directory of Open Access Journals (Sweden)

    Marie Asberg

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

  15. Signal regulatory protein alpha negatively regulates beta2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis.

    Directory of Open Access Journals (Sweden)

    Dan-Qing Liu

    Full Text Available BACKGROUND: Signal regulate protein alpha (SIRPalpha is involved in many functional aspects of monocytes. Here we investigate the role of SIRPalpha in regulating beta(2 integrin-mediated monocyte adhesion, transendothelial migration (TEM and phagocytosis. METHODOLOGY/PRINCIPAL FINDINGS: THP-1 monocytes/macropahges treated with advanced glycation end products (AGEs resulted in a decrease of SIRPalpha expression but an increase of beta(2 integrin cell surface expression and beta(2 integrin-mediated adhesion to tumor necrosis factor-alpha (TNFalpha-stimulated human microvascular endothelial cell (HMEC-1 monolayers. In contrast, SIRPalpha overexpression in THP-1 cells showed a significant less monocyte chemotactic protein-1 (MCP-1-triggered cell surface expression of beta(2 integrins, in particular CD11b/CD18. SIRPalpha overexpression reduced beta(2 integrin-mediated firm adhesion of THP-1 cells to either TNFalpha-stimulated HMEC-1 monolayers or to immobilized intercellular adhesion molecule-1 (ICAM-1. SIRPalpha overexpression also reduced MCP-1-initiated migration of THP-1 cells across TNFalpha-stimulated HMEC-1 monolayers. Furthermore, beta(2 integrin-mediated THP-1 cell spreading and actin polymerization in response to MCP-1, and phagocytosis of bacteria were both inhibited by SIRPalpha overexpression. CONCLUSIONS/SIGNIFICANCE: SIRPalpha negatively regulates beta(2 integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis, thus may serve as a critical molecule in preventing excessive activation and accumulation of monocytes in the arterial wall during early stage of atherosclerosis.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-30

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

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

    International Nuclear Information System (INIS)

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

  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. GCP-2/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors

    International Nuclear Information System (INIS)

    The precise role of chemokines in neovascularization during inflammation or tumor growth is not yet fully understood. We show here that the chemokines granulocyte chemotactic protein-2 (GCP-2/CXCL6), interleukin-8 (IL-8/CXCL8), and monocyte chemotactic protein-1 (MCP-1/CCL2) are co-induced in microvascular endothelial cells after stimulation with pro-inflammatory stimuli. In contrast with its weak proliferative effect on endothelial cells, GCP-2 synergized with MCP-1 in neutrophil chemotaxis. This synergy may represent a mechanism for tumor development and metastasis by providing efficient leukocyte infiltration in the absence of exogenous immune modulators. To mimic endothelial cell-derived GCP-2 in vivo, GCP-2 was intravenously injected and shown to provoke a dose-dependent systemic response, composed of an immediate granulopenia, followed by a profound granulocytosis. By immunohistochemistry, GCP-2 was further shown to be expressed by endothelial cells from human patients with gastrointestinal (GI) malignancies. GCP-2 staining correlated with leukocyte infiltration into the tumor and with the expression of the matrix metalloproteinase-9 (MMP-9/gelatinase B). Together with previous findings, these data suggest that the production of GCP-2 by endothelial cells within the tumor can contribute to tumor development through neovascularization due to endothelial cell chemotaxis and to tumor cell invasion and metastasis by attracting and activating neutrophils loaded with proteases that promote matrix degradation

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

    Science.gov (United States)

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

    2015-11-30

    Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated. PMID:26412140

  1. The expression of selenium-binding protein 1 is decreased in uterine leiomyoma

    Directory of Open Access Journals (Sweden)

    Quddus M Ruhul

    2010-12-01

    Full Text Available Abstract Background Selenium has been shown to inhibit cancer development and growth through the mediation of selenium-binding proteins. Decreased expression of selenium-binding protein 1 has been reported in cancers of the prostate, stomach, colon, and lungs. No information, however, is available concerning the roles of selenium-binding protein 1 in uterine leiomyoma. Methods Using Western Blot analysis and immunohistochemistry, we examined the expression of selenium-binding protein 1 in uterine leiomyoma and normal myometrium in 20 patients who had undergone hysterectomy for uterine leiomyoma. Results and Discussion The patient age ranged from 34 to 58 years with a mean of 44.3 years. Proliferative endometrium was seen in 8 patients, secretory endometrium in 7 patients, and atrophic endometrium in 5 patients. Two patients showed solitary leiomyoma, and eighteen patients revealed 2 to 5 tumors. Tumor size ranged from 1 to 15.5 cm with a mean of 4.3 cm. Both Western Blot analysis and immunohistochemistry showed a significant lower level of selenium-binding protein 1 in leiomyoma than in normal myometrium. Larger tumors had a tendency to show a lower level of selenium-binding protein 1 than smaller ones, but the difference did not reach a statistical significance. The expression of selenium-binding protein 1 was the same among patients with proliferative, secretory, and atrophic endometrium in either leiomyoma or normal myometrium. Also, we did not find a difference of selenium-binding protein 1 level between patients younger than 45 years and older patients in either leiomyoma or normal myometrium. Conclusions Decreased expression of selenium-binding protein 1 in uterine leiomyoma may indicate a role of the protein in tumorigenesis. Our findings may provide a basis for future studies concerning the molecular mechanisms of selenium-binding protein 1 in tumorigenesis as well as the possible use of selenium in prevention and treatment of uterine

  2. Tracking Chemotactic Migration of a Genetically Engineered Bacterium in the Presence of Constructed Nutrient Gradients Within a Sandy Aquifer in Cape Cod, Massachusetts

    Science.gov (United States)

    Harvey, R. W.; Ford, R. M.; Metge, D. W.; Wang, M.; Toepfer, A. A.; McGowan, S. B.

    2008-05-01

    Due to our increasing dependence upon groundwater resources, there is a growing need to remediate shallow aquifers contaminated with chlorinated solvents. Often, trichloroethene (TCE) travels into zones of low permeability thereby making removal difficult by traditional pump-and-treat technologies. In addition, degradation of TCE by native microbial communities can result in buildup of highly toxic intermediates such as vinyl chloride. Bioaugmentation, involving addition of specialized bacterial consortia to an aquifer, can facilitate more complete degradation into harmless byproducts. Also, it is believed that chemotaxis, the ability of bacteria to swim towards higher concentrations of a chemical perceived as beneficial to survival, may expedite movement of introduced bacteria to where they are needed. However, there is no quantitative information about chemotaxis at the field scale and the evidence for bacterial chemotaxis during bioaugmentation has been largely anecdotal. In this study, the chemotactic migration of the bacterium, Pseudomonas stutzeri in a TCE-contaminated, sand- and-gravel aquifer in Cape Cod, Massachusetts was measured. P. stutzeri is known to denitrify as well as degrade a variety of aromatic and chlorinated solvents and is often advocated as a candidate for bioaugmentation. This bacterium was genetically engineered to be resistant to ampicillin and produce blue- fluorescing protein (BFP) in order to facilitate maintaining the bacteria in pure culture and later to track them in the environment. The study involved a natural-gradient injection and recovery test in which vertical gradients of an electron donor (acetate) and acceptor (nitrate) were created within the sandy aquifer sediments above an amendment of the genetically engineered P. stutzeri. The bacteria, nitrate, and acetate were allowed to be advected with the natural flow of groundwater past close-interval, multi-level samplers that were installed downgradient from the points of

  3. Mouse macrophages completely lacking Rho (RhoA, RhoB and RhoC) have severe lamellipodial retraction defects, but robust chemotactic navigation and increased motility

    DEFF Research Database (Denmark)

    Koenigs, Volker; Jennings, Richard; Vogl, Thomas;

    2014-01-01

    RhoA is thought to be essential for coordination of the membrane protrusions and retractions required for immune cell motility and directed migration. Whether the subfamily of Rho (Ras homolog) GTPases (RhoA, RhoB and RhoC) is actually required for the directed migration of primary cells is...... dKO cells, which developed extremely elongated tails. Surprisingly, velocity (of the cell body) was increased, while chemotactic efficiency was preserved, compared to wild-type (WT) macrophages. Randomly migrating RhoA/RhoB dKO macrophages exhibited multiple small protrusions and developed large...... involved in pulling up the rear end and resorbing lamellipodial membrane protrusions. Macrophages lacking Rho proteins migrate faster in vitro, which, in the case of the peritoneum, translates to more rapid in vivo monocyte/macrophage recruitment....

  4. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Lavinas, Tatiana

    2004-07-01

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

  6. Regulating MCP-1 Diffusion in Affinity Hydrogels for Enhancing Immuno-isolation

    OpenAIRE

    Lin, Chien-Chi; Boyer, Patrick D.; Aimetti, Alex A.; Anseth, Kristi S.

    2009-01-01

    Delivering cells using semi-permeable hydrogels is becoming an increasingly important direction in cell based therapies and regenerative medicine applications. Synthetic hydrogels have been functionalized with bioactive motifs to render otherwise inert polymer networks responsive. However, little effort has been focused on creating immuno-isolating materials capable of retarding the transport of small antigenic molecules secreted from the cells delivered with the synthetic carriers. Toward th...

  7. Aging and serum MCP-1 are associated with gut microbiome composition in a murine model

    OpenAIRE

    Conley, Melissa N.; Wong, Carmen P.; Duyck, Kyle M.; Hord, Norman; Ho, Emily; Sharpton, Thomas J

    2016-01-01

    Introduction. Age is the primary risk factor for major human chronic diseases, including cardiovascular disorders, cancer, type 2 diabetes, and neurodegenerative diseases. Chronic, low-grade, systemic inflammation is associated with aging and the progression of immunosenescence. Immunosenescence may play an important role in the development of age-related chronic disease and the widely observed phenomenon of increased production of inflammatory mediators that accompany this process, referred ...

  8. Inflammation und Präatherosklerose bei Insulinresistenz: Bedeutung löslicher MCP-1-Spiegel

    OpenAIRE

    Kocher, Björn Matthias

    2007-01-01

    Einleitung: Die erhöhte kardiovaskuläre Morbidität bei metabolischem Syndrom beruht im Wesentlichen auf atherosklerotischen Gefäßkomplikationen. Ob hier die insulinresistenzassoziierte Dyslipoproteinämie, Veränderungen in der Glukosehomöostase / Hyperinsulinämie oder inflammatorische Mechanismen, neben der essentiellen Hypertonie, von Bedeutung sind, ist noch nicht hinreichend geklärt. Auf inflammatorischer Ebene wird einer gesteigerten endothelialen Monozytenadhäsion und Immigration in d...

  9. Alterations in expression levels of deafness dystonia protein 1 affect mitochondrial morphology

    DEFF Research Database (Denmark)

    Engl, Gertraud; Florian, Stefan; Tranebjærg, Lisbeth;

    2012-01-01

    Deafness-Dystonia-Optic Neuropathy (DDON) Syndrome is a rare X-linked progressive neurodegenerative disorder resulting from mutations in the TIMM8A gene encoding for the deafness dystonia protein 1 (DDP1). Despite important progress in identifying and characterizing novel mutations in this gene...

  10. Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Magistrado, Pamela; Hermsen, Cornelus C;

    2005-01-01

    -encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, which is expressed on the surface of infected erythrocytes where it mediates binding to endothelial receptors. Thus, severe malaria may be caused by parasites expressing PfEMP1 variants that afford parasites optimal sequestration in...

  11. Analyzing Plasmodium falciparum erythrocyte membrane protein 1 gene expression by a next generation sequencing based method

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Petersen, Bent; Seguin-Orlando, Andaine;

    2013-01-01

    Plasmodium falciparum is responsible for most cases of severe malaria and causes >1 million deaths every year. The particular virulence of this Plasmodium species is highly associated with the expression of certain members of the Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) family...

  12. Plasmodium falciparum Erythrocyte Membrane Protein 1 Diversity in Seven Genomes – Divide and Conquer

    DEFF Research Database (Denmark)

    Rask, Thomas Salhøj; Hansen, Daniel Aaen; Theander, Thor G.;

    2010-01-01

    The var gene encoded hyper-variable Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates cytoadhesion of infected erythrocytes to human endothelium. Antibodies blocking cytoadhesion are important mediators of malaria immunity acquired by endemic populations. The development...

  13. *611540 SH3-DOMAIN GRB2-LIKE (ENDOPHILIN)-INTERACTING PROTEIN 1; SGIP1 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 611540 FIELD TI 611540 SH3-DOMAIN GRB2-LIKE (ENDOPHILIN)-INTERACTING PROTEIN 1; SGIP1 F ... differential-display PCR of hypothalamic RNA from lean ... and obese Psammomys obesus (Israeli sand rats), a ... nhibition of Sgip1 hypothalamic expression in both lean ... P. obesus and Sprague-Dawley rats caused a signifi ...

  14. Osteopontin, a chemotactic protein with cytokine-like properties, is up-regulated in muscle injury caused by Bothrops lanceolatus (fer-de-lance) snake venom.

    Science.gov (United States)

    Barbosa-Souza, Valéria; Contin, Daniel Kiss; Filho, Waldemar Bonventi; de Araújo, Albetiza Lôbo; Irazusta, Silvia Pierre; da Cruz-Höfling, Maria Alice

    2011-10-01

    Osteopontin (OPN) is a chemotactic, adhesive protein whose receptors include some integrins and matrix proteins known to have role in inflammatory and repair processes. We examined the time course of OPN expression at acute and chronic stages after intramuscular injection of Bothrops lanceolatus venom in rats. Additionally, we examined the expression of CD68 (a marker for phagocytic macrophages) and the myogenic factors, myoD and myogenin. There was a biphasic upregulation of OPN (6-48 h and 3-14 days post-venom), i.e., during acute inflammation and myogenic cell proliferation and differentiation phases. OPN was detected in CD68 + macrophages, fibroblasts, normal and damaged myofibers, myoblasts and myotubes. Myogenin was expressed in the cytoplasm (atypical pattern) and nucleus of myoblasts and myotubes from 18 h to 7 days, after which it was expressed only in nuclei. Macrophage numbers, OPN and myogenin expression were still elevated at 7, 14 and 7 days. At 3 days, when OPN achieved the peak, some clusters of myoblasts were within regions of intense collagen deposition. Fibrosis may represent limitation for repairing processes and may explain the small diameter of regenerated fibers at 21 days post-venom. The expression of OPN in the course of venom-induced damage and regeneration suggests stages-specific mediation role along the whole process. PMID:21839764

  15. PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1 through dephosphorylation of specific tyrosine residue

    International Nuclear Information System (INIS)

    Highlights: •PTPRT is a brain-specific, expressed, protein tyrosine phosphatase. •PTPRT regulated the interaction of Syntaxin-binding protein 1 with Syntaxin 1. •PTPRT dephosphorylated the specific tyrosine residue of Syntaxin-binding protein 1. •Dephosphorylation of Syntaxin-binding protein 1 enhanced the interaction with Syntaxin 1. •PTPRT appears to regulate the fusion of synaptic vesicle through dephosphorylation. -- Abstract: PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine phosphatase, has been found to regulate synaptic formation and development of hippocampal neurons, but its regulation mechanism is not yet fully understood. Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, was identified as a possible interaction partner and an endogenous substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein, and plays a role as catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1 appeared to be important for SNARE-complex formation. In conclusion, PTPRT could regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a result, the synaptic vesicle fusion appeared to be controlled through dephosphorylation of Syntaxin-binding protein 1

  16. Bigenomic transcriptional regulation of all thirteen cytochrome c oxidase subunit genes by specificity protein 1

    OpenAIRE

    Dhar, Shilpa S.; Johar, Kaid; Wong-Riley, Margaret T. T.

    2013-01-01

    Cytochrome c oxidase (COX) is one of only four known bigenomic proteins, with three mitochondria-encoded subunits and 10 nucleus-encoded ones derived from nine different chromosomes. The mechanism of regulating this multi-subunit, bigenomic enzyme is not fully understood. We hypothesize that specificity protein 1 (Sp1) functionally regulates the 10 nucleus-encoded COX subunit genes directly and the three mitochondrial COX subunit genes indirectly by regulating mitochondrial transcription fact...

  17. Specificity Protein 1 Expression Contributes to Bcl-w-Induced Aggressiveness in Glioblastoma Multiforme

    OpenAIRE

    Lee, Woo Sang; Kwon, Junhye; Yun, Dong Ho; Lee, Young Nam; Woo, Eun Young; Park, Myung-Jin; Lee, Jae-Seon; Han, Young-Hoon; Bae, In Hwa

    2014-01-01

    We already had reported that Bcl-w promotes invasion or migration in gastric cancer cells and glioblastoma multiforme (GBM) by activating matrix metalloproteinase-2 (MMP-2) via specificity protein 1 (Sp1) or β-cateinin, respectively. High expression of Bcl-w also has been reported in GBM which is the most common malignant brain tumor and exhibits aggressive and invasive behavior. These reports propose that Bcl-w-induced signaling is strongly associated with aggressive characteristic of GBM. W...

  18. Regulation of Latent Membrane Protein 1 Signaling through Interaction with Cytoskeletal Proteins

    OpenAIRE

    Holthusen, Kirsten; Talaty, Pooja; Everly, David N.

    2015-01-01

    Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) induces constitutive signaling in EBV-infected cells to ensure the survival of the latently infected cells. LMP1 is localized to lipid raft domains to induce signaling. In the present study, a genome-wide screen based on bimolecular fluorescence complementation (BiFC) was performed to identify LMP1-binding proteins. Several actin cytoskeleton-associated proteins were identified in the screen. Overexpression of these proteins affecte...

  19. Role of macrophage inflammatory protein-1alpha in T-cell-mediated immunity to viral infection

    DEFF Research Database (Denmark)

    Madsen, Andreas N; Nansen, Anneline; Christensen, Jan P; Thomsen, Allan R

    2003-01-01

    The immune response to lymphocytic choriomeningitis virus in mice lacking macrophage inflammatory protein-1alpha (MIP-1alpha) was evaluated. Generation of virus-specific effector T cells is unimpaired in MIP-1alpha-deficient mice. Furthermore, MIP-1alpha is not required for T-cell-mediated virus...... control or virus-induced T-cell-dependent inflammation. Thus, MIP-1alpha is not mandatory for T-cell-mediated antiviral immunity....

  20. Immunocytochemical localization of microtubule-associated protein 1 in rat cerebellum using monoclonal antibodies

    OpenAIRE

    1984-01-01

    Immunohistochemical staining with monoclonal antibodies showed that microtubule-associated protein 1 (MAP1) has a restricted cellular distribution in the rat cerebellum. Anti-MAP1 staining was found only in neurons, where it was much stronger in dendrites than in axons. There were striking variations in the apparent concentration of MAP1 in different classes of neurons. Purkinje cells were the most strongly labeled, while granule cell neurons gave a faint, threshold-level reaction with the an...

  1. Speciifc effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

    Institute of Scientific and Technical Information of China (English)

    Shu Tang; Qiang Wen; Xiao-jian Zhang; Quan-cheng Kan

    2016-01-01

    c-Jun NH2-terminal kinase (JNK)-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB) anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neuronsin vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB com-plexesin vitro andin vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interact-ing protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These ifndings conifrm that JNK-inter-acting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  2. Mice lacking multidrug resistance protein 1a show altered dopaminergic responses to methylenedioxymethamphetamine (MDMA) in striatum

    OpenAIRE

    Scheidweiler, Karl B.; Ladenheim, Bruce; Cadet, Jean Lud; Huestis, Marilyn A.

    2009-01-01

    Multidrug resistance protein 1a (MDR1a) potentiated methylenedioxymethamphetamine (MDMA)-induced decreases of dopamine (DA) and dopamine transport protein in mouse brain one week after MDMA administration. In the present study, we examined if mdr1a wild-type (mdr1a +/+) and knock-out (mdr1a −/−) mice differentially handle the acute effects of MDMA on the nigrostriatal DA system 0–24 h following a single drug injection. 3-way ANOVA revealed significant 2-way interactions of strain X time (F5,1...

  3. GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass

    OpenAIRE

    Menon, Prashanthi; Yin, Guoyong; Smolock, Elaine M.; Zuscik, Michael J.; Yan, Chen; Berk, Bradford C.

    2010-01-01

    G-protein coupled receptor (GPCR) kinase 2 interacting protein-1 (GIT1) is a scaffold protein expressed in various cell types including neurons, endothelial and vascular smooth muscle cells. The GIT1 knockout (KO) mouse has a pulmonary phenotype due to impaired endothelial function. Because GIT1 is tyrosine phosphorylated by Src kinase, we anticipated that GIT1 KO should have a bone phenotype similar to Src KO. Microcomputed tomography of the long bones revealed that GIT1 KO mice have a 2.3-f...

  4. Impaired spine formation and learning in GPCR kinase interacting protein-1 (GIT1) knockout mice

    OpenAIRE

    Menon, Prashanthi; Deane, Rashid; Sagare, Abhay; Lane, Steven M.; Zarcone, Troy J; O’Dell, Michael R.; Yan, Chen; Zlokovic, Berislav V.; Berk, Bradford C.

    2010-01-01

    The G-protein coupled receptor (GPCR)-kinase interacting proteins 1 and 2 (GIT1 and GIT2) are scaffold proteins with ADP-ribosylating factor GTPase activity. GIT1 and GIT2 control numerous cellular functions and are highly expressed in neurons, endothelial cells and vascular smooth muscle cells (VSMC). GIT1 promotes dendritic spine formation, growth and motility in cultured neurons, but its role in brain in vivo is unknown. By using global GIT1 knockout mice (GIT1 KO), we show that deletion o...

  5. Insights from the crystal structure of the sixth BRCT domain of topoisomerase IIβ binding protein 1

    OpenAIRE

    Leung, Charles Chung Yun; Kellogg, Elizabeth; Kuhnert, Anja; Hänel, Frank; Baker, David; Glover, J N Mark

    2009-01-01

    Topoisomerase IIβ binding protein 1 (TopBP1) is a major player in the DNA damage response and interacts with a number of protein partners via its eight BRCA1 carboxy-terminal (BRCT) domains. In particular, the sixth BRCT domain of TopBP1 has been implicated in binding to the phosphorylated transcription factor, E2F1, and poly(ADP-ribose) polymerase 1 (PARP-1), where the latter interaction is responsible for the poly(ADP-ribosyl)ation of TopBP1. To gain a better understanding of the nature of ...

  6. Fragile X mental retardation protein interactions with the microtubule associated protein 1B RNA

    OpenAIRE

    Menon, Lakshmi; Mader, Samantha Ann; Mihailescu, Mihaela-Rita

    2008-01-01

    Fragile X mental retardation syndrome, the most common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP). FMRP has been shown to use its arginine–glycine–glycine (RGG) box to bind to a subset of RNA targets that form a G quadruplex structure. We performed a detailed analysis of the interactions between the FMRP RGG box and the microtubule associated protein 1B (MAP1B) mRNA, a relevant in vivo FMRP target. We show that MAP1B RNA f...

  7. Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle

    OpenAIRE

    Jason K Kim; Gimeno, Ruth E.; Higashimori, Takamasa; Kim, Hyo-Jeong; Choi, Hyejeong; Punreddy, Sandhya; Mozell, Robin L.; TAN, GUO; Stricker-Krongrad, Alain; Hirsch, David J.; Fillmore, Jonathan J.; Liu, Zhen-Xiang; Dong, Jianying; Cline, Gary; Stahl, Andreas

    2004-01-01

    Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism by converting fatty acids into fatty acyl-CoA. To investigate the role of FATP1 in glucose homeostasis and in the pathogenesis of insulin resistance, we examined the e...

  8. Regulation of skeletal muscle regeneration by CCR2-activating chemokines is directly related to macrophage recruitment

    OpenAIRE

    Martinez, Carlo O.; McHale, Matthew J.; Wells, Jason T.; OCHOA, OSCAR; Joel E. Michalek; McManus, Linda M.; Shireman, Paula K.

    2010-01-01

    Muscle regeneration requires CC chemokine receptor 2 (CCR2) expression on bone marrow-derived cells; macrophages are a prominent CCR2-expressing cell in this process. CCR2−/− mice have severe impairments in angiogenesis, macrophage recruitment, and skeletal muscle regeneration following cardiotoxin (CTX)-induced injury. However, multiple chemokines activate CCR2, including monocyte chemotactic proteins (MCP)-1, -3, and -5. We hypothesized that MCP-1 is the chemokine ligand that mediates the i...

  9. The oxygen evolving enhancer protein 1 (OEE) of photosystem II in green algae exhibits thioredoxin activity.

    Science.gov (United States)

    Heide, Heinrich; Kalisz, Henryk M; Follmann, Hartmut

    2004-02-01

    A thioredoxin-like chloroplast protein of the fructosebisphosphatase-stimulating f-type, but with an unusually high molecular mass of 28 kDa has previously been identified and purified to homogeneity in a fractionation scheme for resolution of the acid- and heat-stable, regular-size (12kDa) thioredoxins of the unicellular green algae, Scenedesmus obliquus. An apparently analogous protein of 26 kDa was described in a cyanobacterium, Anabaena sp., but no such large thioredoxin species f exists in the thioredoxin profiles of higher plants. The structure of the 28 kDa protein, which had been envisaged to represent a precursor, or fusion product of the two more specialized, common chloroplast thioredoxins f and m has now been determined by amino acid sequencing. Although it exhibits virtually all the properties and enzyme-modulating activities of a thioredoxin proper this algal protein, surprisingly, does not belong to the thioredoxin family of small redox proteins but is identical with OEE (oxygen evolving enhancer) protein 1, an auxiliary component of the photosystem II manganese cluster. Extracts of Chlorella vulgaris and Chlamydomonas reinhardtii also contain heat-stable protein fractions of 23-26 kDa capable of specifically stimulating chloroplast fructosebisphosphatase in vitro. In contrast, OEE protein 1 from spinach is not able to modulate FbPase or NADP malate dehydrogenase from spinach chloroplasts. A dual function of the OEE protein in algal photosynthesis is envisaged. PMID:15022827

  10. Epilepsy, Behavioral Abnormalities, and Physiological Comorbidities in Syntaxin-Binding Protein 1 (STXBP1 Mutant Zebrafish.

    Directory of Open Access Journals (Sweden)

    Brian P Grone

    Full Text Available Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1, are linked to childhood epilepsies and other neurodevelopmental disorders. Zebrafish STXBP1 homologs (stxbp1a and stxbp1b have highly conserved sequence and are prominently expressed in the larval zebrafish brain. To understand the functions of stxbp1a and stxbp1b, we generated loss-of-function mutations using CRISPR/Cas9 gene editing and studied brain electrical activity, behavior, development, heart physiology, metabolism, and survival in larval zebrafish. Homozygous stxbp1a mutants exhibited a profound lack of movement, low electrical brain activity, low heart rate, decreased glucose and mitochondrial metabolism, and early fatality compared to controls. On the other hand, homozygous stxbp1b mutants had spontaneous electrographic seizures, and reduced locomotor activity response to a movement-inducing "dark-flash" visual stimulus, despite showing normal metabolism, heart rate, survival, and baseline locomotor activity. Our findings in these newly generated mutant lines of zebrafish suggest that zebrafish recapitulate clinical phenotypes associated with human syntaxin-binding protein 1 mutations.

  11. Isolation and characterization of peptidoglycan recognition protein 1 from antler base of sika deer (Cervus nippon).

    Science.gov (United States)

    Jiang, Wei; Yin, Yongguang; Zhou, Yajun; He, Guidan; Qi, Yue

    2014-03-01

    Peptidoglycan recognition proteins (PGRPs) are secreted innate immunity pattern recognition molecules. In this study, a new peptidoglycan recognition protein 1 named cnPGRP1 was isolated from an antler base of sika deer Cervus nippon. The antler base antimicrobial proteins (AAP) were subjected to consecutive chromatographic methods connected to Sephadex G-25 gel filtration column (CM) anion-exchange column, and RP-HPLC. The molecular weight of cnPGRP1 was 17.2 kDa under SDS-PAGE, and peptide mass fingerprint analysis by MALDI-TOF-MS as peptidoglycan recognition protein 1 matched to Dasypus novemcinctus. The matched amino acids sequences were RLYEIIQKWPHYRA. Both Gram-positive and Gram-negative bacteria can be killed by cnPGRP1 in the 50-250 μg/mL range through in vitro. Furthermore, cnPGRP1 has been found to bind Gram-positive bacteria, Gram-negative bacteria, and even fungus. PMID:24360898

  12. Spatiotemporal patterns of the Huntingtin-interacting protein 1-related gene in the mouse head.

    Science.gov (United States)

    Masuda, Tomoyuki; Sakuma, Chie; Ueno, Takayuki; Yamada, Yuriko; Ohmomo, Hideki; Ueda, Shuichi; Yamagishi, Toshiyuki; Yaginuma, Hiroyuki

    2013-12-01

    Huntingtin-interacting protein 1-related (Hip1r) was originally identified due to its homology to Huntingtin-interacting protein 1, which contributes to the development of Huntington's disease (HD). We studied the expression of the mouse Hip1r (mHip1r) gene in the mouse head by in situ hybridization. In early embryogenesis at embryonic day (E) 13, mHip1r expression was especially prominent in the olfactory epithelium, cerebral cortex layer 1, cortical plate, and dentate gyrus. During later development from E15 to E17, strong expression of mHip1r transcripts continued to be observed in the olfactory epithelium, cortical plate, and dentate gyrus. Furthermore, not only the subplate and subventricular zone of the cortex, but also secretory glands, such as the nasal gland and the submandibular gland, were mHip1r-positive. Other positive tissues included the retinal ganglion cells, vomeronasal organ, trigeminal ganglion, and the developing molar tooth. In the adult mouse brain, similar expression patterns were observed in the cerebral cortex layers and other brain regions except the cerebellum. Additionally, by using an antibody against mHip1r, we confirmed these expression patterns at the protein level. Specific expression of mHip1r in the embryonic brain and secretory glands suggests a possible role for Hip1r in normal development and in the pathology of HD. PMID:24712472

  13. Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy.

    Science.gov (United States)

    Pirzer, Rainer; Elmas, Elif; Haghi, Dariusch; Lippert, Christiane; Kralev, Stefan; Lang, Siegfried; Borggrefe, Martin; Kälsch, Thorsten

    2012-03-01

    Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t(0)), after 2-4 days (t(1)) and after 4-7 weeks (t(2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC. PMID:21416113

  14. Synergistic Cytotoxic Effects of Ganoderma lucidum and Bacillus Calmette Guérin on Premalignant Urothelial HUC-PC Cells and Its Regulation on Proinflammatory Cytokine Secretion

    Directory of Open Access Journals (Sweden)

    John Wai-man Yuen

    2012-01-01

    Full Text Available Bacillus Calmette-Guérin (BCG is conventionally used as an adjuvant immunotherapy to reduce the recurrence of bladder cancer. To address the issues of efficacy and safety, an ethanol extract of Ganoderma lucidum (GLe was evaluated for its interaction with BCG. In a model of premalignant human uroepithelial cells (HUC-PC, GLe exerted immediate cytotoxic effects while BCG showed a delayed response, given that both were immunological active in inducing the secretion of interleukin (IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1. Synergistic cytotoxic effects were observed when cells were either coincubated with both drugs or firstly preincubated with GLe. Synergism between GLe and BCG was demonstrated to achieve a complete cytostasis in 24 hours, and such effects were progressed in the subsequent 5 days. However, the pretreatment of GLe resulted in suppression of IL-6, IL-8, and MCP-1 secretions without affecting the cytotoxicity. Given that numerous proinflammatory cytokines are associated with the high side effects toll of BCG, results herein suggested the potential implications of GL to supplement the BCG immunotherapy in bladder cancer, for better efficacy and reducing side effects.

  15. Cordyceps sinensis polysaccharide inhibits PDGF-BB-induced inflammation and ROS production in human mesangial cells.

    Science.gov (United States)

    Wang, Ying; Wang, Yan; Liu, Dan; Wang, Wang; Zhao, Huan; Wang, Min; Yin, Hongping

    2015-07-10

    CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti-inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNFR1), and monocyte chemotactic protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1. Furthermore, CPS-F prevents the PDGF receptor β (PDGFRβ) promoter activity induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF-α, TNFR1, and MCP-1 when PDGFRβ is silenced, thereby suggesting that CPS-F possesses a bidirectional regulatory function. Our findings suggest CPS-F may exert its therapeutic effect for the treatment of glomerulonephritis related to human mesangial cells (HMCs) through the ERK1/2/Akt pathways. PMID:25857968

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

    Science.gov (United States)

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

    2016-01-01

    Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633. PMID:27313852

  17. Monocyte Subsets and Related Chemokines in Carotid Artery Stenosis and Ischemic Stroke

    Science.gov (United States)

    Grosse, Gerrit M.; Schulz-Schaeffer, Walter J.; Teebken, Omke E.; Schuppner, Ramona; Dirks, Meike; Worthmann, Hans; Lichtinghagen, Ralf; Maye, Gerrit; Limbourg, Florian P.; Weissenborn, Karin

    2016-01-01

    Carotid stenosis (CS) is an important cause of ischemic stroke. However, reliable markers for the purpose of identification of high-risk, so-called vulnerable carotid plaques, are still lacking. Monocyte subsets are crucial players in atherosclerosis and might also contribute to plaque rupture. In this study we, therefore, aimed to investigate the potential role of monocyte subsets and associated chemokines as clinical biomarkers for vulnerability of CS. Patients with symptomatic and asymptomatic CS (n = 21), patients with cardioembolic ischemic strokes (n = 11), and controls without any cardiovascular disorder (n = 11) were examined. Cardiovascular risk was quantified using the Essen Stroke Risk Score (ESRS). Monocyte subsets in peripheral blood were measured by quantitative flow cytometry. Plaque specimens were histologically analyzed. Furthermore, plasma levels of monocyte chemotactic protein 1 (MCP-1) and fractalkine were measured. Intermediate monocytes (Mon2) were significantly elevated in symptomatic and asymptomatic CS-patients compared to controls. Mon2 counts positively correlated with the ESRS. Moreover, stroke patients showed an elevation of Mon2 compared to controls, independent of the ESRS. MCP-1 levels were significantly higher in patients with symptomatic than in those with asymptomatic CS. Several histological criteria significantly differed between symptomatic and asymptomatic plaques. However, there was no association of monocyte subsets or chemokines with histological features of plaque vulnerability. Due to the multifactorial influence on monocyte subsets, the usability as clinical markers for plaque vulnerability seems to be limited. However, monocyte subsets may be critically involved in the pathology of CS. PMID:27023515

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

    Directory of Open Access Journals (Sweden)

    Motoko Kawashima

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

  19. L-selectin and P-selectin are novel biomarkers of cervicovaginal inflammation for preclinical mucosal safety assessment of anti-HIV-1 microbicide.

    Science.gov (United States)

    Zhong, Maohua; He, Benxia; Yang, Jingyi; Bao, Rong; Zhang, Yan; Zhou, Dihan; Chen, Yaoqing; Li, Liangzhu; Han, Chen; Yang, Yi; Sun, Ying; Cao, Yuan; Li, Yaoming; Shi, Wei; Jiang, Shibo; Zhang, Xiaoyan; Yan, Huimin

    2012-06-01

    A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens. PMID:22391529

  20. Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1 Potential role of inflammatory mediators

    International Nuclear Information System (INIS)

    Transgenic mice with a targeted disruption of the tumor necrosis factor receptor 1 (TNFR1) gene were used to analyze the role of TNF-α in pro- and anti-inflammatory mediator production and liver injury induced by acetaminophen. Treatment of wild-type mice with acetaminophen (300 mg/kg) resulted in centrilobular hepatic necrosis. This was correlated with expression of inducible nitric oxide synthase (NOS II) and nitrotyrosine staining of the liver. Expression of macrophage chemotactic protein-1 (MCP-1), KC/gro, interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), and connective tissue growth factor (CTGF), inflammatory mediators known to participate in tissue repair, as well as the anti-inflammatory cytokine, interleukin-10 (IL-10), also increased in the liver following acetaminophen administration. TNFR1-/- mice were found to be significantly more sensitive to the hepatotoxic effects of acetaminophen than wild-type mice. This was correlated with more rapid and prolonged induction of NOS II in the liver and changes in the pattern of nitrotyrosine staining. Acetaminophen-induced expression of MCP-1, IL-1β, CTGF, and MMP-9 mRNA was also delayed or reduced in TNFR1-/- mice relative to wild-type mice. In contrast, increases in IL-10 were more rapid and more pronounced. These data demonstrate that signaling through TNFR1 is important in inflammatory mediator production and toxicity induced by acetaminophen

  1. Xanthones from Securidaca inappendiculata exert significant therapeutic efficacy on adjuvant-induced arthritis in mice.

    Science.gov (United States)

    Zuo, Jian; Xia, Yan; Li, Xiang; Chen, Jian-Wei

    2014-06-01

    The study was designed to investigate effects of the xanthones from Securidaca inappendiculata on adjuvant-induced arthritis (AA) mice in vivo. Arthritis severity was evaluated by arthritic score, body weight loss, paw circumference, histological changes and hyperplasia of lymphatic tissues. Plasma samples were collected for estimation of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) using enzyme-linked immunosorbent assay method. The levels of glutathione (GSH), malondialdehyde (MDA), N-acetyl glucosaminidase (NAG) and sialic acid (SA) in liver were assessed by colorimetric method. Xanthones significantly ameliorated the severity of AA indicated by the physical parameters changes, and reverted the abnormal changes of MDA, GSH, NAG and SA in liver. Levels of IL-1, TNF-α, MCP-1 and VEGF reduced dramatically meanwhile. The effects of xanthones on AA were the outcome of the multitargets activities, and probably associated with NF-κB signaling pathway. PMID:24419745

  2. Psoriasin: a novel chemotactic protein

    DEFF Research Database (Denmark)

    Jinquan, T; Vorum, H; Larsen, C G;

    1996-01-01

    Inflammatory skin disorders such as psoriasis show a preferential epidermal infiltration of neutrophils and T lymphocytes. This observation raises a question as to which factors determine the appearance and composition of leukocyte tissue infiltrations. Previously, we described a low molecular ma...

  3. Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4-dependent manner in mice.

    Directory of Open Access Journals (Sweden)

    Dora Lippai

    Full Text Available INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-α (TNFα, monocyte chemotactic protein-1 (MCP1 and interleukin-1-beta (IL-1β. Toll-like receptor-4 (TLR4 pathway induced nuclear factor-κB (NF-κB activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation. METHODS: Wild type (WT, miR-155- and TLR4-knockout (KO mice received 5% ethanol-containing or isocaloric control diet for 5 weeks. Microglia markers were measured by q-RTPCR; inflammasome activation was measured by enzyme activity; TNFα, MCP1, IL-1β mRNA and protein were measured by q-RTPCR and ELISA; phospho-p65 protein and NF-κB were measured by Western-blotting and EMSA; miRNAs were measured by q-PCR in the cerebellum. MiR-155 was measured in immortalized and primary mouse microglia after lipopolysaccharide and ethanol stimulation. RESULTS: Chronic ethanol feeding up-regulated miR-155 and miR-132 expression in mouse cerebellum. Deficiency in miR-155 protected mice from alcohol-induced increase in inflammatory cytokines; TNFα, MCP1 protein and TNFα, MCP1, pro-IL-1β and pro-caspase-1 mRNA levels were reduced in miR-155 KO alcohol-fed mice. NF-κB was activated in WT but not in miR-155 KO alcohol-fed mice. However increases in cerebellar caspase-1 activity and IL-1β levels were similar in alcohol-fed miR-155-KO and WT mice. Alcohol-fed TLR4-KO mice were protected from the induction of miR-155. NF-κB activation measured by phosphorylation of p65 and neuroinflammation were reduced in alcohol-fed TLR4-KO compared to control mice. TLR4 stimulation with

  4. Nuclear Multidrug-Resistance Related Protein 1 Contributes to Multidrug-Resistance of Mucoepidermoid Carcinoma Mainly via Regulating Multidrug-Resistance Protein 1: A Human Mucoepidermoid Carcinoma Cells Model and Spearman's Rank Correlation Analysis

    OpenAIRE

    Bolei Cai; Ye Miao; Yuan Liu; Xiaofang Xu; Sumin Guan; Junzheng Wu; Yanpu Liu

    2013-01-01

    BACKGROUND: Multidrug resistance-related protein 1 (MRP1/ABCC1) and multidrug resistance protein 1 (MDR1/P-glycoprotein/ABCB1) are both membrane-bound drug transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH) and drugs conjugated to GSH. Due to its extraordinary transport properties, MRP1/ABCC1 contributes to several physiological functions and pathophysiological incidents. We previously found that nuclear translocation of MRP1 contributes to multidrug-resistance (MDR) of...

  5. Borrelia burgdorferi Regulates Expression of Complement Regulator-Acquiring Surface Protein 1 during the Mammal-Tick Infection Cycle

    OpenAIRE

    von Lackum, Kate; Miller, Jennifer C.; Bykowski, Tomasz; Riley, Sean P; Woodman, Michael E.; Brade, Volker; Kraiczy, Peter; Stevenson, Brian; Wallich, Reinhard

    2005-01-01

    During the natural mammal-tick infection cycle, the Lyme disease spirochete Borrelia burgdorferi comes into contact with components of the alternative complement pathway. B. burgdorferi, like many other human pathogens, has evolved the immune evasion strategy of binding two host-derived fluid-phase regulators of complement, factor H and factor H-like protein 1 (FHL-1). The borrelial complement regulator-acquiring surface protein 1 (CRASP-1) is a surface-exposed lipoprotein that binds both fac...

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

    Directory of Open Access Journals (Sweden)

    Wu-Yang Huang

    2014-08-01

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

  7. Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    V V Chernykh

    2015-01-01

    Full Text Available Purpose: The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF] in the vitreous of patients with proliferative diabetic retinopathy (PDR and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR. Materials and Methods : Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1, interleukin-4 (IL-4, IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA were simultaneously measured using enzyme-linked immunoassay. Results : Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05 higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (Π < 0.05 positive correlations were observed between vitreous concentrations of VEGF and IL-17ΐ (r = 0.45, VEGF and IL-8 (r = 0.48, VEGF and IL-4 (r = 0.51, PEDF and IL-17ΐ (r = 0.48, PEDF and IL-8 (r = 0.59, MCP-1 and PEDF (r = 0.72, MCP-1 and IL-8 (r0 = 0.45, IL-4 and IL-17ΐ (r = 0.65, IL-4 and IL-8 (r = 0.71, IL-8 and IL-17ΐ (r = 0.59. Conclusions: Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.

  8. Excessive Pro-Inflammatory Serum Cytokine Concentrations in Virulent Canine Babesiosis

    Science.gov (United States)

    Goddard, Amelia; Leisewitz, Andrew L.; Kjelgaard-Hansen, Mads; Kristensen, Annemarie T.; Schoeman, Johan P.

    2016-01-01

    Babesia rossi infection causes a severe inflammatory response in the dog, which is the result of the balance between pro- and anti-inflammatory cytokine secretion. The aim of this study was to determine whether changes in cytokine concentrations were present in dogs with babesiosis and whether it was associated with disease outcome. Ninety-seven dogs naturally infected with B. rossi were studied and fifteen healthy dogs were included as controls. Diagnosis of babesiosis was confirmed by polymerase chain reaction and reverse line blot. Blood samples were collected from the jugular vein at admission, prior to any treatment. Cytokine concentrations were assessed using a canine-specific multiplex assay on an automated analyser. Serum concentrations of interleukin (IL)-2, IL-6, IL-8, IL-10, IL-18, granulocyte-macrophage colony stimulating factor (GM-CSF) and monocyte chemotactic protein-1 (MCP-1) were measured. Twelve of the Babesia-infected dogs died (12%) and 85 survived (88%). Babesia-infected dogs were also divided into those that presented within 48 hours from displaying clinical signs, and those that presented more than 48 hours after displaying clinical signs. Cytokine concentrations were compared between the different groups using the Mann-Whitney U test. IL-10 and MCP-1 concentrations were significantly elevated for the Babesia-infected dogs compared to the healthy controls. In contrast, the IL-8 concentration was significantly decreased in the Babesia-infected dogs compared to the controls. Concentrations of IL-6 and MCP-1 were significantly increased in the non-survivors compared to the survivors. Concentrations for IL-2, IL-6, IL-18 and GM-CSF were significantly higher in those cases that presented during the more acute stage of the disease. These findings suggest that a mixed cytokine response is present in dogs with babesiosis caused by B. rossi, and that an excessive pro-inflammatory response may result in a poor outcome. PMID:26953797

  9. Fat accumulation with altered inflammation and regeneration in skeletal muscle of CCR2-/- mice following ischemic injury.

    Science.gov (United States)

    Contreras-Shannon, Verónica; Ochoa, Oscar; Reyes-Reyna, Sara M; Sun, Dongxu; Michalek, Joel E; Kuziel, William A; McManus, Linda M; Shireman, Paula K

    2007-02-01

    Chemokines recruit inflammatory cells to sites of injury, but the role of the CC chemokine receptor 2 (CCR2) during regenerative processes following ischemia is poorly understood. We studied injury, inflammation, perfusion, capillary formation, monocyte chemotactic protein-1 (MCP-1) levels, muscle regeneration, fat accumulation, and transcription factor activation in hindlimb muscles of CCR2-/- and wild-type (WT) mice following femoral artery excision (FAE). In both groups, muscle injury and restoration of vascular perfusion were similar. Nevertheless, edema and neutrophil accumulation were significantly elevated in CCR2-/- compared with WT mice at day 1 post-FAE and fewer macrophages were present at day 3. MCP-1 levels in post-ischemic calf muscle of CCR2-/- animals were significantly elevated over baseline through 14 days post-FAE and were higher than WT mice at days 1, 7, and 14. In addition, CCR2-/- mice exhibited impaired muscle regeneration, decreased muscle fiber size, and increased intermuscular adipocytes with similar capillaries/mm(2) postinjury. Finally, the transcription factors, MyoD and signal transducers of and activators of transcription-3 (STAT3), were significantly increased above baseline but did not differ significantly between groups at any time point post-FAE. These findings suggest that increases in MCP-1, and possibly, MyoD and STAT3, may modulate molecular signaling in CCR2-/- mice during inflammatory and regenerative events. Furthermore, alterations in neutrophil and macrophage recruitment in CCR2-/- mice may critically alter the normal progression of downstream regenerative events in injured skeletal muscle and may direct myogenic precursor cells in the regenerating milieu toward an adipogenic phenotype. PMID:17020936

  10. 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

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    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.

  11. High-level expression and characterization of a glycosylated human cementum protein 1 with lectin activity.

    Science.gov (United States)

    Romo-Arévalo, Enrique; Arzate, Higinio; Montoya-Ayala, Gonzalo; Rodríguez-Romero, Adela

    2016-01-01

    This work aims to contribute to the knowledge of human cementum protein 1 (CEMP1), its conformational characteristics and influence during the biomineralization process. The results revealed that hrCEMP1 expressed in Pichia pastoris is a 2.4% glycosylated, thermostable protein which possesses a molecular mass of 28 770 Da. The circular dichroism spectrum indicated a secondary structure content of 28.6% of alpha-helix, 9.9% of beta-sheet and 61.5% of random-coil forms. Biological activity assays demonstrated that hrCEMP1 nucleates and regulates hydroxyapatite crystal growth. Hereby, it is demonstrated for the first time that CEMP1 has a (C-type) lectin-like activity and specifically recognizes mannopyranoside. The information produced by this biochemical and structural characterization may contribute to understand more fully the biological functions of CEMP1. PMID:26763148

  12. Involvement of fractalkine and macrophage inflammatory protein-1 alpha in moderate-severe depression

    Directory of Open Access Journals (Sweden)

    Rosaria Alba Merendino

    2004-01-01

    Full Text Available MODERATE-severe depression (MSD is linked to overexpression of proinflammatory cytokines and chemokines. Fractalkine (FKN and macrophage inflammatory protein-1 alpha (MIP-1α are, respectively, members of CX3C and C-C chemokines, and both are involved in recruiting and activating mononuclear phagocytes in the central nervous system. We analysed the presence of FKN and MIP-1α in sera of untreated MSD patients and healthy donors. High FKN levels were observed in all MSD patients as compared with values only detectable in 26% of healthy donors. MIP-1α was measurable in 20% of patients, while no healthy donors showed detectable chemokine levels. In conclusion, we describe a previously unknown involvement of FKN in the pathogenesis of MSD, suggesting that FKN may represent a target for a specific immune therapy of this disease.

  13. Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes

    International Nuclear Information System (INIS)

    The Arabidopsis dynamin-related protein 1A (AtDRP1A) is involved in endocytosis and cell plate maturation in Arabidopsis. Unlike dynamin, AtDRP1A does not have any recognized membrane binding or protein-protein interaction domains. We report that GTPase active AtDRP1A purified from Escherichia coli as a fusion to maltose binding protein forms homopolymers visible by negative staining electron microscopy. These polymers interact with protein-free liposomes whose lipid composition mimics that of the inner leaflet of the Arabidopsis plasma membrane, suggesting that lipid-binding may play a role in AtDRP1A function. However, AtDRP1A polymers do not appear to assemble and disassemble in a dynamic fashion and do not have the ability to tubulate liposomes in vitro, suggesting that additional factors or modifications are necessary for AtDRP1A's in vivo function.

  14. Human Cementum Protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts

    International Nuclear Information System (INIS)

    We recently presented evidence showing that a human cementoblastoma-derived protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of cementoblast differentiation and cementum-matrix mineralization. This protein was shown to be expressed by cementoblasts and progenitor cells localized in the periodontal ligament. In this study we demonstrate that transfection of CEMP1 into human gingival fibroblasts (HGF) induces mineralization and expression of bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline phosphatase activity and proliferation rate and they expressed genes for alkaline phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced biological-type hydroxyapatite. These findings indicate that the CEMP1 might participate in differentiation and mineralization of nonosteogenic cells, and that it might have a potential function in cementum and bone formation

  15. Dynamin-Related Protein 1 Translocates from the Cytosol to Mitochondria during UV-Induced Apoptosis

    International Nuclear Information System (INIS)

    Mitochondria are dynamic structures that frequently divide and fuse with one another to form interconnecting network. This network disintegrates into punctiform organelles during apoptosis. However, the mechanisms involved in these processes are still not well characterized. In this study, we investigate the role of dynamin-related protein 1 (Drp1), a large GTPase that mediates outer mitochondrial membrane fission, in mitochondrial dynamics in response to UV irradiation in human lung adenocarcinoma cells (ASTC-α-1) and HeLa cells. Using time-lapse fluorescent imaging, we find that Drp1 primarily distributes in cytosol under physiological conditions. After UV treatment, Drp1 translocates from cytosol to mitochondria, indicating the enhancement of Drp1 mitochondrial accumulation. Our results suggest that Drp1 is involved in the regulation of transition from an interconnecting network to a punctiform mitochondrial phenotype during UV-induced apoptosis.

  16. Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania

    DEFF Research Database (Denmark)

    Kavishe, Reginald A; Paulo, Petro; Kaaya, Robert D;

    2014-01-01

    recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania. METHODS: A total of 687 Plasmodium......BACKGROUND: Resistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malarial parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu) is the...... in all regions, ranging from 17% - 26%. CONCLUSION: This is the first country-wide survey on Pfmdr1 mutations associated with ACT resistance. Distribution of individual Pfmdr1 mutations at codons 86, 184 and 1246 varies throughout Tanzanian regions. There is a general homogeneity in distribution of...

  17. Uncoupling protein 1 (UCP1 of brown adipocyte, the only uncoupler: historical perspective

    Directory of Open Access Journals (Sweden)

    Daniel eRicquier

    2011-12-01

    Full Text Available Uncoupling protein 1 - UCP1, is a unique mitochondrial membranous protein devoted to adaptive thermogenesis, a specialized function operated by the highly specialized oxidative brown adipocytes. Whereas the family of mitochondrial metabolite carriers comprises ~40 members including UCP1, the UCP1 is specifically identified by its ability to translocate protons through the inner membrane of brown adipocyte mitochondria. Doing that, UCP1 uncouples respiration from ATP synthesis and therefore provokes energy dissipation of oxidative energy as heat while, in parallel it markedly stimulates respiration and activates fatty acid oxidation. UCP1 homologues were identified but they are biochemically and physiologically different from UCP1. Thirty five years after its identification, UCP1 still appears as a fascinating component, and the recent renewal of the interest in human brown adipose tissue makes UCP1 as a potential target for strategies of treatment of metabolic disorders.

  18. X-ray repair cross complementing protein 1 in base excision repair

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour;

    2012-01-01

    X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...... multiprotein DNA repair complexes as well as facilitate the recruitment of DNA repair proteins to sites of DNA damage. Moreover, XRCC1 is present in constitutive DNA repair complexes, some of which associate with the replication machinery. Because of the critical role of XRCC1 in DNA repair, its common...... variants Arg194Trp, Arg280His and Arg399Gln have been extensively studied. However, the prevalence of these variants varies strongly in different populations, and their functional influence on DNA repair and disease remains elusive. Here we present the current knowledge about the role of XRCC1 and its...

  19. Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas

    DEFF Research Database (Denmark)

    Jensen, Stine S; Aaberg-Jessen, Charlotte; Christensen, Karina G;

    2013-01-01

    Targeting of lysosomes is a novel therapeutic anti-cancer strategy for killing the otherwise apoptosis-resistant cancer cells. Such strategies are urgently needed for treatment of brain tumors, especially the glioblastoma, which is the most frequent and most malignant type. The aim of the present...... study was to investigate the presence of lysosomes in astrocytic brain tumors focussing also on the therapy resistant tumor stem cells. Expression of the lysosomal marker LAMP-1 (lysosomal-associated membrane protein-1) was investigated by immunohistochemistry in 112 formalin fixed paraffin embedded...... individual tumor grades. LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. The results suggest that high amounts of lysosomes are present in glioblastomas and in the proposed tumor stem...

  20. Serum concentration and interaction properties of MBL/ficolin associated protein-1

    DEFF Research Database (Denmark)

    Skjoedt, Mikkel-Ole; Hummelshoj, Tina; Palarasah, Yaseelan;

    2011-01-01

    Recently, a novel protein named MBL/ficolin associated protein-1 (MAP-1) derived from the MASP1 gene through differential splicing was identified. In the present study, we established biochemical characteristics, determined the serum level and assessed the interactions between the lectin complement...... pathway (LCP) recognition molecules and MAP-1. We expressed recombinant MAP-1 in CHO DG44 cells, developed a quantitative ELISA assay based on a MAP-1 specific monoclonal capture antibody and measured the serum levels in 100 Danish blood donors. In addition we assessed the association properties between...... without the signal peptide. We found that serum MAP-1 was very stable when subjected to repeated freeze and thaw cycles. The mean serum concentration of MAP-1 was found to be 240ng/ml (range: 115-466ng/ml). MAP-1 was predominantly found in complex with Ficolin-3 and to a lesser degree with Ficolin-2...

  1. Molecular modeling of the human multidrug resistance protein 1 (MRP1/ABCC1)

    International Nuclear Information System (INIS)

    Multidrug resistance protein 1 (MRP1/ABCC1) is a 190 kDa member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters that is clinically relevant for its ability to confer multidrug resistance by actively effluxing anticancer drugs. Knowledge of the atomic structure of MRP1 is needed to elucidate its transport mechanism, but only low resolution structural data are currently available. Consequently, comparative modeling has been used to generate models of human MRP1 based on the crystal structure of the ABC transporter Sav1866 from Staphylococcus aureus. In these Sav1866-based models, the arrangement of transmembrane helices differs strikingly from earlier models of MRP1 based on the structure of the bacterial lipid transporter MsbA, both with respect to packing of the twelve helices and their interactions with the nucleotide binding domains. The functional importance of Tyr324 in transmembrane helix 6 predicted to project into the substrate translocation pathway was investigated

  2. Regulation of skeletal muscle regeneration by CCR2-activating chemokines is directly related to macrophage recruitment.

    Science.gov (United States)

    Martinez, Carlo O; McHale, Matthew J; Wells, Jason T; Ochoa, Oscar; Michalek, Joel E; McManus, Linda M; Shireman, Paula K

    2010-09-01

    Muscle regeneration requires CC chemokine receptor 2 (CCR2) expression on bone marrow-derived cells; macrophages are a prominent CCR2-expressing cell in this process. CCR2-/- mice have severe impairments in angiogenesis, macrophage recruitment, and skeletal muscle regeneration following cardiotoxin (CTX)-induced injury. However, multiple chemokines activate CCR2, including monocyte chemotactic proteins (MCP)-1, -3, and -5. We hypothesized that MCP-1 is the chemokine ligand that mediates the impairments present in CCR2-/- mice. We examined muscle regeneration, capillary density, and cellular recruitment in MCP-1-/- and CCR2-/- mice following injury. Muscle regeneration and adipocyte accumulation, but not capillary density, were significantly impaired in MCP-1-/- compared with wild-type (WT) mice; however, muscle regeneration and adipocyte accumulation impairments were not as severe as observed in CCR2-/- mice. Although tissue levels of MCP-5 were elevated in MCP-1-/- mice compared with WT, the administration of MCP-5 neutralizing antibody did not alter muscle regeneration in MCP-1-/- mice. While neutrophil accumulation after injury was similar in all three mouse strains, macrophage recruitment was highest in WT mice, intermediate in MCP-1-/- mice, and severely impaired in CCR2-/- mice. In conclusion, while the absence of MCP-1 resulted in impaired macrophage recruitment and muscle regeneration, MCP-1-/- mice exhibit an intermediate phenotype compared with CCR2-/- mice. Intermediate macrophage recruitment in MCP-1-/- mice was associated with similar capillary density to WT, suggesting that fewer macrophages may be needed to restore angiogenesis vs. muscle regeneration. Finally, other chemokines, in addition to MCP-1 and MCP-5, may activate CCR2-dependent regenerative processes resulting in an intermediate phenotype in MCP-1-/- mice. PMID:20631294

  3. 白藜芦醇对高糖诱导内皮细胞损伤代谢记忆效应的研究%Effects of resveratrol on high glucose memory-induced injury to endothelial cell

    Institute of Scientific and Technical Information of China (English)

    丁慧; 王鹏; 王颜刚

    2014-01-01

    Cultured human umbilical vein endothelial cells (HUVECs) were divided and assigned to 6 groups:normal control group,mannitol control group,high glucose group,low dose resveratrol group,medium dose resveratrol group,and high dose resveratrol group.HUVECs were pretreated with or without 30 mmol/L glucose plus various concentrations of resveratrol (0.1,1,10 μmol/L) for 16 hours and then incubated with 5.5 mmol/L glucose for 6 days.The levels of vascular cell adhesion molecule 1 (VCAM-1),monocyte chemotactic protein 1 (MCP-1),and plasminogen activator inhibitor 1 (PAI-1) in the culture supernatant were measured by ELISA.NF-κB expression was detected by Western blot.Compared with normal glucose group,high glucose up-regulated the expression of NF-κB,along with the increased levels of VCAM-1,MCP-1,and PAI-1 (all P<0.05),which were still maintained at high levels even after withdrawal of high glucose.Resveratrol treatment down-regulated the expression of NF-κB and lowered the levels of VCAM-1,MCP-1,and PAI-1 (all P<0.05).These results suggest that resveratrol may decrease the secretion of VCAM-1,MCP-1,and PAI-1 and prevent high glucose memory-induced injury to endothelial cell via NF-κB pathway.%人脐静脉内皮细胞分为正常对照组、甘露醇对照组、高糖组和白藜芦醇低、中、高剂量组,细胞于30 mmol/L葡萄糖和0.1、1和10 μmol/L白藜芦醇培养16h后,再以5.5 mmol/L葡萄糖培养6d,应用ELISA法检测细胞培养上清中血管细胞黏附分子1(VCAM-1)、单核细胞趋化蛋白1(MCP-1)和纤溶酶原激活物抑制剂1(PAI-1)水平,以Western印迹法检测细胞内NF-κB蛋白表达.与正常对照组相比,高糖可诱导内皮细胞NF-κB表达上调(P<0.05),同时VCAM-1、MCP-1和PAI-1水平升高(均P<0.05),且在糖浓度恢复正常后仍持续上升.与高糖组相比,白藜芦醇预处理可以明显减少NF-κB表达,降低VCAM-1、MCP-1和PAI-1水平(均P<0.05).结果提示白藜芦醇可

  4. Identification, characterization and antigenicity of the Plasmodium vivax rhoptry neck protein 1 (PvRON1

    Directory of Open Access Journals (Sweden)

    Patarroyo Manuel E

    2011-10-01

    Full Text Available Abstract Background Plasmodium vivax malaria remains a major health problem in tropical and sub-tropical regions worldwide. Several rhoptry proteins which are important for interaction with and/or invasion of red blood cells, such as PfRONs, Pf92, Pf38, Pf12 and Pf34, have been described during the last few years and are being considered as potential anti-malarial vaccine candidates. This study describes the identification and characterization of the P. vivax rhoptry neck protein 1 (PvRON1 and examine its antigenicity in natural P. vivax infections. Methods The PvRON1 encoding gene, which is homologous to that encoding the P. falciparum apical sushi protein (ASP according to the plasmoDB database, was selected as our study target. The pvron1 gene transcription was evaluated by RT-PCR using RNA obtained from the P. vivax VCG-1 strain. Two peptides derived from the deduced P. vivax Sal-I PvRON1 sequence were synthesized and inoculated in rabbits for obtaining anti-PvRON1 antibodies which were used to confirm the protein expression in VCG-1 strain schizonts along with its association with detergent-resistant microdomains (DRMs by Western blot, and its localization by immunofluorescence assays. The antigenicity of the PvRON1 protein was assessed using human sera from individuals previously exposed to P. vivax malaria by ELISA. Results In the P. vivax VCG-1 strain, RON1 is a 764 amino acid-long protein. In silico analysis has revealed that PvRON1 shares essential characteristics with different antigens involved in invasion, such as the presence of a secretory signal, a GPI-anchor sequence and a putative sushi domain. The PvRON1 protein is expressed in parasite's schizont stage, localized in rhoptry necks and it is associated with DRMs. Recombinant protein recognition by human sera indicates that this antigen can trigger an immune response during a natural infection with P. vivax. Conclusions This study shows the identification and characterization of

  5. Expression of Yes-associated protein 1 gene and protein in oral squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Song-ying; HU Ji-an; WANG Hui-ming

    2013-01-01

    Background Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the oral and maxillofaoial region.Yes-associated protein 1 (YAP1) has been implicated as a bona fide oncogene in solid tumors.We seek to elucidate the role of YAP1 in OSCC tissue.Methods We identified YAP1 gene and protein overexpression in 30 OSCC patients and 10 normal oral mucosa tissues by immunohistochemistry,Western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results In the normal oral mucosa by immunohistochemical staining,YAP1 mainly located in both the cytoplasm and nucleus mainly the nuclei of the basal cells.In OSCC,the expression of YAP1 translocated from the nucleus to cytoplasm;YAP1 being mainly located in both the cytoplasm and nucleus of the adjacent mucosa.The expression of YAP1 gradual increased in normal oral mucosa,tumor adjacent mucosa and low grade,middle grade,high grade OSCC tissue by Western blotting.Significant difference was found between the expressions of the normal oral mucosa and OSCC tissue (P <0.05).The coincidence was detected between the normal oral mucosa and OSCC tissue by RT-PCR (P <0.05).Conclusions YAP1 is involved in the carcinogenesis and development of OSCC.There is a transformation between nucleus and cytoplasm.

  6. Identification and characterization a novel transcription factor activator protein-1 in the sea cucumber Apostichopus japonicus.

    Science.gov (United States)

    Yang, Limeng; Li, Chenghua; Chang, Yaqing; Gao, Yinxue; Wang, Yi; Wei, Jing; Song, Jian; Sun, Ping

    2015-08-01

    The transcription factor activator protein-1 (AP-1) is an important gene expression regulator with typical Jun and region-leucine zipper (bZIP) domains and can respond to a plethora of physiological and pathological stimulus. In this study, we identified a novel AP-1 gene in Apostichopus japonicus by transcriptome sequencing and RACE approaches (designated as AjAP-1). The full-length of AjAP-1 was of 2944 bp including a 5' untranslated region (UTR) of 201 bp, a 3' UTR of 1753 bp and a putative open reading frame of 990 bp encoding a polypeptide of 329 amino acid residues. Two representative domains of Jun and bZIP as well as two nuclear localization signals (NLSs) were also detected in deduced amino acid of AjAP-1. Spatial distribution expression indicated that AjAP-1 was ubiquitously expressed in all examined tissues with predominant expression in the body wall, moderate in the tube feet, respiratory tree and colemocytes and slightly weak in the intestine and longitudinal muscle. Time-course expression analysis in intestine and coelomocytes revealed that AjAP-1 both reached its peak expression at 4 h after Vibrio splendidus challenge with a 2.6 and 8.2-fold increase compared to their control groups, respectively. Taken together, all these results suggested that AjAP-1 was a novel immune factor and might be involved in the processes of anti-bacteria response in sea cucumber. PMID:26093208

  7. Circulating renalase, catecholamines, and vascular adhesion protein 1 in hypertensive patients.

    Science.gov (United States)

    Maciorkowska, Dominika; Zbroch, Edyta; Malyszko, Jolanta

    2015-11-01

    The aim of the study was to estimate and correlate circulating levels of renalase, vascular adhesion protein-1 (VAP-1), catecholamines in patients with primary hypertension. The renalase, VAP-1, and catecholamines concentration was estimated in 121 hypertensive patients. The correlation between renalase, VAP-1 levels and catecholamine concentration in blood, blood pressure control, pharmacological therapy, and medical history were taken in to consideration. The median office blood pressure was 145.5/86 mm Hg and was significantly higher than the median home blood pressure measurement value, which was 135/80 mm Hg, P hypertension comparing to healthy individuals (3.83 μg/mL and 248.37 ng/mL, P blood was observed (r = 0.549; P Hypertensive patients with diabetes mellitus had almost statistically significant higher VAP-1 concentration compared with hypertensive patients without diabetes mellitus (Me = 403.22 ng/mL vs. Me = 326,68 ng/mL, P = .064). In multiple regression analysis, renalase was predicted by plasma dopamine and norepinephrine as also diastolic office blood pressure and left ventricle ejection fraction. Circulating renalase and VAP-1 levels are elevated in patients with poor blood pressure control. Its correlation with noradrenalin concentration need further studies to find out the role of renalase as also VAP-1 in pathogenesis and treatment of hypertension. PMID:26403854

  8. Dynamin like protein 1 participated in the hemoglobin uptake pathway of Plasmodium falciparum

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hong-chang; GAO Yu-hui; ZHONG Xiang; WANG Heng

    2009-01-01

    Background During the blood stage of malaria infection, parasites internalize in the host red blood cells and degrade massive amounts of hemoglobin for their development. Although the morphology of the parasite's hemoglobin uptake pathway has been clearly observed, little has been known about its molecular mechanisms. Methods The recombinant proteins from Plasmodium falciparum, dynamin like protein 1 (PfDYN1) and 2 (PfDYN2) GTPase domain, were expressed in E .coli and showed GTPase activity. By using a dynamin inhibitor, dynasore, we demonstrated the involvement of PfDYN1 in the hemoglobin uptake pathway. Results The GTPase activity of the two recombinant proteins was inhibited by dynasore in vitro. Treatment of parasite cultures with 80 μmol/L dynasore at the ring and early trophozoite stage resulted in substantial inhibition of parasite growth and in an obvious decline of hemoglobin quantum. Furthermore, reduced intraceliular hemozoin accumulation and decreased uptake of the FITC-dextran were also observed, together with distinctive changes in the ultrastructure of parasites after the dynasore treatment. Conclusions Our results show that PfDYN1 plays an important role in the hemoglobin uptake pathway of P. Falciparum and suggest its possibility of being a novel target for malaria chemotherapy.

  9. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

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    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.

  10. Glutamate Receptor Interacting Protein 1 Regulates CD4(+) CTLA-4 Expression and Transplant Rejection.

    Science.gov (United States)

    Modjeski, K L; Levy, S C; Ture, S K; Field, D J; Shi, G; Ko, K; Zhu, Q; Morrell, C N

    2016-05-01

    PDZ domains are common 80- to 90-amino-acid regions named after the first three proteins discovered to share these domains: postsynaptic density 95, discs large, and zonula occludens. PDZ domain-containing proteins typically interact with the C-terminus of membrane receptors. Glutamate receptor interacting protein 1 (GRIP1), a seven-PDZ domain protein scaffold, regulates glutamate receptor surface expression and trafficking in neurons. We have found that human and mouse T cells also express GRIP1. T cell-specific GRIP1(-/-) mice >11 weeks old had prolonged cardiac allograft survival. Compared with wild-type T cells, in vitro stimulated GRIP1(-/-) T cells had decreased expression of activation markers and increased apoptotic surface marker expression. Surface expression of the strong T cell inhibitory molecule cytotoxic T lymphocyte antigen-4 (CTLA-4) was increased on GRIP1(-/-) T cells from mice >11 weeks old. CTLA-4 increases with T cell stimulation and its surface expression on GRIP1(-/-) T cells remained high after stimulation was removed, indicating a possible internalization defect in GRIP1-deficient T cells. CTLA-4-blocking antibody treatment following heart transplantation led to complete rejection in T cell GRIP1(-/-) mice, indicating that increased CTLA-4 surface expression contributed to the extended graft survival. Our data indicate that GRIP1 regulates T cell activation by regulating CTLA-4 surface expression. PMID:26601915

  11. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

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    Qin Lan

    2011-12-01

    Full Text Available Abstract Background The nonstructural protein 1 (NSP1 of rotavirus has been reported to block interferon (IFN signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs and (or the β-transducin repeat containing protein (β-TrCP. However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms. Results The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I, but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS, indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way. Conclusions Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.

  12. Improved crystallization and diffraction of caffeine-induced death suppressor protein 1 (Cid1)

    Energy Technology Data Exchange (ETDEWEB)

    Yates, Luke A., E-mail: luke@strubi.ox.ac.uk; Durrant, Benjamin P.; Barber, Michael; Harlos, Karl [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Fleurdépine, Sophie; Norbury, Chris J. [University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Gilbert, Robert J. C., E-mail: luke@strubi.ox.ac.uk [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

    2015-02-21

    The use of truncation and RNA-binding mutations of caffeine induced death suppressor protein 1 (Cid1) as a means to enhance crystallogenesis leading to an improvement of X-ray diffraction resolution by 1.5 Å is reported. The post-transcriptional addition of uridines to the 3′-end of RNAs is an important regulatory process that is critical for coding and noncoding RNA stability. In fission yeast and metazoans this untemplated 3′-uridylylation is catalysed by a single family of terminal uridylyltransferases (TUTs) whose members are adapted to specific RNA targets. In Schizosaccharomyces pombe the TUT Cid1 is responsible for the uridylylation of polyadenylated mRNAs, targeting them for destruction. In metazoans, the Cid1 orthologues ZCCHC6 and ZCCHC11 uridylate histone mRNAs, targeting them for degradation, but also uridylate microRNAs, altering their maturation. Cid1 has been studied as a model TUT that has provided insights into the larger and more complex metazoan enzyme system. In this paper, two strategies are described that led to improvements both in the crystallogenesis of Cid1 and in the resolution of diffraction by ∼1.5 Å. These advances have allowed high-resolution crystallo@@graphic studies of this TUT system to be initiated.

  13. Long form collapsin response mediator protein-1 promotes the migration and invasion of osteosarcoma cells

    Science.gov (United States)

    HOU, HUIGE; CHEN, LIN; ZHA, ZHENGANG; CAI, SHAOHUI; TAN, MINGHUI; GUO, GUOQING; LIU, NING; SHE, GUORONG; XUN, SONGWEI

    2016-01-01

    It has been reported that long form collapsin response mediator protein-1 (LCRMP-1) promotes the metastasis of non-small cell lung cancer. Osteosarcoma (OS) is a human cancer with a high potential for metastasis. The present study aimed to investigate the role of LCRMP-1 in OS metastasis. The expression of LCRMP-1 in OS specimens and cell lines was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Furthermore, the migration and invasion of OS cells with LCRMP-1-knockdown was investigated to examine the role of LCRMP-1 in OS metastasis. In addition, the expression of N-cadherin and matrix metalloproteinases (MMPs), which are involved in cell migration, was evaluated using RT-qPCR. Increased expression of LCRMP-1 was observed in the OS tissues and cell lines, accompanied by the enhanced migration and invasion of the OS cells. LCRMP-1-knockdown resulted in a significant decrease in the expression of N-cadherin and MMPs, as well as inhibition of the migration and invasion of the OS cells. Overexpression of LCRMP-1 promoted OS metastasis. Therefore, LCRMP-1 may be a promising target for the effective treatment of OS.

  14. Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization.

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    Valeriy Demchev

    Full Text Available Fibrinogen like protein 1(Fgl1 is a secreted protein with mitogenic activity on primary hepatocytes. Fgl1 is expressed in the liver and its expression is enhanced following acute liver injury. In animals with acute liver failure, administration of recombinant Fgl1 results in decreased mortality supporting the notion that Fgl1 stimulates hepatocyte proliferation and/or protects hepatocytes from injury. However, because Fgl1 is secreted and detected in the plasma, it is possible that the role of Fgl1 extends far beyond its effect on hepatocytes. In this study, we show that Fgl1 is additionally expressed in brown adipose tissue. We find that signals elaborated following liver injury also enhance the expression of Fgl1 in brown adipose tissue suggesting that there is a cross talk between the injured liver and adipose tissues. To identify extra hepatic effects, we generated Fgl1 deficient mice. These mice exhibit a phenotype suggestive of a global metabolic defect: Fgl1 null mice are heavier than wild type mates, have abnormal plasma lipid profiles, fasting hyperglycemia with enhanced gluconeogenesis and exhibit differences in white and brown adipose tissue morphology when compared to wild types. Because Fgl1 shares structural similarity to Angiopoietin like factors 2, 3, 4 and 6 which regulate lipid metabolism and energy utilization, we postulate that Fgl1 is a member of an emerging group of proteins with key roles in metabolism and liver regeneration.

  15. Nuclear translocation of EGF receptor regulated by Epstein-Barr virus encoded latent membrane protein 1

    Institute of Scientific and Technical Information of China (English)

    TAO; Yongguang; SONG; Xin; TAN; Yunnian; LIN; Xiaofeng; ZH

    2004-01-01

    Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV encoded proteins, and also it has always been the core of the oncogenic mechanism of EBV. Traditional receptor theory demonstrates that cell surface receptors exert biological functions on the membrane, which neither enter into the nucleus nor directly affect the transcription of the target genes. But, advanced studies on nuclear translocation of the epidermal growth factor receptor (EGFR) family have greatly developed our knowledge of the biological function of cell surface receptors. In this study, we used Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1 integrated NPC cell line and the expression of LMP1 in which could be regulated by Tet system. We found that LMP1 could regulate the nuclear translocation of EGFR in a dose-dependent manner from both quantitative and qualitative levels through the Western blot analysis and the immunofluorescent analysis with a laser scanning confocal microscope. We further demonstrated that the nuclear localization sequence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation, and the nuclear accumulation of EGFR regulated by LMP1 was in a ligand-independent manner. These findings provide a novel view that the regulation of LMP1 on the nuclear translocation of EGFR is critical for the process of nasopharyngeal carcinoma.

  16. Specific interaction with cardiolipin triggers functional activation of Dynamin-Related Protein 1.

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    Itsasne Bustillo-Zabalbeitia

    Full Text Available Dynamin-Related Protein 1 (Drp1, a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G, bundle signaling element (BSE and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL. Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.

  17. Immunity against heterosubtypic influenza virus induced by adenovirus and MVA expressing nucleoprotein and matrix protein-1.

    Science.gov (United States)

    Lambe, Teresa; Carey, John B; Li, Yuanyuan; Spencer, Alexandra J; van Laarhoven, Arjan; Mullarkey, Caitlin E; Vrdoljak, Anto; Moore, Anne C; Gilbert, Sarah C

    2013-01-01

    Alternate prime/boost vaccination regimens employing recombinant replication-deficient adenovirus or MVA, expressing Influenza A virus nucleoprotein and matrix protein 1, induced antigen-specific T cell responses in intradermally (ID) vaccinated mice; with the strongest responses resulting from Ad/MVA immunization. In BALB/C mice the immunodominant response was shifted from the previously identified immunodominant epitope to a novel epitope when the antigen was derived from A/Panama/2007/1999 rather than A/PR/8. Alternate immunization routes did not affect the magnitude of antigen-specific systemic IFN-γ response, but higher CD8(+) T-cell IFN-γ immune responses were seen in the bronchoalveolar lavage following intransal (IN) boosting after intramuscular (IM) priming, whilst higher splenic antigen-specific CD8(+) T cell IFN-γ was seen following IM boosting. Partial protection against heterologous influenza virus challenge was achieved following either IM/IM or IM/IN but not ID/ID immunization. These data may be of relevance for the design of optimal immunization regimens for human influenza vaccines, especially for influenza-naïve infants. PMID:23485942

  18. Latent membrane protein 1 of Epstein-Barr virus coordinately regulates proliferation with control of apoptosis.

    Science.gov (United States)

    Dirmeier, Ulrike; Hoffmann, Reinhard; Kilger, Ellen; Schultheiss, Ute; Briseño, Cinthia; Gires, Olivier; Kieser, Arnd; Eick, Dirk; Sugden, Bill; Hammerschmidt, Wolfgang

    2005-03-01

    Latent membrane protein 1 (LMP1), an oncoprotein encoded by Epstein-Barr virus (EBV), is an integral membrane protein, which acts like a constitutively active receptor. LMP1 is critical for some facet of EBV's induction and maintenance of proliferation of infected B cells. It, in part, mimics signaling by the CD40 receptor and has been implicated in regulating proliferation, survival, or both properties of EBV-infected cells. We established a conditional LMP1 allele in the context of the intact EBV genome to define the immediate-early cellular target genes regulated by LMP1 in order to assess its contributions to infected human B cells. The functional analysis of this conditional system indicated that LMP1 specifically induces mitogenic B-cell activation through c-myc and Jun/AP1 family members and confirms its direct role in upregulating expression of multiple genes with opposing activities involved in cell survival. LMP1's signals were found to be essential for the G1/S transition in human B cells; cells lacking LMP1's signals are cell cycle arrested and survive quiescently. LMP1's activities are therefore not required to maintain survival in nonproliferating cells. LMP1 does induce both pro- and antiapoptotic genes whose balance seems to permit survival during LMP1's induction and maintenance of proliferation. PMID:15674340

  19. Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1.

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    Xianpeng Ge

    Full Text Available Cartilage acidic protein 1 (CRTAC1 was recently identified as an elevated protein in the synovial fluid of patients with osteoarthritis (OA by a proteomic analysis. This gene is also upregulated in both human and mouse OA by transcriptomic analysis. The objective of this study was to characterize the expression and function of CRTAC1 in OA. Here, we first confirm the increase of CRTAC1 in cartilage biopsies from OA patients undergoing joint replacement by real-time PCR and immunohistochemistry. Furthermore, we report that proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha upregulate CRTAC1 expression in primary human articular chondrocytes and synovial fibroblasts. Genetic deletion of Crtac1 in mice significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities of post-traumatic OA in female, but not male, animals undergoing the destabilization of medial meniscus (DMM surgery. Taken together, CRTAC1 is upregulated in the osteoarthritic joint and directly induced in chondrocytes and synovial fibroblasts by pro-inflammatory cytokines. This molecule is necessary for the progression of OA in female mice after DMM surgery and thus represents a potential therapy for this prevalent disease, especially for women who demonstrate higher rates and more severe OA.

  20. Roles oflow-density lipoprotein receptor-related protein 1 intumors

    Institute of Scientific and Technical Information of China (English)

    PeipeiXing; ZhichaoLiao; ZhiwuRen; JunZhao; FengjuSong; GuowenWang; KexinChen; Jilong Yang

    2016-01-01

    Low-density lipoprotein receptor-related protein 1 (LRP1, also known as CD91), a multifunctional endocytic and cell signaling receptor, is widely expressed on the surface of multiple cell types such as hepatocytes, ifbroblasts, neu-rons, astrocytes, macrophages, smooth muscle cells, and malignant cells. Emerging invitro and invivo evidence demonstrates that LRP1 is critically involved in many processes that drive tumorigenesis and tumor progression. For example, LRP1 not only promotes tumor cell migration and invasion by regulating matrix metalloproteinase (MMP)-2 and MMP-9 expression and functions but also inhibits cell apoptosis by regulating the insulin receptor, the serine/threonine protein kinase signaling pathway, and the expression of Caspase-3. LRP1-mediated phosphorylation of the extracellular signal-regulated kinase pathway and c-jun N-terminal kinase are also involved in tumor cell proliferation and invasion. In addition, LRP1 has been shown to be down-regulated by microRNA-205 and methylation ofLRP1 CpG islands. Furthermore, a novel fusion gene,LRP1-SNRNP25, promotes osteosarcoma cell invasion and migration. Only by understanding the mechanisms of these effects can we develop novel diagnostic and therapeutic strategies for cancers mediated by LRP1.

  1. Differential Expression of Motility-Related Protein-1 Gene in Gastric Cancer and Its Premalignant Lesions

    Institute of Scientific and Technical Information of China (English)

    YaoXu; JieZheng; WentianLiu; JunXing; YanyunLi; XinGeng; WeimingZhang

    2004-01-01

    OBJECTIVE To identify genes related to gastric cancer and to analyze their expression profiles in different gastric tissues. METHODS The differentially expressed cDNA bands were assayed by fluorescent differential display from gastric cancer specimens, matched with normal gastric mucosa and premalignant lesions. The motility-related protein-1 (MRP-1/CD9) gene expression was studied by Northern blots and reverse transcription polymerase chain reaction (RT-PCR) in different kinds of gastric tissue. RESULTS A differentially expressed cDNA fragment showed lower expression in all gastric cancers compared to the normal gastric mucosa and premalignant lesions; and it was found to be homologous to the MRP-1/CD9 gene. Northern blot analysis confirmed the differential expression. RT-PCR analysis showed that the MRP-1/CD9 gene was expressed at a much lower rate in gastric cancers (0.31 +0.18) compared to the matched normal gastric tissue (0.49+0.24) and premalignant lesions (0.47+0.18)(P<0.05). Furthermore, its expression in intestinal-type of gastric cancer (0.38+0.16) was higher than that expressed in a diffuse-type of gastric cancer (0.22±0.17)(P<0.05). CCONCLUSION The MRP-1/CD9 gene expression was down-regulated in gastric cancer and its expression may be related to the carcinogenic process and histological type of gastric cancer.

  2. The Y-Box Binding Protein 1 Suppresses Alzheimer's Disease Progression in Two Animal Models.

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    N V Bobkova

    Full Text Available The Y-box binding protein 1 (YB-1 is a member of the family of DNA- and RNA binding proteins. It is involved in a wide variety of DNA/RNA-dependent events including cell proliferation and differentiation, stress response, and malignant cell transformation. Previously, YB-1 was detected in neurons of the neocortex and hippocampus, but its precise role in the brain remains undefined. Here we show that subchronic intranasal injections of recombinant YB-1, as well as its fragment YB-11-219, suppress impairment of spatial memory in olfactory bulbectomized (OBX mice with Alzheimer's type degeneration and improve learning in transgenic 5XFAD mice used as a model of cerebral amyloidosis. YB-1-treated OBX and 5XFAD mice showed a decreased level of brain β-amyloid. In OBX animals, an improved morphological state of neurons was revealed in the neocortex and hippocampus; in 5XFAD mice, a delay in amyloid plaque progression was observed. Intranasally administered YB-1 penetrated into the brain and could enter neurons. In vitro co-incubation of YB-1 with monomeric β-amyloid (1-42 inhibited formation of β-amyloid fibrils, as confirmed by electron microscopy. This suggests that YB-1 interaction with β-amyloid prevents formation of filaments that are responsible for neurotoxicity and neuronal death. Our data are the first evidence for a potential therapeutic benefit of YB-1 for treatment of Alzheimer's disease.

  3. Latent membrane protein 1 inhibits apoptosis induced by 60 irradiation via Survivin triggering signal-pathway

    International Nuclear Information System (INIS)

    Objective: To investigate the anti-apoptosis mechanism of EB virus encoden latent membrane protein 1 (LMP1) via the survivin signal transduction pathway after irradiation induction. Methods: Tet-on- LMP1 HNE2 cells, as a model, were detected with morphological assay, flowcytometry and Caspase 3 assay after 60Co irradiation with LMP1 induced by doxycycline. The apoptosis in the anti-sense survivin transfected cells was tested. Results: The results showed that, with LMP1 expression, the apoptosis rates from morphological assay and flowcytometry were 32.7%±2.1% and 6.3%, which showed that they were all lower than that without LMP1 expression (66.0%±3.0% and 29.6%). When anti-sense of survivin was induced, the apoptosis rates were 59.0%±3.2% and 3.0% respectively, and caspase 3 activity was 3.78 nmol/106 cells, which were higher than that of the control (26.0%±2.6%, 8.6% and 2.79 nmol/106). Survivin restrained the cell apoptosis induced by irradiation, but anti-sense of survivin could release this inhibition of cell apoptosis triggered by LMP1 expression. Conclusion: LMP1 inhibits the irradiation-induced cell apoptosis via triggering survivin expression. Survivin may be targeted in some certain therapy

  4. Cysteine-rich protein 1 (CRP1 regulates actin filament bundling

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    Fraley Tamara S

    2005-12-01

    Full Text Available Abstract Background Cysteine-rich protein 1 (CRP1 is a LIM domain containing protein localized to the nucleus and the actin cytoskeleton. CRP1 has been demonstrated to bind the actin-bundling protein α-actinin and proposed to modulate the actin cytoskeleton; however, specific regulatory mechanisms have not been identified. Results CRP1 expression increased actin bundling in rat embryonic fibroblasts. Although CRP1 did not affect the bundling activity of α-actinin, CRP1 was found to stabilize the interaction of α-actinin with actin bundles and to directly bundle actin microfilaments. Using confocal and photobleaching fluorescence resonance energy transfer (FRET microscopy, we demonstrate that there are two populations of CRP1 localized along actin stress fibers, one associated through interaction with α-actinin and one that appears to bind the actin filaments directly. Consistent with a role in regulating actin filament cross-linking, CRP1 also localized to the membrane ruffles of spreading and PDGF treated fibroblasts. Conclusion CRP1 regulates actin filament bundling by directly cross-linking actin filaments and stabilizing the interaction of α-actinin with actin filament bundles.

  5. Effect of Acupuncture on Uncoupling Protein 1 Gene Expression for Brown Adipose Tissue of Obese Rats

    Institute of Scientific and Technical Information of China (English)

    刘志诚; 孙凤岷; 赵东红; 张中成; 孙志; 吴海涛; 徐炳国; 朱苗花; 李朝军

    2003-01-01

    Objective: To explore the effects of acupuncture on the expression of uncoupling protein 1(UCP1) gene of brown adipose tissue (BAT) in obese rats. Methods: The expression of UCP1 gene of BAT was determined with RT-PCR technique. The changes of body weight, Lee′s index, body fat, and the expression of UCP1 gene of BAT in obese rats were observed before and after acupuncture. Resuits:The body weight, Lee′s index, body fat in obese rats were all markedly higher than those in normal rats,but the expression of UCP1 gene of BAT in obese rats was all lower than that in normal rats. There were negative correlation between the obesity index and the expression of UCP1 gene in BAT. After acupuncture the marked effect of weight loss was achieved while the expression of UCP1 gene of BAT obviously increased in obese rats. Conclusion: The abnormal reduction for expression of UCP1 gene of BAT might be an important cause for the obesity. To promote the expression of UCP1 in obese organism might be an important cellular and molecular mechanism in anti-obesity effect by acupuncture.

  6. Stimulation of IGF-binding protein-1 secretion by AMP-activated protein kinase.

    Science.gov (United States)

    Lewitt, M S

    2001-04-20

    Insulin-like growth factor-binding protein-1 (IGFBP-1) is stimulated during intensive exercise and in catabolic conditions to very high concentrations, which are not completely explained by known regulators such as insulin and glucocorticoids. The role of AMP-activated protein kinase (AMPK), an important signaling system in lipid and carbohydrate metabolism, in regulating IGFBP-1 was studied in H4-II-E rat hepatoma cells. Arsenic(III) oxide and 5-aminoimidazole-4-carboxamide-riboside (AICAR) were used as activators. AICAR (150 microM) stimulated IGFBP-1 secretion twofold during a 5-h incubation (P = 0.002). Insulin (100 ng/ml) inhibited IGFBP-1 by 80% (P < 0.001), but this was completely abolished in the presence of 150 microM AICAR. The effect of dexamethasone in stimulating IGFBP-1 threefold was additive to the effect of AICAR (P < 0.001) and, in the presence of AICAR, was incompletely inhibited by insulin. In conclusion AMPK is identified as a novel regulatory pathway for IGFBP-1, stimulating secretion and blocking the inhibitory effect of insulin. PMID:11302732

  7. LDL Receptor-Related Protein-1 (LRP1 Regulates Cholesterol Accumulation in Macrophages.

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    Anna P Lillis

    Full Text Available Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cell formation are incompletely understood. To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cell formation, but the in vivo contribution of the LDL receptor-related protein 1 (LRP1 to this process is not known [corrected]. To investigate the role of LRP1 in cholesterol accumulation in macrophages, we generated mice with a selective deletion of LRP1 in macrophages on an LDL receptor (LDLR-deficient background (macLRP1-/-. After feeding mice a high fat diet for 11 weeks, peritoneal macrophages isolated from Lrp+/+ mice contained significantly higher levels of total cholesterol than those from macLRP1-/- mice. Further analysis revealed that this was due to increased levels of cholesterol esters. Interestingly, macLRP1-/- mice displayed elevated plasma cholesterol and triglyceride levels resulting from accumulation of large, triglyceride-rich lipoprotein particles in the circulation. This increase did not result from an increase in hepatic VLDL biosynthesis, but rather results from a defect in catabolism of triglyceride-rich lipoprotein particles in macLRP1-/- mice. These studies reveal an important in vivo contribution of macrophage LRP1 to cholesterol homeostasis.

  8. Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer.

    Science.gov (United States)

    Friedrich, Teresa; Söhn, Michaela; Gutting, Tobias; Janssen, Klaus-Peter; Behrens, Hans-Michael; Röcken, Christoph; Ebert, Matthias P A; Burgermeister, Elke

    2016-06-01

    Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers. Small DOK1 variants remain in cells of solid tumors and leukemias, albeit, their functions are elusive. To assess the so far unknown role of DOK1 in colorectal cancer (CRC), we generated DOK1 mutants which mimic the domain structure and subcellular distribution of DOK1 protein variants in leukemia patients. We found that cytoplasmic DOK1 activated peroxisome-proliferator-activated-receptor-gamma (PPARγ) resulting in inhibition of the c-FOS promoter and cell proliferation, whereas nuclear DOK1 was inactive. PPARγ-agonist increased expression of endogenous DOK1 and interaction with PPARγ. Forward translation of this cell-based signaling model predicted compartmentalization of DOK1 in patients. In a large series of CRC patients, loss of DOK1 protein was associated with poor prognosis at early tumor stages (*p=0.001; n=1492). In tumors with cytoplasmic expression of DOK1, survival was improved, whereas nuclear localization of DOK1 correlated with poor outcome, indicating that compartmentalization of DOK1 is critical for CRC progression. Thus, DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARγ-agonist, may constitute a potential target for future cancer treatments. PMID:27428427

  9. BRCA-associated protein 1 mutant cholangiocarcinoma: an aggressive disease subtype

    Science.gov (United States)

    Al-Shamsi, Humaid O.; Anand, Deepa; Shroff, Rachna T.; Jain, Apurva; Zuo, Mingxin; Conrad, Claudius; Vauthey, Jean-Nicolas

    2016-01-01

    Background BRCA-associated protein 1, an enzyme encoded by the BAP1 gene, is commonly mutated in uveal melanoma, mesothelioma, and renal cancers. Tumors with BAP1 mutation follow an aggressive course. BAP1 mutations have also been observed in cholangiocarcinoma (CCA). The clinical phenotype of BAP1 mutant CCA may yield useful prognostic and therapeutic information but has not been defined. Methods The records of CCA patients who underwent next-generation sequencing (NGS) were reviewed, and data on clinical, histopathological, genetic, and radiological features; response to therapy; time to progression; and survival were analyzed. Results Twenty-two cases of BAP1-mutation associated CCA were diagnosed from January 1, 2009, to February 1, 2015, at our center. Twenty patients had intrahepatic CCA and two had extrahepatic CCA. Tumor sizes (largest dimension) ranged from 2 to 16 cm (mean, 8.5 cm). Twelve patients had tumors that were poorly differentiated. Majority of the patients had advanced disease at presentation and 13 had bone metastases. Thirteen patients (59%) experienced rapidly progressive disease following primary therapy (chemotherapy or surgical resection). The mean time to tumor progression was 3.8 months after the first line chemotherapy. Conclusions BAP1 mutation in CCA may be associated with aggressive disease and poor response to standard therapies. Therefore, BAP1-targeted therapies need to be investigated. PMID:27563445

  10. Vitamin D represses dentin matrix protein 1 in cementoblasts and osteocytes.

    Science.gov (United States)

    Nociti, F H; Foster, B L; Tran, A B; Dunn, D; Presland, R B; Wang, L; Bhattacharyya, N; Collins, M T; Somerman, M J

    2014-02-01

    Calcium and phosphorus homeostasis is achieved by interplay among hormones, including 1,25(OH)2D3 (1,25D), parathyroid hormone, and fibroblast growth factor 23 (FGF23), and their interactions with other proteins. For example, mutations in dentin matrix protein 1 (DMP-1) result in increased FGF23 and hypophosphatemic rickets. 1,25D is reported to modulate FGF23; thus, we hypothesized that 1,25D may be involved in modulating DMP-1 in an intermediary step. Murine cementoblasts (OCCM-30) and osteocyte-like cells (MLO-Y4 and MLO-A5), known to express DMP-1, were used to analyze effects of 1,25D on DMP-1 expression in vitro. DMP-1 mRNA levels decreased by 50% (p < .05) in the presence of 1,25D in all cell types, while use of a vitamin D receptor (VDR) agonist (EB1089) and antagonist (23S,25S)-DLAM-2P confirmed that VDR pathway activation was required for this response. Further analysis showed that histone deacetylase recruitment was necessary, but neither protein kinase A nor C pathways were required. In conclusion, our results support the hypothesis that 1,25D regulates DMP-1 expression through a VDR-dependent mechanism, possibly contributing to local changes in bone/tooth mineral homeostasis. PMID:24334408

  11. The AUXIN BINDING PROTEIN 1 is required for differential auxin responses mediating root growth.

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    Alexandre Tromas

    Full Text Available BACKGROUND: In plants, the phytohormone auxin is a crucial regulator sustaining growth and development. At the cellular level, auxin is interpreted differentially in a tissue- and dose-dependent manner. Mechanisms of auxin signalling are partially unknown and the contribution of the AUXIN BINDING PROTEIN 1 (ABP1 as an auxin receptor is still a matter of debate. METHODOLOGY/PRINCIPAL FINDINGS: Here we took advantage of the present knowledge of the root biological system to demonstrate that ABP1 is required for auxin response. The use of conditional ABP1 defective plants reveals that the protein is essential for maintenance of the root meristem and acts at least on the D-type CYCLIN/RETINOBLASTOMA pathway to control entry into the cell cycle. ABP1 affects PLETHORA gradients and confers auxin sensitivity to root cells thus defining the competence of the cells to be maintained within the meristem or to elongate. ABP1 is also implicated in the regulation of gene expression in response to auxin. CONCLUSIONS/SIGNIFICANCE: Our data support that ABP1 is a key regulator for root growth and is required for auxin-mediated responses. Differential effects of ABP1 on various auxin responses support a model in which ABP1 is the major regulator for auxin action on the cell cycle and regulates auxin-mediated gene expression and cell elongation in addition to the already well known TIR1-mediated ubiquitination pathway.

  12. The role of vitamin D3 upregulated protein 1 in thioacetamide-induced mouse hepatotoxicity

    International Nuclear Information System (INIS)

    Thioacetamide (TA) is a commonly used drug that can trigger acute hepatic failure (AHF) through generation of oxidative stress. Vitamin D3 upregulated protein 1 (VDUP1) is an endogenous inhibitor of thioredoxin, a ubiquitous thiol oxidoreductase, that regulates cellular redox status. In this study, we investigated the role of VDUP1 in AHF using a TA-induced liver injury model. VDUP1 knockout (KO) and wild-type (WT) mice were subjected to a single intraperitoneal TA injection, and various parameters of hepatic injury were assessed. VDUP1 KO mice displayed a significantly higher survival rate, lower serum alanine aminotransferase and aspartate aminotransferase levels, and less hepatic damage, compared to WT mice. In addition, induction of apoptosis was decreased in VDUP1 KO mice, with the alteration of caspase-3 and -9 activities, Bax-to-Bcl-2 expression ratios, and mitogen activated protein kinase (MAPK) signaling pathway. Importantly, analysis of TA bioactivation revealed lower plasma clearance of TA and covalent binding of [14C]TA to liver macromolecules in VDUP1 KO mice. Furthermore, the level of oxidative stress was significantly less in VDUP1 KO mice than in their WT counterparts, as evident from lipid peroxidation assay. These results collectively indicate that VDUP1 deficiency protects against TA-induced acute liver injury via lower bioactivation of TA and antioxidant effects.

  13. A Computational Approach towards the Understanding of Plasmodium falciparum Multidrug Resistance Protein 1.

    Science.gov (United States)

    Patel, Saumya K; George, Linz-Buoy; Prasanth Kumar, Sivakumar; Highland, Hyacinth N; Jasrai, Yogesh T; Pandya, Himanshu A; Desai, Ketaki R

    2013-01-01

    The emergence of drug resistance in Plasmodium falciparum tremendously affected the chemotherapy worldwide while the intense distribution of chloroquine-resistant strains in most of the endemic areas added more complications in the treatment of malaria. The situation has even worsened by the lack of molecular mechanism to understand the resistance conferred by Plasmodia species. Recent studies have suggested the association of antimalarial resistance with P. falciparum multidrug resistance protein 1 (PfMDR1), an ATP-binding cassette (ABC) transporter and a homologue of human P-glycoprotein 1 (P-gp1). The present study deals about the development of PfMDR1 computational model and the model of substrate transport across PfMDR1 with insights derived from conformations relative to inward- and outward-facing topologies that switch on/off the transportation system. Comparison of ATP docked positions and its structural motif binding properties were found to be similar among other ATPases, and thereby contributes to NBD domains dimerization, a unique structural agreement noticed in Mus musculus Pgp and Escherichia coli MDR transporter homolog (MsbA). The interaction of leading antimalarials and phytochemicals within the active pocket of both wild-type and mutant-type PfMDR1 demonstrated the mode of binding and provided insights of less binding affinity thereby contributing to parasite's resistance mechanism. PMID:25937947

  14. DJ-1 can inhibit microtubule associated protein 1 B formed aggregates

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    Ding Jianqing

    2011-06-01

    Full Text Available Abstract Background Abnormal accumulation and aggregation of microtubule associated proteins (MAPs plays an important role in the pathogenesis of neurodegenerative diseases. Loss-of-function mutation of DJ-1/Park7 can cause early onset of PD. DJ-1, a molecular chaperone, can inhibit α-synuclein aggregation. Currently, little is known whether or not loss of function of DJ-1 contributes to abnormal MAPs aggregation in neurodegenerative disorders such as PD. Results We presented evidence that DJ-1 could bind to microtubule associated protein1b Light Chain (MAP1b-LC. Overexpression of DJ-1 prevented MAP1b-LC aggregation in HEK293t and SH-SY5Y cells while DJ-1 knocking down (KD enhanced MAP1b-LC aggregation in SH-SY5Y cells. The increase in insoluble MAP1b-LC was also observed in the DJ-1 null mice brain. Moreover, in the DJ-1 KD SH-SY5Y cells, overexpression of MAP1B-LC led to endoplasmic reticulum (ER stress-induced apoptosis. Conclusion Our results suggest that DJ-1 acts as a molecular chaperone to inhibit MAP1B aggregation thus leading to neuronal apoptosis. Our study provides a novel insight into the mechanisms that underly the pathogenesis of Parkinson's disease (PD.

  15. Molecular cloning and subcellular localization of Tektin2-binding protein 1 (Ccdc 172) in rat spermatozoa.

    Science.gov (United States)

    Yamaguchi, Airi; Kaneko, Takane; Inai, Tetsuichiro; Iida, Hiroshi

    2014-04-01

    Tektins (TEKTs) are composed of a family of filament-forming proteins localized in cilia and flagella. Five types of mammalian TEKTs have been reported, all of which have been verified to be present in sperm flagella. TEKT2, which is indispensable for sperm structure, mobility, and fertilization, was present at the periphery of the outer dense fiber (ODF) in the sperm flagella. By yeast two-hybrid screening, we intended to isolate flagellar proteins that could interact with TEKT2, which resulted in the isolation of novel two genes from the mouse testis library, referred as a TEKT2-binding protein 1 (TEKT2BP1) and -protein 2 (TEKT2BP2). In this study, we characterized TEKT2BP1, which is registered as a coiled-coil domain-containing protein 172 (Ccdc172) in the latest database. RT-PCR analysis indicated that TEKT2BP1 was predominantly expressed in rat testis and that its expression was increased after 3 weeks of postnatal development. Immunocytochemical studies discovered that TEKT2BP1 localized in the middle piece of rat spermatozoa, predominantly concentrated at the mitochondria sheath of the flagella. We hypothesize that the TEKT2-TEKT2BP1 complex might be involved in the structural linkage between the ODF and mitochondria in the middle piece of the sperm flagella. PMID:24394471

  16. Overexpression of vascular adhesion protein-1 is associated with poor prognosis of astrocytomas.

    Science.gov (United States)

    Kostoro, Joanna; Chang, Shu-Jyuan; Clark Lai, Yen-Chang; Wu, Chun-Chieh; Chai, Chee-Yin; Kwan, Aij-Lie

    2016-06-01

    Vascular adhesion protein-1 (VAP-1) is one of the endothelial adhesion molecules that is believed to play a role in tumor progression and metastasis, supporting cancer cell extravasation. Very few studies have been performed on analyzing the contribution of VAP-1 in brain tumor. Astrocytomas are the most common type of brain tumors, which are classified by World Health Organization (WHO) into four grades according to the degree of malignancy. This study was designed to investigate VAP-1 expression level in different astrocytoma grades and its correlation with clinicopathological features as well as prognosis of astrocytoma patients. Eighty-seven patients with different grades of astrocytoma (WHO Grade I-Grade IV) were enrolled in this study. The expression of VAP-1 was assayed by immunohistochemistry. The correlation between VAP-1 expression and clinicopathological features was evaluated by Chi-square test, and overall survival was analyzed by Kaplan-Meier method. Cox regression analysis was applied to analyze the independent influence of each parameter on overall survival. The expression level of VAP-1 was significantly higher in diffuse astrocytoma than those of pilocytic astrocytoma (p astrocytoma and VAP-1(low) tumors in pilocytic astrocytoma (p astrocytoma. PMID:26935340

  17. FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1

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    Michelle M. Kwon

    2015-11-01

    Full Text Available Fibroblast growth factor 21 (FGF21-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1 levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.

  18. Identification and characterization of the RouenBd1987 Babesia divergens Rhopty-Associated Protein 1.

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    Marilis Rodriguez

    Full Text Available Human babesiosis is caused by one of several babesial species transmitted by ixodid ticks that have distinct geographical distributions based on the presence of competent animal hosts. The pathology of babesiosis, like malaria, is a consequence of the parasitaemia which develops through the cyclical replication of Babesia parasites in a patient's red blood cells, though symptoms typically are nonspecific. We have identified the gene encoding Rhoptry-Associated Protein -1 (RAP-1 from a human isolate of B. divergens, Rouen1987 and characterized its protein product at the molecular and cellular level. Consistent with other Babesia RAP-1 homologues, BdRAP-1 is expressed as a 46 kDa protein in the parasite rhoptries, suggesting a possible role in red cell invasion. Native BdRAP-1 binds to an unidentified red cell receptor(s that appears to be non-sialylated and non-proteinacious in nature, but we do not find significant reduction in growth with anti-rRAP1 antibodies in vitro, highlighting the possibility the B. divergens is able to use alternative pathways for invasion, or there is an alternative, complementary, role for BdRAP-1 during the invasion process. As it is the parasite's ability to recognize and then invade host cells which is central to clinical disease, characterising and understanding the role of Babesia-derived proteins involved in these steps are of great interest for the development of an effective prophylaxis.

  19. [Expression of cyclin-dependent kinase 2-associated protein 1 in chicken embryos of different sexes].

    Science.gov (United States)

    Yang, Yu; Feng, Yan-Ping; Gong, Ping; Huang, Pan; Li, Shi-Jun; Peng, Xiu-Li; Gong, Yan-Zhang

    2009-09-01

    To investigate the expression and functions of cyclin-dependent kinase 2-associated protein 1 (cdk2ap1) screened by suppression subtractive hybridization in chicken embryo development, a pair of primers was designed to amplify the cdk2ap1 fragment by RT-PCR and subsequently the fragment obtained was cloned into the plasmid pGEM-T. Sense and antisense probes labeled with digoxigenin were generated using SP6 and T7 RNA polymerases, respectively, and used to examine cdk2ap1 expression in chicken embryos of both sexes by whole-mount in situ hybridization. In both sexes, cdk2ap1 was expressed in the head mesenchyme, rhombencephalon, optic vesicles, spinal neural tube, and forelimb of 4.0-day-old embryos and the expression in males was significantly higher than that in females. In addition, in the genital ridge and hindlimb of the 4.0-day-old chicken embryo, cdk2ap1 was obviously expressed in the males but not in females. It is supposed that cdk2ap1 may play a role in the sexual differentiation and development of gonad of chicken embryo. PMID:19819846

  20. Fatty acid binding protein 1 is related with development of aspirin-exacerbated respiratory disease.

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    Tae-Hoon Kim

    Full Text Available BACKGROUND: Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the ingestion of aspirin. Although alterations in eicosanoid metabolites play a role in AERD, other immune or inflammatory mechanisms may be involved. We aimed to identify proteins that were differentially expressed in nasal polyps between patients with AERD and aspirin-tolerant asthma (ATA. METHODOLOGY/PRINCIPAL FINDINGS: Two-dimensional electrophoresis was adopted for differential display proteomics. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS. Western blotting and immunohistochemical staining were performed to compare the amount of fatty acid-binding protein 1 (FABP1 in the nasal polyps of patients with AERD and ATA. Fifteen proteins were significantly up- (seven spots or down-regulated in the nasal polyps of patients with AERD (n = 5 compared to those with ATA (n = 8. LC-MS revealed an increase in seven proteins expression and a decrease in eight proteins expression in patients with AERD compared to those with ATA (P = 0.003-0.045. FABP1-expression based on immunoblotting and immunohistochemical analysis was significantly higher in the nasal polyps of patients with AERD compared to that in patients with ATA. FABP1 was observed in epithelial, eosinophils, macrophages, and the smooth-muscle cells of blood vessels in the polyps. CONCLUSIONS/SIGNIFICANCE: Our results indicate that alterations in 15 proteins, including FABP1, may be related to the development of AERD.

  1. Tumor necrosis factor-α-induced protein 1 and immunity to hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Marie C Lin; Nikki P Lee; Ning Zheng; Pai-Hao Yang; Oscar G Wong; Hsiang-Fu Kung; Chee-Kin Hui; John M Luk; George Ka-Kit Lau

    2005-01-01

    AIM: To compare the gene expression profile in a pair of HBV-infected twins.METHODS: The gene expression profile was compared in a pair of HBV-infected twins.RESULTS: The twins displayed different disease outcomes. One acquired natural immunity against HBV,whereas the other became a chronic HBV carrier. Eightyeight and forty-six genes were found to be up- or downregulated in their PBMCs, respectively. Tumor necrosis factor-alpha-induced protein 1 (TNF-αIP1) that expressed at a higher level in the HBV-immune twins was identified and four pairs of siblings with HBV immunity by RTPCR. However, upon HBV core antigen stimulation,TNF-αIP1 was downregulated in PBMCs from subjects with immunity, whereas it was slightly upregulated in HBV carriers. Bioinformatics analysis revealed a K+channel tetramerization domain in TNF-αIP1 that shares a significant homology with some human, mouse, and C elegan proteins.CONCLUSION: TNF-αIP1 may play a role in the innate immunity against HBV.

  2. The alpha hemolysin of Escherichia Coli power the metabolism oxidative of neutrophils human beings in response to the peptide chemotactic FMLP: comparison with the ionophore of calcium A23187

    International Nuclear Information System (INIS)

    The calcium ionophore ionomycin primes polymorphonuclear leukocytes (PMN) for increased superoxide production upon stimulation with the chemotactic peptide FMLP (Helman Finkel, T. et al J Biol Chem 1987; 262: 12589-12596) In this investigation we assessed the effect of PMN priming with either alpha hemolysin (AH) or the calcium ionophore A23187, both of which increase intracellular calcium, on the oxidative metabolism of PMN (as measured by chemiluminescence) in response to secondary stimulation with FMLP. Both A23187 and AH priming increased, the luminol-enhanced chemiluminescence in response to secondary stimulation with FMLP, indicating overstimulation of PMLP oxidative metabolism. Additional experiments using lucigenin as chemiluminescence enhancer showed that A23187, but not AH priming of PMN, increased superoxide release in a manner similar to that reported for ionomycin. These results are discussed in reference to infectious processes involving hemolytic E. coli (Author)

  3. The chemokine system in arteriogenesis and hind limb ischemia.

    Science.gov (United States)

    Shireman, Paula K

    2007-06-01

    Chemokines (chemotactic cytokines) are important in the recruitment of leukocytes to injured tissues and, as such, play a pivotal role in arteriogenesis and the tissue response to ischemia. Hind limb ischemia represents a complex model with arteriogenesis (collateral artery formation) occurring in tissues with normal perfusion while areas exhibiting ischemic necrosis undergo angiogenesis and skeletal muscle regeneration; monocytes and macrophages play an important role in all three of these processes. In addition to leukocyte trafficking, chemokines are produced by and chemokine receptors are present on diverse cell types, including myoblasts, endothelial, and smooth muscle cells. Thus, the chemokine system may have direct effects as well as inflammatory-mediated effects on arteriogenesis, angiogenesis, and skeletal muscle regeneration. This article reviews the complexity of the hind limb ischemia model and the role of the chemokine system in arteriogenesis and the tissue response to ischemia. Special emphasis will be placed on the roles of monocytes/macrophages and CCL2/monocyte chemotactic protein-1 (MCP-1) in these processes. PMID:17544024

  4. Plasmodium falciparum Merozoite Surface Protein-1 Polymorphisms among Asymptomatic Sickle Cell Anemia Patients in Nigeria.

    Science.gov (United States)

    Bamidele Abiodun, Iwalokun; Oluwadun, Afolabi; Olugbenga Ayoola, Aina; Senapon Olusola, Iwalokun

    2016-01-01

    Asymptomatic malaria (ASM) has been implicated in the development of hemolytic crisis in infected sickle cell anemia (SCA) patients worldwide. This study surveyed steady state SCA Nigerian patients for ASM to investigate the influence of malaria prevention behaviors and age on parasitaemia and multiplicity of infection (MOI). A total of 78 steady SCA patients aged 5 - 27 years on routine care at three health facilities in Lagos were investigated for ASM by light microscopy and PCR with a multiplicity of infection determined by genotyping block 2 of merozoite surface protein 1 (msp1) gene of Plasmodium falciparum (P. falciparum). Use of malaria prevention measures was captured using a semi-structured questionnaire. The prevalence rates of ASM (due to Pf only) by microscopy and PCR were found to be 27.3% and 47.4% respectively (P < 0.05) with a Mean + SEM parasite density of 2238.4 + 464.3 parasites/uL. Five distinct msp1 genotypes [K1 (2), MAD20 (2), RO33 (1)] were detected and significant (P<0.05) disparity in allele frequencies (K1, 91.8%, MAD20, 32.4%; RO33, 18.9%) was found. The overall MOI was 1.43 and 37.8% of infections were polyclonal (P<0.05). ASM was associated with non-use of preventive measures and occurred in 62.1% of SCA patients aged < 10y with lower MOI of 1.3 compared to 38.1% in older patients with a higher MOI of 1.5 (P<0.05). We conclude that PCR improved the diagnosis of ASM among Nigerian SCA patients with infections being of low complexity and associated with non-use of preventive interventions and R033 msp1 allele selection. PMID:26853290

  5. Plasmodium falciparum Merozoite Surface Protein-1 Polymorphisms among Asymptomatic Sickle Cell Anemia Patients in Nigeria

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    Iwalokun Bamidele Abiodun

    2016-01-01

    Full Text Available Asymptomatic malaria (ASM has been implicated in the development of hemolytic crisis in infected sickle cell anemia (SCA patients worldwide. This study surveyed steady state SCA Nigerian patients for ASM to investigate the influence of malaria prevention behaviors and age on parasitaemia and multiplicity of infection (MOI. A total of 78 steady SCA patients aged 5 – 27 years on routine care at three health facilities in Lagos were investigated for ASM by light microscopy and PCR with a multiplicity of infection determined by genotyping block 2 of merozoite surface protein 1 (msp1 gene of Plasmodium falciparum (P. falciparum. Use of malaria prevention measures was captured using a semi-structured questionnaire. The prevalence rates of ASM (due to Pf only by microscopy and PCR were found to be 27.3% and 47.4% respectively (P < 0.05 with a Mean + SEM parasite density of 2238.4 + 464.3 parasites/uL. Five distinct msp1 genotypes [K1 (2, MAD20 (2, RO33 (1] were detected and significant (P<0.05 disparity in allele frequencies (K1, 91.8%, MAD20, 32.4%; RO33, 18.9% was found. The overall MOI was 1.43 and 37.8% of infections were polyclonal (P<0.05. ASM was associated with non-use of preventive measures and occurred in 62.1% of SCA patients aged < 10y with lower MOI of 1.3 compared to 38.1% in older patients with a higher MOI of 1.5 (P<0.05. We conclude that PCR improved the diagnosis of ASM among Nigerian SCA patients with infections being of low complexity and associated with non-use of preventive interventions and R033 msp1 allele selection.

  6. Receptor-interacting protein-1 promotes the growth and invasion in gastric cancer.

    Science.gov (United States)

    Zhu, Guangwei; Ye, Jianxin; Huang, Yongjian; Zheng, Wei; Hua, Jin; Yang, Shugang; Zhuang, Jinfu; Wang, Jinzhou

    2016-06-01

    The receptor-interacting protein-1 (RIP-1) is an important molecular in inflammation signaling pathways, but the role of RIP-1 in gastric cancer is largely unknown. In this study, we tested the expression of RIP-1 in gastric cancer samples and analyzed the effects of expression of RIP-1 on the prognosis in gastric cancer patients. We analyzed the role of the RIP-1 in gastric cancer cells and addressed the functional role of RIP-1 using a xenograft mouse model. A lentivirus-based effective RIP-1 siRNA vector was infected into HGC and AGS cells. The effect of RIP-1 siRNA on HGC and AGS cells were investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of RIP-1-siRNA on HGC cells in the mice with subcutaneous xenograft tumor, and preliminarily analyzed the underlying mechanisms. The results indicated that the expression of RIP-1 in the gastric cancer tissues was significantly higher than the expression in the normal gastric tissues. Additionally, RIP-1 immunoreactivity was positive at the site of invasion, but little or no immunoreactivity was detected at the gastric cancer parts of interstitial substance. Gastric cancer patients with high expression of RIP-1 had a poor survival rate. RIP-1 expression in the gastric cancer cell lines were general. HGC-R-1-RNAi-LV inhibited HGC and AGS cell proliferation and invasion ability in vitro. RIP-NF-κB/AP-1-VEGF-C signaling pathways have a crucial role in the regulate the biological functions of HGC cells. HGC-R-1-RNAi-LV suppressed tumor growth in the HGC cell subcutaneous xenograft model. In conclusion, our data indicate that RIP-1 promote the growth and invasion of gastric cancer in vitro and in vivo, additionally providing evidence that targeting RIP-1 may be useful in the treatment of gastric cancer. PMID:27035122

  7. Expression, purification and mass spectrometric analysis of LIM mineralization protein-1 in human lung epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Sreedhara Sangadala; Louisa Titus; Scott D. Boden

    2008-01-01

    LIM mineralization protein-1 (LMP-1) is a novel osteoin ductive protein that has been cloned and shown to induce bone formation both in vitro and in vivo. Detection and evaluation of the possible presence of carbohydrate structures in LMP-1 is an important regulatory consideration for the therapeutic use of recombinantly expressed protein. The sequence of LMP-1 contains a highly conserved N-terminal PDZ domain and three C-terminal LIM domains. The sequence analysis of LMP-I predicts two potential N-glycosylation sites and several O-glycosylation sites. Here, we report the cloning and overexpression of LMP.1 in human lung carcinoma(A549) cells. Even though our group already reported the sequence of LMP-1 cDNA, we undertook this work to clarify whether or not the overexpressed protein undergoes any glycosylation in vivo. The expressed full-length recombinant protein was purified and subjected to chemical analysis and internal sequencing. The absence of any hexosamines (Nacetyl glucosamine or N-acetyl galactosamine) in chemical composition analysis of LMP.I protein revealed that there is little or no post-translational glycosylation of the LMP-1 polypeptide in lung carcinoma cells (A549). We performed in-gel trypsin digestion on purified LMP-I, and the resulting peptide digests were analyzed further using matrix.assisted laser desorption and ionization mass spectrometry for peptide mass finger printing, which produced several exact matches with the corresponding LMP-1 peptides. Separation by high performance liquid chromatography and purification of the desired peptides followed by N-terminal sequencing resulted in many exact LMP-1 matches for several purified peptides, thus establishing the identity of the purified protein as LMP-1.

  8. Expression of Plasmodium falciparum erythrocyte membrane protein 1 in experimentally infected humans

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    Theander Thor G

    2005-04-01

    Full Text Available Abstract Background Parasites causing severe malaria in non-immune patients express a restricted subset of variant surface antigens (VSA, which are better recognized by immune sera than VSA expressed during non-severe disease in semi-immune individuals. The most prominent VSA are the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1 family, which is expressed on the surface of infected erythrocytes where it mediates binding to endothelial receptors. Thus, severe malaria may be caused by parasites expressing PfEMP1 variants that afford parasites optimal sequestration in immunologically naïve individuals and high effective multiplication rates. Methods var gene transcription was analysed using real time PCR and PfEMP1 expression by western blots as well as immune plasma recognition of parasite cultures established from non-immune volunteers shortly after infection with NF54 sporozoites. Results In cultures representing the first generation of parasites after hepatic release, all var genes were transcribed, but GroupA var genes were transcribed at the lowest levels. In cultures established from second or third generation blood stage parasites of volunteers with high in vivo parasite multiplication rates, the var gene transcription pattern differed markedly from the transcription pattern of the cultures representing first generation parasites. This indicated that parasites expressing specific var genes, mainly belonging to group A and B, had expanded more effectively in vivo compared to parasites expressing other var genes. The differential expression of PfEMP1 was confirmed at the protein level by immunoblot analysis. In addition, serological typing showed that immune sera more often recognized second and third generation parasites than first generation parasites. Conclusion In conclusion, the results presented here support the hypothesis that parasites causing severe malaria express a subset of PfEMP1, which bestows

  9. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

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    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  10. Dengue Virus Nonstructural Protein 1 Induces Vascular Leakage through Macrophage Migration Inhibitory Factor and Autophagy.

    Science.gov (United States)

    Chen, Hong-Ru; Chuang, Yung-Chun; Lin, Yee-Shin; Liu, Hsiao-Sheng; Liu, Ching-Chuan; Perng, Guey-Chuen; Yeh, Trai-Ming

    2016-07-01

    Dengue virus (DENV) is the most common mosquito-borne flavivirus; it can either cause mild dengue fever or the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). One of the characteristic features of DHF/DSS is vascular leakage; although DENV nonstructural protein 1 (NS1) has been proved to induce vascular leakage after binding to Toll-like receptor 4, the down-stream mechanism has not yet been fully understood. In the sera of DENV-infected patients, the concentrations of DENV NS1 and inflammatory cytokine macrophage migration inhibitory factor (MIF) are positively correlated with disease severity, but whether DENV NS1 induces vascular leakage through MIF secretion remains unknown. We demonstrated that recombinant NS1 induced vascular leakage and MIF secretion both in human endothelial cell line HMEC-1 and in mice. Furthermore, these phenomena were inhibited in the presence of anti-NS1 antibodies both in vitro and in vivo. DENV NS1 also induced LC3-I to LC3-II conversion and p62 degradation in endothelial cell line, which indicated the formation of autophagy. To clarify whether MIF or autophagy mediated DENV NS1-induced vascular leakage, various inhibitors were applied. The results showed that DENV NS1-induced vascular leakage and VE-cadherin disarray were blocked in the presence of MIF inhibitors, anti-MIF-antibodies or autophagy inhibitors. An Atg5 knockdown clone further confirmed that autophagy formation of endothelial cells was required in NS1-induced vascular leakage. Furthermore, DENV NS1-induced LC3 puncta were also decreased in the presence of MIF inhibitors, indicating that MIF mediated DENV NS1-induced autophagy. Taken together, the results suggest a potential mechanism of DENV-induced vascular leakage and provide possible therapeutic targets against DHF/DSS. PMID:27409803

  11. Dengue Virus Nonstructural Protein 1 Induces Vascular Leakage through Macrophage Migration Inhibitory Factor and Autophagy

    Science.gov (United States)

    Chen, Hong-Ru; Chuang, Yung-Chun; Lin, Yee-Shin; Liu, Hsiao-Sheng; Liu, Ching-Chuan; Perng, Guey-Chuen

    2016-01-01

    Dengue virus (DENV) is the most common mosquito-borne flavivirus; it can either cause mild dengue fever or the more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). One of the characteristic features of DHF/DSS is vascular leakage; although DENV nonstructural protein 1 (NS1) has been proved to induce vascular leakage after binding to Toll-like receptor 4, the down-stream mechanism has not yet been fully understood. In the sera of DENV-infected patients, the concentrations of DENV NS1 and inflammatory cytokine macrophage migration inhibitory factor (MIF) are positively correlated with disease severity, but whether DENV NS1 induces vascular leakage through MIF secretion remains unknown. We demonstrated that recombinant NS1 induced vascular leakage and MIF secretion both in human endothelial cell line HMEC-1 and in mice. Furthermore, these phenomena were inhibited in the presence of anti-NS1 antibodies both in vitro and in vivo. DENV NS1 also induced LC3-I to LC3-II conversion and p62 degradation in endothelial cell line, which indicated the formation of autophagy. To clarify whether MIF or autophagy mediated DENV NS1-induced vascular leakage, various inhibitors were applied. The results showed that DENV NS1-induced vascular leakage and VE-cadherin disarray were blocked in the presence of MIF inhibitors, anti-MIF-antibodies or autophagy inhibitors. An Atg5 knockdown clone further confirmed that autophagy formation of endothelial cells was required in NS1-induced vascular leakage. Furthermore, DENV NS1-induced LC3 puncta were also decreased in the presence of MIF inhibitors, indicating that MIF mediated DENV NS1-induced autophagy. Taken together, the results suggest a potential mechanism of DENV-induced vascular leakage and provide possible therapeutic targets against DHF/DSS. PMID:27409803

  12. Interaction of Human Chloride Intracellular Channel Protein 1 (CLIC1) with Lipid Bilayers: A Fluorescence Study.

    Science.gov (United States)

    Hare, Joanna E; Goodchild, Sophia C; Breit, Samuel N; Curmi, Paul M G; Brown, Louise J

    2016-07-12

    Chloride intracellular channel protein 1 (CLIC1) is very unusual as it adopts a soluble glutathione S-transferase-like canonical fold but can also autoinsert into lipid bilayers to form an ion channel. The conversion between these forms involves a large, but reversible, structural rearrangement of the CLIC1 module. The only identified environmental triggers controlling the metamorphic transition of CLIC1 are pH and oxidation. Until now, there have been no high-resolution structural data available for the CLIC1 integral membrane state, and consequently, a limited understanding of how CLIC1 unfolds and refolds across the bilayer to form a membrane protein with ion channel activity exists. Here we show that fluorescence spectroscopy can be used to establish the interaction and position of CLIC1 in a lipid bilayer. Our method employs a fluorescence energy transfer (FRET) approach between CLIC1 and a dansyl-labeled lipid analogue to probe the CLIC1-lipid interface. Under oxidizing conditions, a strong FRET signal between the single tryptophan residue of CLIC1 (Trp35) and the dansyl-lipid analogue was detected. When considering the proportion of CLIC1 interacting with the lipid bilayer, as estimated by fluorescence quenching experiments, the FRET distance between Trp35 and the dansyl moiety on the membrane surface was determined to be ∼15 Å. This FRET-detected interaction provides direct structural evidence that CLIC1 associates with membranes. The results presented support the current model of an oxidation-driven interaction of CLIC1 with lipid bilayers and also propose a membrane anchoring role for Trp35. PMID:27299171

  13. Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells

    Science.gov (United States)

    Guo, Run-Sheng; Yu, Yue; Chen, Jun; Chen, Yue-Yu; Shen, Na; Qiu, Ming

    2016-01-01

    Background: Brain acid soluble protein 1 (BASP1) is identified as a novel potential tumor suppressor in several cancers. However, its role in thyroid cancer has not been investigated yet. In the present study, the antitumor activities of BASP1 against the growth and migration of thyroid cancer cells were evaluated. Methods: BASP1 expression in thyroid cancer tissues and normal tissues were examined by immunohistochemical staining and the association between its expression and prognosis was analyzed. pcDNA-BASP1 carrying full length of BASP1 cDNA was constructed to restore the expression of BASP1 in thyroid cancer cell lines (BHT-101 and KMH-2). The cell proliferation in vitro and in vivo was evaluated by WST-1 assay and xenograft tumor models, respectively. Cell cycle distribution after transfection was analyzed using flow cytometry. Cell apoptosis after transfection was examined by annexin V/propidium iodide assay. The migration was examined using transwell assay. Results: BASP1 expression was abundant in normal tissues while it is significantly decreased in cancer tissues (P = 0.000). pcDNA-BASP1 restored the expression of BASP1 and significantly inhibited the growth of BHT-101 and KMH-2 cells as well as xenograft tumors in nude mice (P = 0.000). pcDNA-BASP1 induced G1 arrest and apoptosis in BHT-101 and KMH-2 cells. In addition, pcDNA-BASP1 significantly inhibited the cell migration. Conclusions: Downregulation of BASP1 expression may play a role in the tumorigenesis of thyroid cancer. Restoration of BASP1 expression exerted extensive antitumor activities against growth and migration of thyroid cancer cells, which suggested that BASP1 gene might act as a potential therapeutic agent for the treatment of thyroid cancer. PMID:27270539

  14. Molecular cloning and ontogenesis expression of fatty acid transport protein-1 in yellow-feathered broilers

    Institute of Scientific and Technical Information of China (English)

    Yuzhen Song; Jiaying Feng; Lihua Zhou; Gang Shu; Xiaotong Zhu; Ping Gao; Yongliang Zhang; Qingyan Jiang

    2008-01-01

    Fatty acid transport protein-1 (FATP-1) is one of the important transporter proteins involved in fatty acid transmembrane transport and fat deposition. To study the relationship between FATP-1 mRNA expression and fat deposition, chicken (Gallus gallus) FATP-1 sequence was first cloned by rapid amplification of cDNA ends (RACE). Tissue samples of chest muscle, leg muscle, subcutaneous fat, and abdominal fat were collected from six male and six female broilers each, at 22 days, 29 days, and 42 days, respectively. The tissue specificity and ontogenesis expression pattern of the FATP-1 mRNA of yellow-feathered broilers was studied by real-time reverse transcription polymerase chain reaction (RT-PCR), and the fat deposition laws in different tissues were also compared. A 2,488 bp cDNA sequence of chicken FATP-1 was cloned by RACE (GenBank accession no. DQ352834), including 547 bp 3' end untranslated region (URT) and 1,941 bp open reading frame (ORF). Chicken FATP-1 encoded 646 amino acid residues, which shared 83.9% and 83.0% identity with those of human and rat, respectively. The results of quantitative PCR demonstrated a constant FATP-1 mRNA expression level in the chest muscle and subcutaneous fat of both male and female broilers at three stages, whereas the expression level of the FATP-1 mRNA in the leg muscle at 42 days was significantly higher than that at 22 days or 29 days. In the abdominal fat of male broilers, the gene expression significantly increased with age, whereas the female broilers showed a dramatic downregulation of FATP-1 expression in abdominal fat at 42 days. This suggested a typical tissue-and gender-specific expression pattern of chicken FATP-1, mediating the specific process of fatty acid transport or utilization in muscle and adipose tissues.

  15. Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor

    International Nuclear Information System (INIS)

    Two cDNA clones encoding prepro-sphingolipid activator protein 1 (SAP-1) were isolated from a λ gt11 human hepatoma expression library using polyclonal antibodies. These had inserts of ≅ 2 kilobases (λ-S-1.2 and λ-S-1.3) and both were both homologous with a previously isolated clone (λ-S-1.1) for mature SAP-1. The authors report here the nucleotide sequence of the longer two EcoRI fragments of S-1.2 and S-1.3 that were not the same and the derived amino acid sequences of mature SAP-1 and its prepro form. The open reading frame encodes 19 amino acids, which are colinear with the amino-terminal sequence of mature SAP-1, and extends far beyond the predicted carboxyl terminus of mature SAP-1, indicating extensive carboxyl-terminal processing. The nucleotide sequence of cDNA encoding prepro-SAP-1 includes 1449 bases from the assigned initiation codon ATG at base-pair 472 to the stop codon TGA at base-pair 1921. The first 23 amino acids coded after the initiation ATG are characteristic of a signal peptide. The calculated molecular mass for a polypeptide encoded by 1449 bases is ≅ 53 kDa, in keeping with the reported value for pro-SAP-1. The data indicate that after removal of the signal peptide mature SAP-1 is generated by removing an additional 7 amino acids from the amino terminus and ≅ 373 amino acids from the carboxyl terminus. One potential glycosylation site was previously found in mature SAP-1. Three additional potential glycosylation sites are present in the processed carboxyl-terminal polypeptide, which they designate as P-2

  16. Structure and function of epididymal protein cysteine-rich secretory protein-1

    Institute of Scientific and Technical Information of China (English)

    Kenneth P. Roberts; Daniel S. Johnston; Michael A. Nolan; Joseph L. Wooters; Nicole C. Waxmonsky; Laura B. Piehl; Kathy M. Ensrud-Bowlin; David W. Hamilton

    2007-01-01

    Cysteine-rich secretory protein-1 (CRISP-1) is a glycoprotein secreted by the epididymal epithelium. It is a member of a large family of proteins characterized by two conserved domains and a set of 16 conserved cysteine residues. In mammals, CRISP-1 inhibits sperm-egg fusion and can suppress sperm capacitation. The molecular mechanism of action of the mammalian CRISP proteins remains unknown, but certain non-mammalian CRISP proteins can block ion channels. In the rat, CRISP-1 comprises two forms referred to as Proteins D and E. Recent work in our laboratory demonstrates that the D form of CRISP-1 associates transiently with the sperm surface, whereas the E form binds tightly. When the spermatozoa are washed, the E form of CRISP-1 persists on the sperm surface after all D form has dissociated. Cross-linking studies demonstrate different protein-protein interaction patterns for D and E, although no binding partners for either protein have yet been identified. Mass spectrometric analyses revealed a potential post-translational modification on the E form that is not present on the D form. This is the only discernable difference between Proteins D and E, and presumably is responsible for the difference in behavior of these two forms of rat CRISP- 1. These studies demonstrate that the more abundant D form interacts with spermatozoa transiently,possibly with a specific receptor on the sperm surface, consistent with a capacitation-suppressing function during sperm transit and storage in the epididymis, and also confirm a tightly bound population of the E form that could act in the female reproductive tract.

  17. Phylogenomic analysis reveals dynamic evolutionary history of the Drosophila heterochromatin protein 1 (HP1 gene family.

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    Mia T Levine

    Full Text Available Heterochromatin is the gene-poor, satellite-rich eukaryotic genome compartment that supports many essential cellular processes. The functional diversity of proteins that bind and often epigenetically define heterochromatic DNA sequence reflects the diverse functions supported by this enigmatic genome compartment. Moreover, heterogeneous signatures of selection at chromosomal proteins often mirror the heterogeneity of evolutionary forces that act on heterochromatic DNA. To identify new such surrogates for dissecting heterochromatin function and evolution, we conducted a comprehensive phylogenomic analysis of the Heterochromatin Protein 1 gene family across 40 million years of Drosophila evolution. Our study expands this gene family from 5 genes to at least 26 genes, including several uncharacterized genes in Drosophila melanogaster. The 21 newly defined HP1s introduce unprecedented structural diversity, lineage-restriction, and germline-biased expression patterns into the HP1 family. We find little evidence of positive selection at these HP1 genes in both population genetic and molecular evolution analyses. Instead, we find that dynamic evolution occurs via prolific gene gains and losses. Despite this dynamic gene turnover, the number of HP1 genes is relatively constant across species. We propose that karyotype evolution drives at least some HP1 gene turnover. For example, the loss of the male germline-restricted HP1E in the obscura group coincides with one episode of dramatic karyotypic evolution, including the gain of a neo-Y in this lineage. This expanded compendium of ovary- and testis-restricted HP1 genes revealed by our study, together with correlated gain/loss dynamics and chromosome fission/fusion events, will guide functional analyses of novel roles supported by germline chromatin.

  18. Insight into temperature dependence of GTPase activity in human guanylate binding protein-1.

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    Anjana Rani

    Full Text Available Interferon-γ induced human guanylate binding protein-1(hGBP1 belongs to a family of dynamin related large GTPases. Unlike all other GTPases, hGBP1 hydrolyzes GTP to a mixture of GDP and GMP with GMP being the major product at 37°C but GDP became significant when the hydrolysis reaction was carried out at 15°C. The hydrolysis reaction in hGBP1 is believed to involve with a number of catalytic steps. To investigate the effect of temperature in the product formation and on the different catalytic complexes of hGBP1, we carried out temperature dependent GTPase assays, mutational analysis, chemical and thermal denaturation studies. The Arrhenius plot for both GDP and GMP interestingly showed nonlinear behaviour, suggesting that the product formation from the GTP-bound enzyme complex is associated with at least more than one step. The negative activation energy for GDP formation and GTPase assay with external GDP together indicate that GDP formation occurs through the reversible dissociation of GDP-bound enzyme dimer to monomer, which further reversibly dissociates to give the product. Denaturation studies of different catalytic complexes show that unlike other complexes the free energy of GDP-bound hGBP1 decreases significantly at lower temperature. GDP formation is found to be dependent on the free energy of the GDP-bound enzyme complex. The decrease in the free energy of this complex at low temperature compared to at high is the reason for higher GDP formation at low temperature. Thermal denaturation studies also suggest that the difference in the free energy of the GTP-bound enzyme dimer compared to its monomer plays a crucial role in the product formation; higher stability favours GMP but lower favours GDP. Thus, this study provides the first thermodynamic insight into the effect of temperature in the product formation of hGBP1.

  19. Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein

    Science.gov (United States)

    Gray, Madison T.; Ganesh, Munisha S.; Middeldorp, Jaap M.

    2016-01-01

    Objectives: To identify the epitope on α-synuclein (α-syn) to which antibodies against the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) bind and to determine whether antibodies targeting this mimicry domain are present in human sera. Methods: Reactivity of the α-syn-cross-reacting anti-LMP1 monoclonal antibody CS1-4 to a synthetic peptide containing the putative mimicry domain was compared to those in which this domain was mutated and to murine and rat α-syn (which differ from human α-syn at this site) in Western blots. Using ELISA, sera from EBV+ (n = 4) and EBV− (n = 12) donors as well as those with infectious mononucleosis (IM; n = 120), and Hodgkin disease (HD; n = 33) were interrogated for antibody reactivity to synthetic peptides corresponding to regions of α-syn and LMP1 containing the mimicry domain. Results: CS1-4 showed strong reactivity to wild-type human α-syn, but not to the mutant peptides or rodent α-syn. Control EBV− and EBV+ sera showed no reactivity to α-syn or LMP1 peptides. However, a significant proportion of IM and HD sera contained immunoglobulin M (IgM) (59% and 70%, in IM and HD, respectively), immunoglobulin G (IgG) (40% and 48%), and immunoglobulin A (IgA) (28% and 36%) antibodies to both peptides, as well as a significant correlation in the titers of IgM (ρ = 0.606 and 0.664, for IM and HD, respectively), IgG (0.526 and 0.836), and IgA (0.569 and 0.728) antibodies targeting LMP1 and α-syn peptides. Conclusions: Anti-EBV-LMP1 antibodies cross-reacting with a defined epitope in α-syn are present in human patients. These findings may have implications for the pathogenesis of synucleinopathies. PMID:27218119

  20. Controlled release of recombinant human cementum protein 1 from electrospun multiphasic scaffold for cementum regeneration

    Science.gov (United States)

    Chen, Xiaofeng; Liu, Yu; Miao, Leiying; Wang, Yangyang; Ren, Shuangshuang; Yang, Xuebin; Hu, Yong; Sun, Weibin

    2016-01-01

    Periodontitis is a major cause for tooth loss, which affects about 15% of the adult population. Cementum regeneration has been the crux of constructing the periodontal complex. Cementum protein 1 (CEMP1) is a cementum-specific protein that can induce cementogenic differentiation. In this study, poly(ethylene glycol) (PEG)-stabilized amorphous calcium phosphate (ACP) nanoparticles were prepared by wet-chemical method and then loaded with recombinant human CEMP1 (rhCEMP1) for controlled release. An electrospun multiphasic scaffold constituted of poly(ε-caprolactone) (PCL), type I collagen (COL), and rhCEMP1/ACP was fabricated. The effects of rhCEMP1/ACP/PCL/COL scaffold on the attachment proliferation, osteogenic, and cementogenic differentiations of human periodontal ligament cells, (PDLCs) were systematically investigated. A critical size defect rat model was introduced to evaluate the effect of tissue regeneration of the scaffolds in vivo. The results showed that PEG-stabilized ACP nanoparticles formed a core-shell structure with sustained release of rhCEMP1 for up to 4 weeks. rhCEMP1/ACP/PCL/COL scaffold could suppress PDLCs proliferation behavior and upregulate the expression of cementoblastic markers including CEMP1 and cementum attachment protein while downregulating osteoblastic markers including osteocalcin and osteopontin when it was cocultured with PDLCs in vitro for 7 days. Histology analysis of cementum after being implanted with the scaffold in rats for 8 weeks showed that there was cementum-like tissue formation but little bone formation. These results indicated the potential of using electrospun multiphasic scaffolds for controlled release of rhCEMP1 for promoting cementum regeneration in reconstruction of the periodontal complex. PMID:27471382

  1. [Preparation and detection of anti-influenza A virus polymerase basic protein 1 polyclonal antibody].

    Science.gov (United States)

    Qin, Yujie; Zhang, Tinghong; Ye, Xin

    2016-01-01

    Influenza A virus is an enveloped virus that belongs to the Orthomyxoviridae family. It has 8 negative RNA segments that encode 16 viral proteins. The viral polymerase consists of 3 proteins (PB 1, PB2 and PA) which plays an important role in the transcription and replication of the influenza A virus. Polymerase basic protein 1 (PB 1) is a critical member of viral polymerase complex. In order to further study the function of PB1, we need to prepare the PB1 antibody with good quality. Therefore, we amplified PB1 conserved region (nt1648-2265) by PCR and cloned it into pET-30a vector, and transformed into Escherichia coli BL2 1. The expression of His tagged PB 1 protein was induced by IPTG, and His-PB 1 proteins were purified by Ni-NTA resin. For preparation of PB 1 protein antiserum, rabbits were immunized with His-PB 1 fusion protein 3 times. Then the titer of PB 1 polyclonal antibody was measured by indirect ELISA. The antibody was purified by membrane affinity purification and subjected to immunoblotting analysis. Data showed that PB1 antibody can recognize PB 1 protein from WSN virus infected or pCMV FLAG-PB 1 transfected cells. Meanwhile, PB 1 antibody can also recognize specifically other subtype strains of influenza A virus such as H9N2 and H3N2. PB 1 polyclonal antibody we generated will be a useful tool to study the biological function of PB1. PMID:27363203

  2. X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1

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    Scheich Christoph

    2005-12-01

    Full Text Available Abstract Background Human Aortic Preferentially Expressed Protein-1 (APEG-1 is a novel specific smooth muscle differentiation marker thought to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs. Results Good quality crystals that were suitable for X-ray crystallographic studies were obtained following the truncation of the 14 N-terminal amino acids of APEG-1, a region predicted to be disordered. The truncated protein (termed ΔAPEG-1 consists of a single immunoglobulin (Ig like domain which includes an Arg-Gly-Asp (RGD adhesion recognition motif. The RGD motif is crucial for the interaction of extracellular proteins and plays a role in cell adhesion. The X-ray structure of ΔAPEG-1 was determined and was refined to sub-atomic resolution (0.96 Å. This is the best resolution for an immunoglobulin domain structure so far. The structure adopts a Greek-key β-sandwich fold and belongs to the I (intermediate set of the immunoglobulin superfamily. The residues lying between the β-sheets form a hydrophobic core. The RGD motif folds into a 310 helix that is involved in the formation of a homodimer in the crystal which is mainly stabilized by salt bridges. Analytical ultracentrifugation studies revealed a moderate dissociation constant of 20 μM at physiological ionic strength, suggesting that APEG-1 dimerisation is only transient in the cell. The binding constant is strongly dependent on ionic strength. Conclusion Our data suggests that the RGD motif might play a role not only in the adhesion of extracellular proteins but also in intracellular protein-protein interactions. However, it remains to be established whether the rather weak dimerisation of APEG-1 involving this motif is physiogically relevant.

  3. Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

    Energy Technology Data Exchange (ETDEWEB)

    Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Bronson, Roderick T. [Department of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115 (United States); Hornick, Jason L. [Department of Pathology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Cohen, David E. [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Ukomadu, Chinweike, E-mail: cukomadu@partners.org [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2015-09-18

    Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. - Highlights: • Fgl1 knockout mice (Fgl1KO) are more prone to carcinogen-induced liver cancer compared to wild type (WT) mates. • Tumors from the Fgl1KO are molecularly distinct with enhanced Akt and mTOR activity in comparison with Fgl1WT tumors. • Tumors from the Fgl1KO have enhanced expression of Trim35 and Tnfrsf10b, putative HCC tumor suppressors.

  4. Hematopoietic protein-1 regulates the actin membrane skeleton and membrane stability in murine erythrocytes.

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    Maia M Chan

    Full Text Available Hematopoietic protein-1 (Hem-1 is a hematopoietic cell specific member of the WAVE (Wiskott-Aldrich syndrome verprolin-homologous protein complex, which regulates filamentous actin (F-actin polymerization in many cell types including immune cells. However, the roles of Hem-1 and the WAVE complex in erythrocyte biology are not known. In this study, we utilized mice lacking Hem-1 expression due to a non-coding point mutation in the Hem1 gene to show that absence of Hem-1 results in microcytic, hypochromic anemia characterized by abnormally shaped erythrocytes with aberrant F-actin foci and decreased lifespan. We find that Hem-1 and members of the associated WAVE complex are normally expressed in wildtype erythrocyte progenitors and mature erythrocytes. Using mass spectrometry and global proteomics, Coomassie staining, and immunoblotting, we find that the absence of Hem-1 results in decreased representation of essential erythrocyte membrane skeletal proteins including α- and β- spectrin, dematin, p55, adducin, ankyrin, tropomodulin 1, band 3, and band 4.1. Hem1⁻/⁻ erythrocytes exhibit increased protein kinase C-dependent phosphorylation of adducin at Ser724, which targets adducin family members for dissociation from spectrin and actin, and subsequent proteolysis. Increased adducin Ser724 phosphorylation in Hem1⁻/⁻ erythrocytes correlates with decreased protein expression of the regulatory subunit of protein phosphatase 2A (PP2A, which is required for PP2A-dependent dephosphorylation of PKC targets. These results reveal a novel, critical role for Hem-1 in the homeostasis of structural proteins required for formation and stability of the actin membrane skeleton in erythrocytes.

  5. MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines

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    Yu Deng, Hui Deng, Feng Bi, Jing Liu, Lynn T. Bemis, David Norris, Xiao-Jing Wang, Qinghong Zhang

    2011-01-01

    Full Text Available Carboxyl-terminal binding protein 1 (CtBP1 is a transcriptional co-repressor that represses expression of various tumor suppressor genes. In the present study, we identified miR-137 as a potential regulator of CtBP1 expression in melanoma cells. Expression of miR-137 in melanoma cell lines was found to inversely correlate with CtBP1 levels. Target Scan predicted a putative site for miR-137 within the CtBP1 3′ untranslated region (3′UTR at nt 710-716, which is highly conserved across species. To explore the mechanism of miR-137 targeting CtBP1, we performed an Argonaute 2 (Ago2-pull down assay, and miR-137 was identified in complex with CtBP1 mRNA. miR-137 suppressed CtBP1 3' UTR luciferase-reporter activity, and this effect was lost with deletion of the putative 3' UTR target-site. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced expression levels of CtBP1. Furthermore, expression of miR-137 increased the immediate downstream effectors of CtBP1, such as E-cadherin and Bax. The human miR-137 gene is located at chromosome 1p22, which has previously been determined to be a susceptive region for melanoma. This study suggests miR-137 may act as a tumor suppressor by directly targeting CtBP1 to inhibit epithelial-mesenchymal transition (EMT and inducing apoptosis of melanoma cells, thus illustrating a functional link between miR-137 and CtBP1 in melanoma development.

  6. Expression of activator protein-1 (AP-1) family members in breast cancer

    International Nuclear Information System (INIS)

    The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer. We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses. We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01). Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer

  7. Metabolically inert perfluorinated fatty acids directly activate uncoupling protein 1 in brown-fat mitochondria.

    Science.gov (United States)

    Shabalina, Irina G; Kalinovich, Anastasia V; Cannon, Barbara; Nedergaard, Jan

    2016-05-01

    The metabolically inert perfluorinated fatty acids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fatty acid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fatty acids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fatty acids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fatty acids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged. PMID:26041126

  8. Evidence that selenium binding protein 1 is a tumor suppressor in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Emmanuel Ansong

    Full Text Available Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56 is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease.

  9. Systemic administration of the chemokine macrophage inflammatory protein 1α exacerbates inflammatory bowel disease in a mouse model

    OpenAIRE

    Pender, S L-F; Chance, V; Whiting, C V; Buckley, M; Edwards, M.; Pettipher, R; MacDonald, T T

    2005-01-01

    Introduction: Exacerbations of inflammatory bowel disease are thought to be related to concurrent infections. As infections are associated with elevated local and serum concentrations of chemokines, we have determined whether systemic administration of the CC chemokine macrophage inflammatory protein 1α (MIP-1α) exacerbates colitis in a mouse model.

  10. Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains

    DEFF Research Database (Denmark)

    Cham, Gerald K K; Turner, Louise; Lusingu, John;

    2009-01-01

    The binding of erythrocytes infected with mature blood stage parasites to the vascular bed is key to the pathogenesis of malignant malaria. The binding is mediated by members of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. PfEMP1s can be divided into groups, and it has...

  11. Sequence analysis of the Epstein-Barr virus (EBV) latent membrane protein-1 gene and promoter region

    DEFF Research Database (Denmark)

    Sandvej, K; Gratama, J W; Munch, M; Zhou, X G; Bolhuis, R L; Andresen, B S; Gregersen, N; Hamilton-Dutoit, S

    1997-01-01

    Sequence variations in the Epstein-Barr virus (EBV) encoded latent membrane protein-1 (LMP-1) gene have been described in a Chinese nasopharyngeal carcinoma-derived isolate (CAO), and in viral isolates from various EBV-associated tumors. It has been suggested that these genetic changes, which inc...

  12. Characterization of the in vitro binding and inhibition kinetics of primary amine oxidase/vascular adhesion protein-1 by glucosamine.

    LENUS (Irish Health Repository)

    Olivieri, Aldo

    2012-04-01

    Primary-amine oxidase (PrAO) catalyzes the oxidative deamination of endogenous and exogenous primary amines and also functions, in some tissues, as an inflammation-inducible endothelial factor, known as vascular adhesion protein-1. VAP-1 mediates the slow rolling and adhesion of lymphocytes to endothelial cells in a number of inflammatory conditions, including inflammation of the synovium.

  13. Influenza virus non-structural protein 1 (NS1 disrupts interferon signaling.

    Directory of Open Access Journals (Sweden)

    Danlin Jia

    Full Text Available Type I interferons (IFNs function as the first line of defense against viral infections by modulating cell growth, establishing an antiviral state and influencing the activation of various immune cells. Viruses such as influenza have developed mechanisms to evade this defense mechanism and during infection with influenza A viruses, the non-structural protein 1 (NS1 encoded by the virus genome suppresses induction of IFNs-α/β. Here we show that expression of avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling. H5N1 NS1 reduces IFN-inducible tyrosine phosphorylation of STAT1, STAT2 and STAT3 and inhibits the nuclear translocation of phospho-STAT2 and the formation of IFN-inducible STAT1:1-, STAT1:3- and STAT3:3- DNA complexes. Inhibition of IFN-inducible STAT signaling by NS1 in HeLa cells is, in part, a consequence of NS1-mediated inhibition of expression of the IFN receptor subunit, IFNAR1. In support of this NS1-mediated inhibition, we observed a reduction in expression of ifnar1 in ex vivo human non-tumor lung tissues infected with H5N1 and H1N1 viruses. Moreover, H1N1 and H5N1 virus infection of human monocyte-derived macrophages led to inhibition of both ifnar1 and ifnar2 expression. In addition, NS1 expression induces up-regulation of the JAK/STAT inhibitors, SOCS1 and SOCS3. By contrast, treatment of ex vivo human lung tissues with IFN-α results in the up-regulation of a number of IFN-stimulated genes and inhibits both H5N1 and H1N1 virus replication. The data suggest that NS1 can directly interfere with IFN signaling to enhance viral replication, but that treatment with IFN can nevertheless override these inhibitory effects to block H5N1 and H1N1 virus infections.

  14. Mammalian Clusterin associated protein 1 is an evolutionarily conserved protein required for ciliogenesis

    Directory of Open Access Journals (Sweden)

    Pasek Raymond C

    2012-11-01

    Full Text Available Abstract Background Clusterin associated protein 1 (CLUAP1 was initially characterized as a protein that interacts with clusterin, and whose gene is frequently upregulated in colon cancer. Although the consequences of these observations remain unclear, research of CLUAP1 homologs in C. elegans and zebrafish indicates that it is needed for cilia assembly and maintenance in these models. To begin evaluating whether Cluap1 has an evolutionarily conserved role in cilia in mammalian systems and to explore the association of Cluap1 with disease pathogenesis and developmental abnormalities, we generated Cluap1 mutant mice. Methods Cluap1 mutant embryos were generated and examined for gross morphological and anatomical defects using light microscopy. Reverse transcription PCR, β-galactosidase staining assays, and immunofluorescence analysis were used to determine the expression of the gene and localization of the protein in vivo and in cultured cell lines. We also used immunofluorescence analysis and qRT-PCR to examine defects in the Sonic hedgehog signaling pathway in mutant embryos. Results Cluap1 mutant embryos die in mid-gestation, indicating that it is necessary for proper development. Mutant phenotypes include a failure of embryonic turning, an enlarged pericardial sac, and defects in neural tube development. Consistent with the diverse phenotypes, Cluap1 is widely expressed. Furthermore, the Cluap1 protein localizes to primary cilia, and mutant embryos were found to lack cilia at embryonic day 9.5. The phenotypes observed in Cluap1 mutant mice are indicative of defects in Sonic hedgehog signaling. This was confirmed by analyzing hedgehog signaling activity in Cluap1 mutants, which revealed that the pathway is repressed. Conclusions These data indicate that the function of Cluap1 is evolutionarily conserved with regard to ciliogenesis. Further, the results implicate mammalian Cluap1 as a key regulator of hedgehog signaling and as an

  15. Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Pei-Hong Jiang; Yoshiharu Motoo; Stéphane Garcia; Juan Lucio Iovanna; Marie-Josèphe Pébusque; Norio Sawabu

    2006-01-01

    AIM: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1and p53 expression in gastric cancer.METHODS: TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed.RESULTS: TP53INP1 was expressed in 98% (139/142cases) of non-cancerous gastric tissues and was downexpressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%).Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3%vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients).P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues.A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed,loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P= 0.0006).CONCLUSION: TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may

  16. Hemolysin coregulated protein 1 as a molecular gluing unit for the assembly of nanoparticle hybrid structures.

    Science.gov (United States)

    Pham, Tuan Anh; Schreiber, Andreas; Sturm Née Rosseeva, Elena V; Schiller, Stefan; Cölfen, Helmut

    2016-01-01

    Hybrid nanoparticle (NP) structures containing organic building units such as polymers, peptides, DNA and proteins have great potential in biosensor and electronic applications. The nearly free modification of the polymer chain, the variation of the protein and DNA sequence and the implementation of functional moieties provide a great platform to create inorganic structures of different morphology, resulting in different optical and magnetic properties. Nevertheless, the design and modification of a protein structure with functional groups or sequences for the assembly of biohybrid materials is not trivial. This is mainly due to the sensitivity of its secondary, tertiary and quaternary structure to the changes in the interaction (e.g., hydrophobic, hydrophilic, electrostatic, chemical groups) between the protein subunits and the inorganic material. Here, we use hemolysin coregulated protein 1 (Hcp1) from Pseudomonas aeruginosa as a building and gluing unit for the formation of biohybrid structures by implementing cysteine anchoring points at defined positions on the protein rim (Hcp1_cys3). We successfully apply the Hcp1_cys3 gluing unit for the assembly of often linear, hybrid structures of plasmonic gold (Au NP), magnetite (Fe3O4 NP), and cobalt ferrite nanoparticles (CoFe2O4 NP). Furthermore, the assembly of Au NPs into linear structures using Hcp1_cys3 is investigated by UV-vis spectroscopy, TEM and cryo-TEM. One key parameter for the formation of Au NP assembly is the specific ionic strength in the mixture. The resulting network-like structure of Au NPs is characterized by Raman spectroscopy, showing surface-enhanced Raman scattering (SERS) by a factor of 8·10(4) and a stable secondary structure of the Hcp1_cys3 unit. In order to prove the catalytic performance of the gold hybrid structures, they are used as a catalyst in the reduction reaction of 4-nitrophenol showing similar catalytic activity as the pure Au NPs. To further extend the functionality of the

  17. Unilateral macular edema with central retinal vein occlusion in systemic lupus erythematosus: a case report

    Directory of Open Access Journals (Sweden)

    Noma H

    2013-05-01

    Full Text Available Hidetaka Noma,1 Hiroshi Shimizu,1 Tatsuya Mimura21Department of Ophthalmology, Yachiyo Medical Center, Tokyo Women's Medical University, 2Department of Ophthalmology, Medical Center East, Tokyo Women's Medical University, Tokyo, JapanAbstract: Central retinal vein occlusion (CRVO is frequent in patients with systemic lupus erythematosus (SLE, but the treatment of the macular edema with this disease is extremely difficult. We report a case of cystoid macular edema (CME secondary to unilateral CRVO in a patient with SLE that responded to intravitreous injection of an anti-vascular endothelial growth factor (VEGF agent. A 33-year-old Japanese woman was referred to our department with unilateral impairment of vision. Microperimetry (MP-1 showed a cessation of foveal sensitivity. Fluorescein angiography showed CME without ischaemia of the macular region or peripheral retina (nonischemic CRVO. A diagnosis of CME and unilateral nonischemic CRVO combined with SLE was made and intravitreous anti-VEGF therapy was given. A sample of aqueous humor was harvested at the start of intravitreous injection after obtaining informed consent. Then the levels of VEGF and monocyte chemotactic protein (MCP-1 were measured in the aqueous humor by enzyme-linked immunosorbent assay, revealing that VEGF was 234 pg/mL and MCP-1 was 501 pg/mL. Two weeks later, left eye vision improved to 20/20. Optical coherence tomography (OCT showed considerable amelioration of retinal swelling and CME. MP-1 showed a marked increase of foveal sensitivity. However, she had recurrence of edema 3 months later. After harvesting aqueous humor again, intravitreous injection of an anti-VEGF agent was repeated for CME. The aqueous VEGF and MCP-1 levels were 156 pg/mL and 360 pg/mL, respectively. These findings suggest that inflammation was improved by intravitreous injection of bevacizumab. Intravitreous injection of anti-VEGF agents may be effective for CME due to nonischemic CRVO in SLE patients

  18. Dynamic Changes in Equatorial Segment Protein 1 (SPESP1) Glycosylation During Mouse Spermiogenesis.

    Science.gov (United States)

    Suryavathi, Viswanadhapalli; Panneerdoss, Subbarayalu; Wolkowicz, Michael J; Shetty, Jagathpala; Sherman, Nicholas E; Flickinger, Charles J; Herr, John C

    2015-05-01

    ESP1/SPESP1 is a testis-specific, postmeiotic gene expressed in round spermatids that encodes equatorial segment protein 1, an intra-acrosomal protein found in the acrosomal matrix and on the luminal surface of the inner and outer acrosomal membranes within the equatorial segment domain of mature spermatozoa. A comparison of testicular protein extracts with caput, corpus, and caudal epididymal sperm proteins revealed striking differences in the apparent masses of SPESP1 isoforms. The predominant isoforms of SPESP1 in the testis were 77 and 67 kDa, with 47-kDa forms present to a minor degree. In contrast, SPESP1 isoforms of 47 and 43 kDa were found in caput, corpus, and caudal sperm, indicating that SPESP1 undergoes noticeable mass changes during spermiogenesis and/or subsequent transport to the epididymis. On two-dimensional (2D) SDS-PAGE, testicular SPESP1 isoforms resolved as a train of pI values from 4.9 to 5.2. Immunoprecipitated 77-kDa SPESP1 from testis reacted with the glycoprofile stain after one-dimensional and 2D gel electrophoresis, indicating that the 77-kDa testicular isoform was highly glycosylated. One charge variant of the 67-kDa isoform was also glycoprofile positive after 2D gel resolution. The 47- and 43-kDa isoforms of SPESP1 from epididymal sperm did not stain with glycoprofile, suggesting an absence of, or few, glycoprofile-sensitive glycoconjugates in epididymal SPESP1. Treatment of testicular extracts with a variety of glycosidases resulted in mass shifts in immunoreactive SPESP1, indicating that testicular SPESP1 was glycosylated and that terminal sialic acid, N- and O-glycans were present. A mixture of deglycosidase enzymes (including PNGase-F, neuraminidase, beta1-4 galactosidase, endo-alpha-N-acetylgalactosaminidase, and beta N-acetyl-glucosaminidase) completely eliminated the 77- and 67-kDa SPESP1 bands and resulted in the appearance of 75-, 60-, 55-, 50-, 47-, and 43-kDa forms, confirming that both the 77- and 67-kDa testicular forms

  19. Dynamic Changes in Equatorial Segment Protein 1 (SPESP1) Glycosylation During Mouse Spermiogenesis1

    Science.gov (United States)

    Suryavathi, Viswanadhapalli; Panneerdoss, Subbarayalu; Wolkowicz, Michael J.; Shetty, Jagathpala; Sherman, Nicholas E.; Flickinger, Charles J.; Herr, John C.

    2015-01-01

    ESP1/SPESP1 is a testis-specific, postmeiotic gene expressed in round spermatids that encodes equatorial segment protein 1, an intra-acrosomal protein found in the acrosomal matrix and on the luminal surface of the inner and outer acrosomal membranes within the equatorial segment domain of mature spermatozoa. A comparison of testicular protein extracts with caput, corpus, and caudal epididymal sperm proteins revealed striking differences in the apparent masses of SPESP1 isoforms. The predominant isoforms of SPESP1 in the testis were 77 and 67 kDa, with 47-kDa forms present to a minor degree. In contrast, SPESP1 isoforms of 47 and 43 kDa were found in caput, corpus, and caudal sperm, indicating that SPESP1 undergoes noticeable mass changes during spermiogenesis and/or subsequent transport to the epididymis. On two-dimensional (2D) SDS-PAGE, testicular SPESP1 isoforms resolved as a train of pI values from 4.9 to 5.2. Immunoprecipitated 77-kDa SPESP1 from testis reacted with the glycoprofile stain after one-dimensional and 2D gel electrophoresis, indicating that the 77-kDa testicular isoform was highly glycosylated. One charge variant of the 67-kDa isoform was also glycoprofile positive after 2D gel resolution. The 47- and 43-kDa isoforms of SPESP1 from epididymal sperm did not stain with glycoprofile, suggesting an absence of, or few, glycoprofile-sensitive glycoconjugates in epididymal SPESP1. Treatment of testicular extracts with a variety of glycosidases resulted in mass shifts in immunoreactive SPESP1, indicating that testicular SPESP1 was glycosylated and that terminal sialic acid, N- and O-glycans were present. A mixture of deglycosidase enzymes (including PNGase-F, neuraminidase, beta1–4 galactosidase, endo-alpha-N-acetylgalactosaminidase, and beta N-acetyl-glucosaminidase) completely eliminated the 77- and 67-kDa SPESP1 bands and resulted in the appearance of 75-, 60-, 55-, 50-, 47-, and 43-kDa forms, confirming that both the 77- and 67-kDa testicular forms

  20. Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    Dan-Hong Yang; Zai-Yuan Ye; Yuan-Jun Xie; Xu-Jun He; Wen-Juan Xu; Wei-Ming Zhou

    2012-01-01

    AIM:To study the effect of salvianolate on tight junctions (TJs) and zonula occludens protein 1 (ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate (12 mg/kg) treatment group,medium-dose salvianolate (24 mg/kg) treatment group,and high-dose salvianolate (48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group (P < 0.01).The number of microvilli decreased and showed

  1. Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 1b of Escherichia coli

    International Nuclear Information System (INIS)

    This paper reports the sequence of the active site peptide of penicillin-binding protein 1b from Escherichia coli. Purified penicillin-binding protein 1b was labeled with [14C]penicillin G, digested with trypsin, and partially purified by gel filtration. Upon further purification by high-pressure liquid chromatography, two radioactive peaks were observed, and the major peak, representing over 75% of the applied radioactivity, was submitted to amino acid analysis and sequencing. The sequence Ser-Ile-Gly-Ser-Leu-Ala-Lys was obtained. The active site nucleophile was identified by digesting the purified peptide with aminopeptidase M and separating the radioactive products on high-pressure liquid chromatography. Amino acid analysis confirmed that the serine residue in the middle of the sequence was covalently bonded to the [14C]penicilloyl moiety. A comparison of this sequence to active site sequences of other penicillin-binding proteins and beta-lactamases is presented

  2. G protein coupled receptor kinase 2 interacting protein 1 (GIT1) is a novel regulator of mitochondrial biogenesis in heart

    OpenAIRE

    Pang, Jinjiang; Xu, Xiangbin; Getman, Michael R.; Shi, Xi; Belmonte, Stephen L.; Michaloski, Heidi; Mohan, Amy; Blaxall, Burns C.; Berk, Bradford C.

    2011-01-01

    G-protein-coupled receptor (GPCR)-kinase interacting protein-1 (GIT1) is a multi-function scaffold protein. However, little is known about its physiological role in the heart. Here we sought to identify the cardiac function of GIT1. Global GIT1 knockout (KO) mice were generated and exhibited significant cardiac hypertrophy that progressed to heart failure. Electron microscopy revealed that the hearts of GIT1 KO mice demonstrated significant morphological abnormities in mitochondria, including...

  3. Impaired Angiogenesis during Fracture Healing in GPCR Kinase 2 Interacting Protein-1 (GIT1) Knock Out Mice

    OpenAIRE

    Guoyong Yin; Tzong-Jen Sheu; Prashanthi Menon; Jinjiang Pang; Hsin-Chiu Ho; Shanshan Shi; Chao Xie; Elaine Smolock; Chen Yan; Zuscik, Michael J.; Berk, Bradford C.

    2014-01-01

    G protein coupled receptor kinase 2 (GRK2) interacting protein-1 (GIT1), is a scaffold protein that plays an important role in angiogenesis and osteoclast activity. We have previously demonstrated that GIT1 knockout (GIT1 KO) mice have impaired angiogenesis and dysregulated osteoclast podosome formation leading to a reduction in the bone resorbing ability of these cells. Since both angiogenesis and osteoclast-mediated bone remodeling are involved in the fracture healing process, we hypothesiz...

  4. Evolutionary analysis of circumsporozoite surface protein and merozoite surface protein-1 (CSP and MSP-1) sequences of malaria parasites

    OpenAIRE

    Tripathi, Vijay; Gupta, Dwijendra

    2011-01-01

    Malaria, one of the world's most common diseases, is caused by the intracellular protozoan parasite known as Plasmodium. In this study, we have determined the evolutionary relationship of two single-copy proteins, circumsporozoite protein (CSP) and merozoite surface protein-1 (MSP-1), among Plasmodium species using various bioinformatics tools and softwares. These two proteins are major blood stage antigens of Plasmodium species. This study demonstrates that the circumsporozoite protein of Pl...

  5. Protein kinase Cbeta mediates hepatic induction of sterol-regulatory element binding protein-1c by insulin

    OpenAIRE

    Yamamoto, Takashi; Watanabe, Kazuhisa; Inoue, Noriyuki; Nakagawa, Yoshimi; Ishigaki, Naomi; Matsuzaka, Takashi; Takeuchi, Yoshinori; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Suzuki, Hiroaki; Yahagi, Naoya; Gotoda, Takanari; Yamada, Nobuhiro; Shimano, Hitoshi

    2010-01-01

    Sterol-regulatory element binding protein-1c (SREBP-1c) is a transcription factor that controls lipogenesis in the liver. Hepatic SREBP-1c is nutritionally regulated, and its sustained activation causes hepatic steatosis and insulin resistance. Although regulation of SREBP-1c is known to occur at the transcriptional level, the precise mechanism by which insulin signaling activates SREBP-1c promoter remains to be elucidated. Here we show that protein kinase C beta (PKCbeta) is a key mediator o...

  6. Thermal denaturation of barley lipid transfer protein 1 studied by nuclear magnetic resonance and differential scanning calorimetry

    Czech Academy of Sciences Publication Activity Database

    Žídková, Jitka; Matejková, M.; Žídek, L.; Wimmerová, M.; Sklenář, V.; Bobálová, Janette

    2009-01-01

    Roč. 16, 1a (2009), b53. ISSN 1211-5894. [Meeting of the Czech and Slovak Structural Biologists /7./. 12.03.2009-14.03.2009, Nové Hrady] R&D Projects: GA MŠk 1M0570; GA MŠk(CZ) LC06030 Institutional research plan: CEZ:AV0Z40310501 Keywords : thermal denaturation * barley lipid transfer protein 1 * NMR Subject RIV: CB - Analytical Chemistry, Separation

  7. Contribution of Specific Amino Acid Changes in Penicillin Binding Protein 1 to Amoxicillin Resistance in Clinical Helicobacter pylori isolates ▿

    OpenAIRE

    Qureshi, Nadia N.; Morikis, Dimitrios; Schiller, Neal L.

    2010-01-01

    Amoxicillin is commonly used to treat Helicobacter pylori, a major cause of peptic ulcers, stomach cancer, and B-cell mucosa-associated lymphoid tissue lymphoma. Amoxicillin resistance in H. pylori is increasing steadily, especially in developing countries, leading to treatment failures. In this study, we characterize the mechanism of amoxicillin resistance in the U.S. clinical isolate B258. Transformation of amoxicillin-susceptible strain 26695 with the penicillin binding protein 1 gene (pbp...

  8. The Oncoplacental Gene Placenta-Specific Protein 1 Is Highly Expressed in Endometrial Tumors and Cell Lines

    OpenAIRE

    Devor, Eric J.; Leslie, Kimberly K.

    2013-01-01

    Placenta-specific protein 1 (PLAC1) is a small secreted protein expressed exclusively in trophoblast cells in the mammalian placenta. PLAC1 is expressed early in gestation and is maintained throughout. It is thought to function in trophoblast invasion of the uterine epithelium and, subsequently, to anchor the placenta to the epithelium. In recent years, evidence has accumulated that PLAC1 is also expressed in a variety of human solid tumors, notably in breast cancers. We demonstrate for the f...

  9. Dentin matrix protein 1 and dentin sialophosphoprotein in human sound and carious teeth: an immunohistochemical and colorimetric assay

    OpenAIRE

    D. Martini; A. Trirè; Breschi, L.; Mazzoni, A.; Teti, G; Falconi, M; A. Ruggeri Jr

    2013-01-01

    Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) are extracellular matrix proteins produced by odontoblasts involved in the dentin mineralization. The aim this study was to compare the distribution of DMP1 and DSPP in human sound dentin vs human sclerotic dentin. Sixteen sound and sixteen carious human molars were selected, fixed in paraformaldehyde and processed for immunohistochemical detection of DMP1 and DSPP by means of light microscopy, transmission electron microsco...

  10. Nitric Oxide-associated Protein 1 (NOA1) Is Necessary for Oxygen-dependent Regulation of Mitochondrial Respiratory Complexes*

    OpenAIRE

    Heidler, Juliana; Al-Furoukh, Natalie; Kukat, Christian; Salwig, Isabelle; Ingelmann, Marie-Elisabeth; Seibel, Peter; Krüger, Marcus; Holtz, Jürgen; Wittig, Ilka; Braun, Thomas; Szibor, Marten

    2011-01-01

    In eukaryotic cells, maintenance of cellular ATP stores depends mainly on mitochondrial oxidative phosphorylation (OXPHOS), which in turn requires sufficient cellular oxygenation. The crucial role of proper oxygenation for cellular viability is reflected by involvement of several mechanisms, which sense hypoxia and regulate activities of respiratory complexes according to available oxygen concentrations. Here, we focus on mouse nitric oxide-associated protein 1 (mNOA1), which has been identif...

  11. Comprehensive Mapping of Common Immunodominant Epitopes in the West Nile Virus Nonstructural Protein 1 Recognized by Avian Antibody Responses

    OpenAIRE

    Sun, EnCheng; Jing ZHAO; Liu, Nihong; Yang, Tao; Xu, Qingyuan; Qin, Yongli; Bu, Zhigao; Yang, Yinhui; Lunt, Ross A.; Wang, Linfa; Wu, Donglai

    2012-01-01

    West Nile virus (WNV) is a mosquito-borne flavivirus that primarily infects birds but occasionally infects humans and horses. Certain species of birds, including crows, house sparrows, geese, blue jays and ravens, are considered highly susceptible hosts to WNV. The nonstructural protein 1 (NS1) of WNV can elicit protective immune responses, including NS1-reactive antibodies, during infection of animals. The antigenicity of NS1 suggests that NS1-reactive antibodies could provide a basis for se...

  12. Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme

    OpenAIRE

    Tivnan, Amanda; Zakaria, Zaitun; O'Leary, Caitrín; Kögel, Donat; Pokorny, Jenny L.; Sarkaria, Jann N.; Prehn, Jochen H M

    2015-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30–40% response rate, many fall into the range of 10–20%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it's role in BBB ...

  13. Inhibition of Multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme

    OpenAIRE

    Amanda eTivnan; Zaitun eZakaria; Caitrin eO'Leary; Donat eKogel; Pokorny, Jenny L.; Sarkaria, Jann N.; Prehn, Jochen H M

    2015-01-01

    Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with extremely poor prognostic outcome despite intensive treatment. All chemotherapeutic agents currently used have no greater than 30-40% response rate, many fall into the range of 10-20%, with delivery across the blood brain barrier (BBB) or chemoresistance contributing to the extremely poor outcomes despite treatment. Increased expression of the multidrug resistance protein 1(MRP1) in high grade glioma, and it’s role in BB...

  14. Expression of the domain cassette 8 Plasmodium falciparum erythrocyte membrane protein 1 is associated with cerebral malaria in Benin

    DEFF Research Database (Denmark)

    Bertin, Gwladys I; Lavstsen, Thomas; Guillonneau, François;

    2013-01-01

    Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a highly polymorphic adherence receptor expressed on the surface of infected erythrocytes. Based on sequence homology PfEMP-1 variants have been grouped into three major groups A-C, the highly conserved VAR2CSA variants, and semi......-conserved types defined by tandem runs of specific domains ("domain cassettes" (DC)). The PfEMP-1 type expressed determines the adherence phenotype, and is associated with clinical outcome of infection....

  15. Specific T-cell recognition of the merozoite proteins rhoptry-associated protein 1 and erythrocyte-binding antigen 1 of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Jakobsen, P H; Hviid, L; Theander, T G;

    1993-01-01

    The merozoite proteins merozoite surface protein 1 (MSP-1) and rhoptry-associated protein 1 (RAP-1) and synthetic peptides containing sequences of MSP-1, RAP-1, and erythrocyte-binding antigen 1, induced in vitro proliferative responses of lymphocytes collected from Ghanaian blood donors living i...

  16. Correlation of pathogenesis of Toll-like receptor and chemotactic factor with lyme arthritis%Toll样受体和趋化因子与莱姆关节炎发病的相关性

    Institute of Scientific and Technical Information of China (English)

    汪玉娇; 宝福凯; 柳爱华

    2012-01-01

    莱姆病是一种由伯氏疏螺旋体引起,经蜱传播的自然疫源性疾病,也是一种人兽共患病,莱姆关节炎是莱姆病的晚期临床表现,严重者可终生致残,严重影响了人们的健康和生活质量,目前,对莱姆关节炎的致病机制尚不清楚,国内外已经取得了一系列进展,但有待进一步研究.现就Toll样受体和趋化因子与莱姆关节炎发病关系的研究做一综述.%Lyme disease, which is caused by Borrelia burgdorferi and spread by ticks, is a kind of natural foci disease and parasitic zoonoses. Lyme Arthritis is the late clinical manifestation of Lyme disease, it can make patients in lifelong disability in some severe cases and seriously affect healthy and life quality of patients. Until now, We still don't understand the pathogenic mechanism of Lyme Arthritis clearly, although there is a serious progress about it at home and aboard, further study on it is necessary. This article is intent to summarize the researches on relationship between Toll-like receptor, chemotactic factor and Lyme Arthritis.

  17. 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

  18. RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer

    OpenAIRE

    Lee, S. E.; Lee, J. U.; Lee, M. H.; Ryu, M J; S. J. Kim; Kim, Y. K.; Choi, M J; Kim, K.S.; Kim, J. M.; Kim, J.W.; Koh, Y. W.; Lim, D-S; Jo, Y S; Shong, M

    2013-01-01

    The transcription coactivator Yes-associated protein 1 (YAP1) is regulated by the Hippo tumor suppressor pathway. However, the role of YAP1 in thyroid cancer, which is frequently associated with the BRAFV600E mutation, remains unknown. This study aimed to investigate the role of YAP1 in thyroid cancer. YAP1 was overexpressed in papillary (PTC) and anaplastic thyroid cancer, and nuclear YAP1 was more frequently detected in BRAF V600E (+) PTC. In the thyroid cancer cell lines TPC-1 and HTH7, wh...

  19. Neuronal low-density lipoprotein receptor-related protein 1 binds and endocytoses prion fibrils via receptor cluster 4

    DEFF Research Database (Denmark)

    Jen, Angela; Parkyn, Celia J; Mootoosamy, Roy C;

    2010-01-01

    For infectious prion protein (designated PrP(Sc)) to act as a template to convert normal cellular protein (PrP(C)) to its distinctive pathogenic conformation, the two forms of prion protein (PrP) must interact closely. The neuronal receptor that rapidly endocytoses PrP(C) is the low......-density lipoprotein receptor-related protein 1 (LRP1). We show here that on sensory neurons LRP1 is also the receptor that binds and rapidly endocytoses smaller oligomeric forms of infectious prion fibrils, and recombinant PrP fibrils. Although LRP1 binds two molecules of most ligands independently to its receptor...... both prion and LRP1 biology....

  20. Unusual Presentation of Pelizaeus-Merzbacher Disease: Female Patient with Deletion of the Proteolipid Protein 1 Gene

    Directory of Open Access Journals (Sweden)

    Teva Brender

    2015-01-01

    Full Text Available Pelizaeus-Merzbacher disease (PMD is neurodegenerative leukodystrophy caused by dysfunction of the proteolipid protein 1 (PLP1 gene on Xq22, which codes for an essential myelin protein. As an X-linked condition, PMD primarily affects males; however there have been a small number of affected females reported in the medical literature with a variety of different mutations in this gene. No affected females to date have a deletion like our patient. In addition to this, our patient has skewed X chromosome inactivation which adds to her presentation as her unaffected mother also carries the mutation.

  1. Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations

    OpenAIRE

    Yamada, Tadaaki; Takeuchi, Shinji; Fujita, Naoya; Nakamura, Akito; Wang, Wei; Li, Qi; Oda, Makoto; Mitsudomi, Tetsuya; Yatabe, Yasushi; Sekido, Yoshitaka; Yoshida, Junji; Higashiyama, Masahiko; Noguchi, Masayuki; Uehara, Hisanori; Nishioka, Yasuhiko

    2013-01-01

    Despite initial dramatic response, epidermal growth factor receptor (EGFR) mutant lung cancer patients always acquire resistance to EGFR-tyrosine kinase inhibitors (TKIs). Gatekeeper T790M mutation in EGFR is the most prevalent genetic alteration underlying acquired resistance to EGFR-TKI, and EGFR mutant lung cancer cells are reported to be addictive to EGFR/Akt signaling even after acquired T790M mutation. Here, we focused on Akt kinase-interacting protein1 (Aki1), a scaffold protein of PI3...

  2. Poly(A) Binding Protein 1 Enhances Cap-Independent Translation Initiation of Neurovirulence Factor from Avian Herpesvirus

    OpenAIRE

    Tahiri-Alaoui, Abdessamad; Zhao, Yuguang; Sadigh, Yashar; Popplestone, James; Kgosana, Lydia; Smith, Lorraine P.; Nair, Venugopal

    2014-01-01

    Poly(A) binding protein 1 (PABP1) plays a central role in mRNA translation and stability and is a target by many viruses in diverse manners. We report a novel viral translational control strategy involving the recruitment of PABP1 to the 5' leader internal ribosome entry site (5L IRES) of an immediate-early (IE) bicistronic mRNA that encodes the neurovirulence protein (pp14) from the avian herpesvirus Marek’s disease virus serotype 1 (MDV1). We provide evidence for the interaction between an ...

  3. Epigenetic analyses of the insulin-like growth factor binding protein 1 gene in type 1 diabetes and diabetic nephropathy

    OpenAIRE

    Gu, Tianwei; Falhammar, Henrik; Gu, Harvest F.; Brismar, Kerstin

    2014-01-01

    Background Clinical observations have demonstrated that high levels of circulating insulin-like growth factor binding protein-1 (IGFBP-1) are associated with type 1 diabetes (T1D), whereas low serum IGFBP-1 levels are associated with the risk of type 2 diabetes (T2D). Recently, we reported that increased DNA methylation levels in the IGFBP1 gene were associated with T2D. In the present study, we evaluated the epigenetic changes of IGFBP1 in T1D and diabetic nephropathy (DN). Results In total,...

  4. Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) and implications in catabolic conditions

    OpenAIRE

    Lindgren, Björn

    1997-01-01

    This thesis has studied the regulation of IGFBP-1 (insulin-like growth factor binding protein 1), which is one factor regulating the bioavailability of IGF-I with special interest how IGFBP-1 is regulated in vitro and in humans, especially in diabetes and catabolic conditions. The IGFBP-1 cDNA was cloned and used for studies in human hepatoma cells, HepG2, which showed that both insulin and IGF-I could decrease IGFBP-1 in the cell conditioned medium. IGF-I inhibited also IGF...

  5. Identification of multidrug resistance protein 1 (MRP1/ABCC1) as a molecular gate for cellular export of cobalamin

    DEFF Research Database (Denmark)

    Beedholm-Ebsen, Rasmus; van de Wetering, Koen; Hardlei, Tore;

    2010-01-01

    transporters by cellular gene silencing showed a role in cellular Cbl efflux of the ATP-binding cassette (ABC)-drug transporter, ABCC1, alias multidrug resistance protein 1 (MRP1), which is present in the basolateral membrane of intestinal epithelium and in other cells. The ability of MRP1 to mediate ATP...... kidney. In contrast, Cbl accumulates in the terminal part of the intestine of these mice, suggesting a functional malabsorption because of a lower epithelial basolateral Cbl efflux. The identification of this Cbl export mechanism now allows the delineation of a coherent pathway for Cbl trafficking from...

  6. Kinetics of B Cell Responses to Plasmodium falciparum Erythrocyte Membrane Protein 1 in Ghanaian Women Naturally Exposed to Malaria Parasites

    DEFF Research Database (Denmark)

    Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F;

    2014-01-01

    Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why...... acquisition of clinical protection takes years to develop, but it probably involves a range of immune-evasive parasite features, not least of which are PfEMP1 polymorphism and clonal variation. Parasite-induced subversion of immunological memory and expansion of "atypical" memory B cells may also contribute...

  7. Crystallization and preliminary X-ray analysis of the yeast tRNA-thiouridine modification protein 1 (Tum1p)

    International Nuclear Information System (INIS)

    Yeast tRNA-thiouridine modification protein 1 was overpressed in E. coli, purified and crystallized. The crystals belonged to space group I41 and diffracted to a resolution of 1.9 Å. Yeast tRNA-thiouridine modification protein 1 (Tum1p), a crucial component of the Urm1 system, is believed to play important roles in protein urmylation and tRNA-thiouridine modification. Previous studies have demonstrated that the conserved residue Cys259 in the C-terminal rhodanese-like domain of Tum1p is essential for these sulfur-transfer activities. Here, recombinant Tum1p protein has been cloned and overexpressed in Escherichia coli strain BL21 (DE3). After purification, crystals of Tum1p were obtained by the hanging-drop vapour-diffusion method and diffracted to 1.9 Å resolution. The preliminary X-ray data showed that the tetragonal Tum1p crystal belonged to space group I41, with unit-cell parameters a = b = 120.94, c = 48.35 Å. The asymmetric unit of the crystal was assumed to contain one protein molecule, giving a Matthews coefficient of 2.41 Å3 Da−1 and a solvent content of 49.0%

  8. Crystallization and preliminary crystallographic analysis of a calcineurin B-like protein 1 (CBL1) mutant from Ammopiptanthus mongolicus

    International Nuclear Information System (INIS)

    Recombinant calcineurin B-like protein 1 from Ammopiptanthus mongolicus (AmCBL1) was overexpressed, purified and crystallized. Calcineurin B-like protein 1 (CBL1) is a calcium sensor in plants. It transmits the calcium signal through the downstream protein CBL-interacting protein kinase (CIPK). CBL1 and CIPK play crucial roles in the response to environmental stresses such as low K+, osmotic shock, high salt, cold and drought. Recombinant CBL1 from Ammopiptanthus mongolicus (AmCBL1) was overexpressed, purified and crystallized. However, the crystal did not diffract well. A mutant prepared using the surface-entropy method and crystallized using the hanging-drop method at 298 K with PEG 2000 MME as a precipitant diffracted to 2.90 Å resolution. The crystal belonged to space group P21212, with unit-cell parameters a = 99.87, b = 114.42, c = 63.80 Å, α = β = γ = 90.00° and three molecules per asymmetric unit

  9. Therapeutic effects of topical netrin-4 in a corneal acute inflammatory model

    Institute of Scientific and Technical Information of China (English)

    Yun; Han; Yi; Shao; Ting-Ting; Liu; Sang-Ming; Li; Wei; Li; Zu-Guo; Liu

    2015-01-01

    AIM: To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye.METHODS: Eye drops containing netrin-4 or phosphate buffered saline(PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy.Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction(PCR).RESULTS: Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7(P <0.01). The levels of IL-1β, IL-6, intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), monocyte chemotactic protein-1(MCP-1) and macrophage inflammatory protein-1(MIP-1) in corneas were decreased in netrin-4-treated groups(P <0.05). In addition, netrin-4 significantly reduced the expression of leukocyte common antigen 45(CD45) in the alkali-burn cornea(P <0.001).CONCLUSION: Topical netrin-4 accelerated wound healing and reduced the inflammation on alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation.

  10. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes

    International Nuclear Information System (INIS)

    Tea flavonoids such as epigallocatechin gallate (EGCG) protect against vascular diseases such as atherosclerosis via their antioxidant and anti-inflammatory functions. Persistent and widespread environmental pollutants, including polychlorinated biphenyls (PCB), can induce oxidative stress and inflammation in vascular endothelial cells. Even though PCBs are no longer produced, they are still detected in human blood and tissues and thus considered a risk for vascular dysfunction. We hypothesized that EGCG can protect endothelial cells against PCB-induced cell damage via its antioxidant and anti-inflammatory properties. To test this hypothesis, primary vascular endothelial cells were pretreated with EGCG, followed by exposure to the coplanar PCB 126. Exposure to PCB 126 significantly increased cytochrome P450 1A1 (Cyp1A1) mRNA and protein expression and superoxide production, events which were significantly attenuated following pretreatment with EGCG. Similarly, EGCG also reduced DNA binding of NF-κB and downstream expression of inflammatory markers such as monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) after PCB exposure. Furthermore, EGCG decreased endogenous or base-line levels of Cyp1A1, MCP-1 and VCAM-1 in endothelial cells. Most of all, treatment of EGCG upregulated expression of NF-E2-related factor 2 (Nrf2)-controlled antioxidant genes, including glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in a dose-dependent manner. In contrast, silencing of Nrf2 increased Cyp1A1, MCP-1 and VCAM-1 and decreased GST and NQO1 expression, respectively. These data suggest that EGCG can inhibit AhR regulated genes and induce Nrf2-regulated antioxidant enzymes, thus providing protection against PCB-induced inflammatory responses in endothelial cells. -- Highlights: ► PCBs cause endothelial inflammation and subsequent atherosclerosis. ► Nutrition can modulate toxicity by environmental pollutants. ► We

  11. EGCG protects endothelial cells against PCB 126-induced inflammation through inhibition of AhR and induction of Nrf2-regulated genes

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sung Gu [Superfund Research Program, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536 (United States); Han, Seong-Su [Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Toborek, Michal [Department of Neurosurgery, University of Kentucky, Lexington, KY 40536 (United States); Hennig, Bernhard, E-mail: bhennig@uky.edu [Superfund Research Program, University of Kentucky, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, University of Kentucky, Lexington, KY 40536 (United States)

    2012-06-01

    Tea flavonoids such as epigallocatechin gallate (EGCG) protect against vascular diseases such as atherosclerosis via their antioxidant and anti-inflammatory functions. Persistent and widespread environmental pollutants, including polychlorinated biphenyls (PCB), can induce oxidative stress and inflammation in vascular endothelial cells. Even though PCBs are no longer produced, they are still detected in human blood and tissues and thus considered a risk for vascular dysfunction. We hypothesized that EGCG can protect endothelial cells against PCB-induced cell damage via its antioxidant and anti-inflammatory properties. To test this hypothesis, primary vascular endothelial cells were pretreated with EGCG, followed by exposure to the coplanar PCB 126. Exposure to PCB 126 significantly increased cytochrome P450 1A1 (Cyp1A1) mRNA and protein expression and superoxide production, events which were significantly attenuated following pretreatment with EGCG. Similarly, EGCG also reduced DNA binding of NF-κB and downstream expression of inflammatory markers such as monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion protein-1 (VCAM-1) after PCB exposure. Furthermore, EGCG decreased endogenous or base-line levels of Cyp1A1, MCP-1 and VCAM-1 in endothelial cells. Most of all, treatment of EGCG upregulated expression of NF-E2-related factor 2 (Nrf2)-controlled antioxidant genes, including glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), in a dose-dependent manner. In contrast, silencing of Nrf2 increased Cyp1A1, MCP-1 and VCAM-1 and decreased GST and NQO1 expression, respectively. These data suggest that EGCG can inhibit AhR regulated genes and induce Nrf2-regulated antioxidant enzymes, thus providing protection against PCB-induced inflammatory responses in endothelial cells. -- Highlights: ► PCBs cause endothelial inflammation and subsequent atherosclerosis. ► Nutrition can modulate toxicity by environmental pollutants. ► We

  12. Rapid intracellular calcium changes in U937 monocyte cell line: transient increases in response to platelet-activating factor and chemotactic peptide but not interferon-gamma or lipopolysaccharide.

    Science.gov (United States)

    Maudsley, D J; Morris, A G

    1987-06-01

    The dye fura-2, a potentially more sensitive successor to quin2 for measuring intracellular free calcium ion concentrations [(Ca2+]i), has been applied here to investigate the possible involvement of early changes in [Ca2+]i in the stimulation of the human monocyte-macrophage-like cell line U937. The calcium ionophores A23187 and ionomycin, known pharmacological stimuli for macrophages, were found to cause sharp rises in [Ca2+]i as expected. Responses analogous to those reported for a murine macrophage cell (J774) were obtained on stimulation of U937 cells with ATP which caused rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 200 mM). In addition to ATP, several agents known to activate macrophages were used as stimuli. In particular, platelet-activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was found to cause rapid, but transient, increases in [Ca2+]i (from resting levels of about 70 nM to peaks of about 400 nM) even at concentrations as low as 10(-10) M. This contrasts with responses to ATP that were markedly reduced at 10(-6) M compared with 10(-5) M or above, suggesting that PAF is a highly potent stimulus for intracellular calcium mobilization in macrophages. Similar responses were obtained with chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine). On the other hand, two agents known to be potent activators of macrophages, interferon gamma and lipopolysaccharide, had no rapid effect on [Ca2+]i. This may reflect differences in the kinetics of signal-response coupling or alternatively a different mechanism of action by-passing the need for rapid elevation of [Ca2+]i. PMID:3110054

  13. Osteogenic protein-1 increases the fixation of implants grafted with morcellised bone allograft and ProOsteon bone substitute: an experimental study in dogs

    DEFF Research Database (Denmark)

    Baad-Hansen, Thomas Einer; Overgaard, S; Lind, M;

    2007-01-01

    weeks osteogenic protein-1 increased bone formation and the energy absorption of implants grafted with allograft and ProOsteon. A composite of allograft, ProOsteon and osteogenic protein-1 was comparable, but not superior to, allograft used on its own. ProOsteon alone cannot be recommended as a......Impacted bone allograft is often used in revision joint replacement. Hydroxyapatite granules have been suggested as a substitute or to enhance morcellised bone allograft. We hypothesised that adding osteogenic protein-1 to a composite of bone allograft and non-resorbable hydroxyapatite granules...... surrounded by a concentric 3 mm gap. These gaps were randomly allocated to four different procedures in each dog: 1) bone allograft used on its own; 2) ProOsteon used on its own; 3) allograft and ProOsteon used together; or 4) allograft and ProOsteon with the addition of osteogenic protein-1. After three...

  14. PPARα/γ激动剂对糖尿病伴冠心病患者血浆炎症因子的影响%Effects of PPAR α/γ dual agonists on plasma inflammatory cytokine in patients with diabetes complicated with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    韦金儒; 唐泉

    2012-01-01

    目的 探讨联合应用过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)α/γ激动剂对糖尿病伴冠状动脉粥样硬化性心脏病(冠心病)患者血浆炎症因子的影响.方法 将80例伴有糖尿病的冠心病患者分为马来酸罗格列酮组(n=20)、苯扎贝特组(n=20)、马来酸罗格列酮和苯扎贝特联合组(n=20)、常规治疗组(n=20).治疗后,对所有患者随访12周.治疗前后均对所有患者采血,并用酶联免疫吸附法测定患者血浆C反应蛋白、单核细胞趋化蛋白-1 (monocyte chemotactic protein-1,MCP-1),观察患者空腹血糖、空腹胰岛素、胰岛素抵抗指数、糖化血红蛋白-A1c(HbA1c)、血脂、体质量指数的改变.结果 联合组、马来酸罗格列酮组、苯扎贝特组血浆C反应蛋白、MCP-1、空腹血糖、糖化血红蛋白、胰岛素、总胆固醇、三酰甘油、低密度脂蛋白胆固醇浓度和胰岛素抵抗指数治疗12周后比治疗前明显降低,高密度脂蛋白胆固醇明显升高,差异有统计学意义(P<0.05),且联合组上述指标改善最显著.马来酸罗格列酮组、苯扎贝特组、联合组的单核细胞在脂多糖诱导下分泌MCP-1浓度较治疗前降低,以联合组降低最为显著.C反应蛋白的降低与空腹胰岛素和胰岛素抵抗指数的降低呈正相关(r=0.498,P<0.001和r=0.496,P<0.001),与其他因素的变化无相关性(P>0.05);而MCP-1的变化与糖、脂代谢无相关性(P>0.05);C反应蛋白与MCP-1之间也无明显相关性(P>0.05).结论 联合应用马来酸罗格列酮、苯扎贝特能够降低血浆C反应蛋白和MCP-1浓度,降低血糖和血浆胰岛素浓度,减轻胰岛素抵抗,改善辛伐他汀治疗后残存的高三酰甘油和低高密度脂蛋白胆固醇,效果优于单用马来酸罗格列酮或苯扎贝特.%Objectives To observe the effects of combined peroxisome proliferator-activated receptor (PPAR)ot-agonist and PPAR

  15. The Role of Cdkn1A-Interacting Zinc Finger Protein 1 (CIZ1 in DNA Replication and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2016-02-01

    Full Text Available Cdkn1A-interacting zinc finger protein 1 (CIZ1 was first identified in a yeast-2-hybrid system searching for interacting proteins of CDK2 inhibitor p21Cip1/Waf1. Ciz1 also binds to CDK2, cyclin A, cyclin E, CDC6, PCNA, TCF4 and estrogen receptor-α. Recent studies reveal numerous biological functions of CIZ1 in DNA replication, cell proliferation, and differentiation. In addition, splicing variants of CIZ1 mRNA is associated with a variety of cancers and Alzheimer’s disease, and mutations of the CIZ1 gene lead to cervical dystonia. CIZ1 expression is increased in cancers and rheumatoid arthritis. In this review, we will summarize the biological functions and molecular mechanisms of CIZ1 in these physiological and pathological processes.

  16. Molecular energy dissipation in nanoscale networks of dentin matrix protein 1 is strongly dependent on ion valence

    International Nuclear Information System (INIS)

    The fracture resistance of biomineralized tissues such as bone, dentin, and abalone is greatly enhanced through the nanoscale interactions of stiff inorganic mineral components with soft organic adhesive components. A proper understanding of the interactions that occur within the organic component, and between the organic and inorganic components, is therefore critical for a complete understanding of the mechanics of these tissues. In this paper, we use atomic force microscope (AFM) force spectroscopy and dynamic force spectroscopy to explore the effect of ionic interactions within a nanoscale system consisting of networks of dentin matrix protein 1 (DMP1) (a component of both bone and dentin organic matrix), a mica surface and an AFM tip. We find that DMP1 is capable of dissipating large amounts of energy through an ion-mediated mechanism, and that the effectiveness increases with increasing ion valence

  17. Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1 in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Cyril Sobolewski

    2015-08-01

    Full Text Available The RNA-binding protein tristetraprolin (TTP promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE. In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC inhibitors (Trichostatin A, SAHA and sodium butyrate promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells and cervix carcinoma cells (HeLa. We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1. Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer.

  18. Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

    Directory of Open Access Journals (Sweden)

    Naoya Yamashita

    2013-12-01

    Full Text Available Collapsin response mediator protein 1 (CRMP1 is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1-/- mice exhibited behavioral abnormalities related to schizophrenia. The crmp1-/- mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1-/- mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1-/- mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1-/- mouse may model endophenotypes present in this neuropsychiatric disorder.

  19. Golgi localization and dynamics of hyaluronan binding protein 1 (HABP1/p32/C1QBP) during the cell cycle

    Institute of Scientific and Technical Information of China (English)

    Aniruddha SENGUPTA; Bhaswati BANERJEE; Rakesh K. TYAGI; Kasturi DATTA

    2005-01-01

    Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.

  20. Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

    DEFF Research Database (Denmark)

    Bown, Matthew J; Jones, Gregory T; Harrison, Seamus C;

    2011-01-01

    additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p <1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low......-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined...

  1. Hierarchical, domain type-specific acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 in Tanzanian children

    DEFF Research Database (Denmark)

    Cham, Gerald K K; Turner, Louise; Kurtis, Jonathan D;

    2010-01-01

    Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant antigen expressed on the surface of malaria-infected erythrocytes. PfEMP1 attaches to the vascular lining and allows infected erythrocytes to avoid filtration through the spleen. Each parasite genome encodes about 60...... different PfEMP1 variants, each PfEMP1 comprises several domains in its extracellular region, and the PfEMP1 repertoire in different parasites contains domain types that are serologically cross-reactive. In this longitudinal study, we followed 672 children living in an area of high malaria transmission...... which individuals acquire antibodies to different PfEMP1 domains is ordered, and children in areas of endemicity first acquire antibodies to particular PfEMP1 domains encoded by the so-called group A and B/A var genes. The results imply that anti-PfEMP1 antibodies effectively structure PfEMP1 expression...

  2. Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Turner, Louise; Saguti, Fredy;

    2012-01-01

    The clinical outcome of Plasmodium falciparum infections ranges from asymptomatic parasitemia to severe malaria syndromes associated with high mortality. The virulence of P. falciparum infections is associated with the type of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the...... surface of infected erythrocytes to anchor these to the vascular lining. Although var2csa, the var gene encoding the PfEMP1 associated with placental malaria, was discovered in 2003, the identification of the var/PfEMP1 variants associated with severe malaria in children has remained elusive. To identify...... var/PfEMP1 variants associated with severe disease outcome, we compared var transcript levels in parasites from 88 children with severe malaria and 40 children admitted to the hospital with uncomplicated malaria. Transcript analysis was performed by RT-quantitative PCR using a set of 42 primer pairs...

  3. Latent membrane protein 1 is critical for efficient growth transformation of human B cells by epstein-barr virus.

    Science.gov (United States)

    Dirmeier, Ulrike; Neuhierl, Bernhard; Kilger, Ellen; Reisbach, Gilbert; Sandberg, Mark L; Hammerschmidt, Wolfgang

    2003-06-01

    The EBV latent membrane protein 1 (LMP1) is an integral membrane protein that acts like a constitutively activated receptor. LMP1 interacts with members of the tumor necrosis factor receptor-associated factor family, as well as with tumor necrosis factor receptor-associated death domain, resulting in induction of nuclear factor-kappaB, the p38 mitogen-activated protein kinase pathway, and the c-Jun NH(2)-terminal kinase activator protein 1-signaling cascade. The binding of Janus kinase 3 results in activation of signal transducers and activators of transcription. The domain structure of LMP1 has been mapped extensively, but the quantitative contribution of distinct LMP1 domains to the efficiency of B-cell proliferation by EBV has not been determined. On the basis of the maxi-EBV system, which allows us to introduce and study mutations in the context of the complete EBV genome, a panel of 10 EBV mutants with alterations in the LMP1 gene locus was established. The mutant EBVs were tested for their efficiency to induce and maintain proliferation of clonal B-cell lines in vitro. Surprisingly and with reduced frequency, EBV mutants which deleted LMP1's COOH terminus, transmembrane domains, or the entire open reading frame were able to generate proliferating B-cell clones that were dependent on the presence of human fibroblast feeder cells. A B-cell clone carrying the LMP1-null mutant EBV genome was also analyzed for oncogenicity in severe combined immunodeficiency mice. Our results demonstrate that LMP1 is critical but not mandatory for the generation of proliferating B cells in vitro. LMP1 functions greatly contribute to EBV's transformation potential and appear essential for its oncogenicity in severe combined immunodeficiency mice. PMID:12782607

  4. Bone marrow-derived microglia infiltrate into the paraventricular nucleus of chronic psychological stress-loaded mice.

    Directory of Open Access Journals (Sweden)

    Koji Ataka

    Full Text Available BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(lowCCR2(+CXCR4(high, as distinct from CX3CR1(highCCR2(-CXCR4(low resident microglia, and express higher levels of interleukin-1β (IL-1β but lower levels of tumor necrosis factor-α (TNF-α. Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1 in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1 in the bone marrow and increases the frequency of CXCR4(+ monocytes in peripheral circulation. And then a chemokine (C-C motif receptor 2 (CCR2 or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

  5. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

    International Nuclear Information System (INIS)

    Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO2 and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO2 particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO2 nanoparticles

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

    Directory of Open Access Journals (Sweden)

    John Axelsson

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

  7. Surfactant dysfunction and lung inflammation in the female mouse model of lymphangioleiomyomatosis.

    Science.gov (United States)

    Atochina-Vasserman, Elena N; Guo, Chang-Jiang; Abramova, Elena; Golden, Thea N; Sims, Michael; James, Melane L; Beers, Michael F; Gow, Andrew J; Krymskaya, Vera P

    2015-07-01

    Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations of the tumor suppressor genes, tuberous sclerosis complex (TSC) 1 or TSC2. LAM affects women almost exclusively, and it is characterized by neoplastic growth of atypical smooth muscle-like TSC2-null LAM cells in the pulmonary interstitium, cystic destruction of lung parenchyma, and progressive decline in lung function. In this study, we hypothesized that TSC2-null lesions promote a proinflammatory environment, which contributes to lung parenchyma destruction. Using a TSC2-null female murine LAM model, we demonstrate that TSC2-null lesions promote alveolar macrophage accumulation, recruitment of immature multinucleated cells, an increased induction of proinflammatory genes, nitric oxide (NO) synthase 2, IL-6, chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein 1 (MCP1), chemokine (C-X-C motif) ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and up-regulation of IL-6, KC, MCP-1, and transforming growth factor-β1 levels in bronchoalveolar lavage fluid. Bronchoalveolar lavage fluid also contained an increased level of surfactant protein (SP)-D, but not SP-A, significant reduction of SP-B levels, and a resultant increase in alveolar surface tension. Consistent with the growth of TSC2-null lesions, NO levels were also increased and, in turn, modified SP-D through S-nitrosylation, forming S-nitrosylated SP-D, a known consequence of lung inflammation. Progressive growth of TSC2-null lesions was accompanied by elevated levels of matrix metalloproteinase-3 and -9. This report demonstrates a link between growth of TSC2-null lesions and inflammation-induced surfactant dysfunction that might contribute to lung destruction in LAM. PMID:25474372

  8. Bronchoalveolar Lavage Fluid Utilized Ex Vivo to Validate In Vivo Findings: Inhibition of Gap Junction Activity in Lung Tumor Promotion is Toll-Like Receptor 4-Dependent.

    Science.gov (United States)

    Hill, Thomas; Osgood, Ross S; Velmurugan, Kalpana; Alexander, Carla-Maria; Upham, Brad L; Bauer, Alison K

    2013-12-27

    TLR4 protects against lung tumor promotion and pulmonary inflammation in mice. Connexin 43 (Cx43), a gap junction gene, was increased in Tlr4 wildtype compared to Tlr4-mutant mice in response to promotion, which suggests gap junctional intercellular communication (GJIC) may be compromised. We hypothesized that the early tumor microenvironment, represented by Bronchoalveolar Lavage Fluid (BALF) from Butylated hydroxytoluene (BHT; promoter)-treated mice, would produce TLR4-dependent changes in pulmonary epithelium, including dysregulation of GJIC in the Tlr4-mutant (BALB (Lps-d) ) compared to the Tlr4-sufficient (BALB; wildtype) mice. BHT (4 weekly doses) was injected ip followed by BALF collection at 24 h. BALF total protein and total macrophages were significantly elevated in BHT-treated BALB (Lps-d) over BALB mice, similar to previous findings. BALF was then utilized in an ex vivo manner to treat C10 cells, a murine alveolar type II cell line, followed by the scrape-load dye transfer assay (GJIC), Cx43 immunostaining, and quantitative RT-PCR (Mcp-1, monocyte chemotactic protein 1). GJIC was markedly reduced in C10 cells treated with BHT-treated BALB (Lps-d) BALF for 4 and 24 h compared to BALB and control BALF from the respective mice (p < 0.05). Mcp-1, a chemokine, was also significantly increased in the BHT-treated BALB (Lps-d) BALF compared to the BALB mice, and Cx43 protein expression in the cell membrane altered. These novel findings suggest signaling from the BALF milieu is involved in GJIC dysregulation associated with promotion and links gap junctions to pulmonary TLR4 protection in a novel ex vivo model that could assist in future potential tumor promoter screening. PMID:25035812

  9. Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain

    LENUS (Irish Health Repository)

    Lyons, Anthony

    2011-03-31

    Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ). IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFNγ-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  10. Atorvastatin prevents age-related and amyloid-β-induced microglial activation by blocking interferon-γ release from natural killer cells in the brain

    Directory of Open Access Journals (Sweden)

    Clarke Rachael

    2011-03-01

    Full Text Available Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ. IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1 and IFNγ-induced protein 10 kDa (IP-10, expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2 by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  11. Asian sand dust enhances ovalbumin-induced eosinophil recruitment in the alveoli and airway of mice

    International Nuclear Information System (INIS)

    Asian sand dust (ASD) containing sulfate (SO42-) reportedly causes adverse respiratory health effects but there is no experimental study showing the effect of ASD toward allergic respiratory diseases. The effects of ASD and ASD plus SO42- toward allergic lung inflammation induced by ovalbumin (OVA) were investigated in this study. ICR mice were administered intratracheally with saline; ASD alone (sample from Shapotou desert); and ASD plus SO42- (ASD-SO4); OVA+ASD; OVA+ASD-SO4. ASD or ASD-SO4 alone caused mild nutrophilic inflammation in the bronchi and alveoli. ASD and ASD-SO4 increased pro-inflammatory mediators, such as Keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-1 alpha, in bronchoalveolar lavage fluids (BALF). ASD and ASD-SO4 enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. However, a further increase of eosinophils by addition of SO42- was not observed. The two sand dusts synergistically increased interleukin-5 (IL-5) and monocyte chemotactic protein-1 (MCP-1), which were associated with OVA, in BALF. However, the increased levels of IL-5 were lower in the OVA+ASD-SO4 group than in the OVA+ASD group. ASD caused the adjuvant effects to specific-IgG1 production by OVA, but not to specific-IgE. These results suggest that the enhancement of eosinophil recruitment in the lung is mediated by synergistically increased IL-5 and MCP-1. IgG1 antibodies may play an important role in the enhancement of allergic reaction caused by OVA and sand dust. However, extra sulfate may not contribute to an increase of eosinophils

  12. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Yuka; Tada-Oikawa, Saeko [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Ichihara, Gaku [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya (Japan); Yabata, Masayuki; Izuoka, Kiyora [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan); Suzuki, Masako; Sakai, Kiyoshi [Nagoya City Public Health Research Institute, Nagoya (Japan); Ichihara, Sahoko, E-mail: saho@gene.mie-u.ac.jp [Graduate School of Regional Innovation Studies, Mie University, Tsu (Japan)

    2014-07-01

    Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO{sub 2} and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO{sub 2} particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO{sub 2} nanoparticles.

  13. Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment.

    Science.gov (United States)

    Saito, Atsushi; Nikolaidis, Nikolaos M; Amlal, Hassane; Uehara, Yasuaki; Gardner, Jason C; LaSance, Kathleen; Pitstick, Lori B; Bridges, James P; Wikenheiser-Brokamp, Kathryn A; McGraw, Dennis W; Woods, Jason C; Sabbagh, Yves; Schiavi, Susan C; Altinişik, Göksel; Jakopović, Marko; Inoue, Yoshikazu; McCormack, Francis X

    2015-11-11

    Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodium-dependent phosphate cotransporter, has been proposed as a cause of PAM. We show that epithelial deletion of Npt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers. Microliths introduced by adoptive transfer into the lungs of wild-type mice produce marked macrophage-rich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic whole-lung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAM mouse model as a preclinical platform for the development of biomarkers and therapeutic strategies. PMID:26560359

  14. Role of CXCL5 in leukocyte recruitment to the lungs during secondhand smoke exposure.

    Science.gov (United States)

    Balamayooran, Gayathriy; Batra, Sanjay; Cai, Shanshan; Mei, Junjie; Worthen, G Scott; Penn, Arthur L; Jeyaseelan, Samithamby

    2012-07-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the United States. The major cause of COPD is cigarette smoking. Extensive leukocyte influx into the lungs, mediated by chemokines, is a critical event leading to COPD. Although both resident and myeloid cells secrete chemokines in response to inflammatory stimuli, little is known about the role of epithelial-derived chemokines, such as CXC chemokine ligand (CXCL)5, in the pathogenesis of cigarette smoke-induced inflammation. To explore the role of CXCL5, we generated CXCL5 gene-deficient mice and exposed them to secondhand smoke (SHS) for 5 hours/day for 5 days/week up to 3 weeks (subacute exposure). We observed a reduced recruitment of leukocytes to the lungs of CXCL5(-/-) mice compared with their wild-type (WT) counterparts, and noted that macrophages comprised the predominant leukocytes recruited to the lungs. Irradiation experiments performed on CXCL5(-/-) or WT mice transplanted with WT or CXCL5(-/-) bone marrow revealed that resident but not hematopoietic cell-driven CXCL5 is important for mediating SHS-induced lung inflammation. Interestingly, we observed a significant reduction of monocyte chemotactic protein-1 (MCP-1/CC chemokine ligand 2) concentrations in the lungs of CXCL5(-/-) mice. The instillation of recombinant MCP-1 in CXCL5(-/-) mice reversed macrophage recruitment. Our results also show the reduced activation of NF-κB/p65 in the lungs, as well as the attenuated activation of C-Jun N-terminal kinase, p42/44, and p38 mitogen-activated protein kinases and the expression of intercellular adhesion molecule-1 in the lungs of SHS-exposed CXCL5(-/-) mice. Our findings suggest an important role for CXCL5 in augmenting leukocyte recruitment in SHS-induced lung inflammation, and provide novel insights into CXCL5-driven pathogenesis. PMID:22362385

  15. Intraocular cytokines in retinal vein occlusion and its relation to the efficiency of anti-vascular endothelial growth factor therapy

    Directory of Open Access Journals (Sweden)

    Andrey G Shchuko

    2015-01-01

    Full Text Available Purpose: To analyze the change in the concentration of intraocular cytokines (ICs in patients with retinal vein occlusion (RVO before and after intravitreal ranibizumab therapy (IVR, and to find the correlations of IC with clinical activity of RVO and efficiency of treatment. Materials and Methods: Forty-four patients aged 46–79 years old (mean age: 60.7 ± 7.5 years old with RVO and macular edema (18 patients – with central RVO, 26 – with branch RVO treated with IVR were included into the study. The concentrations of 27 cytokines were simultaneously measured in aqueous humor by flow fluorometry using Bio-Plex Pro Human Cytokine Panel, 27-Plex (Bio-Rad Laboratories, USA at baseline and after the first IVR. Control group consisted of 20 age-matched patients. Results: The levels of 11 cytokines (vascular endothelial growth factor [VEGF], receptor antagonist interleukin-1, interleukin-6 [IL-6], IL-8, IL-9, IL-10, IL-12r70, IL-13, IL-15, monocyte chemotactic protein-1 [MCP-1], regulated on activation, normal T expressed and secreted were significantly (P < 0.05 different compared to control and significantly (P < 0.05 changed after IVR both in central and branch RVO. The patients were divided into two groups: the first -"effective" and the second - "partially effective" therapy. The second group characterized by the higher concentrations of VEGF, IL-8, IL-10, IL-17, and MCP-1 at baseline compared to the first group. Conclusion: The patients with RVO were characterized by the increased levels of VEGF and other pro- and anti-inflammatory cytokines and chemokines. Aqueous concentration of cytokines were different in patients with central and branch RVO and significantly changed after IVR. Insufficient response to IVR was associated with activation of immune-inflammatory processes.

  16. Glucose and acute exercise influence factors secreted by circulating angiogenic cells in vitro.

    Science.gov (United States)

    Witkowski, Sarah; Guhanarayan, Gayatri; Burgess, Rachel

    2016-02-01

    Circulating angiogenic cells (CAC) influence vascular repair through the secretion of proangiogenic factors and cytokines. While CAC are deficient in patients with diabetes and exercise has a beneficial effect on CACs, the impact of these factors on paracrine secretion from CAC is unknown. We aimed to determine whether the in vitro secretion of selected cytokines and nitric oxide (NO) from CAC is influenced by hyperglycemia and acute exercise. Colony-forming unit CAC (CFU-CAC) were cultured from young active men (n = 9, 24 ± 2 years) at rest and after exercise under normal (5 mmol/L) and elevated (15 mmol/L) glucose. Preliminary relative multiplex cytokine analysis revealed that CAC conditioned culture media contained three of six measured cytokines: transforming growth factor-beta-1 (TGFβ1), tumor necrosis factor alpha (TNFα), and monocyte chemotactic protein-1 (MCP-1). Single quantitative cytokine analysis was used to determine the concentration of each cytokine from the four conditions. NO was measured via Griess assay. There was a significant effect of CAC exposure to in vivo exercise on in vitro TGFβ1 secretion (P = 0.024) that was independent of glucose concentration. There was no effect of glucose or acute exercise on TNFα or MCP-1 concentration (both P > 0.05). The concentration of NO from CFU-CAC cultured in elevated glucose was lower following acute exercise (P = 0.002) suggesting that exercise did not maintain NO secretion under hyperglycemic conditions. Our results identify paracrine signaling factors that may be responsible for the proangiogenic function of CFU-CAC and an influence of acute exercise and elevated glucose on CFU-CAC soluble factor secretion. PMID:26847726

  17. Evaluation of biomarkers of cell cycle arrest and inflammation in prediction of dialysis or recovery after kidney transplantation.

    Science.gov (United States)

    Pianta, Timothy J; Peake, Philip W; Pickering, John W; Kelleher, Michaela; Buckley, Nicholas A; Endre, Zoltan H

    2015-12-01

    Early prediction of delayed graft function (DGF) after kidney transplantation would facilitate patient management. Cell cycle arrest and inflammation are implicated in the pathogenesis of DGF. We assessed the utility of two novel acute kidney injury (AKI) biomarkers, urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), and five inflammatory markers to predict DGF following deceased-donor kidney transplantation. Serial urine concentrations of TIMP-2 and IGFBP7 were measured immediately after transplantation in 56 recipients along with vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibitory factor (MIF), monocyte chemotactic protein-1 (MCP-1), trefoil factor 3 (TFF3) and chemokine (C-X-C) ligand 16 (CXCL16). Delayed graft function (DGF) was defined as requirement for dialysis within 7 days. Integrated discrimination improvement analysis was used to evaluate whether these biomarkers enhanced prediction of DGF independently of a validated clinical risk prediction model. DGF occurred in 22 patients (39%). At 4 h after kidney reperfusion, the area under the receiver operator characteristic curve (AUC) for VEGF-A was good (AUC > 0.80); for TIMP-2, IGFBP7 and [TIMP-2] × [IGFBP7] fair (AUCs 0.70-0.79); and for MIF, MCP-1, TFF3 and CXCL16 poor (AUC < 0.70). Only TIMP-2 and VEGF significantly enhanced the DGF prediction at 4 and 12 h. The cell cycle arrest marker urinary TIMP-2 and the inflammatory biomarker VEGF-A are potentially useful adjuncts to clinical data for early prediction of DGF. PMID:26174580

  18. Cloning, characterization and sub-cellular localization of gamma subunit of T-complex protein-1 (chaperonin) from Leishmania donovani

    International Nuclear Information System (INIS)

    Highlights: ► The study presents cloning and characterization of TCP1γ gene from L. donovani. ► TCP1γ is a subunit of T-complex protein-1 (TCP1), a chaperonin class of protein. ► LdTCPγ exhibited differential expression in different stages of promastigotes. ► LdTCPγ co-localized with actin, a cytoskeleton protein. ► The data suggests that this gene may have a role in differentiation/biogenesis. ► First report on this chapronin in Leishmania. -- Abstract: T-complex protein-1 (TCP1) complex, a chaperonin class of protein, ubiquitous in all genera of life, is involved in intracellular assembly and folding of various proteins. The gamma subunit of TCP1 complex (TCP1γ), plays a pivotal role in the folding and assembly of cytoskeleton protein(s) as an individual or complexed with other subunits. Here, we report for the first time cloning, characterization and expression of the TCP1γ of Leishmania donovani (LdTCP1γ), the causative agent of Indian Kala-azar. Primary sequence analysis of LdTCP1γ revealed the presence of all the characteristic features of TCP1γ. However, leishmanial TCP1γ represents a distinct kinetoplastid group, clustered in a separate branch of the phylogenic tree. LdTCP1γ exhibited differential expression in different stages of promastigotes. The non-dividing stationary phase promastigotes exhibited 2.5-fold less expression of LdTCP1γ as compared to rapidly dividing log phase parasites. The sub-cellular distribution of LdTCP1γ was studied in log phase promastigotes by employing indirect immunofluorescence microscopy. The protein was present not only in cytoplasm but it was also localized in nucleus, peri-nuclear region, flagella, flagellar pocket and apical region. Co-localization of LdTCP1γ with actin suggests that, this gene may have a role in maintaining the structural dynamics of cytoskeleton of parasite.

  19. Cloning, characterization and sub-cellular localization of gamma subunit of T-complex protein-1 (chaperonin) from Leishmania donovani

    Energy Technology Data Exchange (ETDEWEB)

    Bhaskar,; Kumari, Neeti [Division of Biochemistry, CSIR-Central Drug Research Institute, Chattar Manzil Palace, PO Box 173, Lucknow (India); Goyal, Neena, E-mail: neenacdri@yahoo.com [Division of Biochemistry, CSIR-Central Drug Research Institute, Chattar Manzil Palace, PO Box 173, Lucknow (India)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer The study presents cloning and characterization of TCP1{gamma} gene from L. donovani. Black-Right-Pointing-Pointer TCP1{gamma} is a subunit of T-complex protein-1 (TCP1), a chaperonin class of protein. Black-Right-Pointing-Pointer LdTCP{gamma} exhibited differential expression in different stages of promastigotes. Black-Right-Pointing-Pointer LdTCP{gamma} co-localized with actin, a cytoskeleton protein. Black-Right-Pointing-Pointer The data suggests that this gene may have a role in differentiation/biogenesis. Black-Right-Pointing-Pointer First report on this chapronin in Leishmania. -- Abstract: T-complex protein-1 (TCP1) complex, a chaperonin class of protein, ubiquitous in all genera of life, is involved in intracellular assembly and folding of various proteins. The gamma subunit of TCP1 complex (TCP1{gamma}), plays a pivotal role in the folding and assembly of cytoskeleton protein(s) as an individual or complexed with other subunits. Here, we report for the first time cloning, characterization and expression of the TCP1{gamma} of Leishmania donovani (LdTCP1{gamma}), the causative agent of Indian Kala-azar. Primary sequence analysis of LdTCP1{gamma} revealed the presence of all the characteristic features of TCP1{gamma}. However, leishmanial TCP1{gamma} represents a distinct kinetoplastid group, clustered in a separate branch of the phylogenic tree. LdTCP1{gamma} exhibited differential expression in different stages of promastigotes. The non-dividing stationary phase promastigotes exhibited 2.5-fold less expression of LdTCP1{gamma} as compared to rapidly dividing log phase parasites. The sub-cellular distribution of LdTCP1{gamma} was studied in log phase promastigotes by employing indirect immunofluorescence microscopy. The protein was present not only in cytoplasm but it was also localized in nucleus, peri-nuclear region, flagella, flagellar pocket and apical region. Co-localization of LdTCP1{gamma} with actin suggests

  20. Profiling Signaling Polarity in Chemotactic Cells

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-05-15

    While directional movement requires morphological polarization characterized by formation of a leading pseudopodium at the front and a trailing rear at the back, little is known about how protein networks are spatially integrated to regulate this process. Here, we utilize a unique pseudopodial purification system and quantitative proteomics and phosphoproteomics to map the spatial relationship of 3509 proteins and 228 distinct sites of phosphorylation in polarized cells. Networks of signaling proteins, metabolic pathways, actin regulatory proteins, and kinase-substrate cascades were found to partition to different poles of the cell including components of the Ras/ERK pathway. Also, several novel proteins were found to be differentially phosphorylated at the front or rear of polarized cells and to localize to distinct subcellular structures. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive profile of proteins and their sites of phosphorylation that control cell polarization.

  1. Suppression of Chemotactic Explosion by Mixing

    Science.gov (United States)

    Kiselev, Alexander; Xu, Xiaoqian

    2016-06-01

    Chemotaxis plays a crucial role in a variety of processes in biology and ecology. In many instances, processes involving chemical attraction take place in fluids. One of the most studied PDE models of chemotaxis is given by the Keller-Segel equation, which describes a population density of bacteria or mold which is attracted chemically to substance they secrete. Solutions of the Keller-Segel equation can exhibit dramatic collapsing behavior, where density concentrates positive mass in a measure zero region. A natural question is whether the presence of fluid flow can affect singularity formation by mixing the bacteria thus making concentration harder to achieve. In this paper, we consider the parabolic-elliptic Keller-Segel equation in two and three dimensions with an additional advection term modeling ambient fluid flow. We prove that for any initial data, there exist incompressible fluid flows such that the solution to the equation stays globally regular. On the other hand, it is well known that when the fluid flow is absent, there exists initial data leading to finite time blow up. Thus the presence of fluid flow can prevent the singularity formation. We discuss two classes of flows that have the explosion arresting property. Both classes are known as very efficient mixers. The first class are the relaxation enhancing (RE) flows of (Ann Math:643-674, 2008). These flows are stationary. The second class of flows are the Yao-Zlatos near-optimal mixing flows (Mixing and un-mixing by incompressible flows. arXiv:1407.4163, 2014), which are time dependent. The proof is based on the nonlinear version of the relaxation enhancement construction of (Ann Math:643-674, 2008), and on some variations of the global regularity estimate for the Keller-Segel model.

  2. Identification of c.483C>T polymorphism in the caprine tyrosinase-related protein 1 (TYRP1 gene

    Directory of Open Access Journals (Sweden)

    Marcel Amills

    2012-01-01

    Full Text Available Tyrosinase-related protein 1 (TYRP1 has been shown to play a fundamental role in pigmentation both in human and mouse. In this work, we aimed to characterize the variability of the caprine TYRP1 gene and investigate its segregation in a wide array of goat breeds. By partially sequencing the coding region of the TYRP1 gene in 18 individuals from eight different breeds, we were able to identify a synonymous nucleotide substitution at exon 3 (c.483C>T. An extensive survey of Iberian and Balearic (N=175, Italian (N=99, Swiss (N=54, Asian (N=14, Canarian (N=92 and North African (N=117 goats with different coat colours was carried out. We found that the C-allele has a different distribution in European vs African breeds, being almost fixed in the latter. Moreover, the C-allele showed an increased frequency in white coated breeds (Girgentana, Grigia Molisana, Blanca de Rasquera and Saanen when compared with those displaying a dark pigmentation (Cilentana Nera, Azpi Gorri and Murciano- Granadina. This could be due to genetic drift, migration and other factors associated with the demographic history of breeds under analysis or to a genetic hitchhiking event (c.483C>T frequencies would be shaped by a neighbouring causal mutation differentially selected in white and black goats. More refined studies will be needed to distinguish between these two alternative explanations.

  3. Opposing roles of the two isoforms of ErbB3 binding protein 1 in human cancer cells.

    Science.gov (United States)

    Ko, Hyo Rim; Chang, Yun Sil; Park, Won Soon; Ahn, Jee-Yin

    2016-09-15

    The different functions of the two isoforms of ErbB3 binding protein 1 (Ebp1), p48 and p42, have recently become the focus of interest as they reveal contradictory roles in cell growth promoting ability. The conformational change that crystal structure of p42 was shown to lack α helices at the amino-terminus present in p48 represents the differential binding partners and protein modifications of two Ebp1 isoforms. N-terminal specific phosphorylation by CDK2 and deregulation of the p53 tumor suppressor through specific interaction with HDM2 and Akt activation is postulated to contribute to p48-mediated tumorigenesis. The short isoform p42 Ebp1, which is actual binding partner of ErbB3 has been implicated as a tumor suppressor with many binding partners such as Rb, HDAC2, Sin3A and the p85 subunit of PI3K with HSP70/CHIP, inhibiting its own antiproliferative activity or inhibiting PI3K activity. The aim of the current review is to provide a summary on distinctive cellular functions of two Ebp1 proteins and their molecular partners that might be responsible for the unique functions of each isoform of Ebp1. PMID:27130196

  4. Podocalyxin-like protein 1 is a relevant marker for human c-kit(pos) cardiac stem cells.

    Science.gov (United States)

    Moscoso, Isabel; Tejados, Naiara; Barreiro, Olga; Sepúlveda, Pilar; Izarra, Alberto; Calvo, Enrique; Dorronsoro, Akaitz; Salcedo, Juan Manuel; Sádaba, Rafael; Díez-Juan, Antonio; Trigueros, César; Bernad, Antonio

    2016-07-01

    Cardiac progenitor cells (CPCs) from adult myocardium offer an alternative cell therapy approach for ischaemic heart disease. Improved clinical performance of CPCs in clinical trials requires a comprehensive definition of their biology and specific interactions with the environment. In this work we characterize specific human CPC surface markers and study some of their related functions. c-kit(pos) human CPCs (hCPCs) were characterized for cell surface marker expression, pluripotency, early and late cardiac differentiation markers and therapeutic activity in a rat model of acute myocardial infarction. The results indicate that hCPCs are a mesenchymal stem cell (MSC)-like population, with a similar immunoregulatory capacity. A partial hCPC membrane proteome was analysed by liquid chromatography-mass spectrometry/mass spectrometry and 36 proteins were identified. Several, including CD26, myoferlin and podocalyxin-like protein 1 (PODXL), have been previously described in other stem-cell systems. Suppression and overexpression analysis demonstrated that PODXL regulates hCPC activation, migration and differentiation; it also modulates their local immunoregulatory capacity. Therefore, hCPCs are a resident cardiac population that shares many features with hMSCs, including their capacity for local immunoregulation. Expression of PODXL appears to favour the immature state of hCPCs, while its downregulation facilitates their differentiation. Copyright © 2016 John Wiley & Sons, Ltd. PMID:23897803

  5. Human IgG responses against the N-terminal region of Merozoite Surface Protein 1 of Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Hernando Antonio Del Portillo

    1992-01-01

    Full Text Available The complete primary structure of the gene encoding the Merozoite Surface Protein 1 of Plasmodium vivax (PvMSP-1 revealed the existence of interspecies conserved regions among the analogous proteins of other Plasmodia species. Here, three DNA recombinant clones expressing 50, 200 and 500 amino acids from the N-terminal region of the PvMSP-1 protein were used on ELISA and protein immunoblotting assays to look at the IgG antibody responses of malaria patients from the Brasilian amazon region of Rondônia. The results showed the existance of P. vivax and P. falciparum IgG antibodies directed against PvMSP-1 antigenic determinants expressed in the clones containing the first 200 and the following 500 amino acids of the molecule, but not within the one expressing the most N-terminal 50 amino acids. Interestingly, there was no correlation between the levels of these IgG antibodies and the previous number of malaria infections.

  6. Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry

    Directory of Open Access Journals (Sweden)

    Gisa Gerold

    2015-08-01

    Full Text Available Hepatitis C virus (HCV enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1, which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.

  7. Heterologous expression and in-silico characterization of Pathogenesis related protein1 (CsPR1 gene from Camellia sinensis.

    Directory of Open Access Journals (Sweden)

    Niraj Agarwala*

    2014-01-01

    Full Text Available Pathogenesis related protein1 gene induced after pathogen infection in plantshave been frequently used as marker gene for systemic acquired resistance. We have carried out isolation, annotation and expression of CsPR1, a potential disease resistance gene. The full length cDNA consist of 671 bp in length containing 162 amino acids with a signal peptide of 22 amino acids and 17.92 kDa predicted molecular weight. Recombinant CsPR1 was successfully expressed in BL21(DE3pLysS cells using pET 43.1 EK LIC vector system and was purified. Three dimensional models weregenerated using Phyre2 and I-TASSER and built a compact structureconsisting beta sheets surrounded by alpha helixes. The models werevalidated by MolProbity and RAMPAGE servers. Validation of modelledstructures based on Ramachandran plot, revealed I-TASSER producebetter quality and reliable 3D model. Purified recombinant CsPR1 and insilico generated 3D models from this study provide foundation forcomprehensive functional and structural characterization of CsPR1protein.

  8. Effect of overexpression of uncoupling protein 1 on brown adipose tissue in aP2-Ucp mice

    International Nuclear Information System (INIS)

    The aim of the present study was assess the function of mitochondria in brown fat of the transgenic animals in order to explain the functional involution of brown adipose tissue (BAT). This study was based on measurements of transmembrane electrochemical potential (Δψ) and estimation of [3H]GDP binding to isolated brown fat mitochondria, as well as on immunochemical analysis of trans-gene expression. Fluorescent cationic dye Rhodamine 123 was used to follow the changes in Δψ of isolated brown fat mitochondria. The fluorescence is quenched as the dye is accumulated in mitochondria in response to membrane energization. Titration by the inhibitory ligand of mitochondrial uncoupling protein 1 (UCP1), GDP (in presence of substrate), indicated a 3-fold lower sensitivity to GDP in mitochondria from transgenic compared with non-transgenic animals. Binding of [3H]GDP to both types of brown fat mitochondria was measured. Maximum number of specific GDP-binding sites was estimated from Scatchard plots. In accordance with the activity measurements, number of GDP-binding sites was approximately 3- to 5-fold higher in mitochondria isolated from the transgenic animals. (authors)

  9. Novel Function of Extracellular Matrix Protein 1 in Suppressing Th17 Cell Development in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Su, Pan; Chen, Sheng; Zheng, Yu Han; Zhou, Hai Yan; Yan, Cheng Hua; Yu, Fang; Zhang, Ya Guang; He, Lan; Zhang, Yuan; Wang, Yanming; Wu, Lei; Wu, Xiaoai; Yu, Bingke; Ma, Li Yan; Yang, Zhiru; Wang, Jianhua; Zhao, Guixian; Zhu, Jinfang; Wu, Zhi-Ying; Sun, Bing

    2016-08-15

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS characterized by demyelination and axonal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model for human MS. Although Th17 cells are important for disease induction, Th2 cells are inhibitory in this process. In this article, we report the effect of a Th2 cell product, extracellular matrix protein 1 (ECM1), on the differentiation of Th17 cells and the development of EAE. Our results demonstrated that ECM1 administration from day 1 to day 7 following the EAE induction could ameliorate the Th17 cell responses and EAE development in vivo. Further study of the mechanism revealed that ECM1 could interact with αv integrin on dendritic cells and block the αv integrin-mediated activation of latent TGF-β, resulting in an inhibition of Th17 cell differentiation at an early stage of EAE induction. Furthermore, overexpression of ECM1 in vivo significantly inhibited the Th17 cell response and EAE induction in ECM1 transgenic mice. Overall, our work has identified a novel function of ECM1 in inhibiting Th17 cell differentiation in the EAE model, suggesting that ECM1 may have the potential to be used in clinical applications for understanding the pathogenesis of MS and its diagnosis. PMID:27316685

  10. 5-Hydroxytryptamine 1A and 2B serotonin receptors in neurite outgrowth: involvement of early growth response protein 1.

    Science.gov (United States)

    Anelli, Tonino; Cardarelli, Silvia; Ori, Michela; Nardi, Irma; Biagioni, Stefano; Poiana, Giancarlo

    2013-01-01

    Neurotransmitters play important roles in neurogenesis; in particular, acetylcholine and serotonin may regulate neurite elongation. Acetylcholine may also activate transcription factors such as early growth response protein 1 (EGR-1), which plays a role in neurite extension. N18TG2 neuroblastoma cells (which do not produce neurotransmitters and constitutively express muscarinic acetylcholine receptors) were transfected with constructs containing the cDNA for choline acetyltransferase, 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2B serotonin receptors to study acetylcholine and serotonin interplay in neurite outgrowth. 5-HT1A receptor stimulation causes a decrease in EGR-1 levels and inhibition of neurite outgrowth; 5-HT2B stimulation, however, has no effect. Muscarinic cholinergic stimulation, on the other end, increases EGR-1 levels and fiber outgrowth. Inhibition of EGR-1 binding reduces fiber outgrowth activity. When both cholinergic and 5-HT1A receptors are stimulated, fiber outgrowth is restored; therefore, acetylcholine counterbalances the inhibitory effect of serotonin on neurite outgrowth. These results suggest that EGR-1 plays a role in the interplay of acetylcholine and serotonin in the regulation of neurite extension during development. PMID:24158140

  11. Epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 marker, a novel angiogenesis marker

    Science.gov (United States)

    Serban, Florentina; Artene, Stefan-Alexandru; Georgescu, Ada Maria; Purcaru, Stefana Oana; Tache, Daniela Elise; Alexandru, Oana; Dricu, Anica

    2015-01-01

    Epidermal growth factor, latrophilin, and seven transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), an orphan adhesion G-protein coupled receptor, was reported as a regulator of angiogenesis, also involved in cancer progression and development. More recently, ELTD1 was identified as a potential new tumor marker for high-grade glioma. ELTD1, belongs to the G-protein coupled receptor superfamily that comprises the biggest receptor family in the human genome. Following the discovery of ELTD1 almost a decade ago, only a few research groups have attempted to find its role in normal and tumor cells, important information about this receptor remaining still unknown. The ELTD1 ligand has not currently been identified and intracellular signaling studies have not yet been performed in normal or tumor cells. Although the current published data on ELTD1 function and structure are rather limited, this receptor seems to be very important, not only as biomarker, but also as molecular target in glioblastoma. This review summarizes and discusses the current knowledge on ELTD1 structure, function, and its role in both physiological and tumoral angiogenesis. PMID:26719704

  12. Novel Nuclear Protein ALC-INTERACTING PROTEIN1 is Expressed in Vascular and Mesocarp Cells in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Fang Wang; Dong-Qiao Shi; Jie Liu; Wei-Cai Yang

    2008-01-01

    Pod shattering is an agronomical trait that is a result of the coordinated action of cell differentiation and separation. In Arabidopsis, pod shattering is controlled by a complex genetic network in which ALCATRAZ (ALC), a member of the basic helix-loop-helix family, is critical for cell separation during fruit dehiscence. Herein, we report the identification of ALC-INTERACTiNG PROTEIN1 (ACI1) via the yeast two-hybrid screen. ACI1 encodes a nuclear protein with a lysine-rich domain and a C-terminal serine-rich domain. ACI1 is mainly expressed in the vascular system throughout the plant and mesocarp of the valve in siliques. Our data showed that ACI1 interacts strongly with the N-terminal portion of ALC in yeast cells and in plant cells in the nucleus as demonstrated by bimolecular fluorescence complementation assay. Both ACl1 and ALC share an overlapping expression pattern, suggesting that they likely function together in planta. However, no detectable phenotype was found in plants with reduced ACI1 expression by RNA interference technology, suggesting that ACI1 may be redundant. Taken together, these data indicate that ALC may interact with ACll and its homologs to control cell separation during fruit dehiscence in Arabidopsis.

  13. Dentin matrix protein 1 and dentin sialophosphoprotein in human sound and carious teeth: an immunohistochemical and colorimetric assay

    Directory of Open Access Journals (Sweden)

    D. Martini

    2013-10-01

    Full Text Available Dentin matrix protein 1 (DMP1 and dentin sialophosphoprotein (DSPP are extracellular matrix proteins produced by odontoblasts involved in the dentin mineralization. The aim this study was to compare the distribution of DMP1 and DSPP in human sound dentin vs human sclerotic dentin. Sixteen sound and sixteen carious human molars were selected, fixed in paraformaldehyde and processed for immunohistochemical detection of DMP1 and DSPP by means of light microscopy, transmission electron microscopy (TEM and high-resolution field emission in-lens scanning electron microscopy (FEI-SEM. Specimens were submitted to a pre-embedding or a post-embedding immunolabeling technique using primary antibodies anti DMP1 and anti-DSPP and gold-conjugated secondary antibodies. Other samples were processed for the detection of DMP1 and DSPP levels. Dentin from these samples was mechanically fractured to powder, then a protein extraction and a protein level detection assay were performed. DMP1 and DSPP were more abundant in carious than in sound samples. Immunohistochemical analyses in sclerotic dentin disclosed a high expression of DMP1 and DSPP inside the tubules, suggesting an active biomineralization of dentin by odontoblasts. Furthermore, the detection of small amounts of these proteins inside the tubules far from the carious lesion, as shown in the present study, is consistent with the hypothesis of a preventive defense of all dentin after a noxious stimulus has undermined the tooth.

  14. Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice.

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    Joshua E Basford

    Full Text Available Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1 in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.