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Sample records for chemoattractant protein-1 mcp-1

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

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    Ellingsen, T.; Elling, P; Olson, A.; Elling, H; Baandrup, U; Matsushima, K.; Deleuran, B; Stengaard-Pederse..., K

    2000-01-01

    OBJECTIVE—To examine the localisation of monocyte chemoattractant protein 1 (MCP-1) in the inflamed vessel wall in temporal arteritis (TA) and to measure MCP-1 in plasma both in patients with TA and patients with polymyalgia rheumatica (PMR).
METHODS—By immunohistochemical techniques MCP-1 was localised to the vessel wall in patients with TA. In TA, PMR, and healthy controls MCP-1 was quantified by enzyme linked immunosorbent assay (ELISA) in plasma.
RESULTS—MCP-1 was localised to the majorit...

  2. The production of monocyte chemoattractant protein-1 (MCP-1)/CCL2 in tumor microenvironments.

    Science.gov (United States)

    Yoshimura, Teizo

    2017-02-08

    Infiltration of leukocytes is one of the hallmarks of the inflammatory response. Among the leukocyte populations, neutrophils are the first to infiltrate, followed by monocytes and lymphocytes, suggesting the presence of mediators that specifically recruit these cell types. Cytokine-like chemoattractants with monocyte chemotactic activity, such as lymphocyte-derived chemotactic factor (LDCF) or tumor-derived chemotactic factor (TDCF), were reported as molecules that could play a critical role in the recruitment of monocytes into sites of immune responses or tumors; however, their identities remained unclear. In the 1980s, researchers began to test the hypothesis that leukocyte chemotactic activity is a part of the wider activities exhibited by cytokines, such as interleukin-1 (IL-1). In 1987, we demonstrated, for the first time, the presence of a cytokine like chemoattractant with cell type-specificity (now known as the chemokine interleukin-8 or CXC chemokine ligand 8) that was different from IL-1. This led us to the purification of the second such molecule with monocyte chemotactic activity. This monocyte chemoattractant was found identical to the previously described LDCF or TDCF, and termed monocyte chemoattractant protein-1 (MCP-1). Isolation of MCP-1 created a revolution in not only inflammation but also cancer research that continues today, and MCP-1 has become a molecular target to treat patients with many diseases. In this review, I will first describe a history associated with the discovery of MCP-1 and then discuss complex mechanisms regulating MCP-1 production in tumor microenvironments.

  3. Phyllostachys edulis compounds inhibit palmitic acid-induced monocyte chemoattractant protein 1 (MCP-1 production.

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    Jason K Higa

    Full Text Available BACKGROUND: Phyllostachys edulis Carriere (Poaceae is a bamboo species that is part of the traditional Chinese medicine pharmacopoeia. Compounds and extracts from this species have shown potential applications towards several diseases. One of many complications found in obesity and diabetes is the link between elevated circulatory free fatty acids (FFAs and chronic inflammation. This study aims to present a possible application of P. edulis extract in relieving inflammation caused by FFAs. Monocyte chemoattractant protein 1 (MCP-1/CCL2 is a pro-inflammatory cytokine implicated in chronic inflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and activator protein 1 (AP-1 are transcription factors activated in response to inflammatory stimuli, and upregulate pro-inflammatory cytokines such as MCP-1. This study examines the effect of P. edulis extract on cellular production of MCP-1 and on the NF-κB and AP-1 pathways in response to treatment with palmitic acid (PA, a FFA. METHODOLOGY/PRINCIPAL FINDINGS: MCP-1 protein was measured by cytometric bead assay. NF-κB and AP-1 nuclear localization was detected by colorimetric DNA-binding ELISA. Relative MCP-1 mRNA was measured by real-time quantitative PCR. Murine cells were treated with PA to induce inflammation. PA increased expression of MCP-1 mRNA and protein, and increased nuclear localization of NF-κB and AP-1. Adding bamboo extract (BEX inhibited the effects of PA, reduced MCP-1 production, and inhibited nuclear translocation of NF-κB and AP-1 subunits. Compounds isolated from BEX inhibited MCP-1 secretion with different potencies. CONCLUSIONS/SIGNIFICANCE: PA induced MCP-1 production in murine adipose, muscle, and liver cells. BEX ameliorated PA-induced production of MCP-1 by inhibiting nuclear translocation of NF-κB and AP-1. Two O-methylated flavones were isolated from BEX with functional effects on MCP-1 production. These results may represent a possible

  4. Involvement of spinal monocyte chemoattractant protein-1 (MCP-1) in cancer-induced bone pain in rats.

    Science.gov (United States)

    Hu, Ji-Hua; Zheng, Xiao-Yan; Yang, Jian-Ping; Wang, Li-Na; Ji, Fu-Hai

    2012-05-23

    In this study, we examined the involvement of chemokine monocyte chemoattractant protein-1 (MCP-1) in the spinal cord of a rat model of cancer-induced bone pain (CIBP). In this model, CIBP was established by an intramedullary injection of Walker 256 cells into the tibia of rats. We observed a significant increase in expression levels of MCP-1 and its receptor CCR2 in the spinal cord of CIBP rats. Furthermore, the intrathecal administration of an anti-MCP-1 neutralizing antibody attenuated the mechanical allodynia established in CIBP rats. Likewise, an intrathecal injection of exogenous recombinant MCP-1 induced a striking mechanical allodynia in naïve rats. These results suggest that increases in spinal MCP-1 and CCR2 expression are involved in the development of mechanical allodynia associated with bone cancer rats.

  5. Association between new onset diabetic retinopathy and monocyte chemoattractant protein-1 (MCP-1) polymorphism in Japanese type 2 diabetes.

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    Ninomiya, Hiroyo; Katakami, Naoto; Osonoi, Takeshi; Saitou, Miyoko; Yamamoto, Yuichi; Takahara, Mitsuyoshi; Kawamori, Dan; Matsuoka, Taka-aki; Yamasaki, Yoshimitsu; Shimomura, Iichiro

    2015-06-01

    We longitudinally evaluated the association between monocyte chemoattractant protein-1 (MCP-1) A-2518G polymorphism and new onset of diabetic retinopathy in 758 type 2 diabetic patients. The new onset of retinopathy increased with the increase of the number of G alleles, even after adjustment for age, HbA1c levels, and duration of diabetes.

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

    Science.gov (United States)

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

    2015-09-01

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

  7. 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.

  8. Non-myeloid Cells are Major Contributors to Innate Immune Responses via Production of Monocyte Chemoattractant Protein- 1(MCP-1/CCL2

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    Teizo eYoshimura

    2014-01-01

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1/CCL2 is a chemokine regulating the recruitment of monocytes into sites of inflammation and cancer. MCP-1 can be produced by a variety of cell types, such as macrophages, neutrophils, fibroblasts, endothelial cells and epithelial cells. Notably, macrophages produce high levels of MCP-1 in response to proinflammatory stimuli in vitro, leading to the hypothesis that macrophages are the major source of MCP-1 during inflammatory responses in vivo. In stark contrast to the hypothesis, however, there was no significant reduction in MCP-1 protein or the number of infiltrating macrophages in the peritoneal inflammatory exudates of myeloid cell-specific MCP-1-deficient mice in response to i.p injection of thioglycollate or zymosan A. Furthermore, injection of LPS into skin air pouch also had no effect on local MCP-1 production in myeloid-specific MCP-1-deficient mice. Finally, myeloid-specific MCP-1-deficiency did not reduce MCP-1 mRNA expression or macrophage infiltration in LPS-induced lung injury. These results indicate that non-myeloid cells, in response to a variety of stimulants, play a previously unappreciated role in innate immune responses as the primary source of MCP-1.

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

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    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 G polymorphism may be associated with susceptibility to CAD, especially in Caucasians.

  10. Distribution of monocyte chemoattractant protein-1 (MCP-1 A-2518G) and chemokine receptor (CCR2-V64Ι) gene variants in hyperbilirubinemic newborns.

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    Narter, Fatma; Bireller, Elif Sinem; Engin, Can; Catmakas, Tolga; Narter, Fehmi; Ergen, Arzu; Cakmakoglu, Bedia

    2015-01-01

    Hyperbilirubinemia is one of the most crucial syndromes, which is characterized by high levels of bilirubin, especially when it occurs in newborns. Bilirubin has cytoprotective properties with an antioxidant function and plays several major roles in the inflammation process with its members such as chemokines. The monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C chemokine family and it has been associated with the inflammatory process. There are no data on the chemokine and its receptor genotypes in hyperbilirubinemic newborns to show their distribution. The aim of this study is to investigate the genotypic relationship of MCP-1 and its receptor CCR2-V64Ι with hyperbilirubinemia in Turkish newborns. A total of 85 newborns were included in the study: 20 infants with hyperbilirubinemia (hyperbilirubinemic group) and 65 infants without hyperbilirubinemia (non-hyperbilirubinemic group). Genotyping of MCP-1 A-2518G and CCR2-V64Ι gene polymorphisms were detected by PCR-RFLP, respectively. MCP-1 GG genotype in patients was higher than the controls and this genotype had 2.69 times higher risk for hyperbilirubinemic neonates (P: 0.20). The frequency of MCP-1 A-2518G G+ genotype in patients was higher than the controls (55.0% and 38.5%, respectively). The results of our preliminary study suggest that MCP-1 G+ genotype has the ability to increase the hyperbilirubinemia risk of newborns. These results should be focused on to research on a larger scale to confirm the findings.

  11. Inhibitory effect of microRNA-27b on interleukin 17 (IL-17)-induced monocyte chemoattractant protein-1 (MCP1) expression.

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    Huang, K D; Shen, Y; Wei, X; Zhang, F Q; Liu, Y Y; Ma, L

    2016-07-14

    We investigated the effect of microRNA-27b (miR-27b), a gene expression regulatory factor, on the expression of monocyte chemoattractant protein-1 (MCP1) stimulated by interleukin 17 (IL-17). After IL-17 had been added to H9C2 cardiomyocytes, an miR-27b mimic was transfected into the H9C2 cells. The mRNA expression levels of miR-27b and MCP1 in the H9C2 cells were detected by SYBR green I fluorescence quantitative reverse transcription polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the expression levels of MCP1 protein in the H9C2 cells. The expression of MCP1 mRNA in the H9C2 cells began to increase 2 h after IL-17 stimulation, reached a peak at 4 h, and then decreased. The MCP1 protein level increased gradually in the 24 h following IL-17 stimulation. After transfection with the miR-27b mimic, the expression of miR-27b in the H9C2 cells significantly increased than that in the miRNA negative control group (P < 0.01). The MCP1 mRNA and protein levels in the miR-27b mimic + IL-17 group were significantly reduced than that in the miRNA negative control + IL-17 group (P < 0.01). miR-27b inhibited IL-17-induced MCP1 expression in the H9C2 cells, which demonstrates that treatment with microRNA could alleviate myocardial injury in viral myocarditis.

  12. Monocyte Chemoattractant Protein-1 (MCP-1) as a Potential Therapeutic Target and a Noninvasive Biomarker of Liver Fibrosis Associated With Transient Myeloproliferative Disorder in Down Syndrome.

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    Kobayashi, Kenichiro; Yoshioka, Takako; Miyauchi, Jun; Nakazawa, Atsuko; Yamazaki, Shigeaki; Ono, Hiromi; Tatsuno, Michiko; Iijima, Kenta; Takahashi, Chiaki; Okada, Yoko; Teranishi, Kenji; Matsunaga, Takaaki; Matsushima, Chieko; Inagaki, Mayo; Suehiro, Minoru; Suehiro, Saori; Nishitani, Masahiko; Kubota, Hirohito; Iio, Jun; Nishida, Yoshinobu; Katayama, Tetsuo; Takada, Narito; Watanabe, Kentaro; Yamamoto, Tetsuro; Yasumizu, Ryoji; Matsuoka, Kentaro; Ohki, Kentaro; Kiyokawa, Nobutaka; Maihara, Toshiro; Usami, Ikuya

    2017-03-06

    Liver fibrosis is one of the common complications of transient myeloproliferative disorder (TMD) in Down syndrome (DS), but the exact molecular pathogenesis is largely unknown. We herein report a neonate of DS with liver fibrosis associated with TMD, in which we performed the serial profibrogenic cytokines analyses. We found the active monocyte chemoattractant protein-1 expression in the affected liver tissue and also found that both serum and urinary monocyte chemoattractant protein-1 concentrations are noninvasive biomarkers of liver fibrosis. We also showed a prospective of the future anticytokine therapy with herbal medicine for the liver fibrosis associated with TMD in DS.

  13. Thromboxane A2 receptor-mediated release of matrix metalloproteinase-1 (MMP-1) induces expression of monocyte chemoattractant protein-1 (MCP-1) by activation of protease-activated receptor 2 (PAR2) in A549 human lung adenocarcinoma cells.

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    Li, Xiuling; Tai, Hsin-Hsiung

    2014-08-01

    Matrix metalloproteinases (MMPs) and monocyte chemoattractant protein-1 (MCP-1, CCL2) are known to be upregulated in many tumors. Their roles in tumor invasion and metastasis are being uncovered. How they are related to each other and involved in tumor progression remains to be determined. Earlier it was reported that I-BOP-initiated activation of thromboxane A2 receptor (TP) induced the release of MMP-1, MMP-3, and MMP-9 from lung cancer A549 cells overexpressing TPα (A549-TPα). Herein it was found that MMP-1, but not MMP-3 or MMP-9, induced the expression of MCP-1 in A549 cells. Conditioned medium (CM) from I-BOP activated, MMP-1 siRNA pretreated A549-TPα cells induced greatly attenuated expression of MCP-1 in A549 cells indicating that MMP-1 in the CM contributed significantly to the expression of MCP-1. MMP-1 was shown to activate protease-activated receptor 2 (PAR2) instead of commonly assumed PAR1 to increase the expression of MCP-1 in A549 cells. This conclusion was reached from the following findings: (1) expression of MCP-1 induced by trypsin, a PAR2 agonist, and also PAR2 agonist peptide, was inhibited by a PAR2 antagonist; (2) expression of MCP-1 induced by MMP-1 and by CM from I-BOP activated A549-TPα cells was blocked by a PAR2 antagonist but not by other PAR antagonists; (3) expression of MCP-1 induced by MMP-1 and by CM from I-BOP activated A549-TPα cells was attenuated significantly by pretreatment of cells with PAR2-siRNA. These results suggest that PAR2 is a novel MMP-1 target mediating MMP-1-induced signals in A549 lung cancer cells.

  14. Expression of monocyte chemoattractant protein-1 in IgA nephropathy and its significance%IgA 肾病患者肾脏 MCP-1的表达及意义

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    钱白音; 吴锡信; 麦美芳; 张桦; 李中和; 崔彤霞

    2014-01-01

    Objective To evaluate the role of monocyte chemoattractant protein-1(MCP-1) in the mechanism of pro-gression of IgA nephropathy.Methods A total of 34 patients with biopsy proven IgA nephropathy were studied.The ex-pression of MCP-1 in renal tissues were detected by immunohistochemical staining method; the levels of serum creatinine ( Scr) were examined by sarcosine oxidase method;MCP-1 expression in renal tissue in patients with different degree of tu-bulointerstitial lesions and different levels of Scr were compared.Molecular weight of urinary protein were detected by sodi-um dodecyl sulfate-polyacrylamide gel electrophoresis( SDS-PAGE) , and were further typed;MCP-1 expression in renal tis-sue in patients with different molecular weight of urinary protein were compared.And the relationship between the MCP-1 expression and the twenty-four-hour urine protein quantitation in patients with IgA nephropathy was analyzed by pearson cor-relation analysis.Results MCP-1 expression was mainly in renal tubular epithelial cells of IgA nephropathy patients, and was in positive correlation to twenty-four-hour urine protein quantitation (r=0.34,P140μmol/L group than Scr≤140μmol/L group (P<0.05), and was significantly higher in 10 kD proteinuria group than 23 kD proteinuria group (P<0.05).Conclusion MCP-1 may play an important role in the progression of IgA nephropathy.Low molecular weight urinary protein such as 10 kD protein may have close relationship with the expression of MCP-1 in renal tissue of IgA nephropathy.%目的:观察IgA肾病患者肾脏单核细胞趋化蛋白-1(MCP-1)表达变化,并探讨其作用。方法用免疫组织化学染色法检测34例同步行肾活检诊断明确的IgA肾病患者肾脏MCP-1表达,用肌氨酸氧化酶法检测血清肌酐( Scr),比较不同程度肾小管间质病变及不同血清肌酐水平患者MCP-1的差异。用SDS-PAGE法检测尿蛋白分子量,并进一步分型,对不同分子量尿蛋白患者的MCP

  15. Serum Monocyte Chemoattractant Protein-1 in Pancreatic Cancer

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    Jennifer Sullivan; Qiaoke Gong; Terry Hyslop; Harish Lavu; Galina Chipitsyna; Yeo, Charles J.; Arafat, Hwyda A

    2011-01-01

    Background/Aims. Pancreatic ductal adenocarcinoma (PDA) has etiological association with chronic inflammation. Elevated circulating levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), are found in obese individuals. We hypothesized that serum MCP-1 levels are elevated in obese PDA patients. Methods. ELISA was used to analyze MCP-1 serum levels in PDA (n = 62) and intraductal papillary mucinous neoplasms (IPMN) (n = 27). Recursive partitioning statistical anal...

  16. MCP -1在妊娠期高血压疾病患者血清中的变化及意义%Expression and significance of the monocyte chemoattractant protein - 1 in serum from patients with hypertensive disorder complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    何晓宇; 林晶; 许波

    2012-01-01

    目的 探讨妊娠期高血压疾病患者血清单核细胞趋化蛋白-1 (MCP-1)变化的意义.方法 用ELISA法对21例妊娠期高血压疾病患者(其中轻度子痫前期12例,重度子痫前期9例)血清MCP -1浓度进行测定,并选择同期30例正常孕妇作为对照组.结果 妊娠期高血压疾病患者血清中MCP -1含量显著高于对照组孕妇,并随病情加重呈增加趋势.结论 MCP -1所参与的免疫反应可能是妊娠期高血压疾病的发病机制之一.%Objective: To explore the clinical significance of changes of monocyte chemoattractant protein - 1 (MCP - 1) in patients with hypertensive disorder complicating pregnancy. Methods: EliSA was used to measure the levels mcp - 1 in maternal serumof 21 patients with hypertensive disorder complicating pregnancy (study group) and 30 normal pregnancies (control group). The study group was further divided into two groups; mild preeclampsia pations (12 cases) and severe preeclampsia patients (9 cases). Results ; The levels mcp -1 in serum of patients with hypertensive disorder complicating pregnancy had a increasing trend as hypertensive disorder complicating pregnancy degree elevated. Conclusion: MCP -1 participation in the immune response is possibly one of mechanisms of disease incidence.

  17. Serum Monocyte Chemoattractant Protein-1 in Pancreatic Cancer

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    Jennifer Sullivan

    2011-01-01

    Full Text Available Background/Aims. Pancreatic ductal adenocarcinoma (PDA has etiological association with chronic inflammation. Elevated circulating levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, are found in obese individuals. We hypothesized that serum MCP-1 levels are elevated in obese PDA patients. Methods. ELISA was used to analyze MCP-1 serum levels in PDA (n=62 and intraductal papillary mucinous neoplasms (IPMN (n=27. Recursive partitioning statistical analysis investigated the relationship between log MCP-1 and clinicopathological parameters. Results. Log MCP-1 values were significantly (P<0.05 elevated in patients with BMI ≥ 37.5. In patients with BMI < 37.5, average log MCP-1 values were significantly elevated in PDA patients when compared to IPMN patients. Within the IPMN group, higher log MCP-1 levels correlated with increased age. Recursive partitioning analysis of IPMN versus PDA revealed a strategy of predicting characteristics of patients who are more likely to have cancer. This strategy utilizes log MCP-1 as the primary factor and also utilizes smoking status, gender, and age. Conclusion. MCP-1 is a promising biomarker in pancreatic cancer. The potential of using MCP-1 to distinguish PDA from IPMN patients must be studied in larger populations to validate and demonstrate its eventual clinical utility.

  18. The expression of monocyte chemoattractant protein 1 and RANTES and their significance in the pathogenesis of chronic renal allograft dysfunction%MCP-1、RANTES在慢性移植肾失功肾组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李晏强; 罗皓; 邹和群; 眭维国; 王保瑶; 邹贵勉

    2012-01-01

    目的 探讨单核细胞趋化蛋白-1(MCP-1)和RANTES在慢性移植肾失功(CRAD)患者移植肾组织中的表达及意义.方法 用免疫组织化学技术和计算机真彩色图像分析系统半定量检测32例慢性移植肾失功患者移植肾组织中MCP-1和RANTES的表达,分析与移植肾间质纤维化/小管萎缩程度及炎性细胞浸润程度之间的关系.结果 慢性移植肾失功患者的移植肾组织中MCP-1和RANTES的表达较正常肾组织中明显增加,并随着间质纤维化/小管萎缩及炎症细胞浸润程度而递增.结论 移植肾组织中MCP-1和RANTES的表达升高与慢性移植肾失功的进展有关.%Objective To in vestige the expression of monocyte chemoattractant protein 1 (MCP-l) and RANTES and their significance in the pathogenesis of chronic renal allograft dy sfunction.Method Immunohistochemical assay and computer-assisted genuine colored image analysis system were used to detect the expression of MCP-l and RANTES in the renal allografts of patients with CARD. The relationship between expression level of mcp-land Rantes and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed.Six specimens of healthy renal tissue were used as controls. Results The expressions levels of MCP-l and RANTES were significantly higher in the renal tissues of the patients, compared to normal renal tissues, and the expressions tended to increase with the pathological grades of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue.Conclusion The up-regulated expression of MCP-l and Rantes in transplant kidney tissue may have the relationship win the progressive of the chronic renal allograft dysfunction

  19. Monocyte chemoattractant protein-1 promoter polymorphism and plasma levels in alzheimer’s disease

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    Porcellini, Elisa; Ianni, Manuela; Carbone, Ilaria; Franceschi, Massimo; Licastro, Federico

    2013-01-01

    Background Neurodegenerative disorders such Alzheimer's disease (AD) are often characterized by senile plaques and neurofibrillary tangle. In addition, reactive astrogliosis, microglia activation and a chronic inflammation are found in AD brain. Activated microglia has been reported to express a large number of beta chemokines including monocyte chemoattractant protein-1 (MCP-1). The potential role of MCP-1 in AD pathogenesis is supported by the over expression of MCP-1 associated with an inc...

  20. Relation Between Bone Matrix Proteins and Monocyte Chemoattractant Protein-1 in Renal Small Artery in Diabetic Nephropathy Rats%糖尿病肾病大鼠肾小动脉骨基质蛋白表达及其与MCP-1的关系

    Institute of Scientific and Technical Information of China (English)

    赵安菊; 黄颂敏; 欧三桃; 刘芳; 陈泽君; 胡章学; 唐万欣

    2012-01-01

    of bone matrix proteins and monocyte chemoattractant protein-1 ((MCP-1) in the renal arteriole of diabetic nephropathy CDN) rats and analyze their correlations and roles in diabetic nephropathy. Methods Adult Sprague-Dawley male rats were used to establish the animal model of diabetic nephropathy induced by peritoneal injection of 55 mg/kg of streptozocin. Calcium deposit around the renal arteriole was observed by alizarin red staining. The protein and mRNA levels of core-bind factor alpha 1 (cbfα1), bone morphogenetic protein 2 (BMP-2) and matrix Gla protein (MGP) in renal arteriole of DN rats were detected by immunohistochemistry, in-situ hybridization and real-time PCR. The biochemical indices were detected by routine test. Results ①Blood glucose and Urine protein of 24 h were significantly increased in the renal arteriole of DN rats vs. the control rats (P<0. 05),serum creatinine (SCr) and phosphorus were significantly increased from 12 weeks. ② Little deposit of calcium salt was observed in the renal arteriole of DN rats at the 4th week and a large amount of deposit was observed at 24th week, but no calcium deposit was observed in control rats. ③Cbfal and BMP-2 expressions were significantly increased in the renal arteriole of DN rats from 4 to 24 weeks vs. the control rats. MGP mRNA expression in the renal arteriole of DN rats was significantly decreased from 4 to 24 weeks. MCP-1 expression was obviously upregulated in the renal arteriole of DN rats at 24th week vs. that at 4th and 12th week. No MCP-1 expression was observed in the renal arterioles of control rats. ④MCP-1 were positively correlated with the expression of cbfα1 and BMP-2. Conclusion bone matrix proteins has already expressed in renal arteriole before the formation of vascular calcification. MCP-1 can affect the expression of cbfα1,BMP-2 ;Cbfα1. BMP-2, MGP and MCP-1 may be involved in the formation of vascular lesions of DN.

  1. 细胞内活性氧在糖基化终末产物促人腹膜间皮细胞分泌单核细胞趋化因子1中的作用%The role of reactive oxygen species in the promotion of monocyte chemoattractant protein-1(MCP-1) production by advanced glycation end products-human serum albumin(AGE-HSA)in human peritoneal mesothelial cells

    Institute of Scientific and Technical Information of China (English)

    洪富源; 孙芳; 刘军; 姚建; 黄一新; 唐知还

    2010-01-01

    目的 观察糖基化终末产物(advanced glycation end products,AGEs)对人腹膜间皮细胞(human peritoneal mesothelial cell,HPMC)分泌单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP1)的作用及细胞内活性氧族(reactive oxygen species,ROS)在其中的作用.方法 分别用不同浓度的糖基化人血清白蛋白(advanced glycation end products-human serum albumin,AGE-HSA)及抗氧化剂N-乙酰-L-半胱氨酸(N-acetyl-L-cysteine,NAC)作用于细胞,用逆转录多聚酶链反应(RT-PCR)法和酶联免疫吸附法(ELISA)测定HPMC中MCP-1的表达;再以氧化敏感的荧光染料2,7-二氢二氯荧光素(2.7-dichlorofluorescin,DCFH)染色,流式细胞仪测定ROS强度.结果 AGE-HSA能使细胞内ROS水半明显升高,呈现浓度依赖效应;AGE-HSA同时以时效和量效方式促进HPMC中MCP-1的表达;而NAC能够明显抑制AGE-HSA 所导致的细胞内ROS升高,同时抑制HPMC中MCP-1的分泌.结论 AGE-HSA 可能部分通过诱导细胞内ROS,促进HPMC 表达MCP-1.

  2. Serum monocyte chemoattractant protein-1 is a biomarker in patients with diabetes and periodontitis

    OpenAIRE

    Preethi Radhakrishnan; Padma Srikanth; Seshadri, Krishna G.; Ramya Barani; Maitreya Samanta

    2014-01-01

    Introduction: The role of serum Monocyte Chemoattractant Protein-1 (MCP-1) as a biomarker of periodontitis is well documented; however, its role in diabetic patients with periodontitis is unknown. Aim : This study was conducted to determine the presence and concentration of serum MCP-1 in diabetic patients with and without periodontitis and correlate it glycemic status with periodontitis. Materials and Methods: Adult diabetic patients were enrolled and grouped into group I, II, and III based ...

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

    Science.gov (United States)

    Li, Liangpeng; Zhang, Qian; Peng, Jiahe; Jiang, Chanjui; Zhang, Yan; Shen, Lili; Dong, Jinyu; Wang, Yongchao; Jiang, Yu

    2015-11-27

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

  4. Monocyte chemoattractant protein-1 induces endothelial cell apoptosis in vitro through a p53-dependent mitochondrial pathway

    Institute of Scientific and Technical Information of China (English)

    Xuan Zhang; Xiping Liu; Huifeng Shang; Yan Xu; Minzhang Qian

    2011-01-01

    The cystine-cystine (CC) chemokine monocyte chemoattractant protein-1 (MCP-1) has been established playing a pathogenic role in the development of atherosclerosis due to its chemotactic ability of leading monocytes to locate to subendothelia.Recent studies have revealed more MCP-1 functions other than chemotaxis.Here we reported that various concentrations (0.1-100 ng/ml) of MCP-1 induced human umbilical vein endothelial cell (HUVEC) strain CRL-1730 apoptosis,caspase-9 activation,and a couple of mitochondrial alterations.Moreover,MCP-1 upregulated p53 expression of HUVECs and the p53-specific inhibitor pifithrin-α(PFTα) rescued the MCP-1-induced apoptosis of HUVECs.Furthermore,PKC (protein kinase C) activation or inhibition might also affect HUVECs apoptosis induced by MCP-1.These findings together demonstrate that MCP-1 exerts direct proapoptotic effects on HUVECs in vitro via a p53-dependent mitochondrial pathway.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-12-01

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

  7. Monocyte chemoattractant protein-1 contributes to morphine tolerance in rats with cancer-induced bone pain.

    Science.gov (United States)

    Liu, Lei; Gao, Xiu-Juan; Ren, Chun-Guang; Hu, Ji-Hua; Liu, Xian-Wen; Zhang, Ping; Zhang, Zong-Wang; Fu, Zhi-Jian

    2017-02-01

    Cancer-induced bone pain can severely compromise the life quality of patients, while tolerance limits the use of opioids in the treatment of cancer pain. Monocyte chemoattractant protein-1 (MCP-1) is known to contribute to neuropathic pain. However, the role of spinal MCP-1 in the development of morphine tolerance in patients with cancer-induced bone pain remains unclear. The aim of the present study was to investigate the role of spinal MCP-1 in morphine tolerance in bone cancer pain rats (MTBP rats). Bone cancer pain was induced by intramedullary injection of Walker 256 cells into the tibia of the rats, while morphine tolerance was induced by continuous intrathecal injection of morphine over a period of 9 days. In addition, anti-MCP-1 antibodies were intrathecally injected to rats in various groups in order to investigate the association of MCP-1 with mechanical and heat hyperalgesia using the paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) tests, respectively. Furthermore, MCP-1 and CCR2 expression levels were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, and CCR2 expression levels were measured using RT-qPCR. The results indicated that MCP-1 and CCR2 expression levels were significantly increased in the spinal cord of MTBP rats. Intrathecal administration of anti-MCP-1 neutralizing antibodies was observed to attenuate the mechanical and thermal allodynia in MTBP rats. Therefore, the upregulation of spinal MCP-1 and CCR2 expression levels may contribute to the development of mechanical allodynia in MTBP rats. In conclusion, MCP-1/CCR2 signaling may serve a crucial role in morphine tolerance development in rats suffering from cancer-induced bone pain.

  8. Urinary monocyte chemoattractant protein-1 as a biomarker of lupus nephritis activity in children.

    Science.gov (United States)

    Ghobrial, Emad E; El Hamshary, Azza A; Mohamed, Ashraf G; Abd El Raheim, Yomna A; Talaat, Ahmed A

    2015-01-01

    Systemic lupus erythematosus (SLE) is a life-long, life-limiting and multi-systemic autoimmune disease. Glomerulonephritis is one of the most serious manifestations of SLE. Younger children have an increased incidence, severity and morbidity of lupus nephritis (LN) compared with adult-onset disease. Monocyte chemoattractant protein-1 (MCP-1) enhances leukocyte adhesiveness and endothelial permeability in the kidneys of murine and human LN models. Our study aimed to assess the role of urinary MCP-1 in the early diagnosis of LN activity. Sixty children, of whom 45 children aged from six to 12 years old and of both sexes (15 SLE patients without nephritis, 15 active LN and 15 inactive LN) fulfilling the American College of Rheumatology Classification Criteria for SLE were studied in comparison with 15 healthy subjects. We investigated the serum and urinary MCP-1 in all groups using the enzyme-linked immunosorbent assay test. Urinary MCP-1 was significantly higher in active LN in comparison with inactive LN and controls, and also significantly higher in inactive LN in comparison with SLE without nephritis and controls. There was also a significant difference between SLE without nephritis and controls. Serum MCP-1 was significantly higher in the group with active LN in comparison with the inactive group and SLE without nephritis and controls, but there was no significant difference between SLE and controls. The urinary MCP-1 level correlated well with SLE disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary MCP-1 correlates positively with proteinuria, blood urea nitrogen level and creatinine and negatively with hemoglobin and creatinine clearance. We concluded that measurement of MCP-1 in urine may be useful for monitoring the severity of renal involvement in SLE. We recommend measuring urinary MCP-1 in pediatric SLE for the early diagnosis of LN and for the evaluation of the severity of renal involvement.

  9. Auxiliary diagnostic value of monocyte chemoattractant protein-1 of whole blood in active tuberculosis.

    Science.gov (United States)

    Wang, Ying; Li, Hang; Bao, Hong; Jin, Yufen; Liu, Xiaoju; Wu, Xueqiong; Yu, Ting

    2015-01-01

    The aim of this study was to study the expression level of interferon-γ (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) in peripheral blood and its auxiliary diagnostic value in active tuberculosis. A chemiluminescence enzyme immunoassay method was used to detect the levels of IFN-γ and MCP-1 in peripheral blood. Then the receiver operating characteristic curve were drawn to determine the threshold of IFN-γ and MCP-1 for diagnosis of active tuberculosis and to evaluate their diagnostic performance. The specific IFN-γ and MCP-1 levels in the active tuberculosis group were significantly higher than those in the non-tuberculous pulmonary disease group (P 0.05), but the MCP-1 levels in the non-tuberculous respiratory disease group were significantly higher than those of the healthy control group (P < 0.05). The specific IFN-γ and MCP-1 level cut off values were 256 pg/ml and 389 pg/ml as an active tuberculosis diagnostic standard. The sensitivities of IFN-γ and MCP-1 were 57.3% and 92.8%, respectively; specificities were 80% and 80.7%, respectively; the positive predictive values were 76.9% and 84.9%, respectively; negative predictive values were 61.7% and 78.7%, respectively; and accuracy rates were 76.9% and 84.9%, respectively. Compared with the detection of IFN-γ, we observed a better diagnostic performance of MCP-1 in peripheral blood in active tuberculosis. MCP-1 may become one of the active tuberculosis auxiliary diagnostic targets.

  10. Vitamin A supplementation reduces the monocyte chemoattractant protein-1 intestinal immune response of Mexican children.

    Science.gov (United States)

    Long, Kurt Z; Santos, Jose Ignacio; Estrada Garcia, Teresa; Haas, Meredith; Firestone, Mathew; Bhagwat, Jui; Dupont, Herbert L; Hertzmark, Ellen; Rosado, Jorge L; Nanthakumar, Nanda N

    2006-10-01

    The impact of vitamin A supplementation on childhood diarrhea may be determined by the regulatory effect supplementation has on the mucosal immune response in the gut. Previous studies have not addressed the impact of vitamin A supplementation on the production of monocyte chemoattractant protein 1 (MCP-1), an essential chemokine involved in pathogen-specific mucosal immune response. Fecal MCP-1 concentrations, determined by an enzyme-linked immuno absorption assay, were compared among 127 Mexican children 5-15 mo of age randomized to receive a vitamin A supplement ( or =12 mo, 45,000 iu) every 2 mo or a placebo as part of a larger vitamin A supplementation trial. Stools collected during the summer months were screened for MCP-1 and gastrointestinal pathogens. Values of MCP-1 were categorized into 3 levels (nondetectable, or =median). Multinomial logistic regression models were used to determine whether vitamin A-supplemented children had different categorical values of MCP-1 compared with children in the placebo group. Differences in categorical values were also analyzed stratified by gastrointestinal pathogen infections and by diarrheal symptoms. Overall, children who received the vitamin A supplement had reduced fecal concentrations of MCP-1 compared with children in the placebo group (median pg/mg protein +/- interquartile range: 284.88 +/- 885.35 vs. 403.39 +/- 913.16; odds ratio 0.64, 95% CI 0.42-97, P = 0.03). Vitamin A supplemented children infected with enteropathogenic Escherichia coli (EPEC) had reduced MCP-1 levels (odds ratio = 0.38, 95% CI 0.18-0.80) compared with children in the placebo group. Among children not infected with Ascaris lumbricoides vitamin A supplemented children had reduced MCP-1 levels (OR = 0.62, 95% CI 0.41-0.94). These findings suggest that vitamin A has an anti-inflammatory effect in the gastrointestinal tract by reducing MCP-1 concentrations.

  11. Tick saliva increases production of three chemokines including monocyte chemoattractant protein-1, a histamine-releasing cytokine.

    Science.gov (United States)

    Langhansová, H; Bopp, T; Schmitt, E; Kopecký, J

    2015-02-01

    The effect of Ixodes ricinus tick saliva on the production of various cytokines and chemokines by mouse splenocytes was tested by a cytokine array. We demonstrated a strong upregulation of three chemokines, monocyte chemoattractant protein-1 (MCP-1), thymus-derived chemotactic agent 3 (TCA-3) and macrophage inflammatory protein 2 (MIP-2). MCP-1 could be induced by tick saliva itself. While TCA-3 and MIP-2 are engaged in Th2 polarization of the host immune response associated with tick feeding, MCP-1 may act as a histamine release factor, increasing blood flow into the feeding lesion thus facilitating tick engorgement in the late, rapid feeding phase.

  12. Data on early postoperative changes in aqueous monocyte chemoattractant protein-1 levels after phacoemulsification.

    Science.gov (United States)

    Kawai, Motofumi; Inoue, Toshihiro; Yoshida, Akitoshi; Tanihara, Hidenobu

    2016-12-01

    The data presented in this article are related to the research article entitled "Elevated levels of monocyte chemoattractant protein-1 in the aqueous humor after phacoemulsification" (M. Kawai, T. Inoue, M. Inatani, N. Tsuboi, K. Shobayashi, A. Matsukawa, A. Yoshida, H, 2012) [1]. The mean (±SE) aqueous MCP-1 levels (pg/ml) were 31.2±12.5, 1931.2±910.7, 2172.2±1015.7, 3315.4 ±1535.8, 3015.9 ±914.4, 2709.0 ±738.7, 72.8 ±26.9, and 207.1±62.9 at 0, 3, 6, 12, 24, 48, 168, and 720 h after phacoemulsification, respectively. The immunohistochemical analysis showed a number of MCP-1 positive inflammatory cells in the anterior chamber and conjunctiva. There were some MCP-1 positive cells in the corneal endothelium.

  13. Die Analyse der Inhibition des Monozyten chemotaktischen Proteins-1 (MCP-1) und der Stimulation durch MCP-1 auf die Koloniebildung und die Zytokinexpression von Plattenepithelkarzinomen der Kopf-Hals-Region im FLAVINO-Assay

    OpenAIRE

    Körner, Carolin

    2015-01-01

    Das Monozyten chemotaktische Protein-1 (MCP-1) ist ein CC-Chemokin, das in seiner Rolle als Chemoattraktor auf Monozyten in der Genese von Malignomen eine wesentliche Rolle spielt. Dabei kann es sowohl zur lokalen Tumorabwehr als auch zur Tumorgenese, Tumor-angiogenese und Metastasierung beitragen. Die vorliegende Arbeit untersucht die MCP-1-Inhibition und die Stimulation durch MCP-1 auf die Koloniebildung und die Zytokinexpression von Plattenepithelkarzinomen der Kopf-Hals-Region (HNSCC) im ...

  14. Effect of monocyte chemoattractant protein-1 on chemotactic gene expression by macrophage cell line U937

    Institute of Scientific and Technical Information of China (English)

    BIAN Guang-xing; GUO Bao-yu; MIAO Hong; QIU Lei; CAO Dong-mei; DAO Shu-yan; ZHANG Ran

    2004-01-01

    Objective: To study the chemotactic superfamily genes expression profiling of macrophage line U937 treated with monocyte chemoattractant protein-1 (MCP-1) using gene chip technique. Methods: Total RNA from macrophage line U937 (as control) and U937 with MCP-1 was extracted, made reverse transcript to cDNA and tested with gene expression chip HO2 human. Results: Some chemotactic-related gene expressions were changed in all analyzed genes. Regulated upon activation, normal T cell expressed and secreted (RANTES) was up-regulated over 2-fold and 7 chemotactic-related genes (CCR2, CCR5, CCL16, GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2) were down-regulated over 2-fold inMCP-1 treated U937 cells at mRNA level. Conclusion: MCP-1 can influence some chemokines and receptors expression in macrophage in vitro, in which MCP-1 mainly down-regulates the chemotactic genes expression of those influencing neutrophilic granulocyte (GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2). Another novel finding is that it can also down-regulate the mRNA level of CCR5, which plays a critical role in many disorders and illnesses.

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

    Directory of Open Access Journals (Sweden)

    Sabah Alharazy

    2015-01-01

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

  16. Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α in alcoholic liver disease

    OpenAIRE

    Fisher, N; Neil, D.; Williams, A.; Adams, D.

    1999-01-01

    BACKGROUND—Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1α (MIP-1α).
AIMS—To determine whether concentrations of chemokines in the peripheral circulation reflect disease activity, and whether chemokine secretion is restricted to the liver or is part of a systemic inflammatory response in alcoholic liver disease.
PATIENTS—Fifty one patients with alcoholic liver disease and 12 healthy co...

  17. 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

  18. 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.

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

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    Simmons Zachary

    2009-02-01

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

  20. 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

  1. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Ingrid Stroo

    Full Text Available Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2, the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  2. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

    Science.gov (United States)

    Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J D; Butter, Loes M; Florquin, Sandrine; Leemans, Jaklien C

    2015-01-01

    Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R) injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2), the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  3. Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with diabetic nephropathy risk.

    Science.gov (United States)

    Su, Ning; Li, Hong-Yan; Huang, Miao-Fang; Jiang, Zong-Pei; Zhou, Tian-Biao

    2015-02-01

    Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A/G gene polymorphism and diabetic nephropathy (DN) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for DN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2014, and eligible investigations were synthesized using meta-analysis method. Four studies were identified for the analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all the included studies were form Asian population. The association between MCP-1 A/G gene polymorphism and DN susceptibility was not found (A allele: OR = 1.19; 95% CI: 0.97-1.45; p = 0.10; AA genotype: OR = 1.27; 95% CI: 0.95-1.70; p = 0.11; GG genotype: OR = 0.77; 95% CI: 0.57-1.05; p = 0.10). In the sensitive analysis, according to the control source from hospital, we found that AA genotype was associated with the DN risk (OR = 1.45; 95% CI: 1.05-2.00; p = 0.02). However, other associations were not found in the sensitive analysis according to the control source from hospital or population. Our results indicate that AA homozygous might be a significant genetic molecular marker to predict the diabetes mellitus patients developing into DN. However, more investigations are required to further clarify this association.

  4. Correlation between Serum Level of Monocyte Chemoattractant Protein-1 and Postoperative Recurrence of Spinal Tuberculosis in the Chinese Han Population.

    Directory of Open Access Journals (Sweden)

    Dan He

    Full Text Available To correlate serum level of monocyte chemoattractant protein-1 (MCP-1 with postoperative recurrence of spinal tuberculosis in the Chinese Han population.Patients of Han nationality with newly diagnosed spinal tuberculosis were consecutively included in this study. At different time points postoperatively, serum level of MCP-1 was determined using an enzyme linked immunosorbent assay. Recurrence of spinal tuberculosis after surgery and during the follow-up period was recorded. The correlation between serum MCP-1 level and recurrence of spinal tuberculosis was analyzed.A total of 169 patients with spinal tuberculosis were included in the study and followed up for an average of 2.2 ± 1.3 years (range, 1-5 years. Of these patients, 11 had postoperative recurrence of spinal tuberculosis. The patients' serum level of MCP-1 increased significantly after postoperative recurrence of spinal tuberculosis. Once the symptoms of recurrence were cured, the serum level of MCP-1 decreased significantly and it did not differ from patients without disease recurrence.Postoperative recurrence of spinal tuberculosis is likely to increase the serum level of MCP-1.

  5. Monocyte Chemoattractant Protein-1 and Large Artery Structure and Function in Young Individuals: The African-PREDICT Study.

    Science.gov (United States)

    Kriel, Johanna I; Fourie, Carla M T; Schutte, Aletta E

    2017-01-01

    To better understand hypertension development, the authors determined whether monocyte chemoattractant protein-1 (MCP-1) is associated with arterial stiffness (pulse wave velocity [PWV]) and carotid intima-media wall thickness (cIMT) in a young apparently healthy black and white population (N=403, aged 20-30 years). Carotid-femoral PWV, central systolic blood pressure, and cIMT were measured, and MCP-1, reactive oxygen species, inflammatory markers (interleukin 6, tumor necrosis factor α), and endothelial activation (intercellular adhesion molecule, vascular cell adhesion molecule) were determined from blood samples. Although carotid-femoral PWV and cIMT were similar between blacks and whites, black men and women showed higher central systolic blood pressure, MCP-1, and reactive oxygen species than whites (all P<.05). In addition, black women had higher brachial blood pressure and interleukin 6 (all P<.001). A consistent positive association only in black women between cIMT and MCP-1 in multiple regression analyses was found (R²=0.151, β=0.248; P=.021). In this model, cIMT was also independently associated with vascular cell adhesion molecule (β=0.251; P=.022). The authors found elevated central systolic blood pressure and MCP-1 in young blacks, where cIMT was independently associated with MCP-1 in black women.

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549). RESULTS: Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P

  7. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Silva, Mariana Ruiz; 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 duri

  8. Short communication: localization and expression of monocyte chemoattractant protein-1 in different subcutaneous and visceral adipose tissues of early-lactating dairy cows.

    Science.gov (United States)

    Häussler, S; Sacré, C; Friedauer, K; Dänicke, S; Sauerwein, H

    2015-09-01

    The present study aimed to examine the mRNA abundance of the monocyte chemoattractant protein-1 (MCP-1) and to localize the MCP-1 protein in different subcutaneous (s.c.) and visceral (v.c.) fat depots in high-yielding dairy cows. Early-lactating German Holstein cows (n=25) were divided into a control (CON) and a conjugated linoleic acids (CLA)-supplemented group to investigate potential effects of dietary CLA treatment on MCP-1. The MCP-1 was localized in different s.c. and v.c. adipose tissue (AT) by immunohistochemistry, whereas the mRNA abundance was investigated using quantitative PCR. Albeit the infiltration of immune cells into bovine AT has been demonstrated to be only marginal, both MCP-1 protein and mRNA could be detected in bovine AT depots. The MCP-1 protein was localized both in the cytoplasm of adipocytes and in the cytoplasm of cells from the stromal vascular fraction; however, the number of MCP-1-positive cells was low. The mRNA abundances of MCP-1 were higher in v.c. compared with s.c. AT. Moreover, neither mRNA abundance nor protein expression of MCP-1 was seriously influenced by CLA supplementation of early-lactating dairy cows.

  9. A three-dimensional in vitro model to demonstrate the haptotactic effect of monocyte chemoattractant protein-1 on atherosclerosis-associated monocyte migration.

    Science.gov (United States)

    Ghousifam, Neda; Mortazavian, Hamid; Bhowmick, Rudra; Vasquez, Yolanda; Blum, Frank D; Gappa-Fahlenkamp, Heather

    2017-04-01

    Monocyte transendothelial migration is a multi-step process critical for the initiation and development of atherosclerosis. The chemokine monocyte chemoattractant protein-1 (MCP-1) is overexpressed during atheroma and its concentration gradients in the extracellular matrix (ECM) is critical for the transendothelial recruitment of monocytes. Based on prior observations, we hypothesize that both free and bound gradients of MCP-1 within the ECM are involved in directing monocyte migration. The interaction between a three-dimensional (3D), cell-free, collagen matrix and MCP-1; and its effect on monocyte migration was measured in this study. Our results showed such an interaction existed between MCP-1 and collagen, as 26% of the total MCP-1 added to the collagen matrix was bound to the matrix after extensive washes. We also characterized the collagen-MCP-1 interaction using biophysical techniques. The treatment of the collagen matrix with MCP-1 lead to increased monocyte migration, and this phenotype was abrogated by treating the matrix with an anti-MCP-1 antibody. Thus, our results indicate a binding interaction between MCP-1 and the collagen matrix, which could elicit a haptotactic effect on monocyte migration. A better understanding of such mechanisms controlling monocyte migration will help identify target cytokines and lead to the development of better anti-inflammatory therapeutic strategies.

  10. Enrichment of Two Isomeric Heparin Oligosaccharides Exhibiting Different Affinities toward Monocyte Chemoattractant Protein-1.

    Science.gov (United States)

    Miller, Rebecca L; Dykstra, Andrew B; Wei, Wei; Holsclaw, Cynthia; Turnbull, Jeremy E; Leary, Julie A

    2016-12-06

    Chemokine-GAG interactions are crucial to facilitate chemokine immobilization, resulting in the formation of chemokine gradients that guide cell migration. Here we demonstrate chromatographic isolation and purification of two heparin hexasaccharide isomers that interact with the oligomeric chemokine Monocyte Chemoattractant Protein-1 (MCP-1)/CCL2 with different binding affinities. The sequences of these two hexasaccharides were deduced from unique MS/MS product ions and HPLC compositional analysis. Ion mobility mass spectrometry (IM-MS) showed that the two isolated oligosaccharides have different conformations and both displayed preferential binding for one of the two distinct conformations known for MCP-1 dimers. A significant shift in arrival time distribution of close to 70 Å(2) was observed, indicating a more compact protein:hexasaccharide conformation. Clear differences in the MS spectra between bound and unbound protein allowed calculation of Kd values from the resulting data. The structural difference between the two hexasaccharides was defined as the differential location of a single sulfate at either C-6 of glucosamine or C-2 of uronic acid in the reducing disaccharide, resulting in a 200-fold difference in binding affinity for MCP-1. These data indicate sequence specificity for high affinity binding, supporting the view that sulfate position, and not simply the number of sulfates, is important for heparan sulfate protein binding.

  11. Effects of Tumor Necrosis Factor-α on Podocyte Expression of Monocyte Chemoattractant Protein-1 and in Diabetic Nephropathy

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    Choon Hee Chung

    2015-02-01

    Full Text Available Background/Aims: Tumor necrosis factor (TNF-α is believed to play a role in diabetic kidney disease. This study explores the specific effects of TNF-α with regard to nephropathy-relevant parameters in the podocyte. Methods: Cultured mouse podocytes were treated with recombinant TNF-α and assayed for production of monocyte chemoattractant protein-1 (MCP-1 by enzyme-linked immunosorbent assay (ELISA. TNF-α signaling of MCP-1 was elucidated by antibodies against TNF receptor (TNFR 1 or TNFR2 or inhibitors of nuclear factor-kappaB (NF-κB, phosphatidylinositol 3-kinase (PI3K or Akt. In vivo studies were done on male db/m and type 2 diabetic db/db mice. Levels of TNF-α and MCP-1 were measured by RT-qPCR and ELISA in the urine, kidney and plasma of the two cohorts and correlated with albuminuria. Results: Podocytes treated with TNF-α showed a robust increase (∼900% in the secretion of MCP-1, induced in a dose- and time-dependent manner. Signaling of MCP-1 expression occurred through TNFR2, which was inducible by TNF-α ligand, but did not depend on TNFR1. TNF-α then proceeded via the NF-κB and the PI3K/Akt systems, based on the effectiveness of the inhibitors of those pathways. For in vivo relevance to diabetic kidney disease, TNF-α and MCP-1 levels were found to be elevated in the urine of db/db mice but not in the plasma. Conclusion: TNF-α potently stimulates podocytes to produce MCP-1, utilizing the TNFR2 receptor and the NF-κB and PI3K/Akt pathways. Both TNF-α and MCP-1 levels were increased in the urine of diabetic db/db mice, correlating with the severity of diabetic albuminuria.

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

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    Supanat Worawichawong

    2016-12-01

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

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

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    Isabel Graupera

    Full Text Available 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.To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis.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.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; p<0.05; median (IQR. Furthermore, urine levels of MCP-1 were significantly associated with mortality (1.01 (1-3.6 vs 0.5 (0.2-1.1 μg/g creat, in dead and alive patients at 3 months; p<0.05. Patients with higher levels of urine MCP-1 (above percentile 75th had higher probability of development of hepatic 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.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

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

    Science.gov (United States)

    Lee, Y H; Bae, S-C

    2016-03-20

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

  15. Isoprenaline increases serum levels of monocyte chemoattractant protein-1 and tissue inhibitor of matrix metalloproteinases type Ⅰ in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    LEI He-ping; ZHANG Meng-zhen; YANG Xiang-yu; HOU Xing-hua; LIN Qiu-xiong; YANG Min; ZHONG Shi-long

    2016-01-01

    Background Treatment of rats with the beta-adrenergic agonist Isoprenaline (ISO) results in cardiac hypertrophy and myocardial fibrosis.In the present work,we aimed to study the in vivo effects of ISO on serum levels of monocyte chemoattractant protein-1 and tissue inhibitor of matrix metalloproteinases type Ⅰ in Wistar rats.Methods ISO (5 mg· kg-1) or Saline were injected subcutaneously into Wistar rats once a day for 3 or 7 consecutive days.Ventricular remodeling and cardiac function were evaluated by echocardiography.Sections of heart were stained with hematoxylin-eosin (HE) for histopathology or with Masson's trichrome for collagen visualization.In addition,heart tissue immunohistochemistry for α-SMA was also analyzed.The serum levels of tissue inhibitor of matrix metalloproteinases type Ⅰ (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1) were determined by Luminex multiplex technology.Results ISO induced cardiac dysfunction in rats after 3 or 7 days of treatment.ISO caused significant increase of myocardial disorder and fibrosis withincreased α-SMA expression.ISO treated aats showed a significant increase in the serum levels of TIMP-1 and MCP-1.Conclusions Our study suggests that ISO induces profound cardiac remodeling accompanied with increase of serum TIMP-1 and MCP-1.

  16. Chemically induced neuronal damage and gliosis: enhanced expression of the proinflammatory chemokine, monocyte chemoattractant protein (MCP)-1, without a corresponding increase in proinflammatory cytokines(1).

    Science.gov (United States)

    Little, A R; Benkovic, S A; Miller, D B; O'Callaghan, J P

    2002-01-01

    Enhanced expression of proinflammatory cytokines and chemokines has long been linked to neuronal and glial responses to brain injury. Indeed, inflammation in the brain has been associated with damage that stems from conditions as diverse as infection, multiple sclerosis, trauma, and excitotoxicity. In many of these brain injuries, disruption of the blood-brain barrier (BBB) may allow entry of blood-borne factors that contribute to, or serve as the basis of, brain inflammatory responses. Administration of trimethyltin (TMT) to the rat results in loss of hippocampal neurons and an ensuing gliosis without BBB compromise. We used the TMT damage model to discover the proinflammatory cytokines and chemokines that are expressed in response to neuronal injury. TMT caused pyramidal cell damage within 3 days and a substantial loss of these neurons by 21 days post dosing. Marked microglial activation and astrogliosis were evident over the same time period. The BBB remained intact despite the presence of multiple indicators of TMT-induced neuropathology. TMT caused large increases in whole hippocampal-derived monocyte chemoattractant protein (MCP)-1 mRNA (1,000%) by day 3 and in MCP-1 (300%) by day 7. The mRNA levels for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, cytokines normally expressed during the earliest stage of inflammation, were not increased up to 21 days post dosing. Lipopolysaccharide, used as a positive control, caused large inductions of cytokine mRNA in liver, as well as an increase in IL-1beta in hippocampus, but it did not result in the induction of astrogliosis. The data suggest that enhanced expression of the proinflammatory cytokines, TNF-alpha, IL-1beta and IL-6, is not required for neuronal and glial responses to injury and that MCP-1 may serve a signaling function in the damaged CNS that is distinct from its role in proinflammatory events.

  17. Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes.

    Science.gov (United States)

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

    2014-11-01

    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 increased cardiac monocyte infiltration, endoplasmic reticulum (ER) stress, apoptosis, fibrosis and left ventricular dysfunction. Ex4 treatment for 8 weeks improved cardiac function and reduced monocyte infiltration, fibrosis and apoptosis in MHC-MCP1 mice. Ex4 enhanced expression of the ER chaperone glucose-regulated protein-78 (GRP78), decreased expression of the pro-apoptotic ER stress marker CCAAT/-enhancer-binding protein homologous protein (CHOP) and increased expression of the ER calcium regulator Sarco/Endoplasmic Reticulum Calcium ATPase-2a (SERCA2a). These findings suggest that the Glp1r is a viable target for treating cardiomyopathies associated with stimulation of pro-inflammatory factors.

  18. The potential role of monocyte chemoattractant protein-1 for major depressive disorder.

    Science.gov (United States)

    Pae, Chi-Un

    2014-07-01

    The immune hypothesis of major depressive disorder (MDD) fits well with the supposed interaction between genetic and environmental factors in disorders with a complicated etiopathogenesis. It has been suggested that infectious diseases are associated with MDD in that cytokines may play a critical role as a key modulator in the transition between infection and the development of MDD. It has been also suggested that antidepressants have immunomodulatory effects on some cytokines and cytokine receptors, although the exact mechanism has not yet been fully elucidated. Among cytokines, monocyte chemoattractant protein-1 (MCP-1) is especially well known and has attracted considerable interest owing to its immunomodulatory functions. MCP-1 is expressed in highly regionalized neuronal areas in the brain, leading to kind of modulation of neuronal activity and neuroendocrine functions commonly seen in patients with MDD. Additionally, it is involved in the control of other cytokines that have been consistently proposed as associated with the development of MDD. It also has a possible role in the neurodegenerative process of a number of central nervous system (CNS) diseases. Hence, this paper draws from the perspective of immunology to offer several suggestions about the role of MPC-1 in the development of MDD.

  19. Insulin Resistance, Inflammation, and Obesity: Role of Monocyte Chemoattractant Protein-1 (orCCL2 in the Regulation of Metabolism

    Directory of Open Access Journals (Sweden)

    Anna Rull

    2010-01-01

    Full Text Available To maintain homeostasis under diverse metabolic conditions, it is necessary to coordinate nutrient-sensing pathways with the immune response. This coordination requires a complex relationship between cells, hormones, and cytokines in which inflammatory and metabolic pathways are convergent at multiple levels. Recruitment of macrophages to metabolically compromised tissue is a primary event in which chemokines play a crucial role. However, chemokines may also transmit cell signals that generate multiple responses, most unrelated to chemotaxis, that are involved in different biological processes. We have reviewed the evidence showing that monocyte chemoattractant protein-1 (MCP-1 or CCL2 may have a systemic role in the regulation of metabolism that sometimes is not necessarily linked to the traffic of inflammatory cells to susceptible tissues. Main topics cover the relationship between MCP-1/CCL2, insulin resistance, inflammation, obesity, and related metabolic disturbances.

  20. IgE in the absence of allergen induces the expression of monocyte chemoattractant protein-1 in the rat basophilic cell-line RBL-2H3.

    Science.gov (United States)

    Ahn, Ki Bum; Jeon, Jun Ho; Kang, Seok-Seong; Chung, Dae Kyun; Yun, Cheol-Heui; Han, Seung Hyun

    2014-11-01

    Recently, basophils have been suggested to produce inflammatory mediators in response to IgE in the absence of allergens. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the initiation of inflammatory responses by recruiting various immune cells to the site of allergic inflammation. In the present study, we examined whether IgE under allergen-free conditions could stimulate basophils and lead to the production of MCP-1. Exposure of the rat basophilic cell-line RBL-2H3 to IgE without allergen resulted in a dose- and time-dependent induction of MCP-1 expression at both the mRNA and protein level. Although allergen was not necessary for IgE-induced MCP-1 expression, it was essential for degranulation as determined by β-hexosaminidase release assay. IgE enhanced phosphorylation of MAP kinases including ERK, p38 kinase, and JNK. However, IgE-induced MCP-1 expression was attenuated by inhibitors for JNK and PKC. Concomitantly, IgE induced activation of AP-1, which is an important transcription factor for MCP-1 gene expression in RBL-2H3 cells. Taken together, our results suggest that IgE alone is sufficient to stimulate basophils to increase expression of MCP-1, which in turn might contribute to the inflammatory response.

  1. Monocyte chemoattractant protein-1-deficiency impairs the expression of IL-6, IL-1β and G-CSF after transient focal ischemia in mice.

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    Jan-Kolja Strecker

    Full Text Available Monocyte chemoattractant protein-1 (MCP-1, a chemokine secreted by neurons and astrocytes following stroke is known to aggravate ischemia-related damage. Previous studies revealed that MCP-1-deficient mice develop smaller infarcts and have an improved neurological outcome, whereas mice overexpressing MCP-1 show worsened brain damage and impaired neurological function. The aim of the present study was to elucidate the molecular background of the enhanced recovery in MCP-1-deficient mice after stroke. For this purpose, we (1 performed expression analyses on crucial post-stroke related inflammatory genes in MCP-1-deficient mice compared to wildtype controls, (2 analyzed a possible impact of MCP-1 on astrocyte activation (3 investigated the cellular origin of respective inflammatory cytokines and (4 analyzed the impact of MCP-1 secretion on the migration of both neutrophil granulocytes and T-cells. Here we report that MCP-1-deficiency leads to a shift towards a less inflammatory state following experimental occlusion of the middle cerebral artery including an impaired induction of interleukin-6, interleukin-1β and granulocyte-colony stimulating factor expression as well as a subsequent diminished influx of hematogenous cells. Additionally, MCP-1-deficient mice developed smaller infarcts 36 hours after experimental stroke. Investigations revealed no differences in transcription of tumor necrosis factor-α and astrogliosis 12 and 36 hours after onset of ischemia. These novel results help to understand post ischemic, inflammatory mechanisms and might give further arguments towards therapeutical interventions by modulation of MCP-1 expression in post stroke inflammation.

  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 chemoattractant protein-1 gene polymorphism and its serum level have an impact on anthropometric and biochemical risk factors of metabolic syndrome in Indian population.

    Science.gov (United States)

    Madeshiya, A K; Singh, S; Dwivedi, S; Saini, K S; Singh, R; Tiwari, S; Konwar, R; Ghatak, A

    2015-04-01

    Monocyte chemoattractant protein-1 (MCP-1), encoded by gene CCL-2 (Chemokine C-C motif 2), is the ligand of chemokine receptor CCR-2. Concurrent clinical alteration in several metabolic aspects, including central obesity, dysglycemia, dyslipidemia and hypertension, is clinically characterized as metabolic syndrome (MetS). Role of MCP-1 in each of these aspects has been established in vitro and in animal studies as well. We here report genetic association of -2518 A>G MCP-1 (rs 1024611) gene polymorphism and level of MCP-1 with MetS in North Indian subjects. We analysed (n=386, controls and n=384, MetS subjects) for MCP-1 gene polymorphism using PCR-RFLP, its serum level using ELISA, anthropometric (body mass index, waist and hip circumferences, waist-hip ratio and blood pressure) and biochemical (serum lipids, plasma glucose and insulin levels) variables in a genetic association study. The body mass index, waist circumference, hip circumference, waist-hip ratio, blood pressure, serum lipids, insulin and fasting plasma glucose level were significantly high in MetS subjects. Regression analysis showed significant correlation of body mass index, waist and hip circumference, systolic/diastolic blood pressure, fasting glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein fasting insulin and HOMA-IR with MetS. MCP-1 allele and genotype were significantly associated with MetS. Serum MCP-1 level was high in overall cases. In conclusions, the MCP-1 2518A>G (rs 1024611) polymorphism has significant impact on risk of MetS, and MCP-1 level correlates with anthropometric and biochemical risk factors of MetS.

  4. Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus.

    Science.gov (United States)

    Shoukry, Amira; Bdeer, Shereen El-Arabi; El-Sokkary, Rehab H

    2015-10-01

    Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes and, unless arrested, leads to end-stage renal disease. Therefore, early prediction and detection of DN would greatly benefit the disease management and delay its progression. The aim of this study is to evaluate the levels of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary vitamin D-binding protein (uVDBP) in type 2 diabetic patients with different degrees of diabetic nephropathy (DN) and to assess the value of uMCP-1 and uVDBP in the early detection of DN. Seventy-five type 2 diabetic patients with normoalbuminuria (n = 25), microalbuminuria (n = 25), macroalbuminuria (n = 25), and 25 healthy controls were included in this study. Urinary MCP-1 and VDBP levels were evaluated by enzyme-linked immunosorbent assay. A significant elevation in the uMCP-1 and uVDBP levels was found in macroalbuminuric (p diabetic patients compared to that in normoalbuminuric diabetic patients and control subjects (p diagnosis and detection of DN revealed that the cut-off value of uMCP-1 was 110 pg/mg with 92% sensitivity and 100% specificity; whereas, the cut-off value of uVDBP was 550 ng/mg with 96% sensitivity and 84% specificity. The findings of the present study suggest that uMCP-1 and uVDBP may be considered as novel potential diagnostic biomarkers for the early detection of diabetic nephropathy.

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

    Science.gov (United States)

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

    2016-09-02

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

  6. 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

    NARCIS (Netherlands)

    K.H. Løland (Kjetil); O. Bleie (Oyvind); E. Strand (Elin); P.M. Ueland (Per); J. Nordrehaug (Jan); H.M. Garcia-Garcia (Hector); P.W.J.C. Serruys (Patrick); O. Nygård (Ottar)

    2013-01-01

    textabstractBackground: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

  7. Effects of High Estrogen Levels on Monocyte Chemoattractant Protein-1 and Wound Healing.

    Science.gov (United States)

    Plackett, Timothy P; Gregory, Meredith S; Kovacs, Elizabeth J

    2015-02-01

    Objective: Herein, we tested the effects of high levels of supplemental estrogen treatment on cutaneous wound healing. Approach: Female mice were implanted with a 17β-estradiol (E2) secreting pellet or placebo before receiving a full-thickness dermal excisional wound. Mice receiving the E2 pellet attained hormone levels that are comparable to those achieved during pregnancy. At 1, 3, and 5 days after injury, the dermal excision wound was examined for their histologic appearance, rate of closure, and chemokine levels. Results: Wound closure, assessed by percent reepithelialization, was slower in E2-treated mice relative to placebo (42.6%±6.6% vs. 70.0%±5.3%, respectively, 3 days after injury). In addition, there was a marked reduction in the subepithelial inflammatory infiltrate and granulation tissue in E2-treated mice relative to placebo. Wound levels of monocyte chemoattractant protein-1 (MCP-1) were increased by 3 days after injury and continued to rise at 5 days after injury in placebo-treated mice (p<0.01). By contrast, MCP-1 levels were significantly reduced at 3 and 5 days after injury in E2-treated mice relative to placebo-treated controls (p<0.01). This attenuation could be reversed by treatment with an estrogen receptor antagonist. Innovation: High levels of estrogen are able to suppress normal wound closure. Conclusion: Dermal wound healing can be altered by manipulating the gonadal steroid hormone levels. In particular, high levels of estrogen can be utilized to slow down the rate of wound healing through a reduction in the inflammatory response.

  8. Host-derived smooth muscle cells accumulate in cardiac allografts: role of inflammation and monocyte chemoattractant protein 1.

    Directory of Open Access Journals (Sweden)

    Piotr Religa

    Full Text Available Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35+/-2.3% of cells in arterioles (range, 0.08-12.51%. As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41+/-1.03, p = 0.034 and the number of leukocytes (19.1+/-12.7 per 20 high-power fields, p = 0.01. The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1 released from leukocytes was crucial for SMC migration. After heart allotransplantation, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts.

  9. Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

    Science.gov (United States)

    Bojakowski, Krzysztof; Soin, Joanna; Nozynski, Jerzy; Zakliczynski, Michal; Gaciong, Zbigniew; Zembala, Marian; Söderberg-Nauclér, Cecilia

    2009-01-01

    Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs) both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35±2.3% of cells in arterioles (range, 0.08–12.51%). As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41±1.03, p = 0.034) and the number of leukocytes (19.1±12.7 per 20 high-power fields, p = 0.01). The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1) released from leukocytes was crucial for SMC migration. After heart allotransplantion, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts. PMID:19142231

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Ibrahim Salwa

    2008-01-01

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

  12. Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

    OpenAIRE

    Jieshi Xie; Le Yang; Lei Tian; Weiyang Li; Lin Yang; Liying Li

    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 an...

  13. Disruption of Lipid Raft Function Increases Expression and Secretion of Monocyte Chemoattractant Protein-1 in 3T3-L1 Adipocytes.

    Science.gov (United States)

    Lu, Juu-Chin; Chiang, Yu-Ting; Lin, Yu-Chun; Chang, Yu-Tzu; Lu, Chia-Yun; Chen, Tzu-Yu; Yeh, Chia-Shan

    2016-01-01

    The adipocyte is unique in its capacity to store lipids. In addition to triglycerides, the adipocyte stores a significant amount of cholesterol. Moreover, obese adipocytes are characterized by a redistribution of cholesterol with depleted cholesterol in the plasma membrane, suggesting that cholesterol perturbation may play a role in adipocyte dysfunction. We used methyl-β-cyclodextrin (MβCD), a molecule with high affinity for cholesterol, to rapidly deplete cholesterol level in differentiated 3T3-L1 adipocytes. We tested whether this perturbation altered adipocyte secretion of monocyte chemoattractant protein-1 (MCP-1), a chemokine that is elevated in obesity and is linked to obesity-associated chronic diseases. Depletion of cholesterol by MβCD increased MCP-1 secretion as well as the mRNA and protein levels, suggesting perturbation at biosynthesis and secretion. Pharmacological inhibition revealed that NF-κB, but not MEK, p38 and JNK, was involved in MβCD-stimulated MCP-1 biosynthesis and secretion in adipocytes. Finally, another cholesterol-binding drug, filipin, also induced MCP-1 secretion without altering membrane cholesterol level. Interestingly, both MβCD and filipin disturbed the integrity of lipid rafts, the membrane microdomains enriched in cholesterol. Thus, the depletion of membrane cholesterol in obese adipocytes may result in dysfunction of lipid rafts, leading to the elevation of proinflammatory signaling and MCP-1 secretion in adipocytes.

  14. Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections.

    Science.gov (United States)

    Chen, M-F; Weng, K-F; Huang, S-Y; Liu, Y-C; Tseng, S-N; Ojcius, D M; Shih, S-R

    2017-01-01

    It has been proposed that inactivated probiotics may modulate the host immune system and contribute to mitigation of viral infections. This study demonstrated that administration of heat-killed Enterococcus faecalis, a widely used probiotic, can protect host animals against viral infections. The influenza-mediated morbidity and lung inflammation in E. faecalis-treated mice decreased significantly compared with those of the control mice. Furthermore, we found that the protection is associated with production of monocyte chemoattractant protein-1 (MCP-1). The intratracheal injection of a recombinant mouse MCP-1 protein abrogated the antiviral effects elicited by pretreatment with E. faecalis. CC chemokine receptor 2 (CCR2) is a receptor for MCP-1, and the intraperitoneal administration of a CCR2 antagonist effectively inhibited viral pathogenicity. The reduced pathogenicity was also observed in CCR2-deficient mice. Finally, E. faecalis significantly attenuated neuropathogenicity induced by another RNA virus, enterovirus 71. This study demonstrates that killed probiotics can reduce viral disease severity and identify that the MCP-1 pathway might act as a key mediator in the improved antiviral immune response. Our findings suggest that MCP-1 and its related signaling pathway can serve as critical therapeutic targets for development of new antiviral strategies.

  15. Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.

    Science.gov (United States)

    Chang, Alice Y W; Li, Faith C H; Huang, Chi-Wei; Wu, Julie C C; Dai, Kuang-Yu; Chen, Chang-Han; Li, Shau-Hsuan; Su, Chia-Hao; Wu, Re-Wen

    2014-11-01

    Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response.

  16. Hyperhomocysteinemia-Induced Monocyte Chemoattractant Protein-1 Promoter DNA Methylation by Nuclear Factor-κB/DNA Methyltransferase 1 in Apolipoprotein E-Deficient Mice.

    Science.gov (United States)

    Wang, Ju; Jiang, Yideng; Yang, Anning; Sun, Weiwei; Ma, Changjian; Ma, Shengchao; Gong, Huihui; Shi, Yingkang; Wei, Jun

    2013-04-01

    Hyperhomocysteinemia is considered to be a significant risk factor in atherosclerosis and plays an important role in it. The purpose of this study was to determine the molecular mechanism of blood monocyte chemoattractant protein-1 (MCP-1) promoter DNA hypomethylation in the formation of atherosclerosis induced by hyperhomocysteinemia, and to explore the effect of nuclear factor-κB (NF-κB)/DNA methyltransferase 1 (DNMT1) in this mechanism. The atherosclerotic effect of MCP-1 in apolipoprotein E-deficient (ApoE(-/-)) and wild-type C57BL/6J mice was evaluated using atherosclerotic lesion area; serum NF-κB, MCP-1, and DNMT1 levels; and MCP-1 promoter DNA methylation expression. In vitro, the mechanism responsible for the effect of NF-κB/DNMT1 on foam cells was investigated by measuring NF-κB and DNMT1 levels to determine whether NF-κB/DNMT1 had an effect on gene expression. Compared with the control group, atherosclerotic lesions in ApoE(-/-) mice fed a high methionine diet significantly increased, as did the expression of MCP-1. In vitro study showed that pyrrolidine dithiocarbamate treatment down-regulated levels of NF-κB and raised DNMT1 concentrations, confirming the effect of NF-κB/DNMT1 in the MCP-1 promoter DNA methylation process. In conclusion, our results suggest that through NF-κB/DNMT1, MCP-1 promoter DNA hypomethylation may play a key role in formation of atherosclerosis under hyperhomocysteinemia.

  17. Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model.

    Science.gov (United States)

    Cranford, Taryn L; Velázquez, Kandy T; Enos, Reilly T; Bader, Jackie E; Carson, Meredith S; Chatzistamou, Ioulia; Nagarkatti, Mitzi; Murphy, E Angela

    2017-02-01

    Monocyte chemoattractant protein 1 (MCP-1) has been implicated as a major modulator in the progression of mammary tumorigenesis, largely due to its ability to recruit macrophages to the tumor microenvironment. Macrophages are key mediators in the connection between inflammation and cancer progression and have been shown to play an important role in tumorigenesis. Thus, MCP-1 may be a potential therapeutic target in inflammatory and difficult-to-treat cancers such as triple negative breast cancer (TNBC). We examined the effect of MCP-1 depletion on mammary tumorigenesis in a model of TNBC. Tumor measurements were conducted weekly (until 22 weeks of age) and at sacrifice (23 weeks of age) in female C3(1)/SV40Tag and C3(1)/SV40Tag MCP-1 deficient mice to determine tumor numbers and tumorvolumes. Histopathological scoring was performed at 12 weeks of age and 23 weeks of age. Gene expression of macrophage markers and inflammatory mediators were measured in the mammary gland and tumor microenvironment at sacrifice. As expected, MCP-1 depletion resulted in decreased tumorigenesis, indicated by reduced primary tumor volume and multiplicity, and a delay in tumor progression represented by histopathological scoring (12 weeks of age). Deficiency in MCP-1 significantly downregulated expression of macrophage markers in the mammary gland (Mertk and CD64) and the tumor microenvironment (CD64), and also reduced expression of inflammatory cytokines in the mammary gland (TNFα and IL-1β) and the tumor microenvironment (IL-6). These data support the hypothesis that MCP-1 expression contributes to increased tumorigenesis in a model of TNBC via recruitment of macrophages and subsequent increase in inflammatory mediators.

  18. 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

  19. Angiotensin II induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1.

    Science.gov (United States)

    Wu, Zhiyong; Dai, Feifeng; Ren, Wei; Liu, Huagang; Li, Bowen; Chang, Jinxing

    2016-01-01

    Patients with acute aortic dissection (AAD) usually showed acute lung injury (ALI). However, its pathogenesis is still not well defined. Apoptosis of pulmonary microvascular endothelial cells (PMVECs) is closely related to the alveolus-capillary barrier injury and the increased vascular permeability. In this study, we aim to investigate the human PMVECs (hPMVECs) apoptosis induced by angiotensin II (AngII) and monocyte chemoattractant protein-1 (MCP-1) and their potential interaction in the pathogenesis of AAD complicated with ALI. Fifty-eight newly diagnosed AAD, 12 matched healthy individuals were included. Pulmonary tissues of AAD complicated with lung injury were obtained from 2 cadavers to determine the levels of AngII type 1 receptor (AT1-R) and MCP-1. Serum AngII was measured using commercial ELISA kit. H&E staining and immunohistostaining were performed to determine the expression of AT1-R and MCP-1. For the in vitro experiment, hPMVECs were divided into control, AngII group, AngII+Bindarit group and Bindarit group, respectively. Flow cytometry was performed to analyze the apoptosis in each group. Reverse transcription-polymerase chain reaction was performed to determine the mRNA expression of MCP-1. Western blot analysis was performed to evaluate the expression of MCP-1 and apoptosis related protein. Apoptosis of hPMVECs was observed in the lung tissues in the cadavers with AAD complicated with ALI. Besides, the expression of AT1-R and MCP-1 was remarkably elevated. Compared with normal individuals and the non-lung injury AAD patients, the expression of serum AngII was remarkably elevated in AAD patients complicated with ALI. In vitro experiments showed AngII contributed to the apoptosis and elevation of MCP1 in hPMVECs. Besides, it involved in the down-regulation of Bcl-2 protein, and up-regulation of Bax and Caspase-3. Such phenomenon was completely reversed after administration of MCP-1 inhibitor (Bindarit). The production of MCP-1 and cellular

  20. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response...... that in chemokine-dependent inflammatory responses in lung CC chemokines do not necessarily demonstrate redundant function.......The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES...

  1. 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)

    Xiao Han

    2009-01-01

    HIV-assodated 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 could be further elevated by opiates. This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat, including the mediating role of mu opioid receptor (MOR) and CCR2 as well as the possible signal transduction pathways within the cells. Finally, it will make some future perspectives on the exact pathways, new receptors and target cells, and the vulnerability to neurodegeneration with HIV and opiates.

  2. Interrelationships between paraoxonase-1 and monocyte chemoattractant protein-1 in the regulation of hepatic inflammation.

    Science.gov (United States)

    Camps, Jordi; Marsillach, Judit; Rull, Anna; Alonso-Villaverde, Carlos; Joven, Jorge

    2010-01-01

    Oxidative stress and inflammation play a central role in the onset and development of liver diseases irrespective of the agent causing the hepatic impairment. The monocyte chemoattractant protein-1 is intimately involved in the inflammatory reaction and is directly correlated with the degree of hepatic inflammation in patients with chronic liver disease. Recent studies showed that hepatic paraoxonase-1 may counteract the production of the monocyte chemoattractant protein-1, thus playing an anti-inflammatory role. The current review summarises experiments suggesting how paraoxonase-1 activity and expression are altered in liver diseases, and their relationships with the monocyte chemoattractant protein-1 and inflammation.

  3. 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...

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549). RESULTS: Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P ..., suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P

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

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Kana [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Ninomiya, Ken [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Sonoda, Koh-Hei [Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582 (Japan); Miyauchi, Yoshiteru; Hoshi, Hiroko [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Iwasaki, Ryotaro [Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Miyamoto, Hiroya [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Division of Orthopedic Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); and others

    2009-06-05

    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.

  6. Monocyte chemoattractant protein-1 secreted by decidual stromal cells inhibits NK cells cytotoxicity by up-regulating expression of SOCS3.

    Directory of Open Access Journals (Sweden)

    Xiaofei Xu

    Full Text Available BACKGROUND: Decidual stromal cells (DSCs are of particular importance due to their pleiotropic functions during pregnancy. Although previous research has demonstrated that DSCs participated in the regulation of immune cells during pregnancy, the crosstalk between DSCs and NK cells has not been fully elucidated. To address this issue, we investigated the effect of DSCs on perforin expression in CD56(+ NK cells and explored the underlying mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Flow cytometry analysis showed perforin production in NK cells was attenuated by DSC media, and it was further suppressed by media from DSCs pretreated with lipopolysaccharide (LPS. However, the expression of granzyme A and apoptosis of NK cells were not influenced by DSC media. ELISA assays to detect cytokine production indicated that monocyte chemoattractant protein-1 (MCP-1 in the supernatant of DSCs conditioned culture significantly increased after LPS stimulation. The inhibitory effect of DSC media on perforin was abolished by the administration of anti-MCP-1 neutralizing antibody. Notably, reduced perforin expression attenuated the cytotoxic potential of CD56(+ NK cells to K562 cells. Moreover, Suppressor of cytokine signaling 3 (SOCS3 expression in NK cells was enhanced by treatment with MCP-1, as measured by RT-PCR and western blot. Interestingly, MCP-1-induced perforin expression was partly abolished by the siRNA induced SOCS3 knockdown. Western blot analysis suggested that both NF-κB and ERK/MAPKs pathway were involved in the LPS-induced upregulation of MCP-1 in DSCs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that LPS induces upregulation of MCP-1 in DSCs, which may play a critical role in inhibiting the cytotoxicity of NK cells partly by promoting SOCS3 expression. These findings suggest that the crosstalk between DSCs and NK cells may be crucial to maintain pregnancy homeostasis.

  7. Advanced oxidation protein products induce monocyte chemoattractant protein-1 expression via p38 mitogen-activated protein kinase activation in rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    PENG Kan-fu; WU Xiong-fei; ZHAO Hong-wen; SUN Yan

    2006-01-01

    Background Advanced oxidation protein products (AOPPs) are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs).Methods VSMCs were cultured and then co-incubated with AOPP (200 μ mol/L, 400 μ mol/L) for different times with or without pretreatment with specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. RT-PCR and Western blott were used to detect MCP-1 mRNA and protein expression at different time points after AOPP stimulation in rat smooth muscle cells. Western blot was used to detect the expression of phosphorylated p38 MAPK.Results Treatment of VSMC with AOPPs resulted in a significant increase of the expression of MCP- 1 mRNA and protein in time- and dose-dependent manner, and could activated p38 MAPK. Pretreatment of VSMCs with SB203580 resulted in a dose-dependent inhibition of AOPPs-induced MCP-1 mRNA and protein expression.Conclusions AOPPs can stimulate MCP-1 expression via p38 MAPK in VSMCs. This suggests that AOPPs might contribute to the formation of atherosclerosis through this proinflammatory effect.

  8. MCP-1 secretion in lung from nonsmoking patients with coal worker`s pneumoconiosis

    Energy Technology Data Exchange (ETDEWEB)

    Boitelle, A.; Gosset, P.; Vanhee, D.; Wallaert, B.; Tonnel, A.B. [Institut Pasteur, INSERM U416, Lille (France); Copin, M.C.; Gosselin, B. [Service d`anatomie et de cytologie pathologique, CHRU, Lille (France); Marquette, C.H. [Hopital A. Calmette, Clinique des maladies respiratoires, Lille (France)

    1997-03-01

    Exposure to coal dust leads to development of coal worker`s pneumoconiosis (CWP), a disease associated with accumulation of macrophages in lower respiratory tract. Mechanisms controlling monocyte recruitment are still poorly understood. Since monocyte chemoattractant protein-1 (MCP-1) is recognized as a potent chemotactic factor for blood monocytes, we tested for presence of MCP-1 in pulmonary compartment of patients with CWP. Bronchoalveolar lavage fluid (BALF) from 16 nonsmoking control subjects and 27 nonsmoking CWP patients (16 with simple pneumoconiosis (SP) and 11 with progressive massive fibrosis (PMF)) was analysed. Alveolar macrophages (AMs) were purified by adherence and BALF was concentrated 10x by lyophilization. MCP-1 was measured in BALF and in 3 h AM supernatants using a sandwich enzyme-linked immunosorbent assay. Localization of MCP-1 in lung tissue was determined by immunohistochemistry on tissue sections from three patients with CWP and two control subjects. MCP-1 levels were higher in concentrated BALF from patients with SP or PMF (median 370 and 555 pg x mL{sup -1}, respectively) than in those form control subjects (median 11 pg x mL{sup -1}) (p<0.001). Released MCP-1 in AM supernatants was enhanced in patients with CWP (median 83 pg x mL{sup -1}) but compared to controls (median 41 pg x mL{sup -1}) this level did not reach significance. Although significantly increased, AM counts in BALF from patients with CWP did not correlate with MCP-1 levels. MCP-1 levels in BALF correlated with MCP-1 levels in AM supernatants ({rho}=0.47; p<0.02). Data demonstrate that: 1) patients with coal worker`s pneumoconiosis have a marked pulmonary overproduction of monocyte chemoattractant protein-1; and 2) in addition to alveolar macrophages, fibroblasts (probably myofibroblasts) and hyperplastic type II pneumocytes may also be responsible for this increased level of monocyte chemoattractant protein-1 in coal worker`s pneumoconiosis. (EG) 29 refs.

  9. 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

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

    Science.gov (United States)

    Yong, Kok-Khun; Chang, Jer-Hwa; Chien, Ming-Hsien; Tsao, Shih-Ming; Yu, Ming-Chih; Bai, Kuan-Jen; Tsao, Thomas Chang-Yao; Yang, Shun-Fa

    2016-01-29

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

  11. 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.

  12. Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity.

    Science.gov (United States)

    Kano, Fumiya; Matsubara, Kohki; Ueda, Minoru; Hibi, Hideharu; Yamamoto, Akihito

    2017-03-01

    Peripheral nerves (PNs) exhibit remarkable self-repairing reparative activity after a simple crush or cut injury. However, the neuronal transection involving a nerve gap overwhelms their repairing activity and causes persistent paralysis. Here, we show that an implantation of the serum-free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED-CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. In contrast, SHED-CM specifically depleted of a set of anti-inflammatory M2 macrophage inducers, monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9) lost the ability to restore neurological function in this model. Notably, the combination of MCP-1 and sSiglec-9 induced the polarization of M2 macrophages in vitro, resulting in the expression of multiple trophic factors that enhanced proliferation, migration, and differentiation of Schwann cells, blood vessel formation, and nerve fiber extension. Furthermore, the implantation of a collagen graft containing MCP-1/sSiglec-9 into the nerve gap induced anti-inflammatory M2 macrophage polarization, generated a Schwann-cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. The specific elimination of M2 macrophages by Mannosylated-Clodrosome suppressed the MCP-1/sSiglec-9-mediated neurological recovery. Taken together, our data suggest that MCP-1/sSiglec-9 regenerates PNs by inducing tissue-repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries. Stem Cells 2017;35:641-653.

  13. MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma

    Science.gov (United States)

    Wiesner, Philipp; Tafelmeier, Maria; Chittka, Dominik; Choi, Soo-Ho; Zhang, Li; Byun, Young Sup; Almazan, Felicidad; Yang, Xiaohong; Iqbal, Navaid; Chowdhury, Punam; Maisel, Alan; Witztum, Joseph L.; Handel, Tracy M.; Tsimikas, Sotirios; Miller, Yury I.

    2013-01-01

    Lipoprotein oxidation plays an important role in pathogenesis of atherosclerosis. Oxidized low density lipoprotein (OxLDL) induces profound inflammatory responses in vascular cells, such as production of monocyte chemoattractant protein-1 (MCP-1) [chemokine (C-C motif) ligand 2], a key chemokine in the initiation and progression of vascular inflammation. Here we demonstrate that OxLDL also binds MCP-1 and that the OxLDL-bound MCP-1 retains its ability to recruit monocytes. A human MCP-1 mutant in which basic amino acids Arg-18 and Lys-19 were replaced with Ala did not bind to OxLDL. The MCP-1 binding to OxLDL was inhibited by the monoclonal antibody E06, which binds oxidized phospholipids (OxPLs) in OxLDL. Because OxPLs are carried by lipoprotein(a) [Lp(a)] in human plasma, we tested to determine whether Lp(a) binds MCP-1. Recombinant wild-type but not mutant MCP-1 added to human plasma bound to Lp(a), and its binding was inhibited by E06. Lp(a) captured from human plasma contained MCP-1 and the Lp(a)-associated endogenous MCP-1 induced monocyte migration. These results demonstrate that OxLDL and Lp(a) bind MCP-1 in vitro and in vivo and that OxPLs are major determinants of the MCP-1 binding. The association of MCP-1 with OxLDL and Lp(a) may play a role in modulating monocyte trafficking during atherogenesis. PMID:23667177

  14. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Background. The inflammatory markers YKL-40 and monocyte chemoattractant protein-1 (MCP-1) are elevated in morbidly obese patients and decline after weight loss. The objective of our study was to investigate the possible changes of YKL-40 and MCP-1, in both the fasting and the postprandial states...

  16. Effects of TNF-α on the expression of monocyte chemoattractant protein-1 and the corresponding signal transduction pathway in dental follicle cells

    Directory of Open Access Journals (Sweden)

    Ying-chun BI

    2011-02-01

    Full Text Available Objective To study the effect of different concentration of tumor necrosis factor-α(TNF-α on the expression of monocyte chemoattractant protein-1(MCP-1 and the corresponding signal transduction pathway in human dental follicle cells.Methods The 5th passage of human dental follicle cells were co-incubated with 0(control group,5,10,25,50 and 100 ng/ml TNF-α,respectively,for 6 hours.The contents of MCP-1 in the supernatant were measured by using sandwich ELISA,and the expression of MCP-1 mRNA was determined by reverses transcription polymerase chain reaction(RT-PCR.Furthermore,to determine the corresponding signal transduction pathway,the 5th passage of human dental follicle cells were incubated with 25 μmol/L SB203580 to inhibit p38 mitogen-activated protein kinase(p38MARK,with 50 μmol/L PD98059 to inhibit extracellular signal-regulated kinases(ERK,and with 15 μmol/L SP600125 to inhibit c-Jun N-terminal kinases(JNK for 30min,then incubated with TNF-α(10ng/ml for 6h.MCP-1 mRNA was detected by RT-PCR.Results The results of ELISA revealed that 10-100 ng/ml of TNF-α enhanced MCP-1 secretion(P < 0.05 compared to that in human dental follicle cells without TNF-α treatment.Cells treated with 10-50 ng/ml of TNF-α showed a significant increase of MCP-1 mRNA expression(P < 0.05,and the action was inhibited by SP600125,which was the special inhibitor of c-Jun N-terminal kinase(JNK.Conclusion TNF-α may enhance MCP-1 gene expression and secretion in human dental follicle cells,and the activation of JNK signal transduction pathway is required in this process.

  17. Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin ανβ3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells.

    Science.gov (United States)

    You, Jian-Jang; Yang, Chang-Hao; Yang, Chung-May; Chen, Muh-Shy

    2014-01-01

    Diabetes causes a number of metabolic and physiological abnormalities in the retina. Many of the molecular and physiological abnormalities that develop during diabetic retinopathy are due to inflammation. Monocyte chemoattractant protein-1 (MCP-1) is an important factor involved in diabetic retinopathy. In a previous study, we found that cysteine-rich 61 (Cyr61), an important angiogenic factor, also plays an important role in diabetic retinopathy. In addition to the direct effects of Cyr61, we observed that Cyr61 can induce the expression of MCP-1. However, the mechanism through which this occurs is not completely understood in chorioretinal vascular endothelial cells. We therefore investigated the effects of Cyr61 on MCP-1 expression in this cell type. Cyr61 stimulated the expression of MCP-1 at the mRNA, protein, and secreted protein levels in a dose-dependent and time-dependent manner. Both total MCP-1 levels and secreted MCP-1 levels were attenuated during the response to Cyr61 stimulation by pretreatment with integrin ανβ3-blocking antibodies, a FAK inhibitor (PF573228), a PI3K inhibitor (LY294002), and an Akt inhibitor (A6730). Electrophoretic mobility shift assays revealed that the above inhibitors suppressed the activation of NF-κB. Additionally, deletion of the NF-κB-binding element in the MCP-1 gene promoter led to a decrease in expression in luciferase reporter assays. These results show that the induction of MCP-1 by Cyr61 is mediated through the activation of the integrin ανβ3, FAK, PI3K/Akt, and IKK/NF-κB pathways in chorioretinal vascular endothelial cells.

  18. 单核细胞趋化蛋白在视网膜疾病中的表达和作用%The status and progress of studies on monocyte chemoattractant protein-1 in retinal diseases

    Institute of Scientific and Technical Information of China (English)

    王蕾; 张晓敏; 李筱荣

    2016-01-01

    单核细胞趋化蛋白(MCP-1)属于趋化因子CC亚家族,眼部主要表达于视网膜色素上皮(RPE)细胞、光感受器细胞和小胶质细胞.生理状态下适量分泌MCP-1有助于维持RPE细胞和胶质细胞的形态,保证视网膜发挥正常功能.病理状态下RPE细胞、光感受器细胞和小胶质细胞中MCP-1表达明显上升,募集单核-巨噬细胞向炎症部位迁移,促进小胶质细胞活化,在损伤部位吞噬细胞碎片.在视网膜脱离、糖尿病视网膜病变、后部葡萄膜炎和老年性黄斑变性患者眼内液及动物模型的视网膜中,均发现有MCP-1过度表达,且其表达程度与视网膜炎症严重程度密切相关.因此,MCP-1被认为是体现视网膜炎症程度最为客观的指标之一,可作为判断视网膜疾病活动性指标并有望成为视网膜疾病治疗的新靶点.%Monocyte chemoattractant protein-1 (MCP-1) is a cytokine which belongs to the CC chemokine family.Retinal pigment epithelium (RPE) cells,photoreceptors and microglial cells in the retina can secrete MCP-1.Physiological level of MCP-1 is important for preserving morphology of RPE and glial cells,as well as retinal function and gross morphology.MCP-1 is likely released from Müller glia and the RPE cells when retina under stress,and attracts microglia/macrophages to the sites of retinal damage,activates the microglia to ingest cell debris.MCP-1 has been found upregulated in the intraocular fluid of retina in patients and animal models with retinal detachment,posterior uveitis and age-related macular degeneration.The expression of MCP-1 may be response to retinal inflammation.Therefore,it is tempting to speculate that pharmacological targeting of MCP-1 may be a safe and viable strategy in treatment of retinal disease.

  19. Study on MCP-1 related to inflammation induced by biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Ding Tingting [Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University/Shanghai Biomaterials Research and Testing Center, Shanghai 200023 (China); Sun Jiao [Shanghai Key Laboratory of Stomatology, Shanghai 200023 (China); Zhang Ping, E-mail: jiaosun59@yahoo.co [School of Life Science, East China Normal University, Shanghai 200062 (China)

    2009-06-15

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

  20. 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

  1. 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

  2. Intrathecal administration of low-dose nociceptin/orphanin FQ induces allodynia via c-Jun N-terminal kinase and monocyte chemoattractant protein-1.

    Science.gov (United States)

    Kawabata, Kenta; Nishimura, Isamu; Fujiwara, Takeshi; Terauchi, Shoko; Minami, Toshiaki; Ito, Seiji; Okuda-Ashitaka, Emiko

    2016-06-01

    Pathological chronic pain, which is frequently associated with prolonged tissue damage, inflammation, tumour invasion, and neurodegenerative diseases, gives rise to hyperalgesia and allodynia. We previously reported that intrathecal administration of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like receptor, in the femtomole range induces touch-evoked allodynia. N/OFQ has been implicated in multiple signalling pathways, such as inhibition of cAMP production and Ca(2+) channels, or activation of K(+) channels and mitogen-activated protein kinase, although the signalling pathways of N/OFQ-induced allodynia remain unclear. To address these issues, we developed an ex vivo mitogen-activated protein kinase assay by using intact slices of mouse spinal cord. N/OFQ markedly increased the phosphorylation of c-Jun N-terminal kinase (JNK) in the superficial dorsal horn of the spinal cord. The N/OFQ-stimulated JNK phosphorylation was significantly inhibited by pertussis toxin, the phospholipase C inhibitor U73122, and the inositol trisphosphate receptor antagonist Xestospongin C. Intrathecal administration of the JNK inhibitor SP600125 inhibited N/OFQ-evoked allodynia. The N/OFQ-induced increase in JNK phosphorylation was observed in astrocytes that expressed glial fibrillary acidic protein. N/OFQ also induced monocyte chemoattractant protein-1 (MCP-1) release via the JNK pathway, and N/OFQ-induced JNK phosphorylation was observed in MCP-1-immunoreactive astrocytes. Intrathecal administration of the MCP-1 receptor antagonist RS504393 inhibited N/OFQ-evoked allodynia. These results suggest that, in the spinal dorsal horn, N/OFQ induces allodynia through activation of JNK via the phospholipase C-inositol trisphosphate pathway, which is coupled to pertussis toxin-sensitive G-protein, and following the release of MCP-1 from astrocytes.

  3. Systematic meta-analysis of the association between monocyte chemoattractant protein-1 -2518A/G polymorphism and risk of tuberculosis.

    Science.gov (United States)

    Tian, G; Li, X; Li, H; Wang, X; Cheng, B

    2015-05-25

    Numerous studies have been conducted to investigate the association between 2518A/G polymorphisms in the monocyte chemoattractant protein-1 (MCP-1) gene and the risk of tuberculosis (TB). However, the results have been inconsistent and inconclusive. In this study, we performed a meta-analysis to evaluate the association between the MCP-1 -2518A/G polymorphism and TB. The National Center for Biotechnology Information Global Cross Database and Google Scholar database were searched for relative studies. A total of 22 case-control studies that included 7332 cases and 8004 controls for the -2518A/G single-nucleotide polymorphism were identified. The results revealed an association between the MCP-1 -2518A/G polymorphism and human TB susceptibility under a recessive model (GG vs GA+AA), dominant model (GG+GA vs AA), and homozygote comparison (GG vs AA) model for the entire database. For the dominant model, the overall odds ratio was 1.34 (95% confidence interval, 1.10-1.64, P = 0.004). For the recessive model, the overall odds ratio was 1.46 (95% confidence interval, 1.15- 1.86, P = 0.002). For the homozygote comparison, the overall odds ratio was 1.67 (95% confidence interval, 1.20-2.32, P = 0.002). In the subgroup analysis by ethnicity, significantly elevated risks were found in Asians and Americans, but not in Africans and Europeans. We also used the Begg and Egger tests to examine publication bias, and no major publication bias was detected. Our results indicate that there is an association between the MCP-1 -2518A/G polymorphism and human TB susceptibility.

  4. 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.

  5. Monocyte chemoattractant protein-1 in spinal tuberculosis: -362G/C genetic variant and protein levels in Chinese patients.

    Science.gov (United States)

    Guo, Chaofeng; Zhang, Hongqi; Gao, Qile; He, Dan; Tang, Mingxing; Liu, Shaohua; Deng, Ang; Wang, Yuxiang; Lu, Shijin; Li, Jingsong; Yin, Xinhua; Guo, Qiang

    2014-01-01

    The objective of the study is to explore the possible association of the monocyte chemoattractant protein (MCP)-1-362G/C genetic polymorphism and plasma levels of MCP-1 in patients with spinal tuberculosis (TB). The MCP-1-362G/C (rs2857656) polymorphism and blood levels of MCP-1 in patients with spinal TB and healthy subjects were evaluated and compared. Three hundred thirty-two patients and 336 healthy subjects were genotyped using polymerase chain reaction and Sanger DNA sequencing technology. MCP-1 plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. When comparisons were made between patients and controls, the frequency of the MCP-1-362*C minor allele (55.4% versus 47.5%, P = 0.004, odds ratio [OR] = 1.376, 95% confidence interval [CI]: 1.109-1.706) and the carriers of the MCP-1-362*C allele (80.7% versus 71.4%, P = 0.005, OR = 1. 657, 95% CI: 1.167-2.403) were over-represented in patients. The mean MCP-1 plasma level in spinal TB patients was significantly higher than in controls (154.44 ± 68.81 pg/mL versus 36.69 ± 21.71 pg/mL, t = -5.85, P < 0.001). The patients with the CC genotype had the highest MCP-1 level (150.63 ± 73.89 pg/mL), followed by those with the GC genotype (108.63 ± 52.09 pg/mL, t = 2.351, P = 0.022) and GG (91.29 ± 54.31 pg/mL, t = 3.091, P = 0.003) homozygotes. We report the association of the -362G/C genetic polymorphism and increased plasma levels of MCP-1 in patients with spinal TB and nominate the -362*C minor allele as a risk factor for spinal TB in the Chinese population.

  6. 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.

  7. 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.

  8. 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.

  9. Relationship between dietary folate intake and plasma monocyte chemoattractant protein-1 and interleukin-8 in heart failure patients.

    Science.gov (United States)

    Chung, Hye Kyung; Kim, Oh Yoen; Lee, Hyeran; Do, Hyun Joo; Kim, Young Soon; Oh, Jaewon; Kang, Seok-Min; Shin, Min-Jeong

    2011-07-01

    This study aimed to examine the association of dietary vitamin intakes with plasma pro-inflammatory cytokine levels in Korean heart failure patients. Stable outpatients with heart failure were recruited and finally 91 patients were included. Dietary intakes were estimated by a developed semi-quantitative food frequency questionnaire. The simultaneous measurement of 17 cytokines was performed along with analysis of plasma C-reactive protein. Plasma C-reactive protein levels significantly correlated with dietary intakes of vitamin C (r = -0.30, pmonocyte chemoattractant protein-1 significantly correlated with dietary folate intake (r = -0.31, pmonocyte chemoattractant protein-1 (pmonocyte chemoattractant protein-1 and interleukin-8 which indicates dietary folate may have a potentially beneficial role in the prevention and treatment of heart failure.

  10. 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.

  11. MCP-1 Stimulates MMP-9 Expression via ERK 1/2 and p38 MAPK Signaling Pathways in Human Aortic Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Ci-Qiu Yang

    2014-07-01

    Full Text Available Objective: We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1 in the formation and development of human abdominal aortic aneurysm (AAA. Methods: We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs with human recombinant MCP-1. Results: MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9 expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs extracellular signal regulated kinase (ERK, c-Jun amino terminal kinase (JNK1/2 and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway and SB203580 (inhibitor of the p38 MAPK pathway, but not SP600125 (inhibitor of the JNK1/2 pathway. Conclusion: These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.

  12. Effect of acidosis on IL-8 and MCP-1 during hypoxia and reoxygenation in human NT2-N neurons.

    Science.gov (United States)

    Frøyland, Elisabeth; Pedersen, Elena Didenko; Kvissel, Anne-Katrine; Almaas, Runar; Pharo, Anne; Skålhegg, Bjørn Steen; Mollnes, Tom Eirik; Rootwelt, Terje

    2006-10-03

    Inflammation probably plays a significant role in perinatal brain injury. To study the contribution of locally produced cytokines, the effect on cell death of addition of IL-8 and MCP-1 or antibodies to these, and the impact of acidosis, human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and reoxygenated for 21 h. After 3 h of hypoxia with neutral medium, IL-8 was significantly increased compared to controls (150 (100-250)% vs. 100 (85-115)%, p=0.023). After 21 h of neutral reoxygenation, both IL-8 (380 (110-710)% vs. 150 (85-260)%, p=0.041) and monocyte chemoattractant protein-1 (MCP-1) (650 (440-2000)% vs. 310 (230-340)%, p=0.007) were significantly increased compared to controls. After 3 h of hypoxia, both IL-8 (p=0.002) and MCP-1 (p=0.008) were significantly lower in cells with acidotic compared with cells with neutral medium. Acidosis during reoxygenation, however, significantly increased IL-8 release, whereas MCP-1 release was diminished. Similar effects of acidosis were seen in normoxic controls. The cells also secreted RANTES and IP-10, but not 8 other cytokines tested. We found no effect on cell death, measured by MTT assay, of addition of IL-8, MCP-1 or antibodies to these. We conclude that human NT2-N neurons release IL-8 and MCP-1 during 21 h of reoxygenation after 3 h of hypoxia. Acidosis led to a differential effect on IL-8 and MCP-1, with increased IL-8 and decreased MCP-1, both during reoxygenation and in normoxic controls. IL-8 and MCP-1 had no effect on cell death.

  13. Expression of monocyte chemoattractant protein and MCP-1 gene in urothelial carcinoma of renal pelvis and its clinical significance%单核细胞趋化蛋白在肾盂尿路上皮癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    白鑫; 高健刚; 侯四川; 孙小庆; 朱磊一

    2011-01-01

    Objective To investigate the monocyte chemoattractant protein (MCP-1) gene expression of urothelial carcinoma of renal pelvis and adjacent normal tissues and the correlation of the incidence and pathological grading of urothelial carcinoma of renal pelvis.Methods Twenty cases of patients with urothelial carcinoma of renal pelvis( 12 cases of male, 8 cases of female) were taken the blood, carcinoma tissues and adjacent normal tissues.Thirty cases of non-cancer patients( 18 cases of male, 12 cases of female) as control group were taken blood samples.Expression of MCP-1 in plasma were detected by ELISA method quantitative determination,and the expression of MCP-1 in urothelial carcinoma of renal pelvis and adjacent normal tissues were investigated by immunohistochemical method.Real-time quantitative PCR was used to detect the expression of MCP-1 RNA.Results MCP-1 in plasma of urothelial carcinoma patients of renal pelvis was(173.4 ±82.1)pg/ml, higher than that of non-tumor group (91.8 ±34.6) pg/ml (P <0.05).Expression of MCP-1 in high-grade urothelial carcinoma of renal pelvis was(254.1 ± 125.8)pg/ml,while in low-grade urothelial carcinoma of renal pelvis was( 151.3 ± 79.5 ) pg/ml.Immunohistochemistry showed that MCP-1 positive rate in urothelial carcinoma of renal pelvis was 90.0% ( 18/20), and in adjacent normal tissues was 65.0% ( 13/20), with significant differences ( P < 0.01 ).Positive expression rate of MCP-1 in high-grade urothelial carcinoma of renal pelvis was 100.0% (4/4) , while in low-grade urothelial carcinoma of renal pelvis was 87.5% ( 14/16 ).Total RNA and mRNA levels of MCP-1 in the urothelial carcinoma of renal pelvis were statistically significant different compared with adjacent normal tissues group (P < 0.05).Conclusion The upregulation of MCP-1 gene expression is likely to play an important role in the incidence and metastasis of the urothelial carcinoma of renal pelvis.%目的 探讨肾盂尿路上皮癌组织单核细胞趋化蛋白(MCP

  14. Role of macrophage chemoattractant protein-1 in acute inflammation after lung contusion.

    Science.gov (United States)

    Suresh, Madathilparambil V; Yu, Bi; Machado-Aranda, David; Bender, Matthew D; Ochoa-Frongia, Laura; Helinski, Jadwiga D; Davidson, Bruce A; Knight, Paul R; Hogaboam, Cory M; Moore, Bethany B; Raghavendran, Krishnan

    2012-06-01

    Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2(-/-)) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2(-/-) mice when compared with the wild-type (WT) mice. We also found increased release of IL-1β, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2(-/-) mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2(-/-) mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.

  15. Hydrogen sulfide suppresses oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κB (NF-κB) pathway.

    Science.gov (United States)

    Du, Junbao; Huang, Yaqian; Yan, Hui; Zhang, Qiaoli; Zhao, Manman; Zhu, Mingzhu; Liu, Jia; Chen, Stella X; Bu, Dingfang; Tang, Chaoshu; Jin, Hongfang

    2014-04-01

    This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-β-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation.

  16. 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.

  17. Adipocyte progenitor cells initiate monocyte chemoattractant protein-1-mediated macrophage accumulation in visceral adipose tissue

    Directory of Open Access Journals (Sweden)

    Jennifer L. Kaplan

    2015-11-01

    Conclusions: This study provides the first in vivo evidence, to our knowledge, that committed AdPCs in VAT are the initial source of obesity-induced MCP-1 and identifies the helix-loop-helix transcription factor Id3 as a critical regulator of p21Cip1 expression, AdPC proliferation, MCP-1 expression and M1 macrophage accumulation in VAT. Inhibition of Id3 and AdPC expansion, as well as CD44 expression in human AdPCs, may serve as unique therapeutic targets for the regulation of adipose tissue inflammation.

  18. 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)....

  19. Increasing body condition score is positively associated interleukin-6 and monocyte chemoattractant protein-1 in Labrador retrievers.

    Science.gov (United States)

    Frank, Lauren; Mann, Sabine; Levine, Corri B; Cummings, Bethany P; Wakshlag, Joseph J

    2015-10-15

    The accumulation of excess body fat is a growing problem in dogs as well as people. Contrary to prior understanding of adipose tissue, fat is now considered to be an active endocrine organ that promotes a chronic low-grade inflammatory state often characterized by an increase in pro-inflammatory cytokines and chemokines. These have been implicated in several obesity-related disorders such as insulin resistance, cardiovascular disease, and neoplasia. The purpose of this study was to characterize fasting plasma cytokine concentrations in ninety-two healthy client-owned Labrador retriever dogs of various ages and body condition scores. The dogs were grouped according to body condition score (BCS) into three categories, lean, overweight and obese. The following cytokines and chemokines were evaluated; tumor necrosis factor-alpha, interleukin-2, interleukin-6, interleukin-8, and monocyte chemotactic protein-1 (TNF-α, IL-2, IL-6, IL-8, MCP-1). Our results indicated that fasting plasma IL-6 and MCP-1 concentrations are associated with increasing BCS. This data suggest that certain markers of inflammation increase with increasing body condition score, and that dogs, similar to humans, may be fostering a chronic inflammatory state due to obesity.

  20. High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis lung carcinoma

    Science.gov (United States)

    Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesit...

  1. Significance of Expression of Monocyte Chemoattractant Protein-1 in Renal Biopsy Tissue from Immunoglobulin A Nephropathy%IgA肾病患者肾组织单核细胞趋化蛋白-1表达的意义

    Institute of Scientific and Technical Information of China (English)

    杨晓庆; 高进

    2011-01-01

    目的 探讨原发性IgA肾病(IgAN)患者肾组织单核细胞趋化蛋白-1(MCP-1)的表达变化.方法 选择经皮肾组织穿刺活检确诊为IgAN的患者40例.根据肾脏病理Lee氏分级(Ⅰ~Ⅴ级)将纳入研究的患者分为2组:A组20例,病理分级为Ⅰ~Ⅲ级;B组20例,病理分级为Ⅳ~Ⅴ级.对照组20例标本选取手术切除的肾肿瘤、肾囊肿患者远离病变组织的正常肾组织.同时将肾组织的肾小管和肾间质按照Katafuchi标准分为无间质病变组21例,轻度间质病变组8例,中度间质病变组19例和重度间质病变组12例.均采用免疫组织化学方法测定其肾组织中MCP-1的表达(以灰度值反映),观察其肾组织切片的染色强度及染色透光度,灰度值大则MCP-1表达少,反之则表达多.结果 根据肾脏病理Lee分级分组,各组灰度值比较:B组灰度值(68.08±2.37)与A组灰度值(74.50±3.27)比较、B组与对照组灰度值(81.98±3.21)比较、A 组与对照组比较,差异均有统计学意义(Pa<0.01);根据Katafuchi标准分组,无间质病变组、轻度间质病变组、中度间质病变组及重度间质病变组灰度值分别为82.03±3.13、76.44±2.01、71.49±1.69、66.54±1.23,各组比较差异均有统计学意义(Pa<0.01).结论 MCP-1可反映原发性IgAN患者肾组织的病理损害程度,且表达水平与肾组织损害程度有关.%objective To explore the expression of monocyte chemoattractant protein - 1( MCP - 1) in renal biopsy tissue from IgA nephropathy (IgAN) patients. Methods Forty patients were diagnosed as IgAN by renal biopsy, and they were divided into 2 groups according to Lee classification ( Ⅰ - Ⅴ grade) :group A included 20 cases( Lee Ⅰ - Ⅲ grade) and group B included the other 20 cases( Lee Ⅳ - Ⅴgrade). The control group included 20 patients diagnosed as having normal kidney tissue by renal biopsy, whose kidney tissue came from patients whose renal tumors and renal cysts were removed. In the

  2. 3T3-L1 preadipocytes exhibit heightened monocyte-chemoattractant protein-1 response to acute fatty acid exposure.

    Science.gov (United States)

    Dordevic, Aimee L; Konstantopoulos, Nicky; Cameron-Smith, David

    2014-01-01

    Preadipocytes contribute to the inflammatory responses within adipose tissue. Whilst fatty acids are known to elicit an inflammatory response within adipose tissue, the relative contribution of preadipocytes and mature adipocytes to this is yet to be determined. We aimed to examine the actions of common dietary fatty acids on the acute inflammatory and adipokine response in 3T3-L1 preadipocytes and differentiated mature adipocytes. Gene expression levels of key adipokines in 3T3-L1 preadipocytes and adipocytes were determined following incubation with palmitic acid, myristic acid or oleic acid and positive inflammatory control, lipopolysaccharide for 2 and 4 h. Inflammatory kinase signalling was assessed by analysis of nuclear factor-κB, p38-mitogen-activated protein kinase and c-jun amino-terminal kinase phosphorylation. Under basal conditions, intracellular monocyte chemoattractant protein-1 and interleukin-6 gene expression levels were increased in preadipocytes, whereas mature adipocytes expressed increased gene expression levels of leptin and adiponectin. Fatty acid exposure at 2 and 4 h increased both monocyte chemoattractant protein-1 and interleukin-6 gene expression levels in preadipocytes to greater levels than in mature adipocytes. There was an accompanying increase of inhibitor of κB-α degradation and nuclear factor-κB (p65) (Ser536) phosphorylation with fatty acid exposure in the preadipocytes only. The current study points to preadipocytes rather than the adipocytes as the contributors to both immune cell recruitment and inflammatory adipokine secretion with acute increases in fatty acids.

  3. Changes of levels of serum Monocyte chemoattractant protein-1 and Cystatin C in patients with obstructive sleep apnea-hypopnea syndrome complicated by type 2 diabetes%阻塞性睡眠呼吸暂停低通气综合征合并2型糖尿病患者血清单核细胞趋化蛋白1、胱抑素C水平的变化

    Institute of Scientific and Technical Information of China (English)

    杨柳婷; 任寿安

    2012-01-01

    目的 观察阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)合并2型糖尿病(T2DM)患者血清单核细胞趋化蛋白1(MCP-1)、胱抑素C(Cys C)的变化.方法 检测OSAHS合并T2DM患者、单纯OSAHS患者、单纯T2DM患者、正常对照者及20例中、重度OSAHS合并T2DM患者经鼻持续气道止压通气(nCPAP)治疗1个月后血清MCP-1、Cys C的水平.结果 OSAHS合并T2DM患者血清MCP-1、Cys C水平显著升高,且与反映睡眠呼吸暂停病情严重程度的指标有相关性.OSAHS合并T2DM患者nCPAP治疗后,血清MCP-1、Cys C水平明显下降,与治疗前相比差异有统计学意义.结论 MCP-1、Cys C可能通过缺氧、氧化应激、慢性炎症等途径参与OSAHS及其合并T2DM的发生.%Objective To explore the changes of levels of serum Monocyte chemoattractant protein-1 (MCP-1) and Cystatin C (Cys C) in patients with obstructive sleep apnea-bypopnea syndrome (OSAHS)complicated by type 2 diabetes.Methods The levels of serum MCP-1 and Cys C were measured in 25 patients with OSAHS complicated by type 2 diabetes,25 patients with OSAHS,25 patients with type 2 diabetes,25 healthy subjects,20 patients with OSAHS complicated by type 2 diabetes who accepted nCPAP treatment for 1 month.Results The levels of serum MCP-1 and Cys C were significantly higher in patients with OSAHS complicated by type 2 diabetes,and were corrrlated significantly with the index of polysomnography which reflect the severity of obstructive sleep apnea.After the nCPAP treatment for 1 month,the levels of serum MCP-1 and Cys C were significantly lower than before.Conclusions MCP-1 and Cys C may through hypoxia,oxidative stress,chronic inflammation involved in the development of OSAHS and OSAHS complicated by type 2 diabetes.

  4. Biocompatibility of heparin-grafted hemodialysis membranes: impact on monocyte chemoattractant protein-1 circulating level and oxidative status.

    Science.gov (United States)

    Morena, Marion; Jaussent, Isabelle; Chalabi, Lotfi; Bargnoux, Anne-Sophie; Dupuy, Anne-Marie; Badiou, Stéphanie; Rakic, Claire; Thomas, Michel; Canaud, Bernard; Cristol, Jean-Paul; Michel, Françoise

    2010-10-01

    This prospective observational study aimed at evaluating efficacy and biocompatibility performances of the new heparin-coated Evodial dialyzers with/without systemic heparin reduction. After a 4-week wash-out period with reference polysulfone F70S dialyzers, 6 hemodialysis patients were sequentially dialyzed with Evodial, F70S, and Evodial dialyzers using 30% heparin reduction, each period of treatment was 4 weeks. Removal rates (RR) (urea, creatinine, and β2-microglobulin), dialysis dose, and instantaneous clearances (urea and creatinine) were measured as well as inflammatory (C-reactive protein, fibrinogen, interleukin 6, tumor necrosis factor α, and monocyte chemoattractant protein-1) and oxidative stress (OS) (superoxide anion, homocysteine, and isoprostanes) parameters at the end of each study period. Patients treated with Evodial or F70S dialyzers for 4 weeks presented comparable dialysis efficacy parameters including urea and creatinine RR, dialysis dose and instantaneous clearances. By contrast, a significantly lower but reasonably good β2-microglobulin RR was achieved with Evodial dialyzers. Regarding biocompatibility, no significant difference was observed with inflammation and OS except for postdialysis monocyte chemoattractant protein-1 which significantly decreased with Evodial dialyzers. Thirty percent heparinization reduction with Evodial dialyzers did not induce any change in inflammation but led to an improvement in OS as demonstrated by a decrease in postdialysis superoxide production and predialysis homocysteine and isoprostane. This bioactive dialyzer together with heparin dose reduction represents a good trade-off between efficacy and biocompatibility performance (improvement in OS with a weak decrease in efficacy) and its use is encouraging for hemodialysis patients not only in reducing OS but also in improving patient comorbid conditions due to lesser heparin side effects.

  5. 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...... of adiposity in PCOS patients, but were unchanged during insulin sensitizing treatment with pioglitazone. Our data suggests a fat mass independent association between testosterone and MIF levels in PCOS and the effect of anti-androgen treatment on chemokine levels needs to be examined....

  6. Profiling of differentially expressed chemotactic-related genes in MCP-1 treated macrophage cell line using human cDNA arrays

    Institute of Scientific and Technical Information of China (English)

    Guang-Xing Bian; Hong Miao; Lei Qiu; Dong-Mei Cao; Bao-Yu Guo

    2005-01-01

    AIM: To study the global gene expression of chemotactic genes in macrophage line U937 treated with human monocyte chemoattractant protein-1 (MCP-1) through the use of ExpreeChipTMHO2 cDNA array.METHODS: Total RNA was extracted from MCP-1 treated macrophage line U937 and normal U937 cells, reversely transcribed to cDNA, and then screened in parallel with HO2 human cDNA array chip. The scanned result was additionally validated using RT-PCR.RESULTS: The result of cDNA array showed that one chemotactic-related gene was up-regulated more than two-fold (RANTES) and seven chemotactic-related genes were down-regulated more than two-fold (CCR1, CCR5,ccl16, GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2) in MCP-1 treated U937 cells at mRNA level.RT-PCR analysis of four of these differentially expressed genes gave results consistent with cDNA array findings.CONCLUSION: MCP-1 could influence some chemokine and receptor expressions in macrophages in vitro. MCP-1mainly down-regulates the expression of chemotactic genes influencing neutrophilic granulocyte expression (GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2), and the mRNA level of CCR5, which plays a critical role in many disorders and illnesses.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2015-01-01

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

  9. 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.

  10. Rat macrophage inflammatory protein-1alpha, a CC chemokine, acts as a neutrophil chemoattractant in vitro and in vivo.

    Science.gov (United States)

    Takano, K; Al-Mokdad, M; Shibata, F; Tsuchiya, H; Nakagawa, H

    1999-10-01

    Recombinant rat macrophage inflammatory protein-1alpha (rMIP-1alpha) at a concentration of 3x10(-8) M had strong neutrophil chemotactic activity, though the potency of rMIP-1alpha was less than that of cytokine-induced neutrophil chemoattractant (CINC)-1 at lower concentrations. In addition, rMIP-1alpha induced neutrophil chemotaxis in vivo when rMIP-1alpha was injected into the preformed air-pouch on the back of rats. The adhesion of rMIP-1alpha-treated neutrophils to fibrinogen significantly increased, reaching a maximum adhesion at 10(-8) M. Stimulation of neutrophils with rMIP-1alpha induced a transient increase in intracellular free [Ca2+] dose-dependently. rMIP-1alpha still induced an increase in the intracellular [Ca2+] of rat neutrophils stimulated first with CINC-1, CINC-3 or C5a, suggesting that rat neutrophils have a specific receptor for rMIP-1alpha. Supporting these findings, an additive increase in chemotactic potency was found when both rMIP-1alpha and CINC-were added to the lower wells of Boyden chamber in vitro. In addition, high levels of rMIP-1alpha were detected in the inflammatory site of air-pouch/carrageenan-induced inflammation in rats. Our results suggest that rMIP-1alpha acts as a neutrophil chemoattractant and, together with CINCs, plays an important role in infiltration of neutrophils into inflammatory sites in rats.

  11. MCP-1 -2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients.

    Science.gov (United States)

    Ben-Selma, Walid; Harizi, Hedi; Boukadida, Jalel

    2011-11-01

    Monocyte chemoattractant protein-1 (MCP-1) plays crucial role in protective immunity against Mycobacterium tuberculosis (MT). In this study, we examined whether single nucleotide polymorphism (SNP) -2518 A/G (rs 1024611) of MCP-1 affect the susceptibility to active tuberculosis (TB) in Tunisian populations. Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1 -2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -2518 G allele and GG genotype (high MCP-1 producer) frequencies were significantly more elevated in active pulmonary TB group in comparison to control group [34 vs. 22%; P = 0.0007; 15 vs. 5%, P corrected for the number of genotypes (Pc) = 0.015; respectively]. Additionally, they were associated with increased risk development of this clinical form of TB [odds ratio (OR) = 1.83, 95% confidence intervals (CI) = 1.26-2.66; OR = 3.1, 95% CI = 1.28-7.76; respectively]. However, wild type allele -2518 A and AA genotype were over-represented in control group (78 and 62%) and seem to be protective factors against TB. Moreover, -2518 AA genotype was more frequent in control group and was associated with resistance against development of active pulmonary TB (OR = 0.56, 95% CI = 0.35-0.89, Pc = 0.03). Our findings confirm the key role of -2518 A/G SNP of MCP-1 and support its association with resistance/susceptibility to the development of active pulmonary TB in the Tunisian population.

  12. Secreted Ectodomain of SIGLEC-9 and MCP-1 Synergistically Improve Acute Liver Failure in Rats by Altering Macrophage Polarity

    Science.gov (United States)

    Ito, Takanori; Ishigami, Masatoshi; Matsushita, Yoshihiro; Hirata, Marina; Matsubara, Kohki; Ishikawa, Tetsuya; Hibi, Hideharu; Ueda, Minoru; Hirooka, Yoshiki; Goto, Hidemi; Yamamoto, Akihito

    2017-01-01

    Effective treatments for acute liver failure (ALF) are still lacking. We recently reported that a single intravenous administration of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) into the D-galactosamine (D-Gal)-induced rat ALF model improves the liver injury. However, the specific factors in SHED-CM that are responsible for resolving ALF remain unclear. Here we found that depleting SHED-CM of two anti-inflammatory M2 macrophage inducers—monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9)—abolished its ability to resolve rat ALF. Furthermore, treatment with MCP-1/sSiglec-9 alone dramatically improved the survival of ALF rats. This treatment induced anti-inflammatory M2, suppressed hepatocyte apoptosis, and promoted hepatocyte proliferation. Treatment with an M2-depletion reagent (mannosylated clodronate liposomes) suppressed the recovery. In addition, MCP-1 and sSiglec-9 synergistically promoted the M2 differentiation of bone marrow-derived macrophages via CCR2, accompanied by the production of multiple liver-regenerating factors. The conditioned medium from MCP-1/sSiglec-9-activated M2 macrophages, but not from interleukin-4-induced ones, suppressed the D-Gal- and LPS-induced apoptosis of primary hepatocytes and promoted their proliferation in vitro. The unique combination of MCP-1/sSiglec-9 ameliorates rat ALF by inhibiting hepatocellular apoptosis and promoting liver regeneration through the induction of anti-inflammatory/tissue-repairing M2 macrophages. PMID:28272428

  13. Complement 5a Enhances Hepatic Metastases of Colon Cancer via Monocyte Chemoattractant Protein-1-mediated Inflammatory Cell Infiltration.

    Science.gov (United States)

    Piao, Chunmei; Cai, Lun; Qiu, Shulan; Jia, Lixin; Song, Wenchao; Du, Jie

    2015-04-24

    Complement 5a (C5a), a potent immune mediator generated by complement activation, promotes tumor growth; however, its role in tumor metastasis remains unclear. We demonstrate that C5a contributes to tumor metastases by modulating tumor inflammation in hepatic metastases of colon cancer. Colon cancer cell lines generate C5a under serum-free conditions, and C5a levels increase over time in a murine syngeneic colon cancer hepatic metastasis model. Furthermore, in the absence of C5a receptor or upon pharmacological inhibition of C5a production with an anti-C5 monoclonal antibody, tumor metastasis is severely impaired. A lack of C5a receptor in colon cancer metastatic foci reduces the infiltration of macrophages, neutrophils, and dendritic cells, and the role for C5a receptor on these cells were further verified by bone marrow transplantation experiments. Moreover, C5a signaling increases the expression of the chemokine monocyte chemoattractant protein-1 and the anti-inflammatory molecules arginase-1, interleukin 10, and transforming growth factor β, but is inversely correlated with the expression of pro-inflammatory molecules, which suggests a mechanism for the role of C5a in the inflammatory microenvironment required for tumor metastasis. Our results indicate a new and potentially promising therapeutic application of complement C5a inhibitor for the treatment of malignant tumors.

  14. Role of the monocyte chemoattractant protein-1/C-C chemokine receptor 2 signaling pathway in transient receptor potential vanilloid type 1 ablation-induced renal injury in salt-sensitive hypertension.

    Science.gov (United States)

    Wang, Youping; Zhu, Mingjun; Xu, Hui; Cui, Lin; Liu, Weihong; Wang, Xiaoxiao; Shen, Si; Wang, Donna H

    2015-09-01

    Our recent studies indicate that the transient receptor potential vanilloid type 1 (TRPV1) channel may act as a potential regulator of monocyte/macrophage recruitment to reduce renal injury in salt-sensitive hypertension. This study tests the hypothesis that deletion of TRPV1 exaggerates salt-sensitive hypertension-induced renal injury due to enhanced inflammatory responses via monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2)-dependent pathways. Wild type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for four weeks with or without the selective CCR2 antagonist, RS504393. DOCA-salt treatment increased systolic blood pressure (SBP) to the same degree in both strains, but increased urinary excretion of albumin and 8-isoprostane and decreased creatinine clearance with greater magnitude in TRPV1(-/-) mice compared to WT mice. DOCA-salt treatment also caused renal glomerulosclerosis, tubulointerstitial injury, collagen deposition, monocyte/macrophage infiltration, proinflammatory cytokine and chemokine production, and NF-κB activation in greater degree in TRPV1(-/-) mice compared to WT mice. Blockade of the CCR2 with RS504393 (4 mg/kg/day) had no effect on SBP in DOCA-salt-treated WT or TRPV1(-/-) mice compared to their respective controls. However, treatment with RS504393 ameliorated renal dysfunction and morphological damage, and prevented the increase in monocyte/macrophage infiltration, cytokine/chemokine production, and NF-κB activity in both DOCA-salt hypertensive strains with a greater effect in DOCA-salt-treated TRPV1(-/-) mice compared to DOCA-salt-treated WT mice. No differences in CCR2 protein expression in kidney were found between DOCA-salt-treated WT and TRPV1(-/-) mice with or without RS504393 treatment. Our studies for the first time indicate that deletion of TRPV1 aggravated renal injury in salt-sensitive hypertension via enhancing MCP-1

  15. Unfractionated heparin suppresses lipopolysaccharide-induced monocyte chemoattractant protein-1 expression in human microvascular endothelial cells by blocking Krüppel-like factor 5 and nuclear factor-κB pathway.

    Science.gov (United States)

    Li, Xu; Li, Xin; Zheng, Zhen; Liu, Yina; Ma, Xiaochun

    2014-10-01

    Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), apart from anticoagulant activities, contain a variety of biological properties such as anti-inflammatory actions possibly affecting sepsis. Chemokines are vital for promoting the movement of circulating leukocytes to the site of infection and are involved in the pathogenesis of sepsis. The purpose of this study was to investigate the effects and potential mechanisms of UFH on lipopolysaccharide (LPS)-induced chemokine production in human pulmonary microvascular endothelial cells (HPMECs). HPMECs were pretreated with UFH (0.1 U/ml and 1 U/ml), 15 min prior to stimulation with LPS (10 μg/ml). Cells were cultured under various experimental conditions for 2 h and 6 h for analysis. UFH markedly decreased LPS-induced interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression in HPMECs. UFH also attenuated the secretion of these chemokines in culture supernatants. In addition, UFH blocked the chemotactic activities of LPS-stimulated HPMECs supernatants on monocytes migration as expected. UFH inhibited LPS-induced Krüppel-like factor 5 (KLF-5) mRNA and protein levels. Concurrently, UFH reduced nuclear factor (NF)-κB nuclear translocation. Importantly, transfection with siRNA targeting KLF-5 reduced NF-κB activation and chemokines expression. These results demonstrate that interfering with KLF-5 mediated NF-κB activation might contribute to the inhibitory effects of chemokines and monocytes migration by UFH in LPS-stimulated HPMECs.

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

    Directory of Open Access Journals (Sweden)

    Stine Brinkløv Thomsen

    2013-01-01

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

  17. 新疆地区狼疮肾炎患者尿液单核细胞趋化因子1水平及临床意义%The levels of urinary monocyte chemoattractant protein 1 and clinical significance in Xinj iang patients with lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    王彦焱; 赵春梅; 孟岩; 古丽仙·艾尔肯; 张新玉; 贾娜; 罗莉

    2013-01-01

    Objective To investigate urinary levels of monocyte chemoattractant protein 1(MCP-1)in Xin-jiang patients with lupus nephritis(LN),and analyze the relationship of MCP-1 with 24-hour proteinuria and 24-hour urinary albumin-to-creatinine ratio(UACR)in active lupus nephritis.Methods A cross-sec-tional cohort analysis was performed.Urinary MCP-1 levels of 33 active lupus nephritis patients and 35 in-active lupus nephritis were measured by ELISA.Results Urinary MCP-1 levels of active lupus nephritis patients were significantly higher than that of inactive lupus nephritis 468.0(205-1 990)pg/mg Cr vs 131.5 (69-734)pg/mg Cr,P=0.000).The mean age of active lupus nephritis was younger than that of inactive lupus nephritis(25.9 ± 3.7 vs 29.7 ± 3.5,P 0.05).Urinary MCP-1 was strongly correlated with 24-hour proteinuria and 24-hour UACR (r= 0.916,P=0.000 ;r=0.936,P=0.000).Conclusion Urinary MCP-1 concentration is a good biomarker for the j udgment of lupus nephritis flare and activity.Providing the Longitudinal stud-ies are warranted.%目的探讨狼疮肾炎(lupus nephritis,LN)患者尿液中单核细胞趋化因子1(monocyte chemoattractant protein 1MCP-1)的水平及其临床意义。方法采用横断面调查研究分析方法,ELISA法检测33例活动期狼疮肾炎患者和35例缓解期狼疮肾炎患者尿液中 MCP-1水平。结果活动期狼疮肾炎患者 MCP-1水平[468.0(205~1990)pg/mg Cr]明显高于缓解期狼疮肾炎患者[131.5(69~734)pg/mg Cr],差异有统计学意义(P =0.000)。活动期狼疮肾炎组患者年龄(25.9±3.7)岁,缓解期狼疮肾炎组患者年龄(29.7±3.5)岁,两组年龄有统计学差异(P <0.05),活动期狼疮肾炎组患者抗 ds-DNA抗体阳性率高于缓解期狼疮肾炎组患者(P <0.05)。两组在性别和族别上无统计学差异(P >0.05)。活动期狼疮肾炎组患者尿液中MCP-1水平与24 h尿蛋白定量及24 h

  18. Expressions and significances of chemokines MIP-1α,MIP-1β and MCP-1 in autoimmune thyroid disease%趋化因子MIP-1α、MIP-1β、MCP-1在自身免疫性甲状腺疾病中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    任欣会; 张会娟; 高慧祯

    2013-01-01

    Objective:To explore the role and development of chemokines macrophage inflammatory protein-1α (MIP-1α),macrophage inflammatory protein-1 β (MIP-1 β) and monocyte chemoattractant protein-1 (MCP-1) in adults with autoimmune thyroiditis.Methods:Totally 44 cases of Graves disease(GD),19 cases of hashimoto thyroiditis(HT),14 cases of thyroid adenoma,10 cases of multinodular goiter and 8 cases of surrounding normal tissues were collected.Expressions of chemokines MIP-1 α,MIP-1 β and MCP-1 were determined by immunehistochemical method.Results:Chemokines M IP-1α,MIP-1β and MCP-1 were located in the cytoplasm of the thyroid follicular epithelial cells.Expression levels and scores of chemokines MIP-1α,MIP-1 β and MCP-1 were significantly higher in GD and HT than in multinodular goiter and thyroid normal tissues.Conclusions:Chemokines MIP-1α,MIP-1 β and MCP-1 may participate in the development of the autoimmune thyroid diseases and may become new targets of monitoring and treatment of autoimmune thyroid diseases.%目的:探讨趋化因子巨噬细胞炎性蛋白-1α(macrophage inflammatory protein-1d,MIP-1α)、巨噬细胞炎性蛋白-1β(macrophage inflammatory protein-1β3,MIP-1β)和单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)在自身免疫性甲状腺疾病发生发展中的作用.方法:应用免疫组化方法观察MIP-1α、MIP-1β和MCP-1在44例Graves病(Graves disease,GD)和19例桥本甲状腺炎(hashimoto thyroiditis,HT)、14例甲状腺腺瘤、10例结节性甲状腺肿及8例正常甲状腺组织(取自良性腺瘤周围)中的表达情况.结果:MIP-1α、MIP-1β、MCP-1蛋白定位于甲状腺滤泡上皮细胞质,其在GD、TH组织中的表达阳性率及总评分显著高于结节性甲状腺肿及正常甲状腺组织.结论:MIP-1α、MIP-1β、MCP-1可能参与了自身免疫性甲状腺疾病的发生发展,有可能作为自身免疫性甲状腺疾病监测和治疗的新靶点.

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

    Science.gov (United States)

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

    2010-09-01

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

  20. Allelic frequency of the MCP-1 promoter -2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis.

    Science.gov (United States)

    Ozyürek, A Ruhi; Gürses, Dolunay; Ulger, Zülal; Levent, Ertürk; Bakiler, A Rahmi; Berdeli, Afig

    2007-04-01

    Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene -2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the -2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the -2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the -2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.

  1. Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in astrocytes

    OpenAIRE

    Mojsilovic-Petrovic Jelena; Callaghan Debbie; Cui Hong; Dean Clare; Stanimirovic Danica B; Zhang Wandong

    2007-01-01

    Abstract Background Neuroinflammation has been implicated in various brain pathologies characterized by hypoxia and ischemia. Astroglia play an important role in the initiation and propagation of hypoxia/ischemia-induced inflammation by secreting inflammatory chemokines that attract neutrophils and monocytes into the brain. However, triggers of chemokine up-regulation by hypoxia/ischemia in these cells are poorly understood. Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcriptional fact...

  2. Effects of Green tea polyphenols on monocyte chemoattractant protein-1 secretion in human vascular endothelial cells%茶多酚抑制人血管内皮细胞分泌单核细胞趋化蛋白1的研究

    Institute of Scientific and Technical Information of China (English)

    陈北冬; 沈恂; 齐若梅

    2012-01-01

    Objective To evaluate the protective effect of green tea polyphenols (GTP) on human vascular endothelial cells and its mechanism. Methods Human vascular endothelial cells were used as study model. Under baseline and ox-LDL stimulated condition, the cells were pretreated with different concentration of GTP and other antioxidants including Trolox and EGb761, and then monocyte chemoattractant protein-1 ( MCP-1) in cell culture medium was detected. Results GTP had no apparent toxic effects on endothelial cells within 24 h when the concentration less than 200 μmol/L Compared to untreated cells and other antioxidants treated cells, the expression of MCP-1 in GTP treated cells in both gene and protein level was significantly reduced in a dose-dependent manner ( P < 0. 05 ). Conclusions GTP has protective effect on human endothelial cells by inhibiting the expression and secretion of MCP-1.%目的 通过对人血管内皮细胞炎性分子单核细胞趋化蛋白1(MCP-1)的检测,评价茶多酚在血脂异常中对血管内皮的保护作用及其作用机制.方法 应用人血管内皮细胞为研究模型,在基础或者氧化型低密度脂蛋白刺激的条件下,给予不同剂量的茶多酚,并与其他抗氧化剂水溶性维生素E(Trolox)、银杏提取物(EGb761)相比较,检测不同时间点细胞培养基当中的MCP-1含量.结果 24h内浓度小于200 μmol/L的茶多酚对内皮细胞没有明显的毒性作用,并且可以剂量依赖性地抑制内皮MCP-1的分泌(均为P<0.05).与未处理组及其他抗氧化剂组相比,茶多酚处理组显著地降低了MCP-1的基因表达和蛋白分泌水平,并呈剂量依赖性,表现出较好的内皮保护及抗炎作用.结论 与其他抗氧化剂相比,茶多酚可以在脂质氧化的条件下更好地通过抑制炎性因子的表达和分泌来保护内皮细胞.

  3. Effect of Hydrogen Sulfide Inhibiting Monocyte Chemoattractant Protein -1 Secretion in Human Macrophages Stimulated by Oxidized Low Density Lipoprotein%硫化氢抑制氧化型低密度脂蛋白诱导的人巨噬细胞单核细胞趋化蛋白-1分泌的作用

    Institute of Scientific and Technical Information of China (English)

    张巧丽; 闫辉; 唐朝枢; 金红芳; 杜军保

    2012-01-01

    目的 研究气体信号分子硫化氢(H2S)对氧化型低密度脂蛋白(ox-LDL)诱导的人单核细胞白血病细胞(THP-1)来源的人巨噬细胞单核细胞趋化蛋白-1(MCP-1)分泌的影响.方法 将THP-1来源的人巨噬细胞分为4组:正常对照组、ox-LDL组、ox-LDL+ H2S 100组及ox-LDL+H2S 500组.正常对照组:细胞于基础培养基中培养48 h;ox-LDL组:在基础培养基中加入50mg ·L-1ox-LDL,培养48 h;ox-LDL+ H2S 100组在基础培养基中先加入100 μmol·L-1 NaHS,孵育30 min后再加入50 mg·L-1 ox-LDL,培养48 h;ox-LDL+H2S 500组在基础培养基中先加入500 μmol·L-1 NaHS,孵育30 min后再加入50 mg·L-1 ox-LDL,培养48h.用ELISA法检测细胞上清液中MCP-1水平.结果 与正常对照组[(34.58±6.77)μmol·L-1]比较,ox-LDL组[(66.27±7.29)μm0l·L-1]、ox-LDL+H2S100组[(49.45±3.08) μmol·L-1]及ox-LDL+H2S 500组[(46.64±5.47) μmol·L-1]细胞上清液中MCP-1水平均明显升高(Pa<0.05);与ox-LDL组比较,ox-LDL+ H2S 100组及ox-LDL+ H2S 500组细胞上清液中MCP-1水平均明显降低(Pa<0.05).ox-LDL+ H2S 100组细胞上清液中MCP-1水平与ox-LDL+ H2S 500组比较差异无统计学意义(P>0.05).结论 ox-LDL可诱导人巨噬细胞MCP-1分泌增加;给予外源性H2S的供体NaHS可明显抑制ox-LDL诱导的MCP-1分泌增加.%Objective To explore the effect of hydrogen sulfide( H2S) on oxidized - low density lipoprotein(ox - LDL) - stimulated monocyte chemoattractant protein - 1 ( MCP - 1) secretion in THP - 1 - derived macrophage. Methods THP - 1 - derived macrophages were divided into 4 groups:normal control group,ox - LDL group,ox - LDL + H2S 100 group and ox - LDL + H2S 500 group. In the normal control group,cells were cultured in the basal medium for 48 hours;in the ox - LDL group,cells were treated with ox - LDL (50 mg ? L1) for 48 hours;in the ox - LDL + H2S 100 group,cells were pretreated with NaHS (100 fi,mol ? L"') for 30 minutes and then added ox - LDL (50 mg ? L"') to

  4. 单核细胞趋化蛋白-1、癌胚抗原和C-反应蛋白在平阳霉素胸膜固定术中的变化及意义%Changes and significance of monocyte chemoattractant protein-1, carcinoembryonic antigen and C-reactive protein in pingyangmycin pleurodesis

    Institute of Scientific and Technical Information of China (English)

    张鹏; 孙耕耘; 周群

    2011-01-01

    Objective To investigate the mechanism of pingyangmycin (PYM) pleurodesis by detecting the changes of the levels of monocyte chemoattractant protein-1 (MCP-1), carcinoembryonic antigen (CEA), and C-reactive protein (CRP) in malignant pleural effusion (MPE) before and after intrapleural injection with PYM. Methods Thirty-one patients with MPE were intrapleurally injected with PYM. The levels of MCP-1, CEA,CRP and white blood cell count in pleural fluid were detected before and at 6th, 24th, 48th hour after injection. According to therapeutic effect, the patients were divided into effective group and ineffective group. The indexes were compared between groups and before and after treatment. Results Four weeks after PYM administration, the effective rate of MPE control was 58.1% (18/31). The levels of MCP-1 and CEA at 48th hour after treatment were lower than those before treatment (all P<0.05). In effective group, the levels of MCP-1 and CEA began to decrease at 6th hour after treatment (all P <0.05). In ineffective group, MCP-1 level decreased from 48th hour after injection ( P <0.05), there was no statistical significance on CEA level among different time points. The CRP level and white blood cell count in pleural fluid gradually increased after injection, there was statistical significance in effectively group and ineffective group at 24th hour after injection (all P <0.05). CRP level at 6th hour after injection and MCP-1 level at 48th hour after injection in effective group were higher than those in ineffective group (all P <0.05). There was no statistical significance on CEA level and white blood cell count between the two groups at the same time ( )t. Conclusions The intrapleural injection with PYM induces pleurodesis by inflammation and anti-tumor effect.%目的 观察胸膜腔内注射平阳霉素(PYM)后胸腔积液(胸水)中单核细胞趋化蛋白-1(MCP-1)-1、癌胚抗原(CEA)和C-反应蛋白(CRP)水平的变化,探讨PYM

  5. Research Progress on the Role of MCP-1/CCR2 Signaling Axis in the Development of Gastrointestinal Tumors%MCP-1/CCR2信号轴在消化系统肿瘤发生发展中的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘天宇; 曹海龙; 王邦茂

    2016-01-01

    单核细胞趋化蛋白1(MCP-1)/CC 趋化因子受体2(CCR2)信号轴是指由趋化因子 MCP-1与其特异性受体 CCR2相互作用构成的一个与细胞间信息传递和细胞迁移有密切关系的耦联分子对,在肿瘤细胞以及肿瘤微环境中的多种细胞中表达,对肿瘤的发生发展起重要作用。在消化系统肿瘤发生发展过程中, MCP-1/CCR2信号轴的作用越来越受到国内外的关注,相关分子机制研究涉及肿瘤相关巨噬细胞的募集和极化,新生血管生成及异常免疫反应等,可为消化系统肿瘤防治提供新的思路。本文就近年来对 MCP-1/CCR2信号轴与消化系统肿瘤发生发展的研究进展进行综述。%Monocyte chemoattractant protein-1 (MCP-1) / CC chemokine receptor 2 (CCR2) signaling axis is defined as a coupled molecule that was made up by the interaction between chemokine MCP-1 and its specific receptor CCR2 and closely related to the intercellular information transmission and cell migration. MCP-1/CCR2 signal axis is expressed in tu-mor cells and a variety of cells in tumor microenvironment. It plays an important role in the development of tumor. Its role in the development of digestive system neoplasm received increasing attention from researchers in the world. The mechanisms involved the recruitment and polarization of tumor-associated macrophages, angiogenesis and abnormal immune response, etc. It would provide new ideas for the prevention and treatment of gastrointestinal tumors. The present article summarized the recent advances in the role of MCP-1/CCR2 signaling axis in the development of gastrointestinal tumors, and outlined the future prospect.

  6. Prokaryotic expression and in vitro functional analysis of IL-1β and MCP-1 from guinea pig.

    Science.gov (United States)

    Dirisala, Vijaya R; Jeevan, Amminikutty; Ly, Lan H; McMurray, David N

    2013-06-01

    The Guinea pig (Cavia porcellus) is an excellent animal model for studying human tuberculosis (TB) and also for a number of other infectious and non-infectious diseases. One of the major roadblocks in effective utilization of this animal model is the lack of readily available immunological reagents. In order to address this issue, guinea pig interleukin 1 beta (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were efficiently cloned and expressed in a prokaryotic expression vector, and the expressed proteins in soluble form from both the genes were confirmed by N-terminal sequencing. The biological activity of recombinant guinea pig IL-1β was demonstrated by its ability to drive proliferation in thymocytes, and the recombinant guinea pig MCP-1 exhibited chemotactic activity for guinea pig resident peritoneal macrophages. These biologically active recombinant guinea pig proteins will facilitate an in-depth understanding of the role they play in the immune responses of the guinea pig to TB and other diseases.

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

    Directory of Open Access Journals (Sweden)

    Teizo eYoshimura

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Adam J. Wells

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  10. AB45. URO-MCP-1 mice: a model demonstrating UCPPS hallmark symptoms

    OpenAIRE

    Luo, Yi

    2014-01-01

    Introduction and objective Excessive production of monocyte chemotactic protein-1 (MCP-1) has been observed in various inflammatory, chronic pain, and bladder overactive conditions. We have observed that over half of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) express elevated MCP-1 in the urine. This study was to develop a mouse model that secretes MCP-1 by the urothelium to facilitate the study of IC/BPS in humans. Methods A 4.9 Kb transgene consisting of the uroplaki...

  11. Correlation study on MCP-1, MMP-1 gene polymorphism and the incidence of tuberculosis in BCG-vaccinated individuals%卡介苗接种者MCP-1、MMP-1基因多态性与肺结核发病率的相关性研究

    Institute of Scientific and Technical Information of China (English)

    夏小学; 陈江; 张美禄; 沈志成; 余文菁; 卢火佺

    2013-01-01

    目的:探讨我国汉族人群单核细胞趋化蛋白-1(MCP-1)基因-2518位点、基质金属蛋白酶-1(MMP-1)基因-1607位点多态性与肺结核发病的相关性.方法:选择有卡介苗接种史的肺结核患者188例(TB组)与结核菌素皮试阳性的健康者194例(PPD+组).分析两组人群MCP-1-2518 A/G位点、MMP-1-1607 1G/2G位点基因型、等位基因频率及与肺结核发病的关系.结果:两组人群MCP-1-2518A/G位点、MMP-1-1607 1G/2G位点基因型、等位基因频率分布符合Hardy-Weinberg平衡定律.MCP-1-2518 G、MMP-1-1607 2G等位基因的频率分布与肺结核的发病有显著相关性(P<0.01),MCP-1-2518G/G、MMP-1-1607 2G/2G表型易患肺结核(P<0.05).结论:我国汉族人群MCP-1-2518 G/G表型、MMP-1-1607 2G/2G表型与肺结核的发生有显著相关性.%Objective:To investigate the correlation between monocyte chemoattractant protein-1 (MCP-1)gene-2518 loci,matrix metalloproteinase-1 (MMP-1) gene-1607 loci polymorphism and the incidence of tuberculosis in the Chinese Han population.Methods:One hundred and eighty-eight cases of tuberculosis patients (TB group) and 194 healthy volunteers with positive tuberculin skin test (PPD group) were selected as BCG-vaccinated individuals.The genotype and allele frequencies of MCP-1-2518 A/G locus,MMP-1-1607 1G/2G locus,and the relationship with the incidence of TB were analyzed.Results:The MCP-1-2518 A/G locus,MMP -1-1607 1G/2G locus,allele freauency distribution of the two groups conformed to Hardy-Weinberg equilibrium.The significant correlation was found MCP-1-2518 G,MMP-1-1607 2G allele frequency distribution and the incidence of TB (P <0.01),and MCP-1-2518 G/G,MMP-1-1607 2G/2G phenotype were susceptible to tuberculosis (P < 0.05).Conclusion:The MCP-1-2518 G/G,MMP-1-1607 2G/2G phenotype might be associated with susceptibility to tuberculosis in Chinese Han population.

  12. Palmitate induces monocyte chemoattractant protein-1 expression in human aortic vascular smooth muscle cells via toll like receptor 4 signaling pathway%果蝇样受体4介导游离脂肪酸调节人血管平滑肌细胞单核细胞趋化蛋白-1的表达

    Institute of Scientific and Technical Information of China (English)

    高啸波; 权金星; 杨海静; 陈卫; 李伟华; 李永红; 刘静

    2013-01-01

    +parthenolide组、软脂酸+白屈菜红碱组、软脂酸+ wortmannin组和软脂酸+myriocin组MCP-1 mRNA表达分别为1.00±0.02、10.80±1.23、3.49±0.28、10.84±0.24、11.24±0.27和10.62±0.36(F=1313.07,P<0.05);MCP-1蛋白表达分别为(132±8)、(218±12)、(152±4)、(213±12)、(225±7)和(226±9)ng/L(F=106.83,P<0.05).成功地构建并获得TLR4 shRNA腺病毒pGSadeno-TLR4,采用pGSadeno-TLR4感染HA-VSMC阻断TLR.信号后,软脂酸+pGSadeno-TLR4组的NF-κBp65结合活性、MCP-1 mRNA和蛋白表达均显著低于软脂酸组[分别为0.48±0.12比1.24±0.16、1.88±0.33比10.80±1.23、(154±10)比(218±12)ng/L;F =591.86、659.16、118.37,均P<0.01].而对照病毒pGSadeno-GFP对软脂酸诱导的NF-κB p65结合活性和MCP-1表达均无明显影响.结论 TLR4/NF-κB信号通路介导了软脂酸诱导的人主动脉血管平滑肌细胞MCP-1基因表达.%Objective To investigate the role of toll like receptor 4(TLR4)pathway in regulation of monocyte chemoattractant protein-1(MCP-1)by palmitate in human aortic vascular smooth muscle cells (HA-VSMC).Methods To study the time course and dose dependent effects of palmitate on MCP-1 gene expression,HA-VSMC were cultured and treated with 100,200 or 400 μ mol/L of palmitate for 6,12 or 24 h,cells were then harvested at indicated time points,MCP-1 mRNA expression was analyzed with realtime polymerase chain reaction(RT-PCR)and the production of MCP-1 protein in cultural supernatant were tested using enzyme-linked immunosorbent assay(ELISA).To determine the involvement of signaling pathways in regulation of MCP-1 by palmitate,specific inhibitors that block protein kinase C(PKC),phosphotylinosital 3 kinase(PI3K),ceramide or nuclear factor(NF)-κB signaling were added to the serumfree media for 30 min followed by treatment with or without 400 μ mol/L of palmitate for additional 6 h,thereafter,the mRNA and protein expression of MCP-1 were studied.To further clarify the role of TLR4 pathway in induction of MCP-1

  13. Glucagon-like peptide-1 suppresses advanced glycation end product-induced monocyte chemoattractant protein-1 expression in mesangial cells by reducing advanced glycation end product receptor level.

    Science.gov (United States)

    Ishibashi, Yuji; Nishino, Yuri; Matsui, Takanori; Takeuchi, Masayoshi; Yamagishi, Sho-ichi

    2011-09-01

    Advanced glycation end products (AGE) and receptor for AGE (RAGE) interaction elicits reactive oxygen species (ROS) generation and inflammatory reactions, thereby being involved in the development and progression of diabetic nephropathy. Recently, we, along with others, found that glucagon-like peptide-1 (GLP-1), one of the incretins and a gut hormone secreted from L cells in the intestine in response to food intake, could have anti-inflammatory and antithrombogenic properties in cultured endothelial cells. However, the effects of GLP-1 on renal mesangial cells are largely unknown. Therefore, to elucidate the role of GLP-1 in diabetic nephropathy, this study investigated whether and how GLP-1 blocked AGE-induced monocyte chemoattractant protein-1 expression in human cultured mesangial cells. Gene and protein expression was analyzed by quantitative real-time reverse transcription polymerase chain reactions, Western blots, and enzyme-linked immunosorbent assay. The ROS generation was measured with dihydroethidium staining. Glucagon-like peptide-1 receptor (GLP-1R) was expressed in mesangial cells. Glucagon-like peptide-1 inhibited RAGE gene expression in mesangial cells, which was blocked by small interfering RNAs raised against GLP-1R. Furthermore, GLP-1 decreased ROS generation and subsequently reduced monocyte chemoattractant protein-1 gene and protein expression in AGE-exposed mesangial cells. An analogue of cyclic adenosine monophosphate mimicked the effects of GLP-1 on mesangial cells. Our present study suggests that GLP-1 may directly act on mesangial cells via GLP-1R and that it could work as an anti-inflammatory agent against AGE by reducing RAGE expression via activation of cyclic adenosine monophosphate pathway.

  14. PPAR Agonist-Induced Reduction of Mcp1 in Atherosclerotic Plaques of Obese, Insulin-Resistant Mice Depends on Adiponectin-Induced Irak3 Expression

    Science.gov (United States)

    Arnould, Thierry; Tsatsanis, Christos; Holvoet, Paul

    2013-01-01

    Synthetic peroxisome proliferator-activated receptor (PPAR) agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate) and a PPARγ agonist (rosiglitazone) on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO) were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3) and decreased monocyte chemoattractant protein-1 (Mcp1) expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM), we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3−/− BMDM) resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3−/− BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists. PMID:23620818

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

    Directory of Open Access Journals (Sweden)

    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.

  16. PPAR agonist-induced reduction of Mcp1 in atherosclerotic plaques of obese, insulin-resistant mice depends on adiponectin-induced Irak3 expression.

    Directory of Open Access Journals (Sweden)

    Maarten Hulsmans

    Full Text Available Synthetic peroxisome proliferator-activated receptor (PPAR agonists are used to treat dyslipidemia and insulin resistance. In this study, we examined molecular mechanisms that explain differential effects of a PPARα agonist (fenofibrate and a PPARγ agonist (rosiglitazone on macrophages during obesity-induced atherogenesis. Twelve-week-old mice with combined leptin and LDL-receptor deficiency (DKO were treated with fenofibrate, rosiglitazone or placebo for 12 weeks. Only rosiglitazone improved adipocyte function, restored insulin sensitivity, and inhibited atherosclerosis by decreasing lipid-loaded macrophages. In addition, it increased interleukin-1 receptor-associated kinase-3 (Irak3 and decreased monocyte chemoattractant protein-1 (Mcp1 expressions, indicative of a switch from M1 to M2 macrophages. The differences between fenofibrate and rosiglitazone were independent of Pparγ expression. In bone marrow-derived macrophages (BMDM, we identified the rosiglitazone-associated increase in adiponectin as cause of the increase in Irak3. Interestingly, the deletion of Irak3 in BMDM (IRAK3(-/- BMDM resulted in activation of the canonical NFκB signaling pathway and increased Mcp1 protein secretion. Rosiglitazone could not decrease the elevated Mcp1 secretion in IRAK3(-/- BMDM directly and fenofibrate even increased the secretion, possibly due to increased mitochondrial reactive oxygen species production. Furthermore, aortic extracts of high-fat insulin-resistant LDL-receptor deficient mice, with lower adiponectin and Irak3 and higher Mcp1, showed accelerated atherosclerosis. In aggregate, our results emphasize an interaction between PPAR agonist-mediated increase in adiponectin and macrophage-associated Irak3 in the protection against atherosclerosis by PPAR agonists.

  17. LOX - 1介导ox - LDL诱导的血管内皮细胞MCP - 1的表达%Lectin- like oxidized low density lipoprotein receptor - 1 mediates expression of MCP - 1 induced by ox - LDL in cultured human vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    朱惠莲; 唐志红; 夏敏; 马静; 凌文华

    2005-01-01

    目的:观察血凝素氧化低密度脂蛋白受体-1(LOX-1)对氧化LDL(ox-LDL)诱导的人脐静脉内皮细胞(human unbilical vein endothelial cells,HUVECs)表达单核细胞趋化蛋白(monocyte chemoattractant protein-1,MCP-1)基因及蛋白的影响.方法:用RT-PCR和Western blot的方法观察ox-LDL对培养的HUVECs表达LOX-1和MCP-1基因及蛋白的影响,然后用LOX-1的受体阻滞剂爱兰苔胶(carrageenan)和聚肌苷酸[polyinosinic acid,poly(Ⅰ)]与HUVECs预先作用后,再观察内皮细胞表达LOX-1和MCP-1基因和蛋白的变化.结果:用不同浓度的ox-LDL(0 mg/L、10 mg/L、20 mg/L、50 mg/L、100 mg/L)与HUVECs培养24h后,LOX-1和MCP-1的mRNA和蛋白的表达明显增加,呈浓度依赖性;用Carrageenan和polyinosinic acid与HUVECs预先作用2 h后,再加入50 mg/L的ox-LDL培养24 h,与未加Carrageenan和polyinosinic acid相比,HUVECsLOX-1和MCP-1的mRNA和蛋白的表达明显减少.结论:ox-LDL可以调节培养的HUVECsLOX-1和MCP-1基因和蛋白的表达,LOX-1作为ox-LDL的特异性受体,可能介导了ox-LDL诱导血管内皮细胞分泌MCP-1,从而在动脉粥样硬化的发生发展中起着重要的作用.

  18. A role for MCP-1/CCR2 in interstitial lung disease in children

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    Reinhardt Dietrich

    2005-08-01

    Full Text Available Abstract Background Interstitial lung diseases (ILD are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1 promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.

  19. 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.

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

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    Marianne Pons

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

  1. Nicotinamide downregulates gene expression of interleukin-6, interleukin-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α gene expression in HaCaT keratinocytes after ultraviolet B irradiation.

    Science.gov (United States)

    Monfrecola, G; Gaudiello, F; Cirillo, T; Fabbrocini, G; Balato, A; Lembo, S

    2013-03-01

    Ultraviolet (UV) radiation has profound effects on human skin, causing sunburn, inflammation, cellular-tissue injury, cell death, and skin cancer. Most of these effects are mediated by a number of cytokines produced by keratinocytes. In this study we investigated whether nicotinamide (NCT), the amide form of vitamin B3, might have a protective function in reducing the expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-α in UV-irradiated keratinocytes. HaCaT cells were treated with UVB in the presence or absence of NCT, and cytokine mRNA levels were examined by quantitative real-time PCR. NCT significantly downregulated IL-6, IL-10, MCP-1 and TNF-α mRNA expression, whereas it did not exert any significant effect on IL-1β or IL-8 expression. Because of its ability to decrease these cytokine mediators after UV exposure, NCT is a possible therapy to improve or prevent conditions induced or aggravated by UV light.

  2. 山茱萸新苷对EAE中枢神经系统MCP-1表达及CD68阳性细胞浸润的影响%The Impact of Cornuside on the Expression of MCP-1 and the Infiltration of CD68 Positive Cells in the Central Nervous System in EAE

    Institute of Scientific and Technical Information of China (English)

    张荣博; 徐彬; 朱敏姿; 周未莹; 吴忧; 梁顺利; 章水晶; 李铮; 袁强

    2016-01-01

    [目的]研究山茱萸新苷对实验性自身免疫性脑脊髓炎( experimental autoimmune encephalomyelitis, EAE)大鼠中枢神经系统单核细胞趋化蛋白-1( monocyte chemoattractant protein-1MCP-1)表达及CD68阳性细胞浸润的影响。[方法]制备豚鼠全脊髓匀浆免疫抗原,皮下注射至 Lewis大鼠,建立EAE模型。设正常对照组、EAE组、山茱萸新苷组、波尼松组,每天神经功能评分,待症状达到高峰处死实验动物,用RT-PCR、Western Blot法比较各组实验动物中枢神经系统MCP-1 mRNA及蛋白的表达,免疫组织化学染色法比较各组实验动物中枢神经系统 CD68阳性细胞浸润情况。[结果]正常对照组、EAE组、山茱萸新苷组、波尼松组大鼠MCP-1 mRNA的相对表达量分别为(11.265±2.928)、(401.373±55.398)、(124.987±20.244)、(75.465±7.766),MCP-1蛋白相对表达量分别为(7.458±2.570)、(24.155±1.420)、(19.568±0.863)、(17.458±1.630),CD68阳性指数分别为0%、(41.93±12.25)%、(16.08±8.70)%、(5.38±2.88)%。使用单因素方差分析法,MCP-1 mRNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数组间差异显著,均有统计学意义( F=199.734、66.081、35.565,均P=0.000)。山茱萸新苷组与EAE组在神经功能评分、MCP-1 mRNA的相对表达量、MCP-1蛋白相对表达量、CD68阳性指数表达差异均有统计学意义( P=0.002、0.000、0.003、0.013)。[结论]山茱萸新苷可改善 EAE大鼠神经功能,抑制EAE大鼠中枢神经系统MCP-1表达及CD68阳性细胞浸润。%Objective] To explore the impact of cornuside on the expression of MCP-1 and the infiltration of CD68 positive cells in the central nervous system in EAE. [Methods] An EAE model was established by injecting the guinea pig spinal cord homogenate antigen in subcutaneous tissue of Lewis rats. The rats were randomly divided into normal control group, EAE

  3. Expression and significance of the expression of monocyte chemoattractant protein-1, insulin like growth factor I, and matrix metalloproteinase-9 in human abdominal aortic aneurysm%单核巨噬细胞趋化因子1、胰岛素样生长因子Ⅰ和基质金属蛋白酶9在人腹主动脉瘤中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    张蓉; 胡明; 费宇行; 李晶; 张沂

    2011-01-01

    目的 观察单核细胞趋化因子1(MCP-1)、胰岛素样生长因子Ⅰ(IGF-Ⅰ)、基质金属蛋白酶9(MMP-9)在人腹主动脉及腹主动脉瘤中的表达,并探讨其在腹主动脉瘤形成中的病生理作用.方法 2010年6-10月经择期外科手术获取的腹主动脉瘤标本15例,均经常规病理检查证实,采用SP免疫组织化学技术检测IGF-Ⅰ、MCP-1、MMP-9蛋白的表达,并以10例非正常死亡健康成人腹主动脉作为对照,对检测结果进行比较分析.结果 腹主动脉瘤中MCP-1、MMP-9的免疫组化染色强度显著高于对照组(P<0.01),IGF-Ⅰ显著低于对照组(P<0.05).相关性分析显示,腹主动脉瘤组织中IGF-Ⅰ表达与MCP-1、MMP-9呈明显负相关(分别为r=-0.791,P<0.01;r=-0.692,P<0.01),而MCP-1的表达与MMP-9呈明显正相关(r=0.932,P<0.01).结论 IGF-Ⅰ表达减少可能会增加主动脉血管壁中层平滑肌细胞的凋亡,或使增殖平衡失调,而平滑肌细凋亡增多可影响细胞外基质正常结构的维持及修复,促进腹主动脉瘤的发生,MCP-1、IGF-Ⅰ、MMP-9三者的表达失衡可能是腹主动脉瘤的发病机制之一.%Objective To observe the expression of monocyte chemoattractant protein-1 (MCP-1), insulin like growth factor I (IGFI) and matrix metalloproteinase-9 (MMP-9) in the local tissue of human abdominal aorta and abdominal aortic aneurysm, and explore their physiopathological role in the pathogenesis of abdominal aortic aneurysm. Methods The specimens were obtained from 15 patients who underwent elective surgical procedures from June to October in 2010, and its pathology was confirmed by routine pathological examination.The expressions of MCP-1, IGF- I and MMP-9 were determined with SP immunohistochemistry method. Specimens of 10 normal human abdominal aortae were used as control and the results were compared with those of abdominal aortic aneurysm. Results The expressions of MCP-1 and MMP-9 in abdominal aortic aneurysm were

  4. Matrine Inhibits Infiltration of the Inflammatory Gr1hi Monocyte Subset in Injured Mouse Liver through Inhibition of Monocyte Chemoattractant Protein-1

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    Duo Shi

    2013-01-01

    Full Text Available Matrine (Mat is a major alkaloid extracted from Sophora flavescens Ait, an herb which is used in the traditional Chinese medicine for treatment of inflammation, cancer, and other diseases. The present study examined the impact of Mat on the CCl4-induced hepatic infiltration of Gr1hi monocytes to explore the possible mechanisms underlying its anti-inflammatory and antifibrotic effects. The results indicated that Mat protected mice from acute liver injury induced by single intraperitoneal injection of CCl4 and attenuated liver fibrosis induced by repeated CCl4 injection. Meanwhile, the infiltrations of Gr1hi monocytes in both acute and chronic injured livers were all inhibited, and the enhanced hepatic expression of MCP-1 was suppressed. Cellular experiments demonstrated that Mat directly inhibited MCP-1 production in both nonparenchymal cells and hepatic stellate cells derived from CCl4-injured livers. Transwell chemotaxis assays showed that Mat significantly inhibited the chemotactic activity of MCP-1. These results suggest that the anti-inflammatory and antifibrotic effects of Mat could be contributed, at least in part, to its prevention of Gr1hi monocyte infiltration into the injured livers and inhibition of MCP-1 production and activity. These findings extend our understanding of the mechanisms underlying the anti-inflammatory and antifibrotic effects of Mat.

  5. Diesel Particulate Exposed Macrophages Alter Endothelial Cell Expression of eNOS, iNOS, MCP1, and Glutathione Synthesis Genes

    Science.gov (United States)

    Weldy, Chad S.; Wilkerson, Hui-Wen; Larson, Timothy V.; Stewart, James A.; Kavanagh, Terrance J.

    2011-01-01

    There is considerable debate regarding inhaled diesel exhaust particulate (DEP) causing impairments in vascular reactivity. Although there is evidence that inhaled particles can translocate from the lung into the systemic circulation, it has been suggested that inflammatory factors produced in the lung following macrophage particle engulfment also pass into the circulation. To investigate these differing hypotheses, we used in vitro systems to model each exposure. By using a direct exposure system and a macrophage-endothelial cell co-culture model, we compared the effects of direct DEP exposure and exposure to inflammatory factors produced by DEP-treated macrophages, on endothelial cell mRNA levels for eNOS, iNOS, endothelin-1, and endothelin-converting-enzyme-1. As markers of oxidative stress, we measured the effects of DEP treatment on glutathione (GSH) synthesis genes and on total GSH. In addition, we analyzed the effect of DEP treatment on monocyte chemo-attractant protein-1. Direct DEP exposure increased endothelial GCLC and GCLM as well as total GSH in addition to increased eNOS, iNOS and Mcp1 mRNA. Alternatively, inflammatory factors released from DEP-exposed macrophages markedly up-regulated endothelial iNOS and Mcp1 while modestly down-regulating eNOS. These data support both direct exposure to DEP and the release of inflammatory cytokines as explanations for DEP-induced impairments in vascular reactivity. PMID:21920430

  6. Changes and it′s clinical significance of GA and MCP-1 in peripheral blood of patients with acute coronary syndrome%急性冠脉综合征患者血清糖化白蛋白和单核细胞趋化蛋白水平变化的临床意义

    Institute of Scientific and Technical Information of China (English)

    张丽; 冯毅; 马根山

    2011-01-01

    Objective : To explore the correlation between glycated albumin ( GA) , monocyte chemoattractant protein-1( MCP-1) and acute cronary syndrome( ACS). Methods: The levels of GA and MCP-1 in the peripheral blood were measured in 46 patients with ACS ( ACS group) , 32 patients with stable angina pectoris ( SAP group) and 30 patients with chest discomfort and normal coronary angiography( control group) by NBT color and enzymelinked immunosorbent assay (ELISA) . The aspects of coronary artery lesions were analyzed. Results : The levels of GA and MCP-1 in ACS group were significantly higher than those of SAP group and control group ( all P < 0. 01 ) .The degree of coronary artery lesions in ACS group was high than that of SAP group ( P < 0. 05 ) . GA level was positively correlated with MCP-1 level in ACS group (r = 0. 721, P < 0. 01 ). Conclusions: The levels of GA and MCP-1 in peripheral blood may be two useful makers reflecting the unstable of the disease, and there is intrinsic correlation between the levels of GA or MCP-1 in peripheral blood, which implicates that the interaction of factors may facilitate the development of ACS.%目的:探讨急性冠脉综合征(acute coronary syndrome, ACS)患者外周血糖化白蛋白(glycated albumin, GA)、单核细胞趋化蛋白1(monocyte chemoattractant protein-1, MCP-1)水平的变化与ACS发生发展的关系.方法:应用硝基四氮唑兰(NBT)显色法和酶联免疫吸附法分别测定46例ACS患者(ACS组)、32例稳定型心绞痛患者(stable angina pectoris, SAP组)及30例有胸痛、胸闷等症状但冠脉造影正常的患者(对照组)血中GA和MCP-1水平的变化,并分析冠状动脉的病变情况.结果:ACS组血GA、MCP-1水平明显高于SAP组及对照组(均P<0.01);ACS组冠状动脉狭窄程度积分高于SAP组(P<0.05);ACS组血清GA与MCP-1水平有明显相关性(r=0.721,P<0.01).结论:血清GA、MCP-1水平可用于预测ACS的发生, GA和MCP-1在ACS的发生和发展中有重要作用.

  7. Evaluation of the reactivity of sera from patients with systemic lupus erythematosus against the human MCP1.

    Science.gov (United States)

    Bronze-da-Rocha, Elsa; Nóvoa, Ana; Teixeira, Natércia; Vasconcelos, Carlos Silva; Cerveira, Conceição; Castro e Melo, João; Carvalho, Manuel Cirne

    2012-08-01

    This study evaluates metaphase chromosome protein 1 (MCP1), a nuclear antigen, as a diagnostic marker for systemic lupus erythematosus (SLE). Reactivity of sera from 114 Portuguese patients with autoimmune rheumatic disease or from healthy blood donors (HBD), against MCP1, produced in bacteria (bact-MCP1) or in its native form (native-MCP1), was determined by immunoblotting. Predictive and discriminative power of MCP1 reactivity for SLE diagnosis in disease-control groups was evaluated by logistic regression, its diagnostic value determined by receiver-operating characteristic analysis and compared with similar analysis of antinuclear antibody and double-stranded DNA (dsDNA). We demonstrated that native-MCP1, in contrast to bact-MCP1, reacts with SLE sera with significant predictive and discriminative power versus other autoimmune diseases (odds ratio [OR] ≤3.537 and ≥3.265; area under the receiver-operating characteristic curve [AUC] ≤0.643 and ≥0.636) or versus HBD (OR = 5.006; AUC = 0.671), showing a good diagnostic power with high specificity (82.1% versus HBD) and low sensitivity for SLE, similar to those of dsDNA. The reactivity of SLE sera with native-MCP1 was shown to be dependent on the presence of phosphorylated residues. Native-MCP1 was shown to have diagnostic value as a specific marker for SLE diagnosis and, therefore, is a suitable substrate for a new antibody test. The widely reported importance of phosphorylated epitopes as targets for autoantibodies in SLE could also be confirmed for native-MCP1.

  8. 单核细胞趋化蛋白-1和细胞间黏附分子-1与动脉粥样硬化和牙周病的关系%Relation of monocyte chemoattractant protein-1 and intercellular adhesion molecule-1 between atherosclerosis and periodontal disease

    Institute of Scientific and Technical Information of China (English)

    焦丽宁

    2012-01-01

    Coronafy heart disease on the pathologic foundation of atherosclerosis is one of the fatal diseases now, however, there is an association exists between periodontitis and atherosclerosis. Both monocyte chemoattractant protein(MCP)-1 and intercellular adhesion molecule(ICAM) -1 play important roles in the occurrence and development of atherosclerosis and periodontitis. In this article the relationship between atherosclerosis and periodontitis by means of MCP-1 and ICAM-1 is reviewed.%以动脉粥样硬化为病理基础的冠心病是目前主要的致死性疾病之一,而牙周病与动脉粥样硬化之间存在着一定的相关性.单核细胞趋化蛋白(MCP)-1和细胞间黏附分子(ICAM)-1在动脉粥样硬化和牙周病的发生发展中起着重要的作用.本文就MCP-1和ICAM-1以及二者与动脉粥样硬化、牙周病间的关系作一综述.

  9. Effects of Sera from Patients with SLE on ICAM - 1 and MCP- 1 Expression in HUVEC and Fluvastatin Intervention%SLE患者血清对人脐静脉内皮细胞ICAM-1和MCP-1表达的影响及氟伐他汀的干预作用

    Institute of Scientific and Technical Information of China (English)

    梁倩; 李霞; 刘伏友; 刘虹; 许向青; 彭佑铭

    2009-01-01

    Objective: To investigate the effect of ANA- positive and anti - dsDNA antibody - positive sera from patients with SLE on intercellular adhesion molecule - 1 ( ICAM - 1 ) and monocyte chemoattractant protein - 1 (MCP-1 ) released from cul-tured human umbilical vein endothdial cells (HUVEC) and whether fluvastatin can attenuate these effect. Methods:Confluent mono-layers of culturad HUVEC with serum samples (diluted 1:5) were from 15 female patients and 5 normal female controls or with both serum samples and solution of fluvastatin for 24 hours. ICAM- 1 and MCP- 1 concentrations in the culture supernatant were mea-sured by EL1SA and intracellular expressions of ICAM- 1 and MCP- 1 were measured by immunocytochemistry. Results: The ex-pression of ICAM - 1 and MCP - 1 incubated with ANA-positive and anti - dsDNA antibody - positive sera from patient with SLE were higher than HUVEC incubated with ANA-negative sera from patients with SLE(P < 0.01 ) and normal controls( P < 0.01 ).Fluvaststin showed significant inhibition of ANA - positive and anti - dsDNA antibody- positive sera induced ICAM- 1 and MCP - 1expression on HUVEC(P<0.01 ,and P<0.05). Conclusion:ANA- pcsitive and anti- dsDNA antibody- positive sera's ability to activate HUVEC is evidenced by induction of ICAM- 1 and MCP- 1 expression in vitro. Fluvastatin can inhibit up- reguhtion of ICAM- 1 and MCP- 1 on HUVEC by ANA- positive and anti- dsDNA antibody- positive sera from patients with SLE in vitro.%目的:观察抗核抗体(ANA)和抗ds-DNA抗体对人脐静脉血管内皮细胞(HUVEC)细胞间黏附分子-1(ICAM-1)、单核细胞趋化因子-1(MCP-1)表达的影响及他汀类药物氟伐他汀(fluvastatin,flu)干预后的变化,以探讨ANA和抗ds-DNA抗体在系统性红斑狼疮(SLE)血管炎中的致病机制和flu对血管内皮保护作用.方法:体外培养HUVEC,收集女性SLE患者血清(以抗核抗体全套为依据,分3组:ANA阴性、ANA滴度1:80、ANA滴度1:80和抗ds-DNA抗

  10. Expression and significance of MCP-1 in liver tissue of different clinical types of HBV infected patients%不同临床类型HBV感染患者肝组织中单核细胞趋化蛋白-1的表达及意义

    Institute of Scientific and Technical Information of China (English)

    朱陇东; 何爱凤; 朱骏

    2011-01-01

    Objective: To study the expression of raonocyte chemoattractant protein -1 ( MCP-1) in the liver tissue of hepatitis B virus carriers, chronic hepatitis B, hepatitis B liver cirrhosis patient and its clinical pathological significance. Methods: Twenty cases of hepatitis B virus carriers, 18 chronic hepatitis B patients, 13 patients with liver cirrhosis were studied. Their liver tissue were fixed in 10% neutral formalin and paraffin-embedded. 2 cases of normal liver tissue was as control team. The expression of MCP-1 in liver tissue were detected by Immunohistochemical method ( SP) . Results: No expression of MCP-1 In normal liver tissue. Positive expression of MCP-1 rates were 25% , 77.78% , 84. 62% in hepatitis B virus carriers, chronic hepatitis B, hepatitis B liver cirrhosis patients respectively. The difference were significantly. Conclusion: The expression of MCP-1 in liver tissue increase with the development of liver inflammation and fibrosis. MCP-1 may play an important role in pathological processes of liver inflammation and fibrosis. The study of MCP-1 maybe give a new ideas in the diagnosis , pathogenesis and treatment.%研究乙肝病毒(HBV)携带者、慢性乙型肝炎(CHB)、乙型肝炎肝硬化患者肝组织中单核细胞趋化蛋白-1(MCP-1)的表达,并探讨其临床病理意义.方法:20例HBV携带者、18例CHB患者、13例乙型肝炎肝硬化患者肝组织经10%中性甲醛固定后制作石蜡包埋切片,并以两份正常人肝组织作为对照,采用免疫组织化学法(SP法)检测肝组织MCP-1的表达水平.结果:正常肝组织MCP-1无表达,HBV携带者、CHB、乙型肝炎肝硬化患者肝组织MCP-1表达阳性率依次为25%、77.78%、84.62%,差异均有显著性意义.结论:MCP-1在肝组织中的表达随肝脏炎症和纤维化的发展而升高,MCP-1可能在病毒性肝炎肝脏炎症和纤维化的病理过程中起重要作用.MCP-1的研究对乙型病毒性肝炎的病情诊断、发病机制探讨及治疗提供新思路.

  11. Inflammatory biomarkers CRP, MCP-1, serum amyloid alpha and interleukin-18 in patients with HTN and dyslipidemia: impact of diabetes mellitus on metabolic syndrome and the effect of statin therapy.

    Science.gov (United States)

    Rabkin, Simon W; Langer, Anatoly; Ur, Ehud; Calciu, Cristina-Dana; Leiter, Lawrence A

    2013-06-01

    The objective of this study was to determine the relationship of HTN (HTN) and the inflammatory markers C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), amyloid alpha (AA) and interleukin-18 (IL-18) in persons with HTN, considering concomitant diabetes mellitus (DM) or metabolic syndrome (MS). This was a multicenter twelve-week, single-step titration, open-label study of individuals with dyslipidemia, assigned according to their initial risk assessment, to atorvastatin starting doses of 10, 20, 40 or 80 mg. In subjects with HTN (N=677) versus no HTN (N=581), there were significantly (P<0.02) higher levels of CRP, IL-18, MCP-1 and AA but not for IL-18 when combined with DM or MS, and AA or CRP when combined with MS. Systolic blood pressure significantly (P<0.02) correlated with CRP, MCP-1 and AA but not IL-18. The greatest increase in CRP was with HTN plus DM. Statin therapy produced significant dose-dependent reductions in CRP but not with similar changes in other inflammatory markers. In summary, these data suggest a complex relationship between inflammation and HTN with dyslipidemia. Although HTN is associated with an increase in these inflammatory markers, the associated conditions DM or MS lead to different patterns of increases-MCP-1 being the most consistently increased with HTN, the greatest CRP increase was with HTN and DM, and no relationship was found with IL-18 and HTN in the presence of DM or MS. In addition, there are different responses to statins depending on the nature of the inflammatory marker.

  12. Protective effects of MCP-1 inhibitor on a rat model of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Xue-Juan Zhu; Xiao-Ling Ding; Hong Zhang; Jian-Ping Chen; Hui Qiang; Hai-Feng Zhang; Qun Wei

    2010-01-01

    BACKGROUND: Chemokines and their receptors play key roles in the pathogenesis of acute pancreatitis. This study aimed to establish a rat model of severe acute pancreatitis (SAP) for investigating monocyte chemotactic protein-1 (MCP-1) expression in the pathogenesis of the disease. We assessed the effects of the inhibitor of MCP-1, Bindarit, on SAP and explored the mechanisms underlying SAP. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a saline control group (group S), an SAP group (group P), and a Bindarit group (group T). The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the bilio-pancreatic duct. Based on the SAP model, Bindarit was injected intraperitoneally in group T, and 0.5%methyl cellulose was injected intraperitoneally in groups S and P. In group S, saline was retrogradely infused into the bili-pancreatic duct. Serum amylase levels and the histological changes in the pancreas were assessed at different time-points in each group. Expression of MCP-1 in serum was measured by enzyme-linked immunoadsorbent assay (ELISA). MCP-1 protein and mRNA expression levels were detected by immunohistochemistry, Western blotting, and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Serum amylase levels in groups P and T were higher than those in group S. Serum amylase levels were signiifcantly lower in group T than in group P at 6 and 12 hours after operation. The levels of MCP-1 in serum at 6 and 12 hours after operation in group P were signiifcantly higher than in group S, and signiifcantly lower in group T than in group P at 6 and 12 hours after operation. The pathological damage in the pancreas was milder in group T than in group P. MCP-1 protein and mRNA expression levels in the pancreas were higher in groups P and T than in group S. These expression levels were positively correlated with the pathological damage of pancreatic tissues. The activity of MCP-1 in group T was

  13. The change of MCP-1 expression in serum of uveitis%单核细胞趋化蛋白-1在葡萄膜炎患者血清中的表达变化

    Institute of Scientific and Technical Information of China (English)

    何宇; 石晶明; 贾松柏; 唐罗生

    2013-01-01

    目的 检测单核细胞趋化蛋白-1(MCP-1)在急性前葡萄膜炎(AAU)及小柳原田综合征(VKH)患者血清中的表达,探讨其在葡萄膜炎发病中的可能机制.方法 收集62例葡萄膜炎患者(AAU患者43例、VKH患者19例),14例正常对照组,提取血清.将AAU患者分为HLA-B27阳性组17例和HLA-B27阴性组26例;并将VKH患者就诊时是否已使用糖皮质激素治疗分为未使用激素组11例和已使用激素组8例.采用ELISA法检测各组血清中MCP-1的含量,对其进行统计分析.结果 AAU患者HLA-B27阳性组与阴性组血清中MCP-1浓度分别为(115.220±22.698)pg/ml、(102.210±38.689)pg/ml,与正常对照组血清MCP-1浓度(107.900±21.655) pg/ml比较差异无统计学意义(P>0.05).未使用激素治疗的VKH患者外周血清中MCP-1含量(217.370±38.751) pg/ml较正常组显著增高(P<0.05).激素治疗VKH组MCP-1含量(195.480±19.977) pg/ml略低于未治疗组(P >0.05),但仍高于正常组(P<0.05).结论 与正常对照组比较,AAU患者血清MCP-1的表达无明显改变;而VKH患者血清MCP-1的表达上调,推测其可能参与了VKH的病理生理过程,全身使用糖皮质激素可能通过抑制MCP-1表达控制眼部炎症.%Objective To explore the effect of monocyte chemoattractant protein-1 (MCP-1) in uveitis pathogenetic mechanism by detecting the concentration of MCP-1 in serum of AAU and VKH.Methods Sixty-two patients suffered uveitis were collected (43 AAU patients,19 VKH patients),and 14 healthy individuals served as control group.Patients with AAU were divided into HLA-B27 (+) group and HLA-B27 (-) group.Meanwhile,patients with VKH were divided into two groups according to whether steroid was administered systematically or not (VKH patients who had administered steroid systematically (group A); patients without any systemic therapy of steroid (group B).The level of serum MCP-1 was detected by ELISA.Statistic analysis was performed to compare the difference between

  14. Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft.

    Science.gov (United States)

    Gazzaniga, Silvina; Bravo, Alicia I; Guglielmotti, Angelo; van Rooijen, Nico; Maschi, Fabricio; Vecchi, Annunciata; Mantovani, Alberto; Mordoh, José; Wainstok, Rosa

    2007-08-01

    Chemokines such as monocyte chemoattractant protein (MCP)-1 are key agonists that attract macrophages to tumors. In melanoma, it has been previously shown that variable levels of MCP-1/CCL2 appear to correlate with infiltrating macrophages and tumor fate, with low to intermediate levels of the chemokine contributing to melanoma development. To work under such conditions, a poorly tumorigenic human melanoma cell line was transfected with an expression vector encoding MCP-1. We found that M2 macrophages are associated to MCP-1+ tumors, triggering a profuse vascular network. To target the protumoral macrophages recruitment and reverting tumor growth promotion, clodronate-laden liposomes (Clod-Lip) or bindarit were administered to melanoma-bearing mice. Macrophage depletion after Clod-Lip treatment induced development of smaller tumors than in untreated mice. Immunohistochemical analysis with an anti-CD31 antibody revealed scarce vascular structures mainly characterized by narrow vascular lights. Pharmacological inhibition of MCP-1 with bindarit also reduced tumor growth and macrophage recruitment, rendering necrotic tumor masses. We suggest that bindarit or Clod-Lip abrogates protumoral-associated macrophages in human melanoma xenografts and could be considered as complementary approaches to antiangiogenic therapy.

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

    Directory of Open Access Journals (Sweden)

    Palasubramaniam Dharshan

    2011-09-01

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

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

    Directory of Open Access Journals (Sweden)

    C.L.R. Belmiro

    2011-07-01

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

  17. Dexmedetomidine Attenuates Lipopolysaccharide Induced MCP-1 Expression in Primary Astrocyte

    Science.gov (United States)

    Liu, Huan; Faez Abdelgawad, Amro

    2017-01-01

    Background. Neuroinflammation which presents as a possible mechanism of delirium is associated with MCP-1, an important proinflammatory factor which is expressed on astrocytes. It is known that dexmedetomidine (DEX) possesses potent anti-inflammatory properties. This study aimed to investigate the potential effects of DEX on the production of MCP-1 in lipopolysaccharide-stimulated astrocytes. Materials and Methods. Astrocytes were treated with LPS (10 ng/ml, 50 ng/ml, 100 ng/ml, and 1000 ng/ml), DEX (500 ng/mL), LPS (100 ng/ml), and DEX (10, 100, and 500 ng/mL) for a duration of three hours; expression levels of MCP-1 were measured by real-time PCR. The double immunofluorescence staining protocol was utilized to determine the expression of α2-adrenoceptors (α2AR) and glial fibrillary acidic protein (GFAP) on astrocytes. Results. Expressions of MCP-1 mRNA in astrocytes were induced dose-dependently by LPS. Administration of DEX significantly inhibited the expression of MCP-1 mRNA (P < 0.001). Double immunofluorescence assay showed that α2AR colocalize with GFAP, which indicates the expression of α2-adrenoceptors in astrocytes. Conclusions. DEX is a potent suppressor of MCP-1 in astrocytes induced with lipopolysaccharide through α2A-adrenergic receptors, which potentially explains its beneficial effects in the treatment of delirium by attenuating neuroinflammation. PMID:28286770

  18. 牙龈卟啉单胞菌侵入对人血管内皮细胞分泌MCP-1影响的研究%Expression of MCP-1 in vascular endothelial cells invaded by Porphyromonas gingivalis

    Institute of Scientific and Technical Information of China (English)

    邓辉; 徐静; 余溢; 欧阳玉玲; 吴亚菲

    2012-01-01

    目的 通过研究牙龈卟啉单胞菌(porphyrmonas gingivalis,P.g)侵入对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)分泌单核细胞趋化蛋白(MCP-1)的影响,了解P.g对其趋化功能的影响.方法 建立P,g侵入HUVEC的体外模型,采用酶联免疫吸附法( ELISA)研究P.g381和P.g33277菌株侵入HUVEC 6、24 h后的培养上清液中MCP -1浓度.结果 ELISA结果显示当P.g381侵入HUVEC 6、24h和P.g33277侵入HUVEC 6 h时,HUVEC分泌的MCP -1水平升高(P<0.01);P,g33277侵入HUVEC 24 h时,HUVEC分泌的MCP -1水平恢复最初水平(P=0.46);P.g381诱导HUVEC表达MCP -1的水平高于P.g33277 (P <0.01).结论 P.g侵入HUVEC后可促进其表达MCP -1,从而上调其趋化功能,在牙周炎与心血管疾病的相关性中可能发挥作用.%Objective To investigate the expression of monocyte chemoattractanl protein-1 (MCP-1) in human umbilical vein endo-thetial cells ( HUVEC) invaded by porphyrroonas gingivalis (P. g). Methods The models of invasion of P. g into HUVEC were established in vitro. HUVEC were infected with either P. g381 or P. g33277 .then the expression of MCP-1 in supernatant was tested by ELISA. Results The expression of MCP-1 was signicantly upregulated in P. g381 -infected HUVEC at 6h and 24h and in P. g33277-infecled HUVEC at 6h{ P<0.01). The upregulalion ability of P.g381 was significantly greater than P. g33277(P<0.01). Conclusions These data demonstrate that the infection of P. g can increase the expression of MCP-1 and chemolactic function of HDVEC, which may play a role in the relationship between periodontitis and cardiovascular diseases.

  19. 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

  20. An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice

    Science.gov (United States)

    Tieu, Brian C.; Lee, Chang; Sun, Hong; LeJeune, Wanda; Recinos, Adrian; Ju, Xiaoxi; Spratt, Heidi; Guo, Dong-Chuan; Milewicz, Dianna; Tilton, Ronald G.; Brasier, Allan R.

    2009-01-01

    Vascular inflammation contributes to cardiovascular diseases such as aortic aneurysm and dissection. However, the precise inflammatory pathways involved have not been clearly defined. We have shown here that subcutaneous infusion of Ang II, a vasopressor known to promote vascular inflammation, into older C57BL/6J mice induced aortic production of the proinflammatory cytokine IL-6 and the monocyte chemoattractant MCP-1. Production of these factors occurred predominantly in the tunica adventitia, along with macrophage recruitment, adventitial expansion, and development of thoracic and suprarenal aortic dissections. In contrast, a reduced incidence of dissections was observed after Ang II infusion into mice lacking either IL-6 or the MCP-1 receptor CCR2. Further analysis revealed that Ang II induced CCR2+CD14hiCD11bhiF4/80– macrophage accumulation selectively in aortic dissections and not in aortas from Il6–/– mice. Adoptive transfer of Ccr2+/+ monocytes into Ccr2–/– mice resulted in selective monocyte uptake into the ascending and suprarenal aorta in regions of enhanced ROS stress, with restoration of IL-6 secretion and increased incidence of dissection. In vitro, coculture of monocytes and aortic adventitial fibroblasts produced MCP-1– and IL-6–enriched conditioned medium that promoted differentiation of monocytes into macrophages, induced CD14 and CD11b upregulation, and induced MCP-1 and MMP-9 expression. These results suggest that leukocyte-fibroblast interactions in the aortic adventitia potentiate IL-6 production, inducing local monocyte recruitment and activation, thereby promoting MCP-1 secretion, vascular inflammation, ECM remodeling, and aortic destabilization. PMID:19920349

  1. Effect of atorvastatin on advanced glycation end products induced monocyte chemoattractant protein-1 expression in cultured human endothelial cells%阿托伐他汀对晚期糖基化终末产物诱导的人内皮细胞单核细胞趋化蛋白-1mRNA表达影响及其机制的实验研究

    Institute of Scientific and Technical Information of China (English)

    徐尚华; 王科峰; 许昌声; 谢良地

    2011-01-01

    Objective To investigate the effects of atorvastatin on advanced glycation end products (AGE) induced monocyte chemoattractant protein-1(MCP-1) expression in human umbilical vein endothelial cells(HUVECs)and whether this effect could be linked to peroxisome proliferator-activated receptor-γ (PPAR-γ) and nuclear factor-κB(NF-κB).Methods Grouping: (1)Blank control group;(2)BSA group;(3)AGE group:cells were incubated with different concentrations of AGE(10-4,10-3, 10-2 and 10-1g/L)for 24 hours; (4)AGE+Atorvastatin group: cells were incubated with different concentrations of atorvastatin(0.1,1,10 μmol/L)for 1 hour,then incubated with AGE (10-1 g/L) for 24 hours; (5)PPAR-γ agonist(15 d-PGJ2)group: cells were incubated with 15 d-PGJ2(10 μmol/L)for 1 hour,then incubated with AGE (10-1g/L) for 24 hours;(6)PPAR-γ inhibitor(GW9662)group:cells were incubated with GW9662(5000 nmol/L)for 1 hour,then incubated with atorvastatin (1 μmol/L)and AGE (10-1g/L) for 24 hours. Collagenase was used to isolate the endothelial cell from human umbilical vein;RT-PCR was performed to examine the mRNA expression of MCP-1 and PPAR-γ;Western blot was performed to detect NF-κB p65 protein.Results (1) The expression of MCP-1 mRNA was increased in proportion with increasing concentrations of AGEs which could be blocked by atorvastatin in a dose-dependent manner. (2) AGE(10-1g/L)significantly downregulated the expression of PPAR-γ mRNA(0.22±0.08 vs. 0.69±0.09, P<0.01) while upregulated the expression of phospho-NF-κB p65 protein (0.78±0.06 vs. 0.31±0.01,P<0.01) and nonphospho-NF-κB p65 protein (1.61±0.16 vs. 0.59±0.14,P<0.01) comparaed with the control group which could be significantly attenuated by atorvastatin. (3) PPAR-γ agonist decreased the expression of phospho-NF-κB p65 protein (0.21±0.01 vs. 0.78±0.06, P<0.01),nonphospho-NF-κB p65 protein (0.67±0.14 vs. 1.61±0.16,P<0.01)and MCP-1 mRNA (0.17±0.02 vs. 0.93±0.12, P<0.01)compared with AGE(10-1g/L)group. (4) PPAR

  2. Interaction of vascular smooth muscle cells and monocytes by soluble factors synergistically enhances IL-6 and MCP-1 production.

    Science.gov (United States)

    Chen, Li; Frister, Adrian; Wang, Song; Ludwig, Andreas; Behr, Hagen; Pippig, Susanna; Li, Beibei; Simm, Andreas; Hofmann, Britt; Pilowski, Claudia; Koch, Susanne; Buerke, Michael; Rose-John, Stefan; Werdan, Karl; Loppnow, Harald

    2009-04-01

    Inflammatory mechanisms contribute to atherogenesis. Monocyte chemoattractant protein (MCP)-1 and IL-6 are potent mediators of inflammation. Both contribute to early atherogenesis by luring monocytes and regulating cell functions in the vessel wall. MCP-1 and IL-6 production resulting from the interaction of invading monocytes with local vessel wall cells may accelerate atherosclerosis. We investigated the influence of the interaction of human vascular smooth muscle cells (SMCs) with human mononuclear cells (MNCs) or monocytes on IL-6 and MCP-1 production in a coculture model. Interaction synergistically enhanced IL-6 and MCP-1 production (up to 30- and 10-fold, respectively) compared with separately cultured cells. This enhancement was mediated by CD14-positive monocytes. It was dependent on the SMC-to-MNC/monocyte ratio, and as few as 0.2 monocytes/SMC induced the synergism. Synergistic IL-6 production was observed at the protein, mRNA, and functional level. It was mediated by soluble factors, and simultaneous inhibition of IL-1, TNF-alpha, and IL-6 completely blocked the synergism. IL-1, TNF-alpha, and IL-6 were present in the cultures. Blockade of the synergism by soluble glycoprotein 130Fc/soluble IL-6 receptor, as well as the induction of synergistic IL-6 production by costimulation of SMCs with IL-1, TNF-alpha, and hyper-IL-6, suggested the involvement of IL-6 trans-signaling. The contribution of IL-6 was consistent with enhanced STAT3 phosphorylation. The present data suggest that SMC/monocyte interactions may augment the proinflammatory status in the tissue, contributing to the acceleration of early atherogenesis.

  3. Interleukin-4 and 13 induce the expression and release of monocyte chemoattractant protein 1, interleukin-6 and stem cell factor from human detrusor smooth muscle cells: synergy with interleukin-1beta and tumor necrosis factor-alpha

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Andresen, Lars; Alvarez, Susana

    2006-01-01

    Interstitial cystitis is characterized by an increased number of activated MCs in the detrusor muscle. However, to our knowledge the factors that influence the anatomical relationship between MCs and HDSMCs are unknown. MCP-1, IL-6 and SCF have a critical role in the regulation of MC development,...

  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.

  5. The impact of montelukast combined with Ketotifen on the levels of serum TGF-β1 , MCP-1, SDF-1 in asthma suffe- rers%孟鲁司特联合酮替芬对哮喘患者血清TGF-β1、MCP-1、SDF-1水平的影响

    Institute of Scientific and Technical Information of China (English)

    王昕华; 韩曙光; 吕蕾; 赵弘卿

    2016-01-01

    Objective To investigate the impact of montelukast combined with Ketotifen on the levels of transforming growth factor-β1(TGF-β1), monocyte chemoattractant protein-1 (MCP-1), stromal cell derived factor-1 ( SDF-1) in asthma sufferers.Methods 128 cases of asthma patients in Department of Respiration, Wuxi Second People's Hospital Affiliated to Nanjing Medical University from October 2014 to October 2015 were selected and randomly divided into observation group (n =64) and control group ( n =64).Patients of two groups were given symptomatic treatment;patients of the observation group were treated with montelukast combined with Ketotifen orally, while patients of the control group were treated with mon-telukast orally, and both for three months.The levels of TGF-β1 , MCP-1, SDF-1 of two groups before and after treatment were compared.Results The total effective rate of observation group( 96.9%) were higher than control group (84.4%) ( P <0.05).The Asthma Control Test table (ACT) score of observation group (24.25 ±3.98) was significantly higher than control group (20.12 ±4.02) ( P <0.05).The levels of expiratory volume in one second (FEV1) and peak expiratory flow rate (PEF) of observation group were (80.25 ±4.25)%, (7.25 ±0.69) L/min were higher than control group (75.02 ± 3.96)%, (5.82 ±0.70) L/min ( P <0.05).The levels of serum TGF-β1, MCP-1, SDF-1 of observation group (42.2 ± 6.0) ng/ml, (48.6 ±4.0) ρg/ml, (252.4 ±32.2) ng/L after treatment were lower than the control group (48.9 ±5.2) ng/ml, (59.0 ±4.2) ρg/ml, (425.3 ±40.6) ng/L, the difference was statistically significant ( P <0.05).Conclusion Montelukast combined with Ketotifen can effectively reduce serum TGF-β1 , MCP-1, SDF-1 levels in asthmatic patients and improve clinical symptoms, lung function and improve patient outcomes.%目的 观察孟鲁司特联合酮替芬对哮喘患者血清转化生长因子-β1(TGF-β1)、单核细胞趋化蛋白-1(MCP-1)、基质细胞衍生因子-1(SDF-1)

  6. The influence of spleen aminopeptidase lyophilized powder on serum levels of TGF -β1,MCP -1,SDF -1 in pediatric asthma%脾氨肽口服冻干粉对小儿哮喘血清 TGF-β1、MCP-1、SDF-1水平的影响

    Institute of Scientific and Technical Information of China (English)

    严波

    2016-01-01

    目的探讨孟鲁司特联合脾氨肽口服冻干粉对小儿哮喘疗效及血清转化生长因子-β1(TGF-β1)、单核细胞趋化蛋白-1(MCP-1)、基质细胞衍生因子-1(SDF-1)水平的影响。方法选取128例小儿哮喘患儿,根据抽签法分为观察组(64例)及对照组(64例),对照组给予孟鲁司特口服治疗,观察组在对照组基础上加服脾氨肽口服冻干粉。观察两组治疗效果及肺功能改善情况。治疗前后应用 ELISA 法测定两组血清TGF-β1、MCP-1、SDF-1水平。结果观察组总有效率为96.87%高于对照组84.37%,差异有统计学意义(χ2=5.885,P =0.015)。观察组治疗后哮喘控制测试表(ACT)评分(24.25±3.98)分、第一秒呼气容积(FEV1)为(80.25±4.25)%和呼气峰值流速(PEF)(7.25±0.69)L/min,显著高于对照组(20.12±4.02)分、(75.02±3.96)%、(5.82±0.70)L/min(t =7.203,6.757,14.459,26.677,均 P <0.01)。观察组治疗后血清TGF-β1(42.23±6.02)ng/mL、MCP-1(48.56±3.96)ρg/mL、SDF-1(252.36±32.22)ng/L 水平低于对照组(42.23±6.02)ng/mL、(59.02±4.22)ρg/mL、(425.25±40.62)ng/L,差异有统计学意义(t =6.757,14.459,26.677,均 P <0.01)。结论孟鲁司特联合脾氨肽口服冻干粉能有效提高哮喘患儿治疗效果,改善患儿肺功能,其可能机制与降低哮喘患儿血清 TGF-β1、MCP-1、SDF-1水平有关。%Objective To investigate the influence of spleen aminopeptidase lyophilized powder on serum levels of transforming growth factor -β1 (TGF -β1),monocyte chemoattractant protein -1 (MCP -1),stromal cell derived factor 1 (SDF -1 )in pediatric asthma.Methods 128 patients with asthma were randomly divided into observation group(64 cases)and control group (64 cases).Two groups of children were given symptomatic

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

    Directory of Open Access Journals (Sweden)

    Fang Xiao

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

  8. 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.

  9. A MCP1 fusokine with CCR2-specific tumoricidal activity

    Directory of Open Access Journals (Sweden)

    Yuan Liangping

    2011-09-01

    Full Text Available Abstract Background The CCL2 chemokine is involved in promoting cancer angiogenesis, proliferation and metastasis by malignancies that express CCR2 receptor. Thus the CCL2/CCR2 axis is an attractive molecular target for anticancer drug development. Methods We have generated a novel fusion protein using GMCSF and an N-terminal truncated version of MCP1/CCL2 (6-76 [hereafter GMME1] and investigated its utility as a CCR2-specific tumoricidal agent. Results We found that distinct to full length CCL2 or its N-truncated derivative (CCL2 5-76, GMME1 bound to CCR2 on mouse lymphoma EG7, human multiple myeloma cell line U266, or murine and human medulloblastoma cell lines, and led to their death by apoptosis. We demonstrated that GMME1 specifically blocked CCR2-associated STAT3 phosphorylation and up-regulated pro-apoptotic BAX. Furthermore, GMME1 significantly inhibited EG7 tumor growth in C57BL/6 mice, and induced apoptosis of primary myeloma cells from patients. Conclusion Our data demonstrate that GMME1 is a fusokine with a potent, CCR2 receptor-mediated pro-apoptotic effect on tumor cells and could be exploited as a novel biological therapy for CCR2+ malignancies including lymphoid and central nervous system malignancies.

  10. Enforced effect of tk-MCP-1 fusion gene in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Hong Shuhui

    2012-09-01

    Full Text Available Abstract Objective The efficiency of HSV-tk/GCV system is not high because of insufficient gene transfer and incompletely initiative of host antineoplastic potency. The present study was designed to assess the antitumor efficacy of tk-MCP-1 on ovarian cancer in vitro and vivo. Methods A novel bicistronic expression system can help to improve the expression level of a gene in a stable manner. pLXSN/tk-MCP-1 co-expressing tk and MCP-1 genes was constructed using a pLXSN retroviral vector and an internal ribosome entry site sequence by restriction enzyme. Western blot was performed to determine tk and MCP-1 expression in the infected SKOV3. The GCV-sensitively tumoricidal activities of SKOV3/tk-MCP-1 with or without monocytes were compared to those of SKOV3 expressing HSV-tk or MCP-1. We investigated the growth of subcutaneous tumors in SCID mice immuno-reconstituted, and evaluated the antitumor effect of MCP-1 in conjunction with suicide gene. Results The significant GCV-sensitively tumoricidal activity of pLXSN/tk-MCP-1 was observed when compared with those of pLXSN/tk, pLXSN/MCP-1 and pLXSN/neo, especially when monocytes were added. The growth of subcutaneous tumors in SCID mice immuno-reconstituted was markedly suppressed by co-delivery of HSV-tk and MCP-1 genes, and the enhanced antitumor effect was associated with the recruitment of monocytes. Conclusion These results demonstrated pLXSN/tk-MCP-1 presented an enhanced antitumor effects on ovarian cancer by orchestration of immune responses.

  11. Epstein-Barr virus induces MCP-1 secretion by human monocytes via TLR2.

    Science.gov (United States)

    Gaudreault, Eric; Fiola, Stéphanie; Olivier, Martin; Gosselin, Jean

    2007-08-01

    Epstein-Barr virus (EBV) is a gammaherpesvirus infecting the majority of the human adult population in the world. TLR2, a member of the Toll-like receptor (TLR) family, has been implicated in the immune responses to different viruses including members of the herpesvirus family, such as human cytomegalovirus, herpes simplex virus type 1, and varicella-zoster virus. In this report, we demonstrate that infectious and UV-inactivated EBV virions lead to the activation of NF-kappaB through TLR2 using HEK293 cells cotransfected with TLR2-expressing vector along with NF-kappaB-Luc reporter plasmid. NF-kappaB activation in HEK293-TLR2 cells (HEK293 cells transfected with TLR2) by EBV was not enhanced by the presence of CD14. The effect of EBV was abrogated by pretreating HEK293-TLR2 cells with blocking anti-TLR2 antibodies or by preincubating viral particles with neutralizing anti-EBV antibodies 72A1. In addition, EBV infection of primary human monocytes induced the release of MCP-1 (monocyte chemotactic protein 1), and the use of small interfering RNA targeting TLR2 significantly reduced such a chemokine response to EBV. Taken together, these results indicate that TLR2 may be an important pattern recognition receptor in the immune response directed against EBV infection.

  12. MCP-1 expression by rat type II alveolar epithelial cells in primary culture.

    Science.gov (United States)

    Paine, R; Rolfe, M W; Standiford, T J; Burdick, M D; Rollins, B J; Strieter, R M

    1993-05-15

    Recruitment and activation of mononuclear phagocytes are potentially critical regulatory events for control of pulmonary inflammation. Located at the boundary between the alveolar airspace and the interstitium, alveolar epithelial cells are ideally situated to regulate the recruitment and activation of mononuclear phagocytes through the production of cytokines in response to inflammatory stimulation from the alveolar space. To test this hypothesis, we investigated the production of monocyte chemotactic polypeptide-1 (MCP-1), a protein that is chemotactic for and that activates monocytes, by rat type II alveolar epithelial cells in primary culture. Immunocytochemical staining using anti-murine JE, an antibody recognizing rat MCP-1, demonstrated cell-associated MCP-1 Ag throughout the monolayer. The intensity of staining was increased in response to IL-1 beta. When type II epithelial cells formed a tight monolayer on a filter support, there was polar secretion of MCP-1 Ag into the apical compartment by both control and IL-1-stimulated cells as measured by specific MCP-1 ELISA. Northern blot analysis revealed that IL-1 and TNF-alpha stimulated MCP-1 mRNA expression in a dose-dependent manner, whereas dexamethasone blocked MCP-1 expression by cells stimulated with IL-1. In contrast to previous results using transformed epithelial cell lines, MCP-1 mRNA was induced in these primary cultures directly by stimulation with LPS. These data suggest that alveolar epithelial cells may have an important and previously unrecognized role in the initiation and maintenance of inflammatory processes in the lung by recruiting and activating circulating monocytes through the production of MCP-1.

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

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    C Makena Hightower

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

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

    Directory of Open Access Journals (Sweden)

    LaFerla Frank M

    2005-10-01

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

  15. Meta-analysis on the association between MCP-1/CCR2 genes polymorphisms and coronary artery disease%MCP-1/CCR2基因多态性与冠状动脉疾病关联性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    朱军; 蒯正平; 严建军; 王泽穆; 唐建金; 杨志健; 王连生

    2011-01-01

    目的:采用Meta分析探讨单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)基因的G2518A位点及趋化因子受体2(CC chemokine receptor 2,CCR2)基因的G190A位点多态性与冠状动脉疾病(coronary artery disease,CAD)的关联性.方法:通过PubMed,EMbase,CNKI及CBM等数据库搜索关于MCP-1/CCR2基因多态性与CAD关联性的文章.结果:符合纳入标准的共有21篇文献,MCP-1基因的G2518A位点和CCR2基因的G190A位点分别有6 835例CAD患者、11 142例正常对照受试者,以及2 801例CAD患者、5 789例正常对照受试者入选.综合数据表明MCP-1基因的G2518A位点和CCR2基因G190A位点多态性与CAD的发生存在关联[G2518A(P=0.04),G190A(P=0.005)].根据分层分析观察到MCP-1基因的G2518A位点在非亚洲人群中与CAD存在关联性(P=0.04),而在亚洲人群中与CAD不具有统计学意义(P>0.05).结论:MCP-1基因的G2518A位点及CCR2基因的G190A位点多态性与CAD的发生具有统计学意义.%Objective;To assess the association of monocyte chemotactic protein-1 (MCP-l)gene G2518A and CC chemokine receptor 2(CCR2) gene G190A polymorphisms with coronary artery disea9e(CAD). Methods:Databases, including PubMed, Embase, CNKI and CBM, were searched to get the association studies on MCP-1/CCR2,RANTES/CCR5 genes polymorphisms and CAD. Results: A total of 21 case-control studies were identified. The Meta-analysis included 6 835(MCP-1-G2518A) CAD case and 11 142 controls,2 801 CAD cases and 5 789 controls(CCR2-G190A),respectively. MCP-1 gene G2518A polymorphism was significantly associated with CAD(P = 0.04). The CCR2 gene G190A polymorphism was also significantly associated with the presence of CAD(P = 0.005). In stratified analysis by race, the MCP-1 gene G2518A polymorphism was significantly associated with the presence of CAD in non-Asian (P = 0.04), while not in Asian (P>0.05). Conclusion:Our results showed that the MCP-1 gene G2518A and CCR2 gene G190A polymorphisms were

  16. Monocyte chemotactic protein-1 expression in coronary atherosclerosis plaque of sudden coronary death patients

    Institute of Scientific and Technical Information of China (English)

    冯相平

    2006-01-01

    Objective To investigate the expression of monocyte chemotactic protein 1 (MCP-1) in coronary atherosclerosis plaque of sudden coronary death (SCD) patients and the relationship between MCP-1 expression and SCD. Methods Autopsy heart samples (n=90) collected during 2001 - 2003 were divided to SCD group (n=

  17. St. John's Wort protein, p27SJ, regulates the MCP-1 promoter.

    Science.gov (United States)

    Mukerjee, Ruma; Deshmane, Satish L; Darbinian, Nune; Czernik, Marta; Khalili, Kamel; Amini, Shohreh; Sawaya, Bassel E

    2008-09-01

    St. John's Wort is commonly known for its antiviral, antidepressant, and cytotoxic properties, but traditionally St. John's Wort has also been used to treat inflammation. In this study, we sought to characterize the mechanisms used by St. John's Wort to treat inflammation by examining the effect of the recently isolated protein from St. John's Wort, p27SJ on the expression of MCP-1. By employing an adenovirus expression vector, we demonstrate that a low concentration of p27SJ upregulates the MCP-1 promoter through the transcription factor C/EBPbeta. In addition, we found that C/EBPbeta-homologous protein (CHOP) or siRNA-C/EBPbeta significantly reduced the ability of p27SJ to activate MCP-1 gene expression. Results from protein-protein interaction studies illustrate the existence of a physical interaction between p27SJ and C/EBPbeta in microglial cells. The use of chromatin immunoprecipitation assay (ChIP) led to the identification of a new cis-element that is responsive to C/EBPbeta within the MCP-1 promoter. Association of C/EBPbeta with MCP-1 DNA was not affected by the presence of p27SJ. The biological activity of MCP-1 produced by cultures of adenovirus-p27SJ transduced cells was increased relative to controls as measured by the transmigration of human Jurkat cells. Thus, we conclude that at high concentration, p27SJ is a potential agent that may be developed as a modulator of MCP-1 leading to the inhibition of the cytokine-mediated inflammatory responses.

  18. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1

    Science.gov (United States)

    Yu, Bo; Shao, Hui; Su, Chang; Jiang, Yuanfeng; Chen, Xiteng; Bai, Lingling; Zhang, Yan; Li, Qiutang; Zhang, Xiaomin; Li, Xiaorong

    2016-01-01

    Although accumulated evidence supports the notion that mesenchymal stem cells (MSCs) act in a paracrine manner, the mechanisms are still not fully understood. Recently, MSC-derived exosomes (MSC-Exos), a type of microvesicle released from MSCs, were thought to carry functional proteins and RNAs to recipient cells and play therapeutic roles. In the present study, we intravitreally injected MSCs derived from either mouse adipose tissue or human umbilical cord, and their exosomes to observe and compare their functions in a mouse model of laser-induced retinal injury. We found that both MSCs and their exosomes reduced damage, inhibited apoptosis, and suppressed inflammatory responses to obtain better visual function to nearly the same extent in vivo. Obvious down-regulation of monocyte chemotactic protein (MCP)-1 in the retina was found after MSC-Exos injection. In vitro, MSC-Exos also down-regulated MCP-1 mRNA expression in primarily cultured retinal cells after thermal injury. It was further demonstrated that intravitreal injection of an MCP-1-neutralizing antibody promoted the recovery of retinal laser injury, whereas the therapeutic effect of exosomes was abolished when MSC-Exos and MCP-1 were administrated simultaneously. Collectively, these results suggest that MSC-Exos ameliorate laser-induced retinal injury partially through down-regulation of MCP-1. PMID:27686625

  19. Parenteral iron formulations differentially affect MCP-1, HO-1, and NGAL gene expression and renal responses to injury.

    Science.gov (United States)

    Johnson, Ali C M; Becker, Kirsten; Zager, Richard A

    2010-08-01

    Despite their prooxidant effects, ferric iron compounds are routinely administered to patients with renal disease to correct Fe deficiency. This study assessed relative degrees to which three clinically employed Fe formulations [Fe sucrose (FeS); Fe gluconate (FeG); ferumoxytol (FMX)] impact renal redox- sensitive signaling, cytotoxicity, and responses to superimposed stress [endotoxin; glycerol-induced acute renal failure (ARF)]. Cultured human proximal tubule (HK-2) cells, isolated proximal tubule segments (PTS), or mice were exposed to variable, but equal, amounts of FeS, FeG, or FMX. Oxidant-stimulated signaling was assessed by heme oxygenase-1 (HO-1) or monocyte chemoattractant protein (MCP)-1 mRNA induction. Cell injury was gauged by MTT assay (HK-2 cells), %LDH release (PTS), or renal cortical neutrophil gelatinase-associated lipoprotein (NGAL) protein/mRNA levels. Endotoxin sensitivity and ARF severity were assessed by TNF-alpha and blood urea nitrogen concentrations, respectively. FeS and FeG induced lethal cell injury (in HK-2 cells, PTS), increased HO-1 and MCP-1 mRNAs (HK-2 cells; in vivo), and markedly raised plasma ( approximately 10 times), and renal cortical ( approximately 3 times) NGAL protein levels. Both renal and extrarenal (e.g., hepatic) NGAL production likely contributed to these results, based on assessments of tissue and HK-2 cell NGAL mRNA. FeS pretreatment exacerbated endotoxemia. However, it conferred marked protection against the glycerol model of ARF (halving azotemia). FMX appeared to be "bioneutral," as it exerted none of the above noted FeS/FeG effects. We conclude that 1) parenteral iron formulations that stimulate redox signaling can evoke cyto/nephrotoxicity; 2) secondary adaptive responses to this injury (e.g., HO-1/NGAL induction) can initiate a renal tubular cytoresistant state; this suggests a potential new clinical application for intravenous Fe therapy; and 3) FMX is bioneutral regarding these responses. The clinical

  20. Puerarin reduces serum levels of advanced glycation end products and monocyte chemoattractant protein-1 in diabetic rats%葛根素降低糖尿病大鼠血清糖基化终产物水平和单核细胞趋化蛋白1含量

    Institute of Scientific and Technical Information of China (English)

    陆静; 刘乃丰; 张丽容

    2004-01-01

    目的研究葛根素对糖尿病大鼠糖基化终产物(AGEs)水平和单核细胞趋化蛋白1(MCP-1)表达的影响.方法将大鼠随机分为正常对照组(CON)、糖尿病组(DM)、糖尿病氨基胍治疗组(AG)和糖尿病葛根素治疗组(PU).腹腔注射链脲佐菌素诱导糖尿病模型,检测血清中AGEs(荧光法)和MCP-1(ELISA)水平;病理切片PAS染色及电镜观察肾组织的病理改变.免疫组化检测肾皮质MCP-1的蛋白表达水平.结果 DM组血清AGEs和MCP-1水平较PU组和AG组明显增高(均P<0.05);电镜发现两个治疗组的肾小球基底膜和心肌细胞病理改变程度比糖尿病组轻;肾小球内皮细胞和系膜区MCP-1免疫组化染色阳性细胞数明显比糖尿病组少.结论葛根素能降低糖尿病大鼠血清AGEs和MCP-1水平,减少肾皮质中MCP-1的表达,减轻肾脏和心肌的病变程度.

  1. Changes of serum levels of MCP-1 and SCF in patients with acute coronary syndromes%急性冠状动脉综合征患者血清单核细胞趋化蛋白-1和干细胞因子的变化

    Institute of Scientific and Technical Information of China (English)

    邓争荣; 李尚俭; 朱宏海; 王军奎; 官功昌; 梁磊; 刘新宏; 陈新义

    2011-01-01

    Objective:To investigate the changes of serum monocyte chemotactic protein 1 (MCP 1) and stem cell factor (SCF) in patients with acute coronary syndrome (A CS) and theirs possible relationship with ACS.Method:41 patients with acute myocardial infarction (AMI), 45 patients with unstable angina (UA) and 32 con trols were enrolled. The serum levels of MCP- 1 and SCF were measured by ELISA in all subjects. Result:The set um levels of MCP- 1 in AMI and UA patients were significantly higher than that in controls (P<0.01 and P< 0.05). The serum levels of SCF in AMI and UA patients were slightly higher than in controls, but there were not significantly different among three groups. The serum levels of MCP -1 and SCF in AMI patients were not related to white blood cells、neutrophil and blood fat. Conclusion:The serum level of MCP -1 in ACS patients, especialy in AMI patients, was significantly increase. The serum levels of SCF in ACS patients was slightly increase. MCP -1 and SCF might be associated with pathogenesis of ACS and cardiac repair after myocardial infarction.%目的:检测急性冠状动脉综合征(ACS)患者血清单核细胞趋化蛋白-1(MCP-1)和干细胞因子(SCF)的变化,探讨MCP-1和SCF与ACS的关系.方法:纳入急性心肌梗死患者41例,不稳定型心绞痛患者45例,对照组32例,应用ELISA法测定其血清MCP-1和SCF的水平.结果:心肌梗死组和心绞痛组MCP-1水平均明显高于对照组(P<0.01和P<0.05).心肌梗死组及心绞痛组SCF水平略高于对照组,但差异无统计学意义.心肌梗死组MCP-1及SCF水平与血白细胞数、中性粒细胞比率及血脂等水平均无明显相关性.结论:ACS患者尤其是急性心肌梗死患者血MCP-1明显升高,SCF亦有所增加.MCP-1和SCF可能与ACS的发生发展及梗死后的心肌修复有关.

  2. Effects of leflunomide on renal pathology and expression of MCP-1 in renal tissue in rat experimental IgA nephropathy model%Leflunomide对实验性IgA肾病大鼠肾脏病理及MCP-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    汤颖; 娄探奇; 成彩联; 陈珠江; 张俊

    2006-01-01

    目的观察leflunomide对实验性IgA肾病(IgA nephropathy IgA N)大鼠肾脏病理及肾组织单核细胞趋化因子(monocyte chemoattractive peptide1,MCP-1)表达的影响,了解其作用机制.方法建立IgAN大鼠模型,随机分成leflunomide组,强的松组,模型对照组,并同时设立正常对照组.行免疫荧光、光镜检查,并用免疫组化和RT-PCR方法分别检测肾组织MCP-1蛋白和基因水平的表达.结果与模型对照组相比,leflunomide组免疫复合物在肾脏的沉积明显减少,系膜区基质增生程度显著减轻(P<0.01);Leflunomide在基因和蛋白水平均能够有效抑制MCP-1在肾组织的表达(P<0.05).结论Leflunomide能够减少免疫复合物在肾脏的沉积,减轻系膜区基质增生,并且下调MCP-1在肾脏的表达,减少局部炎症反应,减轻肾脏损害,保护肾脏.

  3. 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.

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

    Science.gov (United States)

    de-Oliveira-Pinto, Luzia Maria; Gandini, Mariana; Freitas, Laís Picinini; Siqueira, Marilda Mendonça; Marinho, Cíntia Ferreira; Setúbal, Sérgio; Kubelka, Claire Fernandes; Cruz, Oswaldo Gonçalves; Oliveira, Solange Artimos de

    2012-02-01

    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.

  5. Research of MCP-1 expression in rat's retina injured by ischemia-reperfusion%MCP-1在大鼠视网膜缺血再灌注损伤中的表达及意义研究

    Institute of Scientific and Technical Information of China (English)

    游志鹏; 姜德咏; 李国栋; 赵宏伟

    2003-01-01

    目的了解MCP-1在大鼠视网膜缺血再灌注损伤中的表达及意义.方法建立大鼠视网膜缺北血再灌注模型,以SABC法检测MCP-1在视网膜中的表达,统计学分析.结果MCP-1在视网膜缺血再灌注6 h开始表达,第24小时达到最高峰,48 h开始表达减弱.结论MCP-1在视网膜缺血再灌注损伤中起重要作用.%Objective:The retina ischemia- reperfusion injury is caused by many factors. A lot of cell factors take part in it. Many researches suggest MCP - 1 has special effect on leukocyte and lymphocyte. The research try to study the effect of MCP - 1 in rat's retina ischemia- reperfusion injury. Methods: To employ the rat's retina ischemia- reperfusion model and use SABC method to test the expression of MCP- 1 on retina. Results: There was no MCP - 1 expressed in retina after ischemia- reperfusion injury for one hour. MCP- 1 began to express in retina after ischemia- reperfusion injury for six hours, and expressed at most after ischemia- reperfusion injury for 24 hours. Then it began to decrease in 48 hours after ischemia - repeffusion injury, but it still expressed in retina in seventy- two hours after ischemia- reperfusion injury. Conclusions: MCP- 1 plays an important role in rat's retina ischemia- reperfusion injury.

  6. 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

  7. 5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability

    Directory of Open Access Journals (Sweden)

    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

  8. Monocyte chemotactic protein-1 gene polymorphism and spontaneous bacterial peritonitis

    Institute of Scientific and Technical Information of China (English)

    Levent; Filik

    2010-01-01

    I read with great interest the article by Gbele et al published in issue 44 of World J Gastroenterol 2009.The results of their study indicate that-2518 Monocyte chemotactic protein-1(MCP-1)genotype AA is a risk factor for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.However,there are some items that need to be discussed.

  9. NCBI nr-aa BLAST: CBRC-MMUS-09-0220 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available mo sapiens] gb|AAA19120.1| MCP-1 receptor dbj|BAA06253.1| monocyte chemoattractant protein 1 receptor [Homo ...sapiens] gb|AAC51636.1| monocyte chemoattractant protein 1 receptor [Homo sapiens

  10. NCBI nr-aa BLAST: CBRC-HSAP-26-0009 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available mo sapiens] gb|AAA19120.1| MCP-1 receptor dbj|BAA06253.1| monocyte chemoattractant protein 1 receptor [Homo ...sapiens] gb|AAC51636.1| monocyte chemoattractant protein 1 receptor [Homo sapiens

  11. Characterization of endocannabinoid-mediated induction of myeloid-derived suppressor cells involving mast cells and MCP-1.

    Science.gov (United States)

    Jackson, Austin R; Hegde, Venkatesh L; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2014-04-01

    Endocannabinoids are lipid-signaling molecules found in the nervous system; however, their precise role in the periphery is unclear. In the current study, we observed that a single i.p. administration of AEA caused rapid induction of MDSCs. The MDSCs contained a mixture of granulocytic and monocytic subtypes and expressed Arg-1 and iNOS. The MDSCs suppressed T cell proliferation in vitro and used iNOS to mediate their effect. Moreover, adoptive transfer of MDSCs led to suppression of mBSA-induced DTH. Through the use of pharmacological inhibition, as well as genetic knockout mice, we found that the induction of MDSCs by AEA was CB1-dependent. The induction of MDSCs by AEA was reduced significantly in mast cell-deficient mice, while maintained in LPS-insensitive mice, showing that the induction of MDSCs by AEA was dependent, at least in part, on mast cells and independent of TLR4. Chemokine analysis of AEA- treated WT mice showed an early spike of MCP-1, which was decreased in Kit(W/W-sh) mice, showing a role of mast cells in the secretion of MCP-1 in response to AEA. Also, use of antibodies against MCP-1 or mice deficient in MCP-1 confirmed the role played by MCP-1. Interestingly, MCP-1 played a significant role in the induction of monocytic but not granulocytic MDSCs. Our studies demonstrate for the first time that endocannaboinids activate CB1 on mast cells to induce MCP-1, which facilitates recruitment of monocytic MDSCs.

  12. Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Teizo eYoshimura

    2015-06-01

    Full Text Available The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC, because MCP-1 mRNA was highly expressed in tumors grown in both WT and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.

  13. Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma.

    Science.gov (United States)

    Yoshimura, Teizo; Liu, Mingyong; Chen, Xin; Li, Liangzhu; Wang, Ji Ming

    2015-01-01

    The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma, and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both wild type (WT) and MCP-1(-/-) mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα(-/-) mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα(-/-) mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly, tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.

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

    Directory of Open Access Journals (Sweden)

    David Patsouris

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

  15. 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.

  16. 尿单核细胞趋化蛋白1和血清胱抑素C在糖尿病肾病早期诊断中的临床意义%Clinical Significance of Urinary Monocyte Chemoattractant Protein-1 and Serum Cystatin C in the Early Diagnosis of Diabetic Nephropathy

    Institute of Scientific and Technical Information of China (English)

    柯箫韵; 余育才

    2011-01-01

    目的 探讨尿单核细胞趋化蛋白1(UMCP-1)和血清胱抑素C(CysC)在糖尿病肾病(DN)早期诊断中的临床意义.方法 依据尿清蛋白排泄率(UAER)将137例2型糖尿病(T2DM)患者分为3组:DN临床组(46例)、DN早期组(48例)及DN前期组(43例),另选择体检健康者50例作为对照组.分别检测各组受检者的UMCP-1[以UMCP-1/尿肌酐(UCr)表示,即UMCP-1/UCr]、血清CysC、尿微量清蛋白(UMA)和血肌酐(SCr)水平.结果 DN前期组患者UMCP-1、血清CysC水平较对照组显著升高,差异有统计学意义(P<0.05);DN早期组、DN临床组患者UMCP-1、血清CysC和UMA水平分别与DN前期组、对照组比较亦显著升高,差异有统计学意义(P<0.01);DN临床组患者SCr水平显著高于对照组和DN前期组,差异有统计学意义(P<0.01).相关分析显示,UMCP-1/UCr和CysC均与UMA呈正相关(P<0.05).结论 UMCP-1联合血清CysC检测有助于DN的早期诊断.%Objective To explore the clinical significance of urinary monocyte chemoattractant protein -1 ( UMCP-1 ) and serum cystatin C ( CysC ) in the early diagnosis of diabetic nephropathy. Methods Based on urinary albumin excretion rate ( UAER ), 137 patients with type 2 diabetes were divided into three groups: diabetic nephropathy group ( clinical group,46 cases ), early group of diabetic nephropathy ( early group, 48 cases ), and pre - diabetic nephropathy group ( pre - stage group, 43 cases ) . Fifty healthy subjects were enrolled as controls. UMCP -1 [ in the form of UMCP -1/urinary creatinine ( UMCP - 1/UCr ) ], serum CysC, microalbuminuria ( UMA ) and serum creatinine ( SCr ) concentrations were detected in all groups. Results Levels of UMCP -1 and serum CysC were significantly higher in the pre - stage group than in the control group ( P < 0. 05 ) . Levels of UMCP - 1, serum CysC and UMA were higher in the early group and the clinical group than in the pre -stage group and the control group ( P <0. 01 ) . Relation analysis revealed

  17. Monocyte chemotactic protein 1 increases homing of mesenchymal stem cell to injured myocardium and neovascularization following myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To investigate the effect of MCP-1 on mesenchymal stem cells(MSCs) homing to injured myocardium in a rat myocardial infarction(MI) model. Methods:Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein 1(MCP-1) expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1,2, 4,7,14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 106 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results:Self-generating MCP-1 expression was increased at the first day, peaked at the 7th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-Mi group(P = 0.000), the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups (P = 0.000). Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups(P= 0.000). Neovascularization in MCP-1 injected group significantly increased compared with that of other groups(P = 0.000). Conclusion: Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.

  18. 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.

  19. 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.

  20. Prostaglandin EP2 and EP4 receptors modulate expression of the chemokine CCL2 (MCP-1) in response to LPS-induced renal glomerular inflammation.

    Science.gov (United States)

    Zahner, Gunther; Schaper, Melanie; Panzer, Ulf; Kluger, Malte; Stahl, Rolf A K; Thaiss, Friedrich; Schneider, André

    2009-08-27

    The pro-inflammatory chemokine CCL2 [chemokine (Cys-Cys motif) ligand 2; also known as MCP-1 (monocyte chemotactic protein-1)] is up-regulated in the glomerular compartment during the early phase of LPS (lipopolysaccharide)-induced nephritis. This up-regulation also occurs in cultured MCs (mesangial cells) and is more pronounced in MCs lacking the PGE2 (prostaglandin E2) receptor EP2 or in MCs treated with a prostaglandin EP4 receptor antagonist. To examine a possible feedback mechanism of EP receptor stimulation on CCL2 expression, we used an in vitro model of MCs with down-regulated EP receptor expression. Selectively overexpressing the various EP receptors in these cells then allows the effects on the LPS-induced CCL2 expression to be examined. Cells were stimulated with LPS and CCL2 gene expression was examined and compared with LPS-stimulated, mock-transfected PTGS2 [prostaglandin-endoperoxide synthase 2, also known as COX-2 (cyclo-oxygenase-2)]-positive cells. Overexpression of EP1, as well as EP3, had no effect on LPS-induced Ccl2 mRNA expression. In contrast, overexpression of EP2, as well as EP4, significantly decreased LPS-induced CCL2 expression. These results support the hypothesis that PTGS2-derived prostaglandins, when strongly induced, counter-balance inflammatory processes through the EP2 and EP4 receptors in MCs.

  1. Early alterations in blood and brain RANTES and MCP-1 expression and the effect of exercise frequency in the 3xTg-AD mouse model of Alzheimer's disease.

    Science.gov (United States)

    Haskins, Morgan; Jones, Terry E; Lu, Qun; Bareiss, Sonja K

    2016-01-01

    Exercise has been shown to protect against cognitive decline and Alzheimer's disease (AD) progression, however the dose of exercise required to protect against AD is unknown. Recent studies show that the pathological processes leading to AD cause characteristic alterations in blood and brain inflammatory proteins that are associated with the progression of AD, suggesting that these markers could be used to diagnosis and monitor disease progression. The purpose of this study was to determine the impact of exercise frequency on AD blood chemokine profiles, and correlate these findings with chemokine brain expression changes in the triple transgenic AD (3xTg-AD) mouse model. Three month old 3xTg-AD mice were subjected to 12 weeks of moderate intensity wheel running at a frequency of either 1×/week or 3×/week. Blood and cortical tissue were analyzed for expression of monocyte chemotactic protein-1 (MCP-1) and regulated and normal T cell expressed and secreted (RANTES). Alterations in blood RANTES and MCP-1 expression were evident at 3 and 6 month old animals compared to WT animals. Three times per week exercise but not 1×/week exercise was effective at reversing serum and brain RANTES and MCP-1 expression to the levels of WT controls, revealing a dose dependent response to exercise. Analysis of these chemokines showed a strong negative correlation between blood and brain expression of RANTES. The results indicate that alterations in serum and brain inflammatory chemokines are evident as early signs of Alzheimer's disease pathology and that higher frequency exercise was necessary to restore blood and brain inflammatory expression levels in this AD mouse model.

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

    OpenAIRE

    Rogil José de Almeida Torres; Lucia Noronha; Antonio Marcelo Barbante Casella; Thaís Isabel Lumikoski; Leonardo Brandão Précoma; Caroline Luzia de Almeida Torres; Andréa Luchini; Mario Claudio Soares Sturzeneker; Dalton Bertolim Précoma

    2012-01-01

    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 colester...

  3. 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.

  4. 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

  5. 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.

  6. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein.

    OpenAIRE

    Navab, M; Imes, S S; Hama, S Y; Hough, G P; Ross, L.A.; Bork, R W; Valente, A. J.; Berliner, J A; Drinkwater, D C; Laks, H

    1991-01-01

    Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from t...

  7. Monocyte Chemotactic Protein-1 Promotes the Myocardial Homing of Mesenchymal Stem Cells in Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Yunzeng Zou

    2013-04-01

    Full Text Available Dilated cardiomyopathy (DCM is the most common form of non-ischemic cardiomyopathy that leads to heart failure. Mesenchymal stem cells (MSCs are under active investigation currently as a potential therapy for DCM. However, little information is available about the therapeutic potential of intravenous administration of MSCs for DCM. Moreover, how MSCs home to the myocardium in DCM is also unclear. DCM was induced by intraperitoneally administering Doxorubicin and MSCs or vehicles were infused through the internal jugular vein. Cardiac functions including the percentage of fractional shortening, left ventricular diastolic dimension, left ventricular end-diastolic pressure, and left ventricular maximum dp/dt were evaluated by echocardiographic and hemodynamic studies. Fibrosis was determined by Masson’s trichrome staining. The mRNA expression levels of monocyte chemotactic protein-1 (MCP-1, stromal cell-derived factor-1 (SDF-1, macrophage inflammatory protein-1α (MIP-1α, and monocyte chemotactic protein-3 (MCP-3 were determined using real time polymerase chain reactions and the protein expression level of MCP-1 was detected with Western blot. The MSCs expression of C-C chemokine receptor type 2 (CCR2, a MCP-1 receptor, was confirmed by Western blot and flow cytometry analysis. The chemotactic effects of MCP-1/CCR2 were checked by assessing the migration in vitro and in vivo. MSCs transplantation improved the cardiac function and decreased the myocardial fibrosis of mice with DCM. MCP-1 was up-regulated in dilated myocardial tissue both at the mRNA and protein level while SDF-1, MIP-1α and MCP-3 remain unchanged. CCR2 was present in MSCs. MCP-1 promoted MSCs migration in vitro while CCR2 inhibition decreased the migration of MCP-1 to the dilated heart. This study provides direct evidences that peripheral intravenous infusion of MSCs can support the functional recovery of DCM. In addition, novel insights into the myocardial homing factor of MSCs

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

    Directory of Open Access Journals (Sweden)

    David Christopher Nieman

    2016-09-01

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

  9. Monocyte chemotactic protein-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet

    Science.gov (United States)

    Obesity is a risk factor for cancer. Adipose tissue produces pro-inflammatory adipokines that contribute obesity-related malignant progression. This study investigated the effects of monocyte chemotactic protein-1 (MCP-1) deficiency on pulmonary metastasis of Lewis lung carcinoma (LLC) in male C57...

  10. Pyrrolidine dithiocarbamate (PDTC) inhibits the overexpression of MCP-1 and attenuates microglial activation in the hippocampus of a pilocarpine-induced status epilepticus rat model.

    Science.gov (United States)

    Lv, Rilang; Xu, Xiaoyun; Luo, Zheng; Shen, Nan; Wang, Feng; Zhao, Yongbo

    2014-01-01

    The aim of this study was to investigate the effects of pyrrolidine dithiocarbamate (PDTC) on MCP-1 expression and microglial activation in the hippocampus of a rat model of pilocarpine (PILO)-induced status epilepticus (SE). Moreover, seizure susceptibility, frequency and severity as well as brain damage were analyzed and changes in behavior were recorded. Chemokine MCP-1 expression and microglial activation were detected by immunohistochemistry (IHC). Fluoro-Jade C (FJC) and NeuN staining were used for the evaluation of tissue damage. Our results showed that although SE resulted in the upregulation of MCP-1 and microglial activation in the rat hippocampus 24 h after seizure onset, pretreatment with PDTC significantly inhibited the MCP-1 overexpression and attenuated the microglial activation. These effects were accompanied by neurodegenerative amelioration. To the best of our knowledge, these findings indicated for the first time that the activation of the nuclear factor-κB (NF-κB) pathway may contribute to MCP-1 upregulation and microglial activation in the context of epilepsy. PDTC was also shown to exert anticonvulsant activity and to have a neuroprotective effect on the hippocampal CA1 and CA3 regions, potentially through attenuating microglial activation.

  11. CD8 T cells are involved in skeletal muscle regeneration through facilitating MCP-1 secretion and Gr1(high) macrophage infiltration.

    Science.gov (United States)

    Zhang, Jing; Xiao, Zhicheng; Qu, Chao; Cui, Wei; Wang, Xiaonan; Du, Jie

    2014-11-15

    Inflammatory microenvironments play a key role in skeletal muscle regeneration. The infiltration of CD8 T cells into injured muscle has been reported. However, the role of CD8 T cells during skeletal muscle regeneration remains unclear. In this study, we used cardiotoxin-induced mouse skeletal muscle injury/regeneration model to investigate the role of CD8 T cells. Muscle regeneration was impaired and matrix deposit was increased in CD8α-deficient mice compared with wild-type (WT) mice whose CD8 T cells were infiltrated into damaged muscle after cardiotoxin injection. Adoptive transfer of CD8 T cells to CD8α-deficient mice improved muscle regeneration and inhibited matrix remodeling. Compared with WT mice, CD8α deficiency limited the recruitment of Gr1(high) macrophages (MPs) into muscle, resulting in the reduction of satellite cell number. The expression of MCP-1 (MCP-1/CCL2), which regulates the migration of Gr1(high) MPs, was reduced in CD8α-deficient mice compared with WT mice. Coculture CD8 T cells with MPs promoted MCP-1 secretion. The i.m. injection of MCP-1 markedly promoted the recruitment of Gr1(high) MPs and improved muscle regeneration in CD8α-deficient mice. We conclude that CD8 T cells are involved in skeletal muscle regeneration by regulating the secretion of MCP-1 to recruit Gr1(high) MPs, which facilitate myoblast proliferation.

  12. 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).

    Science.gov (United States)

    Rempel, Lisienny C T; Finco, Alessandra B; Maciel, Rayana A P; Bosquetti, Bruna; Alvarenga, Larissa M; Souza, Wesley M; Pecoits-Filho, Roberto; Stinghen, Andréa E M

    2015-05-14

    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.

  13. Controlled Pseudopod Extension of Human Neutrophils Stimulated with Different Chemoattractants

    OpenAIRE

    Zhelev, Doncho V.; Alteraifi, Abdullatif M.; Chodniewicz, David

    2004-01-01

    The formation of pseudopods and lamellae after ligation of chemoattractant sensitive G-protein coupled receptors (GPCRs) is essential for chemotaxis. Here, pseudopod extension was stimulated with chemoattractant delivered from a micropipet. The chemoattractant diffusion and convection mass transport were considered, and it is shown that when the delivery of chemoattractant was limited by diffusion there was a strong chemoattractant gradient along the cell surface. The diffusion-limited delive...

  14. 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

  15. 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.

  16. 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.

  17. 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. 

  18. Leflunomide对实验性IgA肾病大鼠肾脏TGF -β1、MCP-1表达的影响%Effects of leflunomide on TGF-β1, MCP-1 expression in renal tissue in a rat experimental IgA nephropathy model

    Institute of Scientific and Technical Information of China (English)

    汤颖; 娄探奇; 成彩联; 游宇平; 冯智英

    2007-01-01

    目的:分别从基因和蛋白水平研究leflunomide对实验性IgA肾病(IgAN)大鼠肾组织转化生长因子(TGF-β1)、单核细胞趋化因子(MCP-1)水平的影响,了解其作用机制.方法:建立IgAN大鼠模型,随机分成leflunomide组、强的松组、模型对照组,并同时设立正常对照组.用免疫组化、RT-PCR的方法分别检测和比较各组肾组织TGF-β1、MCP-1蛋白和基因的表达水平.结果:Leflunomide组TGF-β1、MCP-1表达均明显低于模型对照组(P<0.05);leflunomide组与激素组相比,TGF-β1、MCP-1表达无明显差异.结论:Leflunomide可通过下调TGF-β1、MCP-1在肾脏的表达,减少局部炎症反应,延缓肾脏纤维化的进程,从而保护肾脏.

  19. Monocyte chemotactic protein-1 attenuates and high-fat diet exacerbates bone loss in mice with pulmonary metastasis of Lewis lung carcinoma

    Science.gov (United States)

    Bone can be adversely affected by obesity and cancer-associated complications including wasting. The objective of this study was to determine whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects found in male C57BL/6 mice with Lewis lung...

  20. 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.

  1. 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.

  2. 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.

  3. 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%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

    Institute of Scientific and Technical Information of China (English)

    贾丽超; 周明学; 张蕾; 刘卫红

    2014-01-01

    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分为正常组、模型组、立普妥组、当归芍药散组(n =15)。采用高脂饮食联合脂多糖注射造成小鼠代谢性炎性反应模型。造模5周后,开始灌胃给药,每天2次,当归芍药散2.2 g/ kg,立普妥0.003 g/ kg。正常对照组和模型组灌服等体积蒸馏水。连续灌胃5周。处死后采血和取肝脏,检测各组小鼠血清胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)和低密度脂蛋白胆固醇(low density lipoprotein,LDL-C)浓度,并采用流式细胞术检测血清炎性反应因子 IL-6和 MCP-1浓度。反转录聚合酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)法测定肝脏 NF-κB 和 PPARγmRNA 的表达。结果与模型组相比,当归芍药散组小鼠血清 TC 和 LDL-C 水平明显降低(P<0.01),肝脏组织中 NF-κB mRNA 的表达降低,差异有统计学意义(P<0.05),PPARγmRNA 的表达提高,差异有统计学意义(P<0.05)。结论当归芍药散可降低代谢性炎性反应小鼠血脂和血清炎性反应因子 IL-6和 MCP-1浓度,并可通过调控核转录因子 NF-κB 和 PPARγ受体,抑制小鼠体内代谢性炎性反应,从而可能对早期动脉粥样硬化起到干预作用。%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

  4. Clinical value of detection on serum monocyte chemotactant protein-1 and vascular endothelial cadherin levels in patients with acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Xia Zhou; Cheng Zhang

    2016-01-01

    Objective: To study the correlation of serum monocyte chemotactant protein-1 (MCP-1) and vascular endothelia cadherin (VE-cadherin) levels in patients with acute cerebral infarction, and nerve injury molecules, interleukins and matrix metalloproteinases. Methods: A total of 86 patients with acute cerebral infarction treated in our hospital from April 2012 to October 2015 were selected as the observation group and 50 healthy subjects in the same period treated in our hospital were selected as the control group. The serums were collected and the contents of MCP-1, VE-cadherin, heart-type fatty acid binding protein (H-FABP), S100 calcium binding protein B (S100B), neuron-specific enolase (NSE), interleukin-lb (IL-1b), IL-6, IL-17, IL-18, matrix metalloproteinase-2 (MMP2), MMP3 and MMP9 were measured. Results: The serum contents of MCP-1, VE-cadherin, H-FABP, S100B, NSE, IL-1b, IL-6, IL-17, IL-18, MMP2, MMP3 and MMP9 in observation group were significantly higher than those of control group. Carotid artery plaque formation and unstable plaque properties will increase the serum contents of MCP-1, VE-cadherin, H-FABP, S100B, NSE, IL-1b, IL-6, IL-17, IL-18, MMP2, MMP3 and MMP9 in patients with cerebral infarction. The serum levels of MCP-1, VE-cadherin and the contents of H-FABP, S100B, NSE, IL-1b, IL-6, IL-17, IL-18, MMP2, MMP3 and MMP9 were positively correlated. Conclusions: The serum levels of VE-cadherin and MCP-1 were significantly increased in patients with acute cerebral infarction. MCP-1 and VE-cadherin can increase the secretion of interleukins and matrix metalloproteinases, which can result in the carotid artery plaque formation, unstable plaque properties and the injury of nerve function.

  5. Clinical value of detection on ser um monocyte chemotactant protein-1 and vascular endothelial cadher in levels in patients with acute cerebral infarction

    Directory of Open Access Journals (Sweden)

    Xia Zhou

    2016-11-01

    Full Text Available Objective: To study the correlation of serum monocyte chemotactant protein-1 (MCP-1 and vascular endothelia cadherin (VE-cadherin levels in patients with acute cerebral infarction, and nerve injury molecules, interleukins and matrix metalloproteinases. Methods: A total of 86 patients with acute cerebral infarction treated in our hospital from April 2012 to October 2015 were selected as the observation group and 50 healthy subjects in the same period treated in our hospital were selected as the control group. The serums were collected and the contents of MCP-1, VE-cadherin, heart-type fatty acid binding protein (H-FABP, S100 calcium binding protein B (S100B, neuron-specific enolase (NSE, interleukin-lb (IL-1b, IL-6, IL-17, IL-18, matrix metalloproteinase-2 (MMP2, MMP3 and MMP9 were measured. Results: The serum contents of MCP-1, VE-cadherin, H-FABP, S100B, NSE, IL-1b, IL- 6, IL-17, IL-18, MMP2, MMP3 and MMP9 in observation group were significantly higher than those of control group. Carotid artery plaque formation and unstable plaque properties will increase the serum contents of MCP-1, VE-cadherin, H-FABP, S100B, NSE, IL-1b, IL-6, IL-17, IL-18, MMP2, MMP3 and MMP9 in patients with cerebral infarction. The serum levels of MCP-1, VE-cadherin and the contents of H-FABP, S100B, NSE, IL-1b, IL-6, IL-17, IL-18, MMP2, MMP3 and MMP9 were positively correlated. Conclusions: The serum levels of VE-cadherin and MCP-1 were significantly increased in patients with acute cerebral infarction. MCP-1 and VE-cadherin can increase the secretion of interleukins and matrix metalloproteinases, which can result in the carotid artery plaque formation, unstable plaque properties and the injury of nerve function.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Adipokines play important regulatory roles in the pathophysiology of obesity and insulin resistance. We measured plasma and interstitial concentrations of the adipokines adiponectin, resistin, leptin, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8...

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

    Directory of Open Access Journals (Sweden)

    Stephen Wood

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

  8. Effect of huatan tongluo therapy combined with urokinase thrombolysis on PAF MCP-1 in different brain regions in rats with acute cerebral infarction%化痰通络法联合尿激酶溶栓对急性脑梗死大鼠不同脑区PAF、MCP-1的影响

    Institute of Scientific and Technical Information of China (English)

    周震; 张玉莲; 郭家奎; 王占奎; 刘爽; 张琳琳

    2010-01-01

    [目的]通过观察化痰通络法联合尿激酶溶栓对急性脑梗死大鼠不同脑区血小板活化因子(PAF)和核细胞趋化蛋白-1(MCP-1)的影响.[方法]SD大鼠136只,随机分为5组,即正常组、假手术组、模型组、尿激酶组、化痰通络法联合尿激酶组.采用自身栓子法制备大鼠大脑中动脉栓塞模型,分别给予中药灌胃及尿激酶溶栓,Elisa法检测化痰通络法联合尿激酶溶栓对急性脑梗死后6h、72h、7d、14d脑组织PAF、MCP-1蛋白表达的影响.[结果]化痰通络法联合尿激酶溶栓能明显抑制PAF、MCP-1蛋白的表达.[结论]中药联合溶栓可减少溶栓后再梗死,其机制可能与抑制PAF、MCP-1表达有关.

  9. Controlled pseudopod extension of human neutrophils stimulated with different chemoattractants.

    Science.gov (United States)

    Zhelev, Doncho V; Alteraifi, Abdullatif M; Chodniewicz, David

    2004-07-01

    The formation of pseudopods and lamellae after ligation of chemoattractant sensitive G-protein coupled receptors (GPCRs) is essential for chemotaxis. Here, pseudopod extension was stimulated with chemoattractant delivered from a micropipet. The chemoattractant diffusion and convection mass transport were considered, and it is shown that when the delivery of chemoattractant was limited by diffusion there was a strong chemoattractant gradient along the cell surface. The diffusion-limited delivery of chemoattractant from a micropipet allowed for maintaining an almost constant chemoattractant concentration at the leading edge of single pseudopods during their growth. In these conditions, the rate of pseudopod extension was dependent on the concentration of chemoattractant in the pipet delivering chemoattractant. The pseudopod extension induced using micropipets was oscillatory even in the presence of a constant delivery of chemoattractant. This oscillatory pseudopod extension was controlled by activated RhoA and its downstream effector kinase ROCK and was abolished after the inhibition of RhoA activation with Clostridium botulinium C3 exoenzyme (C3) or the blocking of ROCK activation with Y-27632. The ability of the micropipet assay to establish a well-defined chemoattractant distribution around the activated cell over a wide range of molecular weights of the used chemoattractants allowed for comparison of the effect of chemoattractant stimulation on the dynamics of pseudopod growth. Pseudopod growth was stimulated using N-formylated peptide (N-formyl-methionyl-leucyl-phenylalanine (fMLP)), platelet activating factor (PAF), leukotriene B4 (LTB(4)), C5a anaphylotoxin (C5a), and interleukin-8 (IL-8), which represent the typical ligands for G-protein coupled chemotactic receptors. The dependence of the rate of pseudopod extension on the concentration of these chemoattractants and their equimolar mixture was measured and shown to be similar for all chemoattractants. The

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  11. 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 circ...

  12. 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

    BACKGROUND: 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 evalu...

  13. 六味地黄汤对单侧输尿管结扎大鼠肾间质MCP-1及TGF-β1表达的影响%Effect of Liuweidihuang Decoction on Expression of Tubuloninterstitial MCP - 1 and TGF - β1 in Unilateral Ureter Ligation Rats

    Institute of Scientific and Technical Information of China (English)

    彭亚军; 张继波; 何泽云; 李杨; 刘芳洁; 李颂婷; 崔晓燕

    2009-01-01

    Objective:To observe the effect of Liuweidihuang decoction(LD)on expression of monocyte chemotactic protein (MCP-1) and transforming growth factor(TGF-β1) in unilateral ureter obstraction(UUO) rats. Methods: Seventy- two male Sprague- Dawley rats were randomly divided into four groups: the model group, the sham- operation group, the Enalapril group and LD group. The kidneys of rats were harversted at 7,14 and 21 d after the operation, lmmunohistochemistry was used on the renal tissue for MCP- 1 and TGF-β1after7,14 and 21 day. Histological changes were also observed by HE and Masson staining. Results:Compared with those in the sham-operation group, the levels of MCP- 1 and TGF-β1expression was obviously higher than those in the other groups on day 7,14,and 21(P<0.05).The MCP- 1 and TGF-β1of in LD group was higher than that in Enalapril group on day 7,14,and 21(P<0.05). Conclusion: LD can decrease the expression of the UUO MCP- 1 and level and TGF-β1andreduce tubuloninterstitial injury,and LD can be an axillary drug for obstruct kidney disease.%目的:观察六味地黄汤对单侧输尿管梗阻(UUO)大鼠模型中单核趋化蛋白-1(MCP-1)及转化生长因子-β1(TGF-β1)表达的影响.方法:将72只雄性SD大鼠随机分为模型组、依那普利组、六味地黄汤组、假手术组,行UUO术后即预药物干预.于术后第7、14、21天分别处死各组大鼠.用HE和Masson染色法观察各组大鼠术后不同时间点肾脏病理改变,用免疫组化法检测肾小管间质MCP-1及TGF-β1表达.结果:与假手术组比较,其余3组各时间点MCP-1及TGF-β1表达均明显高于假手术组(P<0.05);六味地黄汤组的MCP-1和TGF-β1表达明显低于模型组各时间点(P<0.05),高于依那普利组(P<0.05).结论:六味地黄汤可下调MCP-1和TGF-β1的表达,减缓UUO大鼠肾小管间质损害,可作为梗阻性肾病辅助用药.

  14. 吡那地尔对术后持续性疼痛大鼠脊髓JNK/MCP-1释放的影响%Effect of pinacidil on JNK/MCP-1 expression in spinal cord of a rat model of persistent postoperative pain

    Institute of Scientific and Technical Information of China (English)

    朱翔; 曹苏; 秦毅彬; 佘庆; 丁晶晶; 杨建平

    2016-01-01

    目的:观察吡那地尔(pinacidil)对术后持续性疼痛大鼠脊髓JNK/MCP-1释放的影响.方法:随机将35只大鼠分为正常组(Control组)、假手术组(Sham组)、切割+牵拉皮肤肌肉组(SMIR组)、溶剂+SMIR组(Vehicle组)、吡那地尔+SMIR(Pina组)、吡那地尔+格列苯脲+SMIR组(Pina +Gli组)、格列苯脲+SMIR组(Gli组)等7组.检测各组机械刺激缩足反射痛阈值(MWT),Western blot/ELISA法检测脊髓JNK/MCP-1蛋白表达.结果:(1)与Sham组相比,SMIR组MWT在术后3d开始降低(P<0.01),并持续21 d(P<0.001)以上;(2) SMIR术后持续显著上调脊髓JNK/MCP-1的表达(P<0.01);(3)鞘内注射吡那地尔显著下调术后SMIR诱导的脊髓JNK/MCP-1表达(P<0.01)和上调MWT(P <0.01),格列苯脲能阻断吡那地尔所引起的上述变化(P<0.05).结论:吡那地尔能抑制切割及牵拉皮肤肌肉所致的术后持续性疼痛,其机制可能与抑制JNK/MCP-1的上调有关.

  15. Induction of mitochondrial uncoupling enhances VEGF₁₂₀ but reduces MCP-1 release in mature 3T3-L1 adipocytes: possible regulatory mechanism through endogenous ER stress and AMPK-related pathways.

    Science.gov (United States)

    Miyokawa-Gorin, Kaoru; Takahashi, Kazuto; Handa, Keiko; Kitahara, Atsuko; Sumitani, Yoshikazu; Katsuta, Hidenori; Tanaka, Toshiaki; Nishida, Susumu; Yoshimoto, Katsuhiko; Ohno, Hideki; Ishida, Hitoshi

    2012-03-01

    Although white adipocytes contain a larger number of mitochondria per cytoplasmic volume, adipocyte mitochondrial uncoupling to reduce the efficiency of ATP production on cellular function including secretory regulation of bioactive molecules such as VEGF and MCP-1 remains to be elucidated. Here we induce mitochondrial uncoupling under hypoxia-independent conditions in mature 3T3-L1 adipocytes using a metabolic uncoupler, dinitrophenol (DNP). MCP-1 release was significantly decreased by 26% (poxidative stress was observed. Treatment with thapsigargin, which can induce exogenous endoplasmic reticulum (ER) stress, clearly attenuated MCP-1 release (pmetabolic syndrome and type 2 diabetes.

  16. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Cushing, S.D.; Berliner, J.A.; Valente, A.J.; Territo, M.C.; Navab, M.; Parhami, F.; Gerrity, R.; Schwartz, C.J.; Fogelman, A.M.

    1990-07-01

    After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemotactic protein 1 (MCP-1) that is constitutively produced by the human glioma U-105MG cell line. Antibody that had been prepared against cultured baboon smooth muscle cell chemotactic factor (anti-SMCF) did not inhibit monocyte migration induced by the potent bacterial chemotactic factor f-Met-Leu-Phe. However, anti-SMCF completely inhibited the monocyte chemotactic activity found in the media of U-105MG cells, EC, and SMC before and after exposure to MM-LDL. Moreover, monocyte migration into the subendothelial space of a coculture of EC and SMC that had been exposed to MM-LDL was completely inhibited by anti-SMCF. Anti-SMCF specifically immunoprecipitated 10-kDa and 12.5-kDa proteins from EC. Incorporation of (35S)methionine into the immunoprecipitated proteins paralleled the monocyte chemotactic activity found in the medium of MM-LDL stimulated EC and the levels of MCP-1 mRNA found in the EC. We conclude that SMCF is in fact MCP-1 and MCP-1 is induced by MM-LDL.

  17. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells.

    OpenAIRE

    Cushing, S D; Berliner, J A; Valente, A. J.; Territo, M C; Navab, M; Parhami, F; Gerrity, R; Schwartz, C J; Fogelman, A M

    1990-01-01

    After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemotactic protein 1 (MCP-1) that is constitutively produced by the human ...

  18. CHANGE AND CLINICAL SIGNIFICANCE OF IL-16, IL-35, MCP-1 LEVELS OF BRONCHIAL ASTHMA CHILDREN WITH ACUTE EPISODES%支气管哮喘儿童血清IL-16、IL-35、MCP-1的水平变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    林志波; 黄海忠

    2015-01-01

    目的 探讨支气管哮喘儿童血清中IL-16、IL-35、单核细胞趋化蛋白-1(MCP-1)的水平变化及临床意义.方法 选择2012年1月至2014年6月60例哮喘急性发作期患儿为研究对象.选择36例哮喘缓解期患儿为疾病对照组.选择2012年1月至2014年6月期间健康儿童40例为健康对照组.统计受试者血清IL-16、IL-35、MCP-1水平,并对血清IL-16、IL-35、MCP-1水平与年龄、病程、性别、哮喘严重程度、病情进行相关性分析.结果 哮喘急性发作期血清IL-16、MCP-1水平均高于哮喘缓解期、健康对照组(p<0.01);缓解期患儿血清IL-16、MCP-1水平高于健康对照组(p<0.01);哮喘急性发作期血清IL-35水平均低于哮喘缓解期、健康对照组(p<0.01);缓解期患儿血清IL-35水平低于健康对照组(p<0.01);哮喘中重度组血清IL-16、MCP-1水平均高于轻度组、对照组(p<0.01);轻度组患儿血清IL-16、MCP-1水平高于对照组(p<0.01);哮喘中重度组血清IL-35水平均低于轻度组、对照组(p<0.01);轻度组患儿血清IL-35水平低于对照组(p<0.01);治疗后哮喘急性发作期患儿血清IL-16、MCP-1水平低于治疗前(p<0.001),治疗后哮喘急性发作期患儿血清IL-35水平高于治疗前(p<0.001);血清IL-16、MCP-1水平与哮喘严重程度、病情呈正相关(p<0.05);血清IL-35水平与哮喘严重程度、病情呈负相关(p<0.05).血清IL-16水平与血清MCP-1水平呈正相关(p<0.05),与血清IL-35水平呈负相关(p<0.05),血清MCP-1水平与血清IL-35水平呈负相关(p<0.05).结论 IL-16、MCP-1在哮喘患儿血中高表达,IL-35在哮喘患儿血中低表达;IL-16、IL-35、MCP-1与哮喘发病及进展密切相关.

  19. Circulating cytokine concentrations in dogs with different degrees of myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Zois, Nora Elisabeth; Moesgaard, Sophia Gry; Kjelgaard-Hansen, Mads

    2012-01-01

    , IL-15, IL-18, keratinocyte-derived chemokine, interferon-c-induced protein and monocyte chemoattractant protein-1 (MCP-1) were measured using a canine-specific multiplex immunoassay. CHF dogs had significantly higher MCP-1 concentrations than dogs with no or minimal MR. Among the CKCS, IL-2 and IL-7...

  20. Mathematics of Experimentally Generated Chemoattractant Gradients.

    Science.gov (United States)

    Postma, Marten; van Haastert, Peter J M

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Julien Braux

    2016-12-01

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

  2. Possible Roles of Proinflammatory and Chemoattractive Cytokines Produced by Human Fetal Membrane Cells in the Pathology of Adverse Pregnancy Outcomes Associated with Influenza Virus Infection

    Directory of Open Access Journals (Sweden)

    Noboru Uchide

    2012-01-01

    Full Text Available Pregnant women are at an increased risk of influenza-associated adverse outcomes, such as premature delivery, based on data from the latest pandemic with a novel influenza A (H1N1 virus in 2009-2010. It has been suggested that the transplacental transmission of influenza viruses is rarely detected in humans. A series of our study has demonstrated that influenza virus infection induced apoptosis in primary cultured human fetal membrane chorion cells, from which a factor with monocyte differentiation-inducing (MDI activity was secreted. Proinflammatory cytokines, such as interleukin (IL-6, tumor necrosis factor (TNF-α, and interferon (IFN-β, were identified as a member of the MDI factor. Influenza virus infection induced the mRNA expression of not only the proinflammatory cytokines but also chemoattractive cytokines, such as monocyte chemoattractant protein (MCP-1, regulated on activation, normal T-cell expressed and secreted (RANTES, macrophage inflammatory protein (MIP-1β, IL-8, growth-regulated oncogene (GRO-α, GRO-β, epithelial cell-derived neutrophil-activating protein (ENA-78, and interferon inducible protein (IP-10 in cultured chorion cells. These cytokines are postulated to associate with human parturition. This paper, therefore, reviews (1 lessons from pandemic H1N1 2009 in pregnancy, (2 production of proinflammatory and chemoattractive cytokines by human fetal membranes and their functions in gestational tissues, and (3 possible roles of cytokines produced by human fetal membranes in the pathology of adverse pregnancy outcomes associated with influenza virus infection.

  3. SIRT1对高糖诱导的系膜细胞NF-κB p65乙酰化及MCP-1表达的影响%Effect of SIRT1 on high glucose-induced NF-κB p65 subunit acetylation and MCP-1 expression in rat mesangial cells

    Institute of Scientific and Technical Information of China (English)

    杜月光; 柴可夫; 汪丽佩

    2014-01-01

    目的 探讨沉默信息调节因子1(SIRT1)对高糖诱导的大鼠肾小球系膜细胞(RMC)核因子κB(NF-κB) p65蛋白乙酰化及单核细胞趋化蛋白1(MCP-1)表达的影响.方法 构建干扰SIRT1基因的shRNA慢病毒质粒pTRC-shSIRT1并进行鉴定.将RMC分为高糖组(用高糖培养液培养)、白藜芦醇(SIRT1激活剂)+高糖组(用含1μmol/L白藜芦醇的低糖培养液培养24 h后,换用高糖培养液培养)、SIRT1 RNAi组(添加干扰病毒pTRC-shSIRT1感染4h后,换用低糖培养液培养)、SIRT1 RNAi+高糖组(添加干扰病毒pTRC-shSIRT1感染4h后,换用高糖培养液培养),同时设正常对照组和甘露醇高渗对照组.以实时荧光定量PCR检测SIRT1、MCP-1的mRNA表达,蛋白质印迹法检测SIRT1和NF-κB p65乙酰化蛋白的表达,ELISA技术检测MCP-1蛋白含量.结果 质粒测序证实干扰SIRT1基因的shRNA慢病毒载体构建成功,且能抑制RMC中SIRT1基因表达(P<0.01).高糖刺激使RMC SIRT1基因表达降低,NF-κB p65蛋白乙酰化增强,MCP-1 mRNA和蛋白水平增高;SIRT1激活剂白藜芦醇可逆转高糖引起的变化;而沉默SIRT1可促进高糖诱导的RMC NF-κB p56乙酰化及MCP-1mRNA和蛋白表达(P<0.05或0.01).结论 SIRT1可抑制高糖诱导的RMC MCP-1表达,其机制可能与NF-κB p56去乙酰化有关.

  4. Effect of 2-BFI on microglia activation and MCP-1 expression in central nervous system of rats with experimental autoimmune en-cephalomyelitis%2- BFI对EAE大鼠中枢神经系统内小胶质细胞及MCP-1的影响

    Institute of Scientific and Technical Information of China (English)

    朱振国; 陈艳艳; 黄艳君; 张元涛; 王新施; 郑荣远

    2014-01-01

    Objective To investigate the effects of 2- (- 2- benzofuranyl)- 2- imidazoline (2- BFI) on microglia activation and MCP- 1 expression in central nervous system (CNS) of rat with experimental autoimmune encephalomyelitis (EAE). Methods Fifty female Sprague- Dawley(SD) rats were randomly divided into five groups:control group(n=10), EAE model group(n=10), low dose (1.5mg/kg ) 2- BFI group (n=10), intermediate dose (3 mg/kg) 2- BFI group (n=10) and high dose (6mg/kg) 2- BFI group (n=10). The model of EAE was induced by injection of guinea pigs spinal cord homogenate (GPSCH)in SD rats. The severity of EAE was scored according to the signs and symptoms. The pathological changes were observed with Hematoxylin- eosin stain-ing and Luxol Fast blue dyeing, then the degree of inflammatory infiltration was evaluated. The changes of activated microglia and MCP- 1 positive cells in brainstem were counted by immunohistochemistry. Results Compared with EAE group, rats in inter-mediate dose 2- BFI treatment groups had lower incidence of disease, prolonged latency, decreased CNS inflammation and de-myelination (P<0.05). Immunohistochemical results showed that the numbers of activated microglia and MCP- 1 positive cells were significantly reduced in intermediate dose 2- BFI group compared with the EAE group (P<0.05). Conclusion 2- BFI at in-termediate dose (3mg/kg) has a beneficial neuroprotective effect on EAE, which may be related to inhibition of microglia activation and reduction of MCP- 1 expression.%目的:观察2-(2-苯并呋喃基)-2-咪唑啉[2-(-2- benzofuranyl)-2- imidazoline,2- BFI]对实验性自身免疫性脑脊髓炎(EAE)大鼠中枢神经系统内小胶质细胞及MCP-1的影响,并探讨其保护EAE大鼠的作用机制。方法50只雌性SD大鼠随机分为EAE组、2- BFI低剂量组、2- BFI中剂量组、2- BFI高剂量组及对照组,每组10只,采用豚鼠脊髓匀浆免疫诱导SD大鼠建立EAE模型,观察每组大鼠发病情况

  5. Expression and the Significance of MCP-1 and FN in Middle Ear Cholesteatoma Epithelium%M CP -1和 FN 在中耳胆脂瘤上皮中的表达和意义

    Institute of Scientific and Technical Information of China (English)

    高燕; 杨一兵; 丛林海; 汤勇; 张帆

    2013-01-01

    目的探讨单核细胞趋化因子(monocyte chemotactic factor ,MCP -1)和纤维连接蛋白(fibronectin , FN)在继发性中耳胆脂瘤上皮中的表达及其对胆脂瘤上皮侵袭能力的影响。方法应用免疫组织化学MaxVi-sionTM法检测MCP-1和FN在30例中耳胆脂瘤上皮、20例胆脂瘤患者耳后正常皮肤、16例非胆脂瘤患者耳后正常皮肤中的表达,应用计算机图像分析系统对其阳性表达灰度值情况及分析,比较三组之间 MCP -1和 FN表达的差异。结果 MCP-1阳性细胞表达主要分布于胆脂瘤上皮全层,其中棘层呈高表达,MCP-1在中耳胆脂瘤上皮中阳性表达率为70%,灰度值为147.2±20.1,强于胆脂瘤患者耳后正常皮肤中的阳性表达(35%,200.8±18.4)和非胆脂瘤患者耳后正常皮肤中的阳性表达(37.5%,193.3±15.5)( P<0.05)。FN阳性细胞主要分布于胆脂瘤上皮全层,基底层、棘层和基质呈高表达,FN在中耳胆脂瘤上皮中阳性表达率为76.7%,灰度值为139.2±18.5,强于胆脂瘤患者耳后正常皮肤中的阳性表达(30%,195.0±12.9)和非胆脂瘤患者耳后正常皮肤中的阳性表达(31.3%,191.6±13.5)(P<0.05)。在30例中耳胆脂瘤上皮组织中,MCP-1和FN的灰度值与胆脂瘤的侵袭能力负相关(rmcp-1=-0.682,rfn =-0.531,P<0.01),MCP-1和FN蛋白的表达不存在线性相关。结论 MCP-1和FN均在成人中耳胆脂瘤中高表达,且与中耳胆脂瘤的侵袭能力呈负相关。%Objective To study the expression of monocyte chemotactic factor -1(MCP-1) and fibronectin (FN ) in secondary acquired middle ear cholesteatoma epithelium ,and to investigate the ability of cholesteatoma of e-rosion .Methods MaxVisionTM immunohistochemical method was used to detect the expression of MCP -1 and FN in the secondary acquired middle ear cholesteatoma tissues from 30 patients

  6. Roles of monocyte chemotactic protein 1 and nuclear factor-κB in immune response to spinal tuberculosis in a New Zealand white rabbit model

    Science.gov (United States)

    Guo, X.H.; Bai, Z.; Qiang, B.; Bu, F.H.; Zhao, N.

    2017-01-01

    This study aimed to explore the roles of monocyte chemotactic protein 1 (MCP-1) and nuclear factor kappa B (NF-κB) in immune response to spinal tuberculosis in a New Zealand white rabbit model. Forty-eight New Zealand white rabbits were collected and divided into four groups: experimental group (n=30, spinal tuberculosis model was established), the sham group (n=15, sham operation was performed) and the blank group (n=3). The qRT-PCR assay and western blotting were applied to detect the mRNA and protein expressions of MCP-1 and NF-κB in peripheral blood. ELISA was used to measure serum levels of MCP-1, NF-κB, IFN-γ, IL-2, IL-4, and IL-10. Flow cytometry was adopted to assess the distributions of CD4+, CD8+ lymphocytes and CD4+ CD25+ Foxp3 lymphocyte subsets. Compared with the sham and blank groups, the mRNA and protein expressions of MCP-1 and NF-κB in the experimental group were significantly increased. The experimental group had lower serum levels of IL-2 and IFN-γ and higher serum level of IL-10 than the sham and blank groups. In comparison to the sham and blank groups, CD4+ T lymphocyte subsets percentage, CD4+/CD8+ ratio and CD4+ CD25+ Foxp3+ Tregs subsets accounting for CD4+ lymphocyte in the experimental group were lower, while percentage of CD8+ T lymphocyte subsets was higher. Our study provided evidence that higher expression of MCP-1 and NF-κB may be associated with decreased immune function of spinal tuberculosis, which can provide a new treatment direction for spinal tuberculosis. PMID:28225889

  7. Efecto de 1- MCP (1-metilciclopropeno y Promalina® en la duración del color de brácteas florales de Tillandsia caacticola (Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Melgarejo Muñoz Luz Marina

    2006-12-01

    Full Text Available Las brácteas florales de Tillandsia cacticola conservan hasta por un año su color cuando no son cortadas de la
    planta; cuando las inflorescencias son cortadas y empacadas su color desaparece rápidamente. Plantas de T.
    cacticola fueron sumergidas completamente en soluciones de AG4+7 + BAP (Promalina y 1-MCP (1- metilciclopropeno a diferentes concentraciones El tratamiento de las plantas con 2,0 mg/l de 1-MCP por 16 h a 23 C retrasó la pérdida del color en las brácteas florales por diez días respecto al testigo sin tratar. Las plantas
    tratadas individualmente con 90 y 180 mg/l de AG4+7 + BAP no mostraron incremento en la duración del
    color de sus brácteas florales e incluso se redujo la duración del color respecto a la del testigo.

  8. Study on the changes and clinical significance of serum MMP-9,MCP-1 level in elderly patients with hypertension and obesity%老年高血压伴肥胖患者血清MMP-9、MCP-1水平的变化及其临床意义的研究

    Institute of Scientific and Technical Information of China (English)

    杜健; 冷吉燕; 李修英; 黄慧琳; 邵明柏

    2011-01-01

    Objective To investigate the changes and clinical significance of serum MMP-9,MCP-1 in elderly patients with hypertension and obesity,Methods According to bringing and removing standard option,subjects were classified as control group、simple obesity group、simple hypertension group and obesity-associated hypertension group.Diagnosis of hypertension under the guidance of China hypertension diagnostic criteria in 2005,diagnosis of obesity by body mass index according to BMI≥25kg/m2(Asia-Pacific standards).A general examination and conventional blood glucose.blood lipids and other biochem ical tests were detected in all subjects,serum concentrations of MMP-9 and MCP-1 levels was measured by the Elisa method.Results(1)BMI,IG,LDL-C in control group ,simple obesity group,simple hypertension group and obesity-associated hypertension group,were increased gradually,and compare each of them there is a statistical significance( P < 0.05 ) ;H D L-C in control group,simple obesity group ,simple hypertension group and obesity-associated hypertension group,were decreased gradually,and compare each of them there is a statistical significance ( P<0.05 ) ;FPG ,SBP ,DBP in simple hypertension group and obesity-associated hypertension group higher than control group ,and compare each of them there is a statistical significance (P<0.05);BMI,SBP ,DBP in simple hypertension group and obesity-associated hypertension group higher than siple obesity group ,and compare each of them there is a statistical significance ( P<0.05 );BMI,FPG ,TG ,TC in obesity-associated hypertension group higher than simple hypertension group ,and compare them there is a statistical significance ( P<0.05 ); (2) serum MMP-9 and MCP-1 concentrations in control group ,simple obesity group ,simple hypertension group and obesity-associated hypertnsion group ,were increased gradually ,and compare each of them there is a statistical significance ( P<0.05 ) .Conclusion M M P-9 and M CP-1 play very

  9. RANTES、MIP-1α、MIP-1β和MCP-1趋化因子在慢性肝病患者的水平%The expression levels of chemokine RANTES, MIP-1α, MIP-1βand MCP-1 in chronic hepatitic diseases patients

    Institute of Scientific and Technical Information of China (English)

    刘宁; 江娜; 罗娜; 乔桂芳; 孙焕芹; 刘金花; 张永宏

    2014-01-01

    目的探讨慢性乙型肝炎(CHB)、乙肝肝硬化(LC)、乙肝相关肝细胞癌(HCC)患者体内正常T细胞表达和分泌调节活化因子(RANTES)、巨噬细胞炎症蛋白(MIP-1α和MIP-1β)和单核细胞趋化蛋白(MCP-1)的表达水平。方法收集2010年2月至2011年11月首都医科大学附属北京佑安医院收治的CHB患者(40例)、LC患者(40例)、HCC患者(53例)的血液标本,采用Luminex 技术检测血清趋化因子RANTES、MIP-1α、MIP-1β和MCP-1的表达水平,并以25例健康志愿者血液标本作为正常对照。结果趋化因子MIP-1α、MIP-1β和MCP-1在正常对照组表达水平的中位数分别为9.590、106.490和72.330 pg/ml,高于CHB组、LC组和HCC组;趋化因子RANTES在HCC组的表达水平为16948.440 pg/ml,依次高于正常对照组、CHB组、LC组,差异有统计学意义(αCHB group>LC group. There was significant difference (α< 0.008) respectively. Conclusion The expression level of chemokines RANTES and the occurrence of HBV-related HCC is closely related. RANTES can be used as indicator in monitoring the occurrence of HBV-related HCC.

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

    DEFF Research Database (Denmark)

    Buchmann, Kurt; Nielsen, Michael Engelbrecht

    1999-01-01

    to be present in fractions with host immunoglobulin and some still undetermined proteins. No clear association between enzyme activity and chemotactic potential was seen. The high chemoattractive effect of serum from various unrelated teleosts corresponds to the low host specificity of I. multifiliis...

  11. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  12. The oncolytic virus dl922-947 reduces IL-8/CXCL8 and MCP-1/CCL2 expression and impairs angiogenesis and macrophage infiltration in anaplastic thyroid carcinoma

    Science.gov (United States)

    Vastolo, Viviana; Di Somma, Sarah; Scamardella, Eloise; Gigantino, Vincenzo; Franco, Renato; Marone, Gianni; Portella, Giuseppe

    2016-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human solid tumor and current treatments are ineffective in increasing patients' survival. Thus, the development of new therapeutic approaches for ATC is needed. We have previously shown that the oncolytic adenovirus dl922-947 induces ATC cell death in vitro and tumor regression in vivo. However, the impact of dl922-947 on the pro-tumorigenic ATC microenvironment is still unknown. Since viruses are able to regulate cytokine and chemokine production from infected cells, we sought to investigate whether dl922-947 virotherapy has such effect on ATC cells, thereby modulating ATC microenvironment. dl922-947 decreased IL-8/CXCL8 and MCP-1/CCL2 production by the ATC cell lines 8505-c and BHT101-5. These results correlated with dl922-947-mediated reduction of NF-κB p65 binding to IL8 promoter in 8505-c and BHT101-5 cells and CCL2 promoter in 8505-c cells. IL-8 stimulates cancer cell proliferation, survival and invasion, and also angiogenesis. dl922-947-mediated reduction of IL-8 impaired ATC cell motility in vitro and ATC-induced angiogenesis in vitro and in vivo. We also show that dl922-947-mediated reduction of the monocyte-attracting chemokine CCL2 decreased monocyte chemotaxis in vitro and tumor macrophage density in vivo. Interestingly, dl922-947 treatment induced the switch of tumor macrophages toward a pro-inflammatory M1 phenotype, likely by increasing the expression of the pro-inflammatory cytokine interferon-γ. Altogether, we demonstrate that dl922-947 treatment re-shape the pro-tumorigenic ATC microenvironment by modulating cancer-cell intrinsic factors and the immune response. An in-depth knowledge of dl922-947-mediated effects on ATC microenvironment may help to refine ATC virotherapy in the context of cancer immunotherapy. PMID:26625205

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

    Science.gov (United States)

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

    2015-08-01

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

  14. HIV-infected patients with lipodystrophy have higher rates of carotid atherosclerosis: The role of monocyte chemoattractant protein-1

    NARCIS (Netherlands)

    B. Coll; S. Parra; C. Alonso-Villaverde; E. de Groot; G. Aragones; M. Montero-Sieburth; M. Tous; J. Camps; J. Joven; L. Masana

    2006-01-01

    Individuals with HIV-1 infection are at increased risk for cardiovascular events, and lipodystrophy is generally associated with proatheroizenic metabolic disturbances. We conducted a case-control study to assess the presence of sub-clinical atherosclerosis in HIV-1-infected patients with or without

  15. Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

    OpenAIRE

    Piotr Religa; Grudzinska, Monika K; Krzysztof Bojakowski; Joanna Soin; Jerzy Nozynski; Michal Zakliczynski; Zbigniew Gaciong; Marian Zembala; Cecilia Söderberg-Nauclér

    2009-01-01

    Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs) both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35+/-2.3% of ce...

  16. The Role of Chemoattractant Receptors in Shaping the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jiamin Zhou

    2014-01-01

    Full Text Available Chemoattractant receptors are a family of seven transmembrane G protein coupled receptors (GPCRs initially found to mediate the chemotaxis and activation of immune cells. During the past decades, the functions of these GPCRs have been discovered to not only regulate leukocyte trafficking and promote immune responses, but also play important roles in homeostasis, development, angiogenesis, and tumor progression. Accumulating evidence indicates that chemoattractant GPCRs and their ligands promote the progression of malignant tumors based on their capacity to orchestrate the infiltration of the tumor microenvironment by immune cells, endothelial cells, fibroblasts, and mesenchymal cells. This facilitates the interaction of tumor cells with host cells, tumor cells with tumor cells, and host cells with host cells to provide a basis for the expansion of established tumors and development of distant metastasis. In addition, many malignant tumors of the nonhematopoietic origin express multiple chemoattractant GPCRs that increase the invasiveness and metastasis of tumor cells. Therefore, GPCRs and their ligands constitute targets for the development of novel antitumor therapeutics.

  17. 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.

    Directory of Open Access Journals (Sweden)

    Maho Suzukawa

    Full Text Available 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.

  18. Arachidonic acid is a chemoattractant for Dictyostelium discoideum cells

    Indian Academy of Sciences (India)

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

    2007-12-01

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

  19. 糖基化终产物通过其受体诱导小鼠足细胞表达单核细胞趋化因子1%Advanced glycation end products-induced MCP-1 expression via its receptor RAGE in mouse podocytes

    Institute of Scientific and Technical Information of China (English)

    顾乐怡; 倪兆慧; 钱家麒; Yasuhiko Tomino

    2006-01-01

    目的了解糖基化终产物(AGE)能否在体外诱导小鼠足细胞表达单核细胞趋化蛋白1(MCP-1)以及其受体RAGE在其中的作用.方法以RT-PCR和ELISA的方法检测AGE、羰甲基化白蛋白(CML)、S100蛋白和RAGE中和抗体对小鼠足细胞的MCP-1的基因和蛋白质表达的影响.结果 (1)未分化和已分化的足细胞都能表达RAGE.(2)AGE和CML以剂量依赖的方式诱导足细胞表达MCP-1mRNA.AGE和CML孵育8 h诱导足细胞产生MCP-1蛋白[分别为(7.44±1.01,8.06±0.96)ng/L],明显高于牛血清白蛋白(BSA)孵育的足细胞[(3.77±0.39)ng/L,均P<0.05],而孵育24 h MCP-1的浓度分别为(87.78±9.32,85.35±9.83和17.95±0.76)ng/L(均P<0.01).(3)RAGE的另外一个配体,S100蛋白,也能以剂量依赖的方式诱导足细胞表达MCP-1 mRNA.RAGE中和抗体完全阻断了AGE、CML和S100的作用.结论 AGE和CML通过RAGE使诱导分化的足细胞表达MCP-1.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    function and an inflammatory profile (monocyte chemoattractant protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF)) were improved following the low-AGE diet. Mechanisms of advanced glycation-related renal damage were investigated in a mouse model of obesity using the AGE...

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

    DEFF Research Database (Denmark)

    Umland, Oliver; Heine, Holger; Miehe, Michaela

    2004-01-01

    in stimulated KG-1a cells and CD34(+) BMCs. Although monokine induced by IFN-gamma, IFN-inducible protein 10, and IFN-gamma were exclusively up-regulated in KG-1a cells, differential expression of monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine, myeloid progenitor inhibitory factor-2...

  2. Cell surface adhesion molecules and cytokine profiles in primary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Ukkonen, Maritta; Wu, Xingchen; Reipert, Birgit

    2007-01-01

    of cytokines in serum or CSF between PPMS and SPMS or controls, but evidence suggesting intrathecal synthesis of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was found in PPMS. The expressions of CSF VLA-4 in PPMS correlated with the total volume of cerebral lesions and the number...

  3. Effect of short-term hyperglycemia on adipose tissue fluxes of selected cytokines in vivo during multiple phases of diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Siklova, Michaela; Simonsen, Lene; Polak, Jan

    2015-01-01

    -1 receptor antagonist (IL-1Ra), TNF-α, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A, and C-reactive protein] in arterial and venous plasma were measured during each dietary phase. The insulin sensitivity of scAT in respect to the antilipolytic effect of insulin during the clamp...

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

    DEFF Research Database (Denmark)

    Madsen, Anne Mette; Saber, Anne Thoustrup; Nordly, Pernille

    2008-01-01

    , the lung tissue mRNA (messenger ribonucleic acid) levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) were increased more than 10-fold if the dust was from the boiler room and 30- to 60-fold if the dust came from the straw storage hall...

  5. Marine bacterial chemoresponse to a stepwise chemoattractant stimulus.

    Science.gov (United States)

    Xie, Li; Lu, Chunliang; Wu, Xiao-Lun

    2015-02-03

    We found recently that polar flagellated marine bacterium Vibrio alginolyticus is capable of exhibiting taxis toward a chemical source in both forward and backward swimming directions. How the microorganism coordinates these two swimming intervals, however, is not known. The work presented herein is aimed at determining the response functions of the bacterium by applying a stepwise chemoattractant stimulus while it is swimming forward or backward. The important finding of our experiment is that the bacterium responds to an identical chemical signal similarly during the two swimming intervals. For weak stimuli, the difference is mainly in the amplitudes of the response functions while the reaction and adaptation times remain unchanged. In this linear-response regime, the amplitude in the forward swimming interval is approximately a factor of two greater than in the backward direction. Our observation suggests that the cell processes chemical signals identically in both swimming intervals, but the responses of the flagellar motor to the output of the chemotaxis network, the regulator CheY-P concentration, are different. The biological significance of this asymmetrical response in polar flagellated marine bacteria is discussed.

  6. The role of chemokines in regualating mast cell recruitment around rat liver tumor

    Institute of Scientific and Technical Information of China (English)

    ZHANGZhi-Yong; RUANYou-Bing

    2001-01-01

    Aim To explore the correlation of stem cell factor (SCF)and monocyte chemoattractant protein-1 (MCP-1) with number difference of mast cell (MC) around the liver tumor.Methods 40 male wistar rats with liver neoplasm were divided into three different groups by numbers of MC in the surroundings of tumor. We performed ELISA for SCF and MCP-1 in serums. And chemotaxis assays of rat peritoneal MCs to SCF and MCP-1 in serums were measured in 48-wellmicroboyden chambers. We also used immunohistochemistryto investigate whether rat MCs express SCF positively.RESULTE There were marked differences in MC numbersaround tumor between different groups. The group that has more MCs around tumor has the higher levels of SCF andMCP-1 in serums and the stronger chemotaxis to ratperitoneal MCs. SCF washigher than MCP-1 in bothchemotactic activity to MCs and levels in serums. And ratMCs positively express SCF.Conclusion SCF and MCP-1 were found to be two particularly efficacious chemoattractants for MCs. The levels of SCF and MCP-1 in serums may be closely correlated with MCs numbers around tumor. The production of SCF by MCs might act on mast cell migration and proliferation of MC.

  7. 脊髓MCP-1-ERK-KIF17∕NR2 B信号通路在大鼠2型糖尿病神经痛维持中的作用%Role of spinal MCP-1-ERK-KIF17∕NR2B signaling pathway in maintenance of type 2 diabetic neuro-pathic pain in rats

    Institute of Scientific and Technical Information of China (English)

    胡涵; 赵佳伊; 曹红; 李军

    2015-01-01

    Objective To explore the role of spinal monocyte chemoattractant protein⁃1 ( MCP⁃1) ⁃extracellular signal⁃regulated protein kinase ( ERK)⁃kinesin superfamily motor protein 17 ( KIF17)∕N⁃methyl⁃D⁃aspartate receptor subunit 2B ( NR2B) signaling pathway in the maintenance of type 2 diabetic neuropathic pain (DNP) in rats. Methods Type 2 diabetes mellitus was induced by a high⁃fat and high⁃sucrose diet and intraperitoneal streptozotocin ( STZ) 35 mg∕kg, and confirmed by fasting blood glucose level≥16�7 mmol∕L 3 days later in male Sprague⁃Dawley rats aged 6 weeks. Type 2 DNP was confirmed when the mechanical paw withdrawal threshold ( MWT ) and thermal paw withdrawl latency ( TWL ) measured on day 14 after STZ administration decreased to< 80% of the baseline value. The rats with type 2 DNP were randomly divided into 4 groups ( n=36 each) using a random number table: type 2 DNP group (group DNP), type 2 DNP +MCP⁃1 neutralizing antibody group (group DM), type 2 DNP +ERK inhibi⁃tor group (group DE) and type 2 DNP + dimethyl sulfoxide group ( group DD). In DM, DE and DD groups, 0�1 ng∕μl MCP⁃1 neutralizing antibody 10 μl, 0�5 μg∕μl U0126 10 μl and 5 % dimethyl sulfoxide 10 μl were injected intrathecally, respectively, once a day for 14 consecutive days starting from 14 days after administration of STZ. Another 36 normal rats fed a common forage diet were adopted as con⁃trol group ( group C) . MWT and TWL were measured before STZ injection and at 1, 3, 7 and 14 days after STZ injection ( T0-4 ) . Nine rats were sacrificed after measurement of pain thresholds at T1-4 , and the lumbar segments ( L4-6 ) of the spinal cord were removed for determination of the expression of phosphoryla⁃ted ERK (p⁃ERK), KIF17 and phosphorylated NR2B (p⁃NR2B) by Western blot. Results Compared with group C, the MWT was significantly decreased, the TWL was shortened, and the expression of p⁃ERK, KIF17 and p⁃NR2B was up⁃regulated at T

  8. 大鼠心脏移植后动态监测血清RANTES和单核细胞趋化蛋白-1的意义%The changes of serum RANTES and MCP-1 following cardiac transplantation in rats and implication

    Institute of Scientific and Technical Information of China (English)

    顾晓; 唐孝达; 杨尚琪; 刘永; 周佩军; 徐达; 王祥慧; 谭建明

    2001-01-01

    Objectives To investigate the implication of serum regulated on activation normal T cell ex pressed and secrected (RANTES) and MCP-1 in cardiac acute allograft rejection a nd the effect of Cyclosporin A (CsA). Methods Four groups of rats underwent the heterotopic cardiac transplantation: untreat ed group, low dose of CsA group, high dose of CsA group and isograft group. Th e se rum RANTES and MCP-1 of recipients were detected by using ELISA method. Results The changes in serum RANTES were correlated wi th the process of acute rejection. RANTES concentrations peaked in the early s tage of acute graft rejection and CsA could delay the peak. The serum peak lev el o f RA NTES was significantly lower than that in untreated group (P<0.05). The serum MCP-1 concentrations peaked 6 h after operation and in severe stages of acute rejection respectively. The first peak of MCP-1 reached later by using Cs A, but CsA did not affect its peak level (P>0.05). The second peak of M CP-1 was decreased or did not occurred in the CsA-treated groups. Conclusions  RANTES concentrations were increased in the early episodes of acute rejection a nd could be used as a marker for diagnosis of acute rejection. MCP-1 not only involved in the ischemia/reperfusion injury but also severe acu te rejection. It may be the important mechanisms of CsA to intervene the acute r ejection by decreasing the release of RANTES and inhibiting its immunological effects.%目的探讨测定血清RANTES(regulated on activation normal T cell expressed and secret ed)和单核细胞趋化蛋白-1(MCP-1)浓度在判断大鼠心脏移植急性排斥反应中的意义及环孢素A (CsA)对它们的影响。方法施行大鼠异位心脏移植术,按术后免疫抑制方案的不同将动物分为未干预组(不给免疫抑制剂)、低剂量CsA组、高剂量CsA组,并设同系移植对照组;采用酶联免疫吸附法检测受者术前及术后不同时段血清RANTES和MCP-1的浓度。

  9. Adrenergic regulation of monocyte chemotactic protein 1 leads to enhanced macrophage recruitment and ovarian carcinoma growth

    Science.gov (United States)

    Armaiz-Pena, Guillermo N.; Gonzalez-Villasana, Vianey; Nagaraja, Archana S.; Rodriguez-Aguayo, Cristian; Sadaoui, Nouara C.; Stone, Rebecca L.; Matsuo, Koji; Dalton, Heather J.; Previs, Rebecca A.; Jennings, Nicholas B.; Dorniak, Piotr; Hansen, Jean M.; Arevalo, Jesusa M.G.; Cole, Steve W.; Lutgendorf, Susan K.; Sood, Anil K.; Lopez-Berestein, Gabriel

    2015-01-01

    Increased adrenergic signaling facilitates tumor progression, but the underlying mechanisms remain poorly understood. We examined factors responsible for stress-mediated effects on monocyte/macrophage recruitment into the tumor microenvironment, and the resultant effects on tumor growth. In vitro, MCP1 was significantly increased after catecholamine exposure, which was mediated by cAMP and PKA. Tumor samples from mice subjected to daily restraint stress had elevated MCP1 gene and protein levels, increased CD14+ cells, and increased infiltration of CD68+ cells. hMCP1 siRNA-DOPC nanoparticles significantly abrogated daily restraint stress-induced tumor growth and inhibited infiltration of CD68+ and F4/80+ cells. In ovarian cancer patients, elevated peripheral blood monocytes and tumoral macrophages were associated with worse overall survival. Collectively, we demonstrate that increased adrenergic signaling is associated with macrophage infiltration and mediated by tumor cell-derived MCP1 production. PMID:25738355

  10. Connecting G protein signaling to chemoattractant-mediated cell polarity and cytoskeletal reorganization

    NARCIS (Netherlands)

    Liu, Youtao; Lacal, Jesus; Firtel, Richard A; Kortholt, Arjan

    2016-01-01

    The directional movement towards extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein coupled receptors (GPCRs) induces symmetry breaking

  11. Antagonists of chemoattractants reveal separate receptors for cAMP, folic acid and pterin in Dictyostelium

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Wit, René J.W. de; Konijn, Theo M.

    1982-01-01

    Adenosine 3’,5’-monophosphate (cAMP), folic acid and pterin are chemoattractants in the cellular slime molds. The cAMP analog, 3’-amino-cAMP, inhibits a chemotactic reaction to cAMP at a concentration at which the analog is chemotactically inactive. The antagonistic effect of 3’-amino-cAMP on the ch

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    CONTEXT: Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. OBJECTIVE: To evaluate if improved body composition during treatment with metformin (M) vs. oral contraceptive pills (OCP) was associated...

  13. A functional study on the migration of human monocytes to human leukemic cell lines and the role of monocyte chemoattractant protein-1

    NARCIS (Netherlands)

    Legdeur, MCJC; Beelen, RHJ; Schuurhuis, GJ; Broekhoven, MG; vandeLoosdrecht, AA; Tekstra, J; Langenhuijsen, MMAC; Ossenkoppele, GJ

    1997-01-01

    In the present study the migration of human monocytes towards the supernatants of five different human myeloid leukemic cell lines, four different human lymphatic leukemic cell lines and blasts derived from three different patients with acute myeloid leukemia (AML) was studied and the role of monocy

  14. Dietary Soy Protein Isolate Ameliorates Atherosclerotic Lesions in Apolipoprotein E-Deficient Mice Potentially by Inhibiting Monocyte Chemoattractant Protein-1 Expression

    Science.gov (United States)

    Soy-based diets reportedly protect against the development of atherosclerosis; however, the underlying mechanism(s) for this protection remains unknown. In this report, the mechanism(s) contributing to the atheroprotective effects of a soy-based diet was addressed using the apolipoprotein E knockout...

  15. High concentrations of circulating interleukin-6 and monocyte chemotactic protein-1 with low concentrations of interleukin-8 were associated with severe chikungunya fever during the 2009-2010 outbreak in Thailand.

    Science.gov (United States)

    Lohachanakul, Jindarat; Phuklia, Weerawat; Thannagith, Montri; Thonsakulprasert, Tipparat; Ubol, Sukathida

    2012-02-01

    The recent outbreak of Chikungunya virus in Thailand caused a rheumatic fever associated with considerable morbidity and fatalities. Thus, it is important to identify biomarker(s) of severe disease induced by this threatening arbovirus. Putative biomarkers in cases of chikungunya fever during an outbreak in the southern part of Thailand in 2009-2010 were identified. Sixty-two patients who had developed fever and myalgia, with or without arthralgia/arthritis, were enrolled and grouped into severe chikungunya fever (CHIKF) (n= 15), mild CHIKF (n= 20) and non-CHIKF (n= 27) to investigate circulating immunological mediators that might serve as markers of severity. Blood samples were taken at presentation (day 1) and 30 days later (day 30) and plasma concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-1 and viral load were measured by ELISA. On day 1, severe CHIKF and mild CHIKF groups had viral loads of 10(8.5) and 10(8.3) of RNA copies/mL, respectively. At presentation, all CHIKF patients had circulating concentrations of IL-6 and MCP-1 higher than did non-CHIKF patients, whereas amongst the CHKF patients, the severe CHIKF patients had higher IL-6 concentrations than did mild CHIKF patients. Interestingly, severe CHIKF patients had significantly lower concentrations of circulating IL-8 than the other groups of patients, suggesting that high concentrations of IL-6 and MCP-1 with low concentrations of IL-8 may be a determinant of severe chikungunya virus infection.

  16. 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

  17. Niflumic acid disrupts marine spermatozoan chemotaxis without impairing the spatiotemporal detection of chemoattractant gradients.

    Science.gov (United States)

    Guerrero, Adán; Espinal, Jesús; Wood, Christopher D; Rendón, Juan M; Carneiro, Jorge; Martínez-Mekler, Gustavo; Darszon, Alberto

    2013-03-15

    In many broadcast-spawning marine organisms, oocytes release chemicals that guide conspecific spermatozoa towards them through chemotaxis. In the sea urchin Lytechinus pictus, the chemoattractant peptide speract triggers a train of fluctuations of intracellular Ca(2+) concentration in the sperm flagella. Each transient Ca(2+) elevation leads to a momentary increase in flagellar bending asymmetry, known as a chemotactic turn. Furthermore, chemotaxis requires a precise spatiotemporal coordination between the Ca(2+)-dependent turns and the form of chemoattractant gradient. Spermatozoa that perform Ca(2+)-dependent turns while swimming down the chemoattractant gradient, and conversely suppress turning events while swimming up the gradient, successfully approach the center of the gradient. Previous experiments in Strongylocentrotus purpuratus sea urchin spermatozoa showed that niflumic acid (NFA), an inhibitor of several ion channels, drastically altered the speract-induced Ca(2+) fluctuations and swimming patterns. In this study, mathematical modeling of the speract-dependent Ca(2+) signaling pathway suggests that NFA, by potentially affecting hyperpolarization-activated and cyclic nucleotide-gated channels, Ca(2+)-regulated Cl(-) channels and/or Ca(2+)-regulated K(+) channels, may alter the temporal organization of Ca(2+) fluctuations, and therefore disrupt chemotaxis. We used a novel automated method for analyzing sperm behavior and we identified that NFA does indeed disrupt chemotactic responses of L. pictus spermatozoa, although the temporal coordination between the Ca(2+)-dependent turns and the form of chemoattractant gradient is unaltered. Instead, NFA disrupts sperm chemotaxis by altering the arc length traveled during each chemotactic turning event. This alteration in the chemotactic turn trajectory disorientates spermatozoa at the termination of the turning event. We conclude that NFA disrupts chemotaxis without affecting how the spermatozoa decode

  18. Differential regulation of chemoattractant-stimulated beta 2, beta 3, and beta 7 integrin activity.

    Science.gov (United States)

    Sadhu, C; Masinovsky, B; Staunton, D E

    1998-06-01

    Leukocyte adhesion to endothelium and extravasation are dynamic processes that require activation of integrins. Chemoattractants such as IL-8 and FMLP are potent activators of leukocyte integrins. To compare the chemoattractant-stimulated activation of three integrins, alpha 4 beta 7, alpha L beta 2, and alpha V beta 3, in the same cellular context, we expressed an IL-8 receptor (IL-8RA) and FMLP receptor (FPR) in the lymphoid cell line JY. Chemoattractants induced a rapid increase in alpha L beta 2- and alpha V beta 3-dependent JY adhesion within 5 min, and it was sustained for 30 min. In contrast, stimulation of alpha 4 beta 7-dependent adhesion was transient, returning to basal levels by 30 min. The activation profiles of the integrins were similar regardless of whether IL-8 or FMLP was used for induction. We also demonstrate that alpha 4 beta 7-dependent adhesion was uniquely responsive to the F actin-disrupting agent cytochalasin D and the protein kinase C (PKC) inhibitor chelerythrin. While alpha V beta 3- and alpha L beta 2-mediated cell adhesion was significantly reduced by cytochalasin D, alpha 4 beta 7-mediated adhesion was enhanced. Chelerythrin inhibited both the IL-8 and PMA activation of alpha L beta 2 and alpha V beta 3. In contrast, inducible alpha 4 beta 7 activity was unaffected, and basal activity was increased. These findings demonstrate that the mechanism of alpha 4 beta 7 regulation by chemoattractants is different from that of alpha L beta 2 and alpha V beta 3 and that it appears to involve distinct cytoskeletal and PKC dependencies. In addition, PKC activity may be a positive or negative regulator of integrin-dependent adhesion.

  19. The Grape Component Resveratrol Interferes with the Function of Chemoattractant Receptors on Phagocytic Leukocytes

    Institute of Scientific and Technical Information of China (English)

    Hengyi Tao; Chunfu Wu; Ye Zhou; Wanghua Gong; Xia Zhang; Pablo Iribarren; Yuqing Zhao; Yingying Le; Jiming Wang

    2004-01-01

    Resveratrol (3, 5, 4'-trihydroxystilbene) (RV) is a constituent of grape seeds with anti-inflammatory and anti-oxidant activities. In this study, we examined the capacity of RV to modulate the function of G protein-coupled chemoattractant receptors, which play important roles in inflammation and immune responses.RV, over a non-cytotoxic concentration range, inhibited chemotactic and calcium mobilization responses of phagocytic cells to selected chemoattractants. At low micromolar concentrations, RV potently reduced superoxide anion production by phagocytic leukocytes in response to the bacterial chemotactic peptide fMLF, a high affinity ligand for formylpeptide receptor FPR, and Aβ42, an Alzheimer's disease-associated peptide and a ligand for the FPR variant FPRL1. In addition, RV reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and the activation of nuclear factor NF-κB induced by formylpeptide receptor agonists. These results suggest that the inhibition of the function of chemoattractant receptors may contribute to the anti-inflammatory properties of RV. Thus, RV may be therapeutically promising for diseases in which activation of formylpeptide receptors contributes to the pathogenic processes. Cellular & Molecular Immunology. 2004;1(1):50-56.

  20. Local modulation of chemoattractant concentrations by single cells: dissection using a bulk-surface computational model

    Science.gov (United States)

    Nolan, M.

    2016-01-01

    Chemoattractant gradients are usually considered in terms of sources and sinks that are independent of the chemotactic cell. However, recent interest has focused on ‘self-generated’ gradients, in which cell populations create their own local gradients as they move. Here, we consider the interplay between chemoattractants and single cells. To achieve this, we extend a recently developed computational model to incorporate breakdown of extracellular attractants by membrane-bound enzymes. Model equations are parametrized, using the published estimates from Dictyostelium cells chemotaxing towards cyclic AMP. We find that individual cells can substantially modulate their local attractant field under physiologically appropriate conditions of attractant and enzymes. This means the attractant concentration perceived by receptors can be a small fraction of the ambient concentration. This allows efficient chemotaxis in chemoattractant concentrations that would be saturating without local breakdown. Similar interactions in which cells locally mould a stimulus could function in many types of directed cell motility, including haptotaxis, durotaxis and even electrotaxis. PMID:27708760

  1. The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Otkjaer, Kristian; Holm, Christian

    2008-01-01

    chemoattractant protein 1 (CCL2/MCP-1) secretion, but not tumour necrosis factor alpha mRNA synthesis or IL-6 secretion. Both IL-20 and IL-24 showed correlations to CCL2/MCP-1 in plasma from rheumatoid arthritis and spondyloarthropathy patients. This study associates IL-20 and IL-24 to the synovium of rheumatoid...... whereas IL-24 protein was observed in endothelial cells and mononuclear cells. IL-20 receptor type 1 and IL-22 receptor were expressed by granulocytes in the synovial fluid. In synovial fluid mononuclear cell cultures, stimulation with recombinant human IL-20 or recombinant human IL-24 induced monocyte...

  2. Assessing the potential for egg chemoattractants to mediate sexual selection in a broadcast spawning marine invertebrate.

    Science.gov (United States)

    Evans, Jonathan P; Garcia-Gonzalez, Francisco; Almbro, Maria; Robinson, Oscar; Fitzpatrick, John L

    2012-07-22

    In numerous species, egg chemoattractants play a critical role in guiding sperm towards unfertilized eggs (sperm chemotaxis). Until now, the known functions of sperm chemotaxis include increasing the effective target size of eggs, thereby promoting sperm-egg encounters, and facilitating species recognition. Here, we report that in the broadcast spawning mussel, Mytilus galloprovincialis, egg chemoattractants may play an unforeseen role in sexual selection by enabling sperm to effectively 'choose' between the eggs of different conspecific females. In an initial experiment, we confirmed that sperm chemotaxis occurs in M. galloprovincialis by showing that sperm are attracted towards unfertilized eggs when given the choice of eggs or no eggs in a dichotomous chamber. We then conducted two cross-classified mating experiments, each comprising the same individual males and females crossed in identical male × female combinations, but under experimental conditions that offered sperm 'no-choice' (each fertilization trial took place in a Petri dish and involved a single male and female) or a 'choice' of a female's eggs (sperm were placed in the centre of a dichotomous choice chamber and allowed to choose eggs from different females). We show that male-by-female interactions characterized fertilization rates in both experiments, and that there was remarkable consistency between patterns of sperm migration in the egg-choice experiment and fertilization rates in the no-choice experiment. Thus, sperm appear to exploit chemical cues to preferentially swim towards eggs with which they are most compatible during direct sperm-to-egg encounters. These results reveal that sperm differentially select eggs on the basis of chemical cues, thus exposing the potential for egg chemoattractants to mediate mate choice for genetically compatible partners. Given the prevalence of sperm chemotaxis across diverse taxa, our findings may have broad implications for sexual selection in other mating

  3. Serum leveis of inflammatory markers in type 2 diabetes patients with chronic periodontitis

    OpenAIRE

    Longo, Priscila Larcher; Artese,Hilana Paula Carillo; RABELO,Marianade Sousa; KAWAMOTO, Dione; Foz, Adriana Moura; ROMITO, Giuseppe Alexandre; Dib, Sérgio Atala; Mayer, Marcia Pinto Alves

    2014-01-01

    Diabetes has been associated with periodontitis, but the mechanisms through which periodontal diseases affect the metabolic control remain unclear. Objective: This study aimed to evaluate serum leveis of inflammatory markers, IL-8, IL-6 and monocyte chemoattractant protein 1 (MCP-1), in type 2 diabetic patients in the presence of chronic periodontitis. Material and Methods: Forty two individuals were enrolled in this study and assigned to one of five groups: diabetes mellitus with inade...

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

    Directory of Open Access Journals (Sweden)

    Michael Wolf

    2014-01-01

    Full Text Available High mobility group box protein-1 (HMGB1 is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

  5. Monocyte-targeting supramolecular micellar assemblies: a molecular diagnostic tool for atherosclerosis.

    Science.gov (United States)

    Chung, Eun Ji; Mlinar, Laurie B; Nord, Kathryn; Sugimoto, Matthew J; Wonder, Emily; Alenghat, Francis J; Fang, Yun; Tirrell, Matthew

    2015-02-18

    Atherosclerosis is a multifactorial inflammatory disease that can progress silently for decades and result in myocardial infarction, stroke, and death. Diagnostic imaging technologies have made great strides to define the degree of atherosclerotic plaque burden through the severity of arterial stenosis. However, current technologies cannot differentiate more lethal "vulnerable plaques," and are not sensitive enough for preventive medicine. Imaging early molecular markers and quantifying the extent of disease progression continues to be a major challenge in the field. To this end, monocyte-targeting, peptide amphiphile micelles (PAMs) are engineered through the incorporation of the chemokine receptor CCR2-binding motif of monocyte chemoattractant protein-1 (MCP-1) and MCP-1 PAMs are evaluated preclinically as diagnostic tools for atherosclerosis. Monocyte-targeting is desirable as the influx of monocytes is a marker of early lesions, accumulation of monocytes is linked to atherosclerosis progression, and rupture-prone plaques have higher numbers of monocytes. MCP-1 PAMs bind to monocytes in vitro, and MCP-1 PAMs detect and discriminate between early- and late-stage atherosclerotic aortas. Moreover, MCP-1 PAMs are found to be eliminated via renal clearance and the mononuclear phagocyte system (MPS) without adverse side effects. Thus, MCP-1 PAMs are a promising new class of diagnostic agents capable of monitoring the progression of atherosclerosis.

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

    CERN Document Server

    Adamatzky, Andrew

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  8. Identification and characterization of new protein chemoattractants in the frog skin secretome.

    Science.gov (United States)

    Leroy, Baptiste; Toubeau, Gerard; Falmagne, Paul; Wattiez, Ruddy

    2006-11-01

    The vomeronasal organ is a chemosensory organ present in most vertebrates and involved in chemical communication. In the last decade, the deciphering of the signal transduction process of this organ has progressed. However, less is known about the vomeronasal organ ligands and their structure-function relationships. Snakes possess a highly developed vomeronasal system that is used in various behaviors such as mating, predator detection, or prey selection, making this group a suitable model for study of the vomeronasal chemoreception. In this work, we used a proteomics approach to identify and characterize proteins from frog cutaneous mucus proteome involved in prey recognition by snakes of the genus Thamnophis. Herein we report the purification and characterization of two proteins isolated from the frog skin secretome that elicit the vomeronasal organ-mediated predatory behavior of Thamnophis marcianus. These proteins are members of the parvalbumin family, which are calcium-binding proteins generally associated to muscular and nervous tissues. This is the first report that demonstrates parvalbumins are not strictly restricted to intracellular compartments and can also be isolated from exocrine secretions. Purified parvalbumins from frog muscle and mucus revealed identical chemoattractive properties for T. marcianus. Snake bioassay revealed the Ca(2+)/Mg(2+) dependence of the bioactivity of parvalbumins. So parvalbumins appear to be new candidate ligands of the vomeronasal organ.

  9. Connecting G protein signaling to chemoattractant-mediated cell polarity and cytoskeletal reorganization.

    Science.gov (United States)

    Liu, Youtao; Lacal, Jesus; Firtel, Richard A; Kortholt, Arjan

    2016-10-07

    The directional movement towards extracellular chemical gradients, a process called chemotaxis, is an important property of cells. Central to eukaryotic chemotaxis is the molecular mechanism by which chemoattractant-mediated activation of G-protein coupled receptors (GPCRs) induces symmetry breaking in the activated downstream signaling pathways. Studies with mainly Dictyostelium and mammalian neutrophils as experimental systems have shown that chemotaxis is mediated by a complex network of signaling pathways. Recently, several labs have used extensive and efficient proteomic approaches to further unravel this dynamic signaling network. Together these studies showed the critical role of the interplay between heterotrimeric G-protein subunits and monomeric G proteins in regulating cytoskeletal rearrangements during chemotaxis. Here we highlight how these proteomic studies have provided greater insight into the mechanisms by which the heterotrimeric G protein cycle is regulated, how heterotrimeric G proteins-induced symmetry breaking is mediated through small G protein signaling, and how symmetry breaking in G protein signaling subsequently induces cytoskeleton rearrangements and cell migration.

  10. Chemoattractant signaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization.

    Directory of Open Access Journals (Sweden)

    Chad E Green

    Full Text Available Tumor-associated macrophages are known to influence cancer progression by modulation of immune function, angiogenesis, and cell metastasis, however, little is known about the chemokine signaling networks that regulate this process. Utilizing CT26 colon cancer cells and RAW 264.7 macrophages as a model cellular system, we demonstrate that treatment of CT26 cells with RAW 264.7 conditioned medium induces cell migration, invasion and metastasis. Inflammatory gene microarray analysis indicated CT26-stimulated RAW 264.7 macrophages upregulate SDF-1alpha and VEGF, and that these cytokines contribute to CT26 migration in vitro. RAW 264.7 macrophages also showed a robust chemotactic response towards CT26-derived chemokines. In particular, microarray analysis and functional testing revealed CSF-1 as the major chemoattractant for RAW 264.7 macrophages. Interestingly, in the chick CAM model of cancer progression, RAW 264.7 macrophages localized specifically to the tumor periphery where they were found to increase CT26 tumor growth, microvascular density, vascular disruption, and lung metastasis, suggesting these cells home to actively invading areas of the tumor, but not the hypoxic core of the tumor mass. In support of these findings, hypoxic conditions down regulated CSF-1 production in several tumor cell lines and decreased RAW 264.7 macrophage migration in vitro. Together our findings suggest a model where normoxic tumor cells release CSF-1 to recruit macrophages to the tumor periphery where they secrete motility and angiogenic factors that facilitate tumor cell invasion and metastasis.

  11. The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for HIV-1 infection.

    Science.gov (United States)

    Frade, J M; Llorente, M; Mellado, M; Alcamí, J; Gutiérrez-Ramos, J C; Zaballos, A; Real, G; Martínez-A, C

    1997-08-01

    The chemokines are a homologous serum protein family characterized by their ability to induce activation of integrin adhesion molecules and leukocyte migration. Chemokines interact with their receptors, which are composed of a single-chain, seven-helix, membrane-spanning protein coupled to G proteins. Two CC chemokine receptors, CCR3 and CCR5, as well as the CXCR4 chemokine receptor, have been shown necessary for infection by several HIV-1 virus isolates. We studied the effect of the chemokine monocyte chemoattractant protein 1 (MCP-1) and of a panel of MCP-1 receptor (CCR2)-specific monoclonal antibodies (mAb) on the suppression of HIV-1 replication in peripheral blood mononuclear cells. We have compelling evidence that MCP-1 has potent HIV-1 suppressive activity when HIV-1-infected peripheral blood lymphocytes are used as target cells. Furthermore, mAb specific for the MCP-1R CCR2 which recognize the third extracellular CCR2 domain inhibit all MCP-1 activity and also block MCP-1 suppressive activity. Finally, a set of mAb specific for the CCR2 amino-terminal domain, one of which mimics MCP-1 activity, has a potent suppressive effect on HIV-1 replication in M- and T-tropic HIV-1 viral isolates. We conjecture a role for CCR2 as a coreceptor for HIV-1 infection and map the HIV-1 binding site to the amino-terminal part of this receptor. This concurs with results showing that the CCR5 amino terminus is relevant in HIV-1 infection, although chimeric fusion of various extracellular domains shows that other domains are also implicated. We discuss the importance of CCR2 structure relative to its coreceptor role and the role of anti-CCR2 receptor antibodies in the prevention of HIV-1 infection.

  12. SD大鼠胰腺癌模型及其化学趋化因子mRNA表达与MC计数的关系研究%Establishment of a model for pancreatic cancer in Sprague-Dawely (SD) rat and study on the relationship among IL-8 ,MCP-1,MIP-1α mRNA and MC count in the rat pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    杨乐平; 杨竹林; 邓星辉; 范文涛; 李清龙

    2007-01-01

    目的 将二甲基苯并蒽(DMBA)置入SD大鼠胰腺内建立胰腺癌模型,在此基础上研究胰腺导管癌和非癌胰腺组织IL-8,MCP-l,MIP-1α mRNA的表达及其与肥大细胞(mast cell,MC)计数的关系.方法 SD大鼠90只,随机分成3组,即DMBA组、TSA干预组和对照组,喂养3~5月处死,观察胰腺癌发生情况;常规石蜡切片行胰腺癌和非癌胰腺组织3种mRNA原位杂交染色及MC免疫组化染色.结果 ①模型组(A组)3~5月癌症发生率为48.7%(18/37).B组3~5月癌症发生率为33.3%(12/36).A组肿块直径明显大于B组(P=0.022),A组和B组纤维肉瘤均发生胰腺外转移.部分A和B组非癌胰腺组织可看到中~重度导管上皮不典型增生.胰腺外主要脏器未见肿瘤发生及其他病变.②除B组胰腺导管癌MCP-1 mRNA阳性率与非癌组织无统计学差异外,A组和B组胰腺导管癌3种mRNA表达阳性率及其评分明显高于非癌组织(P<0.01),C组均呈阴性表达;A组胰腺导管癌3种mRNA表达阳性率及其评分均明显高于B组(P<0.05).③A组和B组胰腺导管癌MC计数明显高于非癌组织和C组(P<0.05);A组胰腺导管癌MC计数明显高于B组(P<0.05);A和B组中3~4月组胰腺导管癌MC计数明显低于5月组(P<0.01).④3种化学趋化因子mRNA阳性胰腺癌MC计数明显高于阴性者(P<0.05),其评分值与MC计数呈密切正相关(rIL-8=0.42,rMCP-1=0.48,rMIP-1α=0.55,P值均<0.05).结论 较大剂量DMBA置入胰实质内可在短期获得较高的SD大鼠胰腺癌发生率,TSA能抑制胰腺癌发生和生长,其作用可能与抑制化学趋化因子的表达和MC浸润有关;3种化学趋化因子和MC可能与胰腺癌发生发展有较密切关系.

  13. A knockout mutation of a constitutive GPCR in Tetrahymena decreases both G-protein activity and chemoattraction.

    Directory of Open Access Journals (Sweden)

    Thomas J Lampert

    Full Text Available Although G-protein coupled receptors (GPCRs are a common element in many chemosensory transduction pathways in eukaryotic cells, no GPCR or regulated G-protein activity has yet been shown in any ciliate. To study the possible role for a GPCR in the chemoresponses of the ciliate Tetrahymena, we have generated a number of macronuclear gene knockouts of putative GPCRs found in the Tetrahymena Genome database. One of these knockout mutants, called G6, is a complete knockout of a gene that we call GPCR6 (TTHERM_00925490. Based on sequence comparisons, the Gpcr6p protein belongs to the Rhodopsin Family of GPCRs. Notably, Gpcr6p shares highest amino acid sequence homologies to GPCRs from Paramecium and several plants. One of the phenotypes of the G6 mutant is a decreased responsiveness to the depolarizing ions Ba²⁺ and K⁺, suggesting a decrease in basal excitability (decrease in Ca²⁺ channel activity. The other major phenotype of G6 is a loss of chemoattraction to lysophosphatidic acid (LPA and proteose peptone (PP, two known chemoattractants in Tetrahymena. Using microsomal [³⁵S]GTPγS binding assays, we found that wild-type (CU427 have a prominent basal G-protein activity. This activity is decreased to the same level by pertussis toxin (a G-protein inhibitor, addition of chemoattractants, or the G6 mutant. Since the basal G-protein activity is decreased by the GPCR6 knockout, it is likely that this gene codes for a constitutively active GPCR in Tetrahymena. We propose that chemoattractants like LPA and PP cause attraction in Tetrahymena by decreasing the basal G-protein stimulating activity of Gpcr6p. This leads to decreased excitability in wild-type and longer runs of smooth forward swimming (less interrupted by direction changes towards the attractant. Therefore, these attractants may work as inverse agonists through the constitutively active Gpcr6p coupled to a pertussis-sensitive G-protein.

  14. Folic acid is a potent chemoattractant of free-living amoebae in a new and amazing species of protist, Vahlkampfia sp.

    Science.gov (United States)

    Maeda, Yasuo; Mayanagi, Taira; Amagai, Aiko

    2009-03-01

    Folic acid (folate; vitamin Bc) is well recognized as essential for the proper metabolism of the essential amino acid methionine as well as for the synthesis of adenine and thymine. A folate deficiency has been Implicated in a wide variety of disorders from Alzheimer's disease to depression and neural tube defects. In the cellular slime molds, including Dictyostelium, vegetative growth-phase cells are known to chemotactically move toward folate that is secreted by bacterial food sources such as Escherichia coli. Intracellular folate signal transductlon, including G proteins, Ca(2+)channels, and the PIP3 pathway, has been reported in D. discoideum. To our surprise, the genuine chemoattractant(s) of free-living protozoan amoebae have remained to be determined, possibly because of lack of a pertinent method for assaying chemotaxis. We recently isolated a primitive free-living amoeba from the soil of Costa Rica and identified it as a new species of the genus Vahlkampfia belonging to Subclass Gymnamoebia, which includes Entamoeba and Acanthamoeba. The amoebae can grow and multiply quite rapidly, engulfing nearby bacteria such as E. coli. Importantly, we have demonstrated here using a quite simple but finely designed chemotaxis assay that the Vahlkampfia amoebae exhibit chemotaxis toward higher folate concentrations. Riboflavin and cyanocobalamin were also found to serve as positive chemoattractants. Among these chemoattractants, folate is of particular importance because its function seems to be evolutionarily conserved as a potent chemoattractant of amoeboid cells in a wide range of organisms as well as in the Protista and cellular slime molds.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  16. Proteolipid protein 1 gene sequencing of hereditary spastic paraplegia

    Institute of Scientific and Technical Information of China (English)

    Yu Gao; Lumei Chi; Yinshi Jin; Guangxian Nan

    2012-01-01

    PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 (PLP1) gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.

  17. CX3CL1(+ Microparticles Mediate the Chemoattraction of Alveolar Macrophages toward Apoptotic Acute Promyelocytic Leukemic Cells

    Directory of Open Access Journals (Sweden)

    Wen-Hui Tsai

    2014-02-01

    Full Text Available Background/Aims: During the resolution phase of inflammation, release of “find-me” signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4 cells. Methods/Results: Apoptotic ATRA-NB4 cells and their conditioning medium (CM enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+ apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells. Conclusion: CX3CL1(+ apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.

  18. 单核细胞趋化蛋白1和骨形成蛋白7在病理性瘢痕中的表达%Expression of monocyte ehemoattraetant protein-1 and bone morphogenic protein-7 in pathologic scars

    Institute of Scientific and Technical Information of China (English)

    李永涛; 王喜梅; 刘林嶓; 张建文; 袁德品

    2011-01-01

    背景:单核细胞趋化蛋白1 是新近明确的对单核/巨噬细胞有趋化和激活双重作用的趋化因子,骨形成蛋白7 作为一种新发现的纤维化负性调节因子逐渐成为抗组织纤维化治疗的研究热点,但两者对病理性瘢痕形成中组织纤维化作用的研究至今鲜有报道.目的:研究单核细胞趋化蛋白1,骨形成蛋白7 在病理性瘢痕中的表达水平.方法:采用免疫组织化学方法检测单核细胞趋化蛋白1、骨形成蛋白7 在25 例瘢痕疙瘩、30 例增生性瘢痕、24 例非病理瘢痕和20 例正常皮肤组织中的表达水平.所有标本均来自2008-07/2010-01 郑州大学第一附属医院整形外科住院患者,且均无皮肤疾病、结缔组织病、传染病、恶性肿瘤和其他重要脏器疾病,术前无射线治疗、激光治疗及免疫治疗史,其中所取瘢痕组织来自于临床诊断明确的瘢痕患者.结果与结论:单核细胞趋化蛋白1 在瘢痕疙瘩、增生性瘢痕中的阳性表达率均高于非病理性瘢痕与正常皮肤组织(P < 0.05),骨形成蛋白7 阳性表达率均降低(P < 0.05),两者阳性表达率在病理性瘢痕(瘢痕疙瘩和增生性瘢痕)中呈明显负相关(r = -0.639,P < 0.01).结果显示,在病理性瘢痕的形成过程中单核细胞趋化蛋白1 表达上调,而骨形成蛋白7 表达下调.%BACKGROUND: Monocyte ehemoattraetant protein-1 (MCP-1) has been shown chemotaxis and activation effect on mononuclear/macrophage. As a newly found negative-regulatory factor, bone morphogenic protein-7 (BMP-7) has aroused increasing attention in the treatment of tissue fibrosis. However, the effects of MCP-1 and BMP-7 on tissue fibrosis during pathologic scars remain poorly understood.OBJECTIVE: To investigate the expression of MCP-1 and BMP-7 in pathologic scars.METHODS: SP immunohistochemical method was used to detect the expressions of MCP-1 and BMP-7 in 25 cases of keloid, 30 cases of hypertrophic scars, 24 cases of

  19. Effects of a multi-component camp-based intervention on inflammatory markers and adipokines in children

    DEFF Research Database (Denmark)

    Huang, T.; Larsen, K. T.; Moller, N. C.

    2015-01-01

    chemoattractant protein-1 (MCP1), leptin, and adiponectin were measured in serum at baseline, 6 weeks and 52 weeks. Results. In comparison with the SIA, the reductions in CRP (P = 0.003) and leptin (p ... arm (DCIA) or the standard intervention arm (SIA). The intervention for the DCIA consisted of a 6-week camp-based intervention and a 46-week family-based intervention. The SIA was offered one weekly physical activity session for 6 weeks and one educational meeting. C-reactive protein (CRP), monocyte...

  20. Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro

    DEFF Research Database (Denmark)

    Chacón, M R; Miranda, M; Jensen, C H

    2008-01-01

    chemoattractant protein-1 (MCP-1), IL-6 (interleukin-6) and adiponectin). CONCLUSION: FA1 serum levels were increased in obese subjects and might influence S(i). The stimulatory effect of FA1 protein on pro-inflammatory cytokines on both immune and adipose cell types could contribute to worsening the inflammatory...... levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-alpha (TNFalpha), monocyte...

  1. The Role of C-C Motif Chemokine Receptor-2 in Human Vein Endothelial Cells Migration%CC类趋化因子受体2在人内皮细胞迁移中的作用

    Institute of Scientific and Technical Information of China (English)

    赵宁; 赵俐杰

    2016-01-01

    目的:探讨CC类趋化因子受体2(CCR2)对人脐静脉血管内皮细胞(HUVECs)迁移的作用。方法 RT-PCR和Western-blot检测单核细胞趋化蛋白-1(MCP1)对HUVECs CCR2蛋白表达的影响。 Transwell实验观察CCR2拮抗剂对HUVECs迁移的影响。结果在 HUVECs中 CCR2蛋白表达存在 MCP1浓度依赖方式, Transwell 实验显示 CCR2拮抗剂(RS504393)抑制细胞迁移(P<0.01)。结论 CCR2对人内皮细胞迁移有促进作用,其作用与MCP1结合相关。%Objective To explore the effect of C-C motif chemokine receptor -2 ( CCR2 ) on the migration of human umbilical vein endothelial cells (HUVECs). Methods The effect of monocyte chemoattractant protein-1 (MCP1) on the expression of CCR2 in HUVECs was measured by RT-PCR and Western blot. The effect of anti-CCR2 polyclonal antibodies (RS504393) on the migration of HUVECs was measured by Transwell migration assay. Results CCR2 was dose-dependently induced by MCP1 in HUVECs. The migrating of cells was significantly inhibited by RS504393. Conclusion CCR2 can accelerate the migration of HUVECs, which may be associated with MCP-1 binding.

  2. Polymorphic membrane protein (PMP) 20 and PMP 21 of Chlamydia pneumoniae induce proinflammatory mediators in human endothelial cells in vitro by activation of the nuclear factor-kappaB pathway.

    Science.gov (United States)

    Niessner, Alexander; Kaun, Christoph; Zorn, Gerlinde; Speidl, Walter; Türel, Zeynep; Christiansen, Gunna; Pedersen, Anna-Sofie; Birkelund, Svend; Simon, Susan; Georgopoulos, Apostolos; Graninger, Wolfgang; de Martin, Rainer; Lipp, Joachim; Binder, Bernd R; Maurer, Gerald; Huber, Kurt; Wojta, Johann

    2003-07-01

    We tested whether polymorphic membrane proteins (PMPs) of Chlamydia pneumoniae might play a role in triggering an inflammatory response in human endothelial cells. Of 15 purified, recombinant chlamydial PMPs tested, 2 (PMP 20 and PMP 21) dose-dependently increased the production of the inflammatory mediators interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1), in cultured human endothelial cells; production of IL-8 was also increased. When endothelial cells were infected by live C. pneumoniae, an increase in the production of IL-6, IL-8, and MCP-1 was seen. We used adenovirus-induced overexpression of IkappaBalpha-an inhibitor of nuclear factor (NF)-kappaB-to demonstrate that PMP 20 and PMP 21 increase the production of IL-6 and MCP-1 in human endothelial cells by activation of the NF-kappaB pathway, because, in cells overexpressing IkappaBalpha, treatment with the respective PMP did not result in increased production of IL-6 and MCP-1. Thus, C. pneumoniae could, by interactions of its PMPs with the endothelium, contribute to the process of vascular injury during the development and progression of atherosclerotic lesions.

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

    LENUS (Irish Health Repository)

    Sookhai, S

    2012-02-03

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

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

    Institute of Scientific and Technical Information of China (English)

    Jiren Zhang; Yubo Wang; Jincheng Zhang

    2012-01-01

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

  5. 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.

  6. Activated niacin receptor HCA2 inhibits chemoattractant-mediated macrophage migration via Gβγ/PKC/ERK1/2 pathway and heterologous receptor desensitization

    Science.gov (United States)

    Shi, Ying; Lai, Xiangru; Ye, Lingyan; Chen, Keqiang; Cao, Zheng; Gong, Wanghua; Jin, Lili; Wang, Chunyan; Liu, Mingyong; Liao, Yuan; Wang, Ji Ming; Zhou, Naiming

    2017-01-01

    The niacin receptor HCA2 is implicated in controlling inflammatory host responses with yet poorly understood mechanistic basis. We previously reported that HCA2 in A431 epithelial cells transduced Gβγ-protein kinase C- and Gβγ-metalloproteinase/EGFR-dependent MAPK/ERK signaling cascades. Here, we investigated the role of HCA2 in macrophage-mediated inflammation and the underlying mechanisms. We found that proinflammatory stimulants LPS, IL-6 and IL-1β up-regulated the expression of HCA2 on macrophages. Niacin significantly inhibited macrophage chemotaxis in response to chemoattractants fMLF and CCL2 by disrupting polarized distribution of F-actin and Gβ protein. Niacin showed a selected additive effect on chemoattractant-induced activation of ERK1/2, JNK and PI3K pathways, but only the MEK inhibitor UO126 reduced niacin-mediated inhibition of macrophage chemotaxis, while activation of ERK1/2 by EGF alone did not inhibit fMLF-mediated migration of HEK293T cells co-expressing HCA2 and fMLF receptor FPR1. In addition, niacin induced heterologous desensitization and internalization of FPR1. Furthermore, niacin rescued mice from septic shock by diminishing inflammatory symptoms and the effect was abrogated in HCA2−/− mice. These results suggest that Gβγ/PKC-dependent ERK1/2 activation and heterologous desensitization of chemoattractant receptors are involved in the inhibition of chemoattractant-induced migration of macrophages by niacin. Thus, HCA2 plays a critical role in host protection against pro-inflammatory insults. PMID:28186140

  7. Distinct Roles of PI(3,4,5)P3 during Chemoattractant Signaling in Dictyostelium : A Quantitative In Vivo Analysis by Inhibition of PI3-Kinase

    NARCIS (Netherlands)

    Loovers, Harriet; Postma, Marten; Keizer-Gunnink, Ineke; Huang, Yi Elaine; Devreotes, Peter N.; Haastert, Peter J.M. van

    2006-01-01

    The role of PI(3,4,5)P3 in Dictyostelium signal transduction and chemotaxis was investigated using the PI3-kinase inhibitor LY294002 and pi3k-null cells. The increase of PI(3,4,5)P3 levels after stimulation with the chemoattractant cAMP was blocked >95% by 60 µM LY294002 with half-maximal effect at

  8. 单核细胞趋化蛋白-1基因多态性与肺结核易感性的关系%The relationship between monocyte chemoattactant protein-1 gene polymorphisms and the susceptibility to pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    杨本付; 庄斌; 李芳; 张春之; 宋爱琴

    2009-01-01

    目的 探讨中国汉族人群单核细胞趋化蛋白-1(MCP-1)基因-2518位点多态性与肺结核发病的关系.方法 2008年3-8月采用1:1配对病例对照设计,用PCR-限制性片段长度多态性分析(RLFP)检测167例肺结核患者和167例对照的MCP-1基因-2518位点的基因型分布.病例组年龄16~77岁,对照组年龄15~78岁,两组患者的中位年龄均为43岁,四分位间距均为30岁;两组均为男110例、女57例,汉族.对一般情况、现病史、既往病史及肺结核相关环境因素进行问卷调查,并进行单因素和多因素条件logistic回归分析.结果 AA、GA和GG基因型在病例组的分布频率分别为21/167(12.6%)、62/167(37.1%)和84/167(50.3%),在对照组的分布频率分别为42/167(25.2%)、83/167(49.7%)和42/167(25.1%).单因素分析结果显示,基因型在病例组和对照组中分布频率的差异有统计学意义(x2=24.041,P<0.01);调整环境因素后,多因素回归分析结果显示,GG基因型与肺结核发病仍有显著性相关性(OR=1.989,95%CI为1.154~3.428,x2=6.124,P<0.05).结论 MCP-1基因-2518位点GG基因型可能与中国汉族人群的肺结核易感性有关.%Objective To explore the possible relationship between the -2518 A/G single nucleotide polymorphisms in monocyte chemoattactant protein-1 ( MCP-1 ) gene of Chinese Han population and the susceptibility to pulmonary tuberculosis. Methods A 1:1 matched case-control study was conducted from March 2008 to August 2008. The - 2518 MCP-1 A/G polymorphisms were detected in 167 pairs of subjects by reaction-restriction fragment length polymorphism (PCR-RLFP) technique. General characteristics, current disease history, past medical history and related environmental factors of tuberculosis were collected using a questionnaire designed by ourselves. Univariate analyses and multivariate conditional logistic analyses were conducted. Results The genotype frequencies of AA, GA and GG in the case group and the control group

  9. 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。

  10. Functional characterization of recombinant rat macrophage inflammatory protein-1 alpha and mRNA expression in pulmonary inflammation.

    Science.gov (United States)

    Shi, M M; Chong, I W; Long, N C; Love, J A; Godleski, J J; Paulauskis, J D

    1998-02-01

    Chemokines are important inflammatory mediators that function by activating and recruiting leukocytes to an inflamed tissue. We have recently cDNA cloned the rat chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) (1). In the present study, we characterize the biological function of recombinant MIP-1 alpha protein and describe expression of its mRNA both in vitro and in a rat model of lung inflammation. In vitro rat rMIP-1 alpha protein was chemotactic for both polymorphonuclear leukocytes (PMNs) and macrophages with maximal activity at 50 nM for both cell types. In in vivo studies, we found that intratracheal instillation of 1 and 5 micrograms of rMIP-1 alpha resulted in a significant (P < 0.05) influx of cells, primarily monocytes/macrophages, into the airspace of the lungs after 6 h. Mean numbers of lavagable PMNs were not elevated significantly (P < 0.05) for either dose of MIP-1 alpha. As a model of inflammation, rats were intratracheally instilled with 0.1 mg/kg bacterial lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) was performed 3 h later. Instillation of LPS resulted in an acute neutrophilia, but no significant change in lavagable macrophages. BAL cells from control animals (saline instilled) displayed no basal mRNA expression of either MIP-1 alpha or MIP-2 (positive control). In contrast, both MIP-1 alpha and MIP-2 mRNA levels increased markedly in BAL cells from rats instilled with LPS. The rat alveolar macrophage cell line (NR8383) also showed increased MIP-1 alpha mRNA levels in response to LPS (10 micrograms/ml) with a maximal increase after 6-8 h. The induction of MIP-1 alpha mRNA expression by LPS in NR8383 cells was attenuated by cotreatment with the antioxidants N-acetylcysteine and dimethylsulfoxide, suggesting that the induction of MIP-1 alpha mRNA by LPS is mediated via the generation of reactive oxygen species. We conclude that MIP-1 alpha is a potent chemoattractant for macrophages in vivo, and its mRNA expression in

  11. Revisiting Apoplastic Auxin Signaling Mediated by AUXIN BINDING PROTEIN 1.

    Science.gov (United States)

    Feng, Mingxiao; Kim, Jae-Yean

    2015-10-01

    It has been suggested that AUXIN BINDING PROTEIN 1 (ABP1) functions as an apoplastic auxin receptor, and is known to be involved in the post-transcriptional process, and largely independent of the already well-known SKP-cullin-F-box-transport inhibitor response (TIR1) /auxin signaling F-box (AFB) (SCF(TIR1/AFB)) pathway. In the past 10 years, several key components downstream of ABP1 have been reported. After perceiving the auxin signal, ABP1 interacts, directly or indirectly, with plasma membrane (PM)-localized transmembrane proteins, transmembrane kinase (TMK) or SPIKE1 (SPK1), or other unidentified proteins, which transfer the signal into the cell to the Rho of plants (ROP). ROPs interact with their effectors, such as the ROP interactive CRIB motif-containing protein (RIC), to regulate the endocytosis/exocytosis of the auxin efflux carrier PIN-FORMED (PIN) proteins to mediate polar auxin transport across the PM. Additionally, ABP1 is a negative regulator of the traditional SCF(TIR1/AFB) auxin signaling pathway. However, Gao et al. (2015) very recently reported that ABP1 is not a key component in auxin signaling, and the famous abp1-1 and abp1-5 mutant Arabidopsis lines are being called into question because of possible additional mutantion sites, making it necessary to reevaluate ABP1. In this review, we will provide a brief overview of the history of ABP1 research.

  12. Osteogenic protein-1 is required for mammalian eye development.

    Science.gov (United States)

    Solursh, M; Langille, R M; Wood, J; Sampath, T K

    1996-01-17

    Osteogenic Protein-1 (OP-1/BMP-7) is a bone morphogenetic protein in the transforming growth factor-beta superfamily and has been shown to be expressed temporally and spatially during epithelial-mesenchymal interactions mediating tissue morphogenesis in early embryogenesis. In order to identify the primary role(s) for OP-1 in development, we carried out whole rat embryo cultures, over a 72-h period from primitive streak stages to early limb bud stages, in rat sera containing either OP-1 blocking antibodies (10 micrograms/ml) or nonreactive IgG. Rat embryos cultured with control antibodies developed normally, while those cultured with anti-OP-1 antibodies consistently exhibited over-all reduced size and absence of eyes. Histological sections revealed a greater reduction in neural retina development in the embryos treated with anti-OP-1 blocking antibodies. In situ hybridization and immunolocalization analyses indicate that OP-1 is expressed in the neuroepithelium of the optic vesicle at E11.5, is limited to the presumptive neural retina and developing lens placode, and is subsequently expressed in the neural retina, lens and developing cornea at E12.5-E13.5. Our results indicate that OP-1 mediates the inductive signals involved in mammalian eye development.

  13. Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis.

    Science.gov (United States)

    Sun, Yao; Weng, Yuteng; Zhang, Chenyang; Liu, Yi; Kang, Chen; Liu, Zhongshuang; Jing, Bo; Zhang, Qi; Wang, Zuolin

    2015-12-04

    Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser(89) is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S(89) was substituted with G(89) (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.

  14. SP600125对1型糖尿病小鼠颈动脉内皮功能及单核细胞趋化蛋白1表达的影响%The Effect of SP600125 on Endothelial Function and Monocyte Chemotactic Protein-1 Expression in Carotid Artery in Type 1 Diabetic Mice

    Institute of Scientific and Technical Information of China (English)

    王启章; 陈茂刚; 李达文; 刘朝来; 徐格林; 刘新峰

    2011-01-01

    Aim The incidence of stroke in diabetes is increasing seriously, which is associated with endothelial dysfunction and increased inflammation in carotid artery.Our study is to investigate the effect of c-Jun arnino-terminal ki-nase (JNK) specific inhibitor SP600125 on carotid endothelial function and monocyte chemotactic protein-1 (MCP-1) expression in type 1 diabetes. Methods Animals were divided into five groups in this study. The 1st group was C57BL/6 wild type male mice; the 2nd group was INS2AKUTI male mice, intraperitoneal injection with 0. 9% normal saline (NS) each day for 8 weeks; the 3rd, 4th, 5th group were INS2AKITA male mice, intraperitoneal injection with SP600125 10 mg/kg, 20 mg/kg, 30 mg/kg respectively each day for consecutive 8 weeks. Then the mice were killed and sreum my-eloperoxidase (MPO) , malondialdehyde (MDA) , nitric oxide (NO) , total nitric oxide synthase (TNOS) were measured. HE staining was performed in carotid artery and immunohistochemistry was performed to investigate MCP-1 protein expression in endothelial cells of carotid artery. P-JNK, JNK, MCP-1 protein expression in carotid artery was measured by Western blot, signal transducer and activator of transcription-1 (STAT-1) DNA binding activity was assayed by electro-phoretic mobility shift assay (EMSA). Results Compared with wild type mice, serum MPO and MDA expression increased prominently (P <0. 05) , whereas TNOS, NO decreased and p-JNK/JNK, MCP-1 expression increased significantly in INS2AKITA mice (P<0.05); STAT-1 DNA binding activity increased prominently in type 1 diabetic group compared with that in control group (P <0. 05). Compared with type 1 diabetic mice, after treatment with SP600125, MPO decreased and NO, TNOS increased and p-JNK/JNK, endothelial MCP-1 expression decreased (P<0. 05). The effects of SP600125 on MPO, NO, TNOS, MCP-1 were increased accordingly as the dose of SP600125 increased. As the dose of SP600125 increased, MCP-1 protein expression decreased 21. 82

  15. Macrophage inflammatory protein-1 alpha expression in interstitial lung disease.

    Science.gov (United States)

    Standiford, T J; Rolfe, M W; Kunkel, S L; Lynch, J P; Burdick, M D; Gilbert, A R; Orringer, M B; Whyte, R I; Strieter, R M

    1993-09-01

    Mononuclear phagocyte (M phi) recruitment and activation is a hallmark of a number of chronic inflammatory diseases of the lung, including sarcoidosis and idiopathic pulmonary fibrosis (IPF). We hypothesized that macrophage inflammatory protein-1 (MIP-1 alpha), a peptide with leukocyte activating and chemotactic properties, may play an important role in mediating many of the cellular changes that occur in sarcoidosis and IPF. In initial experiments, we demonstrated that human rMIP-1 alpha exerted chemotactic activities toward both polymorphonuclear leukocytes and monocytes, and these activities were inhibited by treatment with rabbit anti-human MIP-1 alpha antiserum. In support of the potential role of MIP-1 alpha in interstitial lung disease, we detected MIP-1 alpha in the bronchoalveolar lavage fluid of 22/23 patients with sarcoidosis (mean 443 +/- 76 pg/ml) and 9/9 patients with IPF (mean 427 +/- 81 pg/ml), whereas detectable MIP-1 alpha was found in only 1/7 healthy subjects (mean 64 +/- 64 pg/ml). In addition, we found a 2.5- and 1.8-fold increase in monocyte chemotactic activity in BALF obtained from patients with sarcoidosis and IPF respectively, as compared to healthy subjects, and this monocyte chemotactic activity, but not neutrophil chemotactic activity, was reduced by approximately 22% when bronchoalveolar lavage fluid from sarcoidosis and IPF patients were preincubated with rabbit antihuman MIP-1 alpha antibodies. To determine the cellular source(s) of MIP-1 alpha within the lung, we performed immunohistochemical analysis of bronchoalveolar lavage cell pellets, transbronchial biopsies, and open lung biopsies obtained from patients with IPF and sarcoidosis. Substantial expression of cell-associated MIP-1 alpha was detected in M phi, including both alveolar AM phi and interstitial M phi. In addition, interstitial fibroblasts within biopsies obtained from sarcoid and IPF patients also expressed immunoreactive MIP-1 alpha. Minimal to no detectable MIP-1

  16. Intraocular soluble intracellular adhesion molecule-1 correlates with subretinal fluid height of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Dan Zhu

    2014-01-01

    Full Text Available Objective: To investigate the correlations between aqueous concentrations of vascular endothelial growth factor (VEGF, monocyte chemoattractant protein-1 (MCP-1, soluble intracellular adhesion molecule-1 (sICAM-1 and diabetic macular edema (DME. Materials and Methods: VEGF, MCP-1 and sICAM-1 concentrations in aqueous humor samples of 22 patients with DME and 23 patients with cataract of a control group were measured with solid-phase chemiluminescence immunoassay. Results: Aqueous VEGF (89.2 ± 58.5 pg/ml versus 48.5 ± 27.8 pg/ml, P = 0.006, MCP-1 (684.2 ± 423.4 pg/ml versus 432.4 ± 230.4 pg/ml, P = 0.019 and sICAM-1 (3213.8 ± 2581.6 pg/ml versus 260.2 ± 212.2 pg/ml, P < 0.001 all vary significantly between DME group and control group. Maximum height of submacular fluid measured by Optical coherence tomography (OCT was significantly associated with aqueous sICAM-1 (r = -0.45, P = 0.034. The maximum height of macular thickness measured by OCT was not significantly associated with either VEGF (P = 0.300, MCP-1 (P = 0.320 or sICAM-1 (P = 0.285. Conclusions: Our results suggest that sICAM-1 may majorly contribute to the formation of subretinal fluid in DME patients and imply that MCP-1 and sICAM-1 may be the potential therapy targets, besides VEGF.

  17. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

    Science.gov (United States)

    Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

    2016-06-01

    Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH.

  18. Human recombinant macrophage inflammatory protein-1 alpha and -beta and monocyte chemotactic and activating factor utilize common and unique receptors on human monocytes.

    Science.gov (United States)

    Wang, J M; Sherry, B; Fivash, M J; Kelvin, D J; Oppenheim, J J

    1993-04-01

    The human macrophage inflammatory proteins-1 alpha and -beta (MIP-1 alpha and -beta), which are also known as LD78 and ACT2, respectively, are distinct but highly related members of the chemoattractant cytokine (chemokine) family. rMIP-1 alpha and -beta labeled with 125I specifically bind to human peripheral blood monocytes, the monocytic cell line THP-1, peripheral blood T cells, and the YT cell line. Steady state binding experiments revealed approximately 3000 high affinity binding sites/cell for MIP-1 alpha on human monocytes and on THP-1 cells, with Kd values of 383 pM and 450 pM, respectively. Human MIP-1 alpha and -beta had nearly identical affinities for the binding sites and each competed equally well for binding. Human monocyte chemotactic and activating factor (MCAF), a member of the same chemokine family, consistently displaced about 25% of human MIP-1 alpha and -beta binding on monocytes but not on YT cells, which did not bind MCAF. On the other hand, human rMIP-1 alpha and -beta partially inhibited binding of radiolabeled MCAF to monocytes. Both MIP-1 alpha and -beta were chemotactic for human monocytes. Preincubation of monocytes with human rMIP-1 alpha or -beta markedly reduced cell migration towards the other cytokine, whereas preincubation with human rMCAF only partially desensitized the monocyte chemotaxis response to human rMIP-1 alpha or -beta. These data suggest the existence of three subtypes of receptors, i.e., one unique receptor shared by MIP-1 alpha and -beta, a second unique receptor for MCAF, and a third species that recognizes both MCAF and MIP-1 peptides.

  19. L-Arogenate is a chemoattractant which can be utilized as the sole source of carbon and nitrogen by Pseudomonas aeruginosa

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, R.S.; Song, Jian; Gu, Wei; Jensen, R.A. [Univ. of Florida, Gainesville, FL (United States)

    1997-02-01

    L-Arogenate is a commonplace amino acid in nature in consideration of its role as a ubiquitous precursor of L-phenylalanine and/or L-tyrosine. However, the questions of whether it serves as a chemoattractant molecule and whether it can serve as a substrate for catabolism have never been studied. We found that Pseudomonas aeruginosa recognizes L-arogenate as a chemoattractant molecule which can be utilized as a source of both carbon and nitrogen. Mutants lacking expression of either cyclohexadienyl dehydratase or phenylalanine hydroxylase exhibited highly reduced growth rates when utilizing L-arogenate as a nitrogen source. Utilization of L-arogenate as a source of either carbon or nitrogen was dependent upon {sub S}{sup 54}, as revealed by the use of an rpoN null mutant. The evidence suggests that catabolism of L-arogenate proceeds via alternative pathways which converge at 4-hydroxyphenylpyruvate. In one pathway, prephenate formed in the periplasm by deamination of L-arogenate is converted to 4-hydroxyphenylpyruvate by cyclohexadienyl dehydrogenase. The second route depends upon the sequential action of periplasmic cyclohexadienyl dehydratase, phenylalanine hydroxylase, and aromatic aminotransferase. 32 refs., 5 figs., 4 tabs.

  20. CSF markers of Alzheimer’s pathology and microglial activation are associated with altered white matter microstructure in asymptomatic adults at risk for Alzheimer’s disease

    Science.gov (United States)

    Melah, Kelsey E; Lu, Sharon Yuan-Fu; Hoscheidt, Siobhan M; Alexander, Andrew L; Adluru, Nagesh; Destiche, Daniel J; Carlsson, Cynthia M; Zetterberg, Henrik; Blennow, Kaj; Okonkwo, Ozioma C; Gleason, Carey E; Dowling, N Maritza; Bratzke, Lisa C; Rowley, Howard A; Sager, Mark A; Asthana, Sanjay; Johnson, Sterling C; Bendlin, Barbara B

    2015-01-01

    Background The immune response in Alzheimer’s disease (AD) involves activation of microglia which may remove β-amyloid. However, overproduction of inflammatory compounds may exacerbate neural damage in Alzheimer’s disease. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. Objective To determine whether neuroinflammation exacerbates neural damage in preclinical AD. Methods We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age=60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Aβ42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. Results Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Aβ42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. Conclusion Inflammation may play a role in neural damage in preclinical AD. PMID:26836182

  1. Soya-cerebroside, an extract of Cordyceps militaris, suppresses monocyte migration and prevents cartilage degradation in inflammatory animal models.

    Science.gov (United States)

    Liu, Shan-Chi; Chiu, Ching-Peng; Tsai, Chun-Hao; Hung, Chun-Yin; Li, Te-Mao; Wu, Yang-Chang; Tang, Chih-Hsin

    2017-02-22

    Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include the secretion of inflammatory molecules, such as proinflammatory cytokines. Interleukin-1beta (IL-1β) is the prototypical inflammatory cytokine that activates OA synovial cells to release cytokines and chemokines in support of the inflammatory response. The monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes in response to inflammation. We show in this study that IL-1β-induced MCP-1 expression and monocyte migration in OA synovial fibroblasts (OASFs) is effectively inhibited by soya-cerebroside, an extract of Cordyceps militaris. We found that soya-cerebroside up-regulated of microRNA (miR)-432 expression via inhibiting AMPK and AKT signaling pathways in OASFs. Soya-cerebroside also effectively decreased monocyte infiltration and prevented cartilage degradation in a rat inflammatory model. Our findings are the first to demonstrate that soya-cerebroside inhibits monocyte/macrophage infiltration into synoviocytes, attenuating synovial inflammation and preventing cartilage damage by reducing MCP-1 expression in vitro and in vivo. Taken together, we suggest a novel therapeutic strategy based on the use of soya-cerebroside for the management of OA.

  2. Elevated Concentration of Interferon-Inducible Protein of 10 kD (IP-10) Is Associated With Coronary Atherosclerosis.

    Science.gov (United States)

    Niki, Toshiyuki; Soeki, Takeshi; Yamaguchi, Koji; Taketani, Yoshio; Yagi, Shusuke; Iwase, Takashi; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Sata, Masataka

    2015-05-13

    Several studies have shown that various chemokines are more highly expressed in atherosclerotic plaques than in normal vessel walls. In the present study, we investigated the relationship between coronary atherosclerosis and noteworthy chemokines, including interferon-inducible protein of 10 kD (IP-10); monocyte chemoattractant protein 1 (MCP-1); regulated on activation, normal T-cell expressed and secreted (RANTES); and high-sensitivity C-reactive protein (hsCRP), an established marker of atherosclerotic disease. We studied 28 patients who underwent coronary angiography because of suspected coronary artery disease (CAD). CAD was defined as stenosis of more than 50% of the vessel diameter on coronary angiograms. Blood samples were obtained both from the aorta and the coronary sinus (CS) just before coronary angiography. Relative to CAD (-) patients, those who were CAD (+) tended to have higher plasma concentrations of IP-10 in the aorta, as well as significantly higher transcoronary concentration gradients of circulating IP-10. There were no significant differences between the two groups in aortic plasma concentrations or transcoronary concentration gradients of MCP-1, RANTES, and hsCRP. Furthermore, both the aortic plasma concentrations and transcoronary concentration gradients of IP-10 correlated with the Gensini score (r = 0.58 and r = 0.63, respectively, P < 0.01), while the plasma MCP-1, RANTES, and serum hsCRP concentrations did not. This study suggests that IP-10 is a good surrogate marker of coronary atherosclerosis.

  3. Serum leveis of inflammatory markers in type 2 diabetes patients with chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Priscila Larcher LONGO

    2014-04-01

    Full Text Available Diabetes has been associated with periodontitis, but the mechanisms through which periodontal diseases affect the metabolic control remain unclear. Objective: This study aimed to evaluate serum leveis of inflammatory markers, IL-8, IL-6 and monocyte chemoattractant protein 1 (MCP-1, in type 2 diabetic patients in the presence of chronic periodontitis. Material and Methods: Forty two individuals were enrolled in this study and assigned to one of five groups: diabetes mellitus with inadequate glycemic control and periodontitis (DMI+P, n = 10, diabetes mellitus with adequate glycemic control and periodontitis (DMA+P, n = 10, diabetes mellitus without periodontitis (DM, n = 10, periodontitis without diabetes (P, n=6, and neither diabetes nor periodontitis (H, n = 6. Periodontal clinical examination included visible plaque index (PL, gingival bleeding index (GB, probing depth (PD, attachment level (AL and bleeding on probing (BP. Glycemic control was evaluated by serum concentration of glycated hemoglobin (HbAlc. Inflammatory serum markers IL-8, IL-6 and (MCP-1 were measured by ELISA. Results: DMI+P and DMA+P groups presented higher PD (p=0.025 and AL (p=0.003 values when compared to the P group. There were no significant differences among groups for IL-6, IL-8 and MCP-1 serum levels. Conclusions: Although periodontitis was more severe in diabetic patients, the serum levels of the investigated inflammatory markers did not differ among the groups.

  4. Hemodynamic, Thyroid and Immunomodulatory Effects of Heroin in Rats

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    Ismail M. Maulood

    2016-05-01

    Full Text Available Diacetylmorphine (heroin has many effects on the body system; it exerts effects on cardiovascular, immune and endocrine systems. The aim of the this study is to investigate the short-term effects of low and high doses of heroin on systolic blood pressure (SBP, thyroid hormones and monocyte chemoattractant protein-1 (MCP-1. The experimental rats were divided into three groups, each with six individuals and the treatments were continued for seven days. SBP significantly reduced by heroin administration in the second dose as compared with the control group. A marked decrease in the serum NO level was also noticed after first (low and second (high dose of administration as compared with control group. The present results also revealed that serum MCP-1 was statistically increased in the second dose of heroin group. Statistical analysis showed that both serum T3 and T4 levels were reduced significantly by heroin administration. In conclusions, for the first time, our findings suggested that diacetylmorphine could affect immune system through MCP-1 elevation. As well as heroin may affect cardiac and liver functions via increasing troponin-T and bilirubin levels.

  5. Inflammatory Markers and Obstructive Sleep Apnea in Obese Children: The NANOS Study

    Directory of Open Access Journals (Sweden)

    Alex Gileles-Hillel

    2014-01-01

    Full Text Available Introduction. Obesity and obstructive sleep apnea syndrome (OSA are common coexisting conditions associated with a chronic low-grade inflammatory state underlying some of the cognitive, metabolic, and cardiovascular morbidities. Aim. To examine the levels of inflammatory markers in obese community-dwelling children with OSA, as compared to no-OSA, and their association with clinical and polysomnographic (PSG variables. Methods. In this cross-sectional, prospective multicenter study, healthy obese Spanish children (ages 4–15 years were randomly selected and underwent nocturnal PSG followed by a morning fasting blood draw. Plasma samples were assayed for multiple inflammatory markers. Results. 204 children were enrolled in the study; 75 had OSA, defined by an obstructive respiratory disturbance index (RDI of 3 events/hour total sleep time (TST. BMI, gender, and age were similar in OSA and no-OSA children. Monocyte chemoattractant protein-1 (MCP-1 and plasminogen activator inhibitor-1 (PAI-1 levels were significantly higher in OSA children, with interleukin-6 concentrations being higher in moderate-severe OSA (i.e., AHI > 5/hrTST; P<0.01, while MCP-1 levels were associated with more prolonged nocturnal hypercapnia (P<0.001. Conclusion. IL-6, MCP-1, and PAI-1 are altered in the context of OSA among community-based obese children further reinforcing the proinflammatory effects of sleep disorders such as OSA. This trial is registered with ClinicalTrials.gov NCT01322763.

  6. Soya-cerebroside, an extract of Cordyceps militaris, suppresses monocyte migration and prevents cartilage degradation in inflammatory animal models

    Science.gov (United States)

    Liu, Shan-Chi; Chiu, Ching-Peng; Tsai, Chun-Hao; Hung, Chun-Yin; Li, Te-Mao; Wu, Yang-Chang; Tang, Chih-Hsin

    2017-01-01

    Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include the secretion of inflammatory molecules, such as proinflammatory cytokines. Interleukin-1beta (IL-1β) is the prototypical inflammatory cytokine that activates OA synovial cells to release cytokines and chemokines in support of the inflammatory response. The monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes in response to inflammation. We show in this study that IL-1β-induced MCP-1 expression and monocyte migration in OA synovial fibroblasts (OASFs) is effectively inhibited by soya-cerebroside, an extract of Cordyceps militaris. We found that soya-cerebroside up-regulated of microRNA (miR)-432 expression via inhibiting AMPK and AKT signaling pathways in OASFs. Soya-cerebroside also effectively decreased monocyte infiltration and prevented cartilage degradation in a rat inflammatory model. Our findings are the first to demonstrate that soya-cerebroside inhibits monocyte/macrophage infiltration into synoviocytes, attenuating synovial inflammation and preventing cartilage damage by reducing MCP-1 expression in vitro and in vivo. Taken together, we suggest a novel therapeutic strategy based on the use of soya-cerebroside for the management of OA. PMID:28225075

  7. Role of Hyperhomocysteinemia in the Regulation of Oxidative Stress and Inflammatory Responses in the Kidney: Protective Effect of Folic Acid Supplementation

    Science.gov (United States)

    Hwang, Sun-Young

    Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) level, is an independent risk factor for cardiovascular disease. Folic acid supplementation can effectively reduce blood Hcy levels. Recent studies have demonstrated that hyperhomocysteinemia is also associated with kidney disease. However, the underlying mechanisms remain unclear. The overall objective of the study was to investigate the biochemical and molecular mechanisms of Hcy-induced kidney injury and the effect of folic acid supplementation on Hcy-induced kidney injury. Hyperhomocysteinemia was induced in Sprague-Dawley rats by feeding a high-methionine diet for 12 weeks. An elevation of serum total Hcy level was observed in hyperhomocysteinemic rats. Hyperhomocysteinemia-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation resulted in oxidative stress in the kidney. Reduction of oxidative stress by inhibiting superoxide anion production effectively ameliorated hyperhomocysteinemia-induced kidney injury. Inflammatory responses such as increased chemokine expression have been implicated as one of the mechanisms of kidney disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in kidney disease. Nuclear factor-kappa B (NF-kappaB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism responsible for such an effect in rat kidneys as well as in human kidney proximal tubular cells.

  8. Anti-Inflammatory Activity of Bioaccessible Fraction from Eryngium foetidum Leaves

    Directory of Open Access Journals (Sweden)

    Suwitcha Dawilai

    2013-01-01

    Full Text Available Eryngium foetidum (EF has long been used as a medicinal plant and culinary spice in tropical regions. Phytochemicals in its leaves have been proposed to be responsible for the anti-inflammatory and antioxidant activities. The present study used in vitro digestion coupled with Caco-2 cells to assess such activities. Caco-2 cells were incubated with aqueous fraction from simulated digestion (bioaccessible fraction of EF leaves with/without bile extract prior to stimulation with interleukin-1 beta (IL-1β. Monocyte chemoattractant protein-1 (MCP-1 and IL-8 in culture media and the intracellular reactive oxygen species (ROS were measured. Approximately 24% β-carotene and 35% lutein of leaves were present in the aqueous fraction. The transfer of caffeic and chlorogenic acids to the aqueous fraction was 76%–81%, while that of kaempferol was 48%. Prior incubation of Caco-2 cells with the bioaccessible fraction suppressed IL-1β activated IL-8 and MCP-1 by 33%, but the fraction lacking mixed micelles decreased IL-8 and MCP-1 levels only by 11%. The pretreatment of Caco-2 cells with the bioaccessible fraction of EF reduced ROS by 34%; the fraction lacking mixed micelles decreased ROS by 28%. These data suggest that bioactive compounds partitioning in mixed micelles play a significant role to suppress the proinflammatory insult but with a modest antioxidant effect.

  9. Adipocytes from New Zealand Obese Mice Exhibit Aberrant Proinflammatory Reactivity to the Stress Signal Heat Shock Protein 60

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    Tina Märker

    2014-01-01

    Full Text Available Adipocytes release immune mediators that contribute to diabetes-associated inflammatory processes. As the stress protein heat shock protein 60 (Hsp60 induces proinflammatory adipocyte activities, we hypothesized that adipocytes of diabetes-predisposed mice exhibit an increased proinflammatory reactivity to Hsp60. Preadipocytes and mature adipocytes from nonobese diabetic (NOD, New Zealand obese (NZO, and C57BL/6J mice were analyzed for Hsp60 binding, Hsp60-activated signaling pathways, and Hsp60-induced release of the chemokine CXCL-1 (KC, interleukin 6 (IL-6, and macrophage chemoattractant protein-1 (MCP-1. Hsp60 showed specific binding to (pre-adipocytes of NOD, NZO, and C57BL/6J mice. Hsp60 binding involved conserved binding structure(s and Hsp60 epitopes and was strongest to NZO mouse-derived mature adipocytes. Hsp60 exposure induced KC, IL-6, and MCP-1 release from (pre-adipocytes of all mouse strains with a pronounced increase of IL-6 release from NZO mouse-derived adipocytes. Compared to NOD and C57BL/6J mouse derived cells, Hsp60-induced formation of IL-6, KC, and MCP-1 from NZO mouse-derived (pre-adipocytes strongly depended on NFκB-activation. Increased Hsp60 binding and Hsp60-induced IL-6 release by mature adipocytes of NZO mice suggest that enhanced adipocyte reactivity to the stress signal Hsp60 contributes to inflammatory processes underlying diabetes associated with obesity and insulin resistance.

  10. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Felix Kaspar

    2016-01-01

    Full Text Available Objective. This study compared acute and late effect of single-bout endurance training (ET and high-intensity interval training (HIIT on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL, IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1, insulin growth factor 1 (IGF-1, and C-reactive protein (CRP. Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p=0.047 and a decrease of MCP-1 (−17.9%; p=0.03. Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

  11. The Correlation Research between Retinol Binding Protein 4 and Inflammatory Cytokines of Patients with Coronary Heart Disease%冠心病患者炎性因子的变化及其与血清视黄醇结合蛋白4水平的相关性研究

    Institute of Scientific and Technical Information of China (English)

    吴桂平; 付鑫; 张彦红; 邹慕蔚; 万多

    2014-01-01

    Objective To discuss the relationship between the high sensitivity C-reactive protein(hs-CRP),interleukin-6,monocyte chemoattractant protein-1 and Retinol binding protein 4 of patients with coronary heart disease. Methods The healthy group, AS group and CHD group were collected. The serum level of RBP4, hs-CRP, IL-6, MCP-1 was measured.Results Compared with the healthy group, The serum level of RBP4 and hs-CRP, IL-6. MCP-1 were higher in AS and CHD group that in healthy group (P<0.05 or P<0.01).Correlation analysis showed that The serum level of RBP4 and hs-CRP,IL-6.MCP-1 were signiifeantly positive correlation in AS and CHD group. Conclusion RBP4 involve the Inlfammatory reaction process of Atherosclerosis, which could partake the the occurrence of coronary heart disease development through many ways directly or indirectly.%目的:探讨冠心病患者血清高敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、MCP-1与视黄醇结合蛋白4(RBP4)的相关性。方法分别收集健康组、动脉粥样硬化组、CHD组患者,检测其空腹血清RBP4、hs-CRP、IL-6、MCP-1水平。结果与健康组相比,AS组、CHD组患者血清RBP4、hs-CRP、IL-6、MCP-1含量明显升高(P<0.05或P<0.01);相关性分析显示AS组、CHD组患者血清RBP4与炎性因子hs-CRP、IL-6、MCP-1呈正相关。结论 RBP4参与了动脉粥样硬化的炎性反应过程,其可能通过多种途径直接或间接地参与冠心病的发生发展。

  12. 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

  13. Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Warner, R L

    1997-01-01

    The C-X-C chemokines of the IL-8 family possess potent chemotactic activity for neutrophils, but their in vivo role in inflammatory responses is not well understood. In the IgG immune complex-induced model of acute lung inflammatory injury in the rat we have evaluated the roles of two rat...... chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... by 125I-labeled albumin leakage from the pulmonary vasculature) and reduced neutrophil accumulation in the lung (as determined by myeloperoxidase (MPO content) and neutrophil counts in bronchoalveolar lavage (BAL) fluids); however, no change in TNF-alpha levels in BAL fluids was found. Chemotactic...

  14. Significance of monocyte chemotactic protein-1 in specimens of proliferative vitreoretinopathy%增生性玻璃体视网膜病变组织中的单核细胞趋化因子-1的意义

    Institute of Scientific and Technical Information of China (English)

    韩泉洪; 惠延年; 石一宁; 马吉献; 杜红俊

    2001-01-01

    目的增生性玻璃体视网膜病变(PVR)是多种细胞和细胞因子参与的一种眼内创伤修复反应. 单核细胞趋化蛋白-1(MCP-1)对巨噬细胞和淋巴细胞有特异趋化作用. 本研究目的在于了解视网膜脱离后不同时期的组织中MCP-1的表达与巨噬细胞和淋巴细胞的关系. 方法选用视网膜手术取材标本,包括孔源性视网膜脱离的视网膜下液中的细胞成份,B级PVR玻璃体手术集取物以及PVR C/D的视网膜增殖膜,免疫组化法检测其中MCP-1,CD68和CD3表达状态. 结果视网膜下液中细胞成份MCP-1的表达均为阴性或弱阳性,B级PVR手术集取物以及增殖膜中,MCP-1表达阳性程度随PVR等级的升高而逐渐增高. CD68阳性细胞(巨噬细胞)与CD3阳性细胞(T-淋巴细胞)的比例随PVR病变程度的增加而降低. 结论 MCP-1对视网膜脱离后的愈合过程和PVR增殖膜的形成有调节作用.%AIM To investigate the relationship between the presence of MCP-1 and macrophages and T-lymphocytes in specimens obtained from retinal detachment and PVR eyes. METHODS Specimens were obtained during retinal surgery, including cellular components of subretinal fluids in rhegmatogenous retinal detachment (RD), fluids collections during vitrectomy for PVR grade B, and epiretinal membranes from PVR grade C or D. Immunohistochemical detection was performed to examine the distribution of MCP-1, and the presence of CD68 or CD3 positive cells in these specimens. RESULTS The expression of MCP-1 was negative or very weak in cells of subretinal fluid from RD. As a function of the increase of PVR grade, MCP-1 expression became stronger while the rate of CD68 (+)/CD3 (+) decreased. CONCLUSION MCP-1 may modulate the wound healing after retinal detachment and the formation of epiretinal membranes in PVR.

  15. X-box-binding protein 1-modified neural stem cells for treatment of Parkinson's disease.

    Science.gov (United States)

    Si, Lihui; Xu, Tianmin; Wang, Fengzhang; Liu, Qun; Cui, Manhua

    2012-04-01

    X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson's disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson's disease in rats.

  16. X-box-binding protein 1-modified neural stem cells for treatment of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Lihui Si; Tianmin Xu; Fengzhang Wang; Qun Liu; Manhua Cui

    2012-01-01

    X-box-binding protein 1-transfected neural stem cells were transplanted into the right lateral ventricles of rats with rotenone-induced Parkinson's disease. The survival capacities and differentiation rates of cells expressing the dopaminergic marker tyrosine hydroxylase were higher in X-box-binding protein 1-transfected neural stem cells compared to non-transfected cells. Moreover, dopamine and 3,4-dihydroxyphenylacetic acid levels in the substantia nigra were significantly increased, α-synuclein expression was decreased, and neurological behaviors were significantly ameliorated in rats following transplantation of X-box-binding protein 1-transfected neural stem cells. These results indicate that transplantation of X-box-binding protein 1-transfected neural stem cells can promote stem cell survival and differentiation into dopaminergic neurons, increase dopamine and 3,4-dihydroxyphenylacetic acid levels, reduce α-synuclein aggregation in the substantia nigra, and improve the symptoms of Parkinson's disease in rats.

  17. Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks

    DEFF Research Database (Denmark)

    Andersen, Martin; Boesen, Mikael; Ellegaard, Karen

    2014-01-01

    (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model. RESULTS: Tissue samples from......INTRODUCTION: Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study...... procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema...

  18. Systemic and Local CC Chemokines Production in a Murine Model of Listeria monocytogenes Infection

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Repeated intragastric inoculation of Listeria monocytogenes into BALB/c mice resulted in prolonged bacteraemia and severe hepatic infection. Bacteria could also be isolated from the brain tissue of all experimental mice. During the inflammatory process, chemokine concentrations typically increased at the local site in comparison to the systemic level. The liver-to-serum ratio was more pronounced in the case of macrophage inflammatory protein 1 α (MIP-1 α , suggesting its role in the inflammatory response in the liver. The ratio of brain-to-serum concentration of monocyte chemoattractant protein 1 (MCP-1 remained the same as in the control animals, while it was lower in the infected mice, both in the case MIP-1 α and in the case of regulated on activation, normal T cell expressed and secreted (RANTES. This is in correlation with slight inflammatory infiltrates found in the brain tissue early in infection.

  19. Methodological constraints in interpreting serum paraoxonase-1 activity measurements: an example from a study in HIV-infected patients

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    Joven Jorge

    2010-03-01

    Full Text Available Abstract Background Paraoxonase-1 (PON1 is an antioxidant enzyme that attenuates the production of the monocyte chemoattractant protein-1 (MCP-1 in vitro. Although oxidation and inflammation are closely related processes, the association between PON1 and MCP-1 has not been completely characterised due, probably, to that the current use of synthetic substrates for PON1 measurement limits the interpretation of the data. In the present study, we explored the relationships between the circulating levels of PON1 and MCP-1 in human immunodeficiency virus-infected patients in relation to the multifunctional capabilities of PON1. Methods We measured selected variables in 227 patients and in a control group of 409 participants. Serum PON1 esterase and lactonase activities were measured as the rates of hydrolysis of paraoxon and of 5-(thiobutyl-butyrolactone, respectively. Oxidised LDL and MCP-1 concentrations were determined by enzyme-linked immunosorbent assay. High-density lipoproteins cholesterol, apolipoprotein A-I, and C-reactive protein concentrations were measured by standard automated methods. Results There were significant relationships between PON1 activity and several indices of oxidation and inflammation in control subjects and in infected patients. However, these relationships varied not only with disease status but also on the type of substrate used for PON1 measurement. Conclusion The present study is a cautionary tale highlighting that results of clinical studies on PON1 may vary depending on the methods used as well as the disease studied. Until more specific methods using physiologically-akin substrates are developed for PON1 measurement, we suggest the simultaneous employment of at least two different substrates in order to improve the reliability of the results obtained.

  20. Lecithin-Bound Iodine Prevents Disruption of Tight Junctions of Retinal Pigment Epithelial Cells under Hypoxic Stress

    Directory of Open Access Journals (Sweden)

    Masahiko Sugimoto

    2016-01-01

    Full Text Available Aim. We investigated whether lecithin-bound iodine (LBI can protect the integrity of tight junctions of retinal pigment epithelial cells from hypoxia. Method. Cultured human retinal pigment epithelial (ARPE-19 cells were pretreated with LBI. To mimic hypoxic conditions, cells were incubated with CoCl2. We compared the integrity of the tight junctions (TJs of control to cells with either LBI alone, CoCl2 alone, or LBI + CoCl2. The levels of cytokines in the conditioned media were also determined. Results. Significant decrease in the zonula occludens-1 (ZO-1 intensity in the CoCl2 group compared to the control (5787.7 ± 4126.4 in CoCl2 group versus 29244.6 ± 2981.2 in control; average ± standard deviation. But the decrease was not significant in the LBI + CoCl2 (27189.0 ± 11231.1. The levels of monocyte chemoattractant protein-1 (MCP-1 and Chemokine (C-C Motif Ligand 11 (CCL-11 were significantly higher in the CoCl2 than in the control (340.8 ± 43.3 versus 279.7 ± 68.3 pg/mL for MCP-1, and 15.2 ± 12.9 versus 12.5 ± 6.1 pg/mL for CCL-11. With LBI pretreatment, the levels of both cytokines were decreased to 182.6 ± 23.8 (MCP-1 and 5.46 ± 1.9 pg/mL for CCL-11. Blockade of MCP-1 or CCL-11 also shows similar result representing TJ protection from hypoxic stress. Conclusions. LBI results in a protective action from hypoxia.

  1. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Guo Zhixin

    2012-08-01

    Full Text Available Abstract Background Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2 and nicotinamide adenine dinucleotide phosphate (NADPH oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1 in aorta in type 2 diabetic rats. Methods Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ. Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4, monocyte chemoattractant protein-1(MCP-1 and connective tissue growth factor (CTGFin the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-κB in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d by gavage for 12 weeks. Results Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P Conclusions Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-κB in the abdominal aorta in diabetic rats.

  2. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1

    OpenAIRE

    2016-01-01

    Although accumulated evidence supports the notion that mesenchymal stem cells (MSCs) act in a paracrine manner, the mechanisms are still not fully understood. Recently, MSC-derived exosomes (MSC-Exos), a type of microvesicle released from MSCs, were thought to carry functional proteins and RNAs to recipient cells and play therapeutic roles. In the present study, we intravitreally injected MSCs derived from either mouse adipose tissue or human umbilical cord, and their exosomes to observe and ...

  3. Administration of Myelin Basic Protein Peptides Encapsulated in Mannosylated Liposomes Normalizes Level of Serum TNF-α and IL-2 and Chemoattractants CCL2 and CCL4 in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Yakov Lomakin

    2016-01-01

    Full Text Available We have previously shown that immunodominant MBP peptides encapsulated in mannosylated liposomes (Xemys effectively suppressed experimental allergic encephalomyelitis (EAE. Within the frames of the successfully completed phase I clinical trial, we investigated changes in the serum cytokine profile after Xemys administration in MS patients. We observed a statistically significant decrease of MCP-1/CCL2, MIP-1β/CCL4, IL-7, and IL-2 at the time of study completion. In contrast, the serum levels of TNF-α were remarkably elevated. Our data suggest that the administration of Xemys leads to a normalization of cytokine status in MS patients to values commonly reported for healthy subjects. These data are an important contribution for the upcoming Xemys clinical trials.

  4. Administration of Myelin Basic Protein Peptides Encapsulated in Mannosylated Liposomes Normalizes Level of Serum TNF-α and IL-2 and Chemoattractants CCL2 and CCL4 in Multiple Sclerosis Patients.

    Science.gov (United States)

    Lomakin, Yakov; Belogurov, Alexey; Glagoleva, Irina; Stepanov, Alexey; Zakharov, Konstantin; Okunola, John; Smirnov, Ivan; Genkin, Dmitry; Gabibov, Alexander

    2016-01-01

    We have previously shown that immunodominant MBP peptides encapsulated in mannosylated liposomes (Xemys) effectively suppressed experimental allergic encephalomyelitis (EAE). Within the frames of the successfully completed phase I clinical trial, we investigated changes in the serum cytokine profile after Xemys administration in MS patients. We observed a statistically significant decrease of MCP-1/CCL2, MIP-1β/CCL4, IL-7, and IL-2 at the time of study completion. In contrast, the serum levels of TNF-α were remarkably elevated. Our data suggest that the administration of Xemys leads to a normalization of cytokine status in MS patients to values commonly reported for healthy subjects. These data are an important contribution for the upcoming Xemys clinical trials.

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

    LENUS (Irish Health Repository)

    Costello, Richard W

    2012-02-01

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

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

    LENUS (Irish Health Repository)

    Costello, Richard W

    2011-05-01

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

  7. Metformin inhibits nuclear factor-κB activation and inflammatory cytokines expression induced by high glucose via adenosine monophosphate-activated protein kinase activation in rat glomerular mesangial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Gu Junfei; Ye Shandong; Wang Shan; Sun Wenjia; Hu Yuanyuan

    2014-01-01

    Background The renoprotective mechanisms of adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist-metformin have not been stated clearly.We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB (NF-κB),monocyte chemoattractant protein-1 (MCP-1),intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-β1) induced by high glucose (HG) in cultured rat glomerular mesangial cells (MCs).Methods MCs were cultured in the medium with normal concentration glucose (group NG,5.6 mmol/L),high concentration glucose (group HG,25 mmol/L) and different concentrations of metformin (group M1,M2,M3).After 48-hour exposure,the supernatants and MCs were collected.The expression of NF-κB,MCP-1,ICAM-1,and TGF-β1 mRNA was analyzed by real time polymerase chain reaction.Westem blotting was used to detect the expression of AMPK,phospho-Thr-172 AMPK (p-AMPK),NF-κB p65,MCP-1,ICAM-1,and TGF-β1 protein.Results After stimulated by HG,the expression of NF-κB,MCP-1,ICAM-1,TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG (P <0.05).Both genes and protein expression of NF-κB,MCP-1,ICAM-1,TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P <0.05).The expression of p-AMPK increased with the rising of metformin concentration,presenting the opposite trend,while the level of total-AMPK protein was unchanged with exposure to HG or metformin.Conlusion Metformin can suppress the expression of NF-κB,MCP-1,ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation,which may partlv contribute to its reno-protection.

  8. 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...

  9. 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...

  10. Low density lipoprotein receptor related protein 1 variant interacts with saturated fatty acids in Puerto Ricans

    Science.gov (United States)

    Low density lipoprotein related receptor protein 1 (LRP1) is a multi-functional endocytic receptor that is highly expressed in adipocytes and the hypothalamus. Animal models and in vitro studies support a role for LRP1 in adipocyte metabolism and leptin signaling, but genetic polymorphisms have not ...

  11. 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

    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...

  12. 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...

  13. Deficiency of lymph node-resident dendritic cells (DCs) and dysregulation of DC chemoattractants in a malnourished mouse model of Leishmania donovani infection.

    Science.gov (United States)

    Ibrahim, Marwa K; Barnes, Jeffrey L; Osorio, E Yaneth; Anstead, Gregory M; Jimenez, Fabio; Osterholzer, John J; Travi, Bruno L; Ahuja, Seema S; White, A Clinton; Melby, Peter C

    2014-08-01

    Malnutrition is thought to contribute to more than one-third of all childhood deaths via increased susceptibility to infection. Malnutrition is a significant risk factor for the development of visceral leishmaniasis, which results from skin inoculation of the intracellular protozoan Leishmania donovani. We previously established a murine model of childhood malnutrition and found that malnutrition decreased the lymph node barrier function and increased the early dissemination of L. donovani. In the present study, we found reduced numbers of resident dendritic cells (conventional and monocyte derived) but not migratory dermal dendritic cells in the skin-draining lymph nodes of L. donovani-infected malnourished mice. Expression of chemokines and their receptors involved in trafficking of dendritic cells and their progenitors to the lymph nodes was dysregulated. C-C chemokine receptor type 2 (CCR2) and its ligands (CCL2 and CCL7) were reduced in the lymph nodes of infected malnourished mice, as were CCR2-bearing monocytes/macrophages and monocyte-derived dendritic cells. However, CCR7 and its ligands (CCL19 and CCL21) were increased in the lymph node and CCR7 was increased in lymph node macrophages and dendritic cells. CCR2-deficient mice recapitulated the profound reduction in the number of resident (but not migratory dermal) dendritic cells in the lymph node but showed no alteration in the expression of CCL19 and CCL21. Collectively, these results suggest that the malnutrition-related reduction in the lymph node barrier to dissemination of L. donovani is related to insufficient numbers of lymph node-resident but not migratory dermal dendritic cells. This is likely driven by the altered activity of the CCR2 and CCR7 chemoattractant pathways.

  14. Up-regulation of the chemo-attractive receptor ChemR23 and occurrence of apoptosis in human chondrocytes isolated from fractured calcaneal osteochondral fragments.

    Science.gov (United States)

    Sena, Paola; Manfredini, Giuseppe; Benincasa, Marta; Mariani, Francesco; Smargiassi, Alberto; Catani, Fabio; Palumbo, Carla

    2014-06-01

    To study the expression level of a panel of pro/anti-apoptotic factors and inflammation-related receptors in chondral fragments from patients undergoing surgical treatment for intra-articular calcaneal fractures, cartilage fragments were retrieved from calcaneal fractures of 20 patients subjected to surgical treatment. Primary cultures were performed using chondral fragments from fractured and control patients. Chondrocyte cultures from each patient of the fractured and control groups were subjected to immunofluorescence staining and quantitatively analyzed under confocal microscopy. Proteins extracted from the cultured chondrocytes taken from the fractured and control groups were processed for Western blot experiments and densitometric analysis. The percentage of apoptotic cells was determined using the cleaved PARP-1 antibody. The proportion of labelled cells was 35% for fractured specimens, compared with 7% for control samples. Quantification of caspase-3 active and Bcl-2 proteins in chondrocyte cultures showed a significant increase of the apoptotic process in fractured specimens compared with control ones. Fractured chondrocytes were positively stained for ChemR23 with statistically significant differences with respect to control samples. Densitometric evaluation of the immunoreactive bands confirmed these observations. Human articular chondrocytes obtained from patients with intra-articular calcaneal fractures express higher levels of pivotal pro-apoptotic factors, and of the chemo-attractive receptor ChemR23, compared with control cultures. On the basis of these observations, the authors hypothesize that consistent prolonged chondrocyte death, associated with the persistence of high levels of pro-inflammatory factors, could enhance the deterioration of cartilage tissue with consequent development of post-traumatic arthritis following intra-articular bone fracture.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lim, So-Hee; Moon, Jeonghee [Biomedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Lee, Myungkyu [Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Lee, Jae-Ran, E-mail: leejr@kribb.re.kr [Biomedical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of)

    2013-09-13

    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. 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.

  17. Cloning and characterization of the rat multidrug resistance-associated protein 1

    OpenAIRE

    Yang, Ziping; Li, Cheryl S. W.; Shen, Danny D.; Ho, Rodney J. Y.

    2002-01-01

    Multidrug resistance-associated protein 1 (MRP1) was originally shown to confer resistance of human tumor cells to a broad range of natural product anticancer drugs. MRP1 has also been shown to mediate efflux transport of glutathione and glucuronide conjugates of drugs and endogenous substrates. An ortholog of MRP1 in the mouse has been cloned and characterized. Significant functional differences between murine and human MRP1 have been noted. Since drug disposition and pharmacology studies of...

  18. Glutathione depletion regulates both extrinsic and intrinsic apoptotic signaling cascades independent from multidrug resistance protein 1

    OpenAIRE

    2014-01-01

    Glutathione (GSH) depletion is an important hallmark of apoptosis. We previously demonstrated that GSH depletion, by its efflux, regulates apoptosis by modulation of executioner caspase activity. However, both the molecular identity of the GSH transporter(s) involved and the signaling cascades regulating GSH loss remain obscure. We sought to determine the role of multidrug resistance protein 1 (MRP1) in GSH depletion and its regulatory role on extrinsic and intrinsic pathways of apoptosis. In...

  19. High Mobility Group Box Protein-1 Correlates with Renal Function in Chronic Kidney Disease (CKD)

    OpenAIRE

    Bruchfeld, Annette; Qureshi, Abdul Rashid; Lindholm, Bengt; Barany, Peter; Yang, Lihong; Stenvinkel, Peter; Tracey, Kevin J.

    2007-01-01

    Chronic kidney disease (CKD) is associated with inflammation and malnutrition and carries a markedly increased risk of cardiovascular disease (CVD). High Mobility Group Box Protein-1 (HMGB-1) is a 30-kDa nuclear and cytosolic protein known as a transcription and growth factor, recently identified as a proinflammatory mediator of tissue injury. Recent data implicates HMGB-1 in endotoxin lethality, rheumatoid arthritis, and atherosclerosis. The aim of this post-hoc, cross-sectional study was to...

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

    OpenAIRE

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

    2015-01-01

    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 b...

  1. A possible role of LIM mineralization protein 1 in tertiary dentinogenesis of dental caries treatment.

    Science.gov (United States)

    Wang, Xiao-Ying; Zhang, Qi; Chen, Zhi

    2007-01-01

    Dental caries is a slowly progressive infectious disease with high risks. In response to dental caries stimuli, the tertiary dentin might be formed, protecting the dental pulp. Tertiary dentinogenesis contributes greatly to the treatment of carious lesions as well as the preservation and restoration of entire tooth function. A number of studies have found that application of exogenous growth factors such as transforming growth factors and bone morphogenetic proteins on unexposed pulps are able to signal tertiary dentinogenesis. Since precise mechanism of tertiary dentinogenesis is still not clear, more potential signaling factors might contribute to this process. Dentinogenesis shares many similarities with osteogenesis. The factors involved in osteogenesis and bone repair such as bone morphogenetic proteins 2, 7 and core binding factor alpha1 play important roles in dentinogenesis. LIM mineralization protein 1 is a critical positive regulator of osteoblast differentiation, bone formation and repair. It is logical to postulate that LIM mineralization protein 1 might be involved in odontoblast differentiation and dentin formation both in normal and in pathological conditions. Application of LIM mineralization protein 1 might be a promising approach for inducing tertiary dentinogenesis in dental caries treatment.

  2. Application of Translational Medicine Concept in Chinese Materia Medica:Effect and Mechanism of Mahuang and Wuweizi on Pulmonary Fibrosis

    Institute of Scientific and Technical Information of China (English)

    QIN Hai-zhi; DONG Wei-tao

    2015-01-01

    Objective:To explore the effect and mechanism of Mahuang (Herba Ephedra) and Wuweizi (Schisandra Chinesis) on pulmonary ifbrosis based on translation medicine theory. Methods: Totally 90 Wistar rats were divided into 6 groups. Pulmonary ifbrosis models of rats were established by drip of bleomycin A5 through trachea while sham-operation group was infused with equivalent normal saline instead of bleomycin A5 into trachea. Sham-operation group and negative control group were performed with normal saline gavage while positive control group with subcutaneous injection of hydrocortisone, Mahuang group and Wuweizi group with gavage of Mahuang and Wuweizi concentrated decoction, respectively, whereas combined group was treated with gavage of Mahuang concentrated decoction during the ifrst 7 days and with Wuweizi concentrated decoction in the ensuing 21 days. On the 7th day and 28th day, pulmonary alveolitis and fibrosis in different groups were observed and the expression levels of serum vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), thrombospondin-1 (TSP-1), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) were detected and compared. Results: All models of groups were successfully established. Compared with negative control group, the levels of VEGF, Ang-2, MCP-1 and MIP-1α decreased in different degrees but TSP-1 increased in other groups after medication for 7 days and 28 days. Conclusion: Mahuang and Wuweizi have intervention effects on pulmonary fibrosis, the mechanism of which might be related to the inhibition of excessive angiogenesis through inhibiting the expression of MCP-1 and MIP-1α, lowering the level of proangiogenic factors (Ang-2 and BEGF), and enhancing the level of angiogenesis inhibiting factor (TSP-1).

  3. 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.

  4. Impaired LDL Receptor-Related Protein 1 Translocation Correlates with Improved Dyslipidemia and Atherosclerosis in apoE-Deficient Mice

    DEFF Research Database (Denmark)

    Gordts, Philip L S M; Bartelt, Alexander; Nilsson, Stefan K;

    2012-01-01

    Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE.......Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1) dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE....

  5. The nonstructural protein 1 papain-like cysteine protease was necessary for porcine reproductive and respiratory syndrome virus nonstructural protein 1 to inhibit interferon-β induction.

    Science.gov (United States)

    Shi, Xibao; Zhang, Gaiping; Wang, Li; Li, Xuewu; Zhi, Yubao; Wang, Fangyu; Fan, Jianming; Deng, Ruiguang

    2011-06-01

    Porcine reproductive and respiratory syndrome virus nonstructural protein 1 (nsp1) could be auto-cleaved into nsp1α and nsp1β, both of which had the papain-like cysteine protease activities. Previous studies have shown that porcine reproductive and respiratory syndrome virus nsp1 was an interferon (IFN) antagonist. However, the mechanism by which nsp1 inhibited IFN-β production was unclear. Here, we used site-directed mutagenesis that inactivated the papain-like cysteine protease activities of nsp1 to explore whether the papain-like cysteine protease activities were required for nsp1 to disrupt IFN-β production. The results showed that mutations that inactivated papain-like cysteine protease activity of nsp1α made nsp1 lose its IFN antagonism activity, whereas mutations that inactivated papain-like cysteine protease activity of nsp1β did not influence the IFN antagonism activity of nsp1. In conclusion, our present work indicated that the papain-like cysteine protease activity of nsp1α was necessary for nsp1 to inhibit IFN-β induction.

  6. Low-density lipoprotein receptor-related protein-1 facilitates heme scavenging after intracerebral hemorrhage in mice.

    Science.gov (United States)

    Wang, Gaiqing; Manaenko, Anatol; Shao, Anwen; Ou, Yibo; Yang, Peng; Budbazar, Enkhjargal; Nowrangi, Derek; Zhang, John H; Tang, Jiping

    2016-06-17

    Heme-degradation after erythrocyte lysis plays an important role in the pathophysiology of intracerebral hemorrhage. Low-density lipoprotein receptor-related protein-1 is a receptor expressed predominately at the neurovascular interface, which facilitates the clearance of the hemopexin and heme complex. In the present study, we investigated the role of low-density lipoprotein receptor-related protein-1 in heme removal and neuroprotection in a mouse model of intracerebral hemorrhage. Endogenous low-density lipoprotein receptor-related protein-1 and hemopexin were increased in ipsilateral brain after intracerebral hemorrhage, accompanied by increased hemoglobin levels, brain water content, blood-brain barrier permeability and neurological deficits. Exogenous human recombinant low-density lipoprotein receptor-related protein-1 protein reduced hematoma volume, brain water content surrounding hematoma, blood-brain barrier permeability and improved neurological function three days after intracerebral hemorrhage. The expression of malondialdehyde, fluoro-Jade C positive cells and cleaved caspase 3 was increased three days after intracerebral hemorrhage in the ipsilateral brain tissues and decreased with recombinant low-density lipoprotein receptor-related protein-1. Intracerebral hemorrhage decreased and recombinant low-density lipoprotein receptor-related protein-1 increased the levels of superoxide dismutase 1. Low-density lipoprotein receptor-related protein-1 siRNA reduced the effect of human recombinant low-density lipoprotein receptor-related protein-1 on all outcomes measured. Collectively, our findings suggest that low-density lipoprotein receptor-related protein-1 contributed to heme clearance and blood-brain barrier protection after intracerebral hemorrhage. The use of low-density lipoprotein receptor-related protein-1 as supplement provides a novel approach to ameliorating intracerebral hemorrhage brain injury via its pleiotropic neuroprotective effects.

  7. Cannabinoid Receptor–Interacting Protein 1a Modulates CB1 Receptor Signaling and Regulation

    OpenAIRE

    Smith, Tricia H.; Blume, Lawrence C.; Straiker, Alex; Cox, Jordan O.; David, Bethany G.; McVoy, Julie R. Secor; Sayers, Katherine W.; Poklis, Justin L.; Abdullah, Rehab A.; Egertová, Michaela; Chen, Ching-Kang; Mackie, Ken; Maurice R. Elphick; Howlett, Allyn C; Selley, Dana E

    2015-01-01

    Cannabinoid CB1 receptors (CB1Rs) mediate the presynaptic effects of endocannabinoids in the central nervous system (CNS) and most behavioral effects of exogenous cannabinoids. Cannabinoid receptor–interacting protein 1a (CRIP1a) binds to the CB1R C-terminus and can attenuate constitutive CB1R-mediated inhibition of Ca2+ channel activity. We now demonstrate cellular colocalization of CRIP1a at neuronal elements in the CNS and show that CRIP1a inhibits both constitutive and agonist-stimulated ...

  8. [Nonstructural protein 1 of tick-borne encephalitis virus activates the expression of immunoproteasome subunits].

    Science.gov (United States)

    Kuzmenko, Y V; Starodubova, E S; Karganova, G G; Timofeev, A V; Karpov, V L

    2016-01-01

    The interaction of viral proteins with host cell components plays an important role in antiviral immune response. One of the key steps of antiviral defense is the formation of immunoproteasomes. The effect of nonstructural protein 1 (NS1) of tick-borne encephalitis virus on the immunoproteasome formation was studied. It was shown that cell expression of NS1 does not reduce the efficacy of the immunoproteasome generation in response to interferon-γ stimulation and even increases the content of the immunoproteasome subunits without the interferon-γ treatment. Thus, NS1 of tick-borne encephalitis virus activates, rather than blocks the mechanisms of immune defense in the cell.

  9. Adenylyl Cyclase-Associated Protein 1 in the Development of Head and Neck Squamous Cell Carcinomas.

    Science.gov (United States)

    Kakurina, G V; Kondakova, I V; Cheremisina, O V; Shishkin, D A; Choinzonov, E L

    2016-03-01

    We compared the content of adenylyl cyclase-associated protein 1 (CAP1) in the blood and tissues of patients with head and neck squamous cell carcinomas (with and without regional metastases), patients with chronic inflammatory diseases aggravated by laryngeal and laryngopharyngeal dysplasia, and healthy individuals. The data suggest that serum CAP1 concentration correlated with the depth of primary tumor invasion and the presence of regional metastases. In cancer patients, the serum level of CAP1 was lower than in patients with laryngeal and laryngopharyngeal dysplasia, which can be of importance for differential and timely diagnostics of malignant tumors.

  10. Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models.

    Science.gov (United States)

    Zollo, Massimo; Di Dato, Valeria; Spano, Daniela; De Martino, Daniela; Liguori, Lucia; Marino, Natascia; Vastolo, Viviana; Navas, Luigi; Garrone, Beatrice; Mangano, Giorgina; Biondi, Giuseppe; Guglielmotti, Angelo

    2012-08-01

    Prostate and breast cancer are major causes of death worldwide, mainly due to patient relapse upon disease recurrence through formation of metastases. Chemokines are small proteins with crucial roles in the immune system, and their regulation is finely tuned in early inflammatory responses. They are key molecules during inflammatory processes, and many studies are focusing on their regulatory functions in tumor growth and angiogenesis during metastatic cell seeding and spreading. Bindarit is an anti-inflammatory indazolic derivative that can inhibit the synthesis of MCP-1/CCL2, with a potential inhibitory function in tumor progression and metastasis formation. We show here that in vitro, bindarit can modulate cancer-cell proliferation and migration, mainly through negative regulation of TGF-β and AKT signaling, and it can impair the NF-κB signaling pathway through enhancing the expression of the NF-κB inhibitor IkB-α. In vivo administration of bindarit results in impaired metastatic disease in prostate cancer xenograft mice (PC-3M-Luc2 cells injected intra-cardially) and impairment of local tumorigenesis in syngeneic Balb/c mice injected under the mammary gland with murine breast cancer cells (4T1-Luc cells). In addition, bindarit treatment significantly decreases the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in 4T1-Luc primary tumors. Overall, our data indicate that bindarit is a good candidate for new therapies against prostate and breast tumorigenesis, with an action through impairment of inflammatory cell responses during formation of the tumor-stroma niche microenvironment.

  11. 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.

  12. Role of osteogenic protein-1/bone morphogenetic protein-7 in spinal fusion

    Directory of Open Access Journals (Sweden)

    Justin Munns

    2009-10-01

    Full Text Available Justin Munns, Daniel K Park, Kern SinghDepartment of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, USAAbstract: Osteogenic protein-1 (OP-1, also known as bone morphogenetic protein-7 (BMP-7, is a protein in the TGF-β family of cellular proteins that has shown potential for application in patients undergoing spinal fusion due to its proven osteoinductive effects, particularly in patients with spondylolisthesis. OP-1 initiates numerous processes at the cellular level, acting on mesenchymal stem cells (MSCs, osteoblasts, and osteoclasts to stimulate bone growth. Animal studies of OP-1 have provided strong evidence for the ability of OP-1 to initiate ossification in posterolateral arthrodesis. Promising findings in early clinical trials with OP-1 prompted FDA approval for use in long bone nonunions in 2001 and subsequently for revision posterolateral arthrodesis in 2004 under a conditional Humanitarian Device Exemption. Larger clinical trials have recently shown no notable safety concerns or increases in adverse events associated with OP-1. However, a recent clinical trial has not conclusively demonstrated the noninferiority of OP-1 compared to autograft in revision posterolateral arthrodesis. The future of OP-1 application in patients with spondylolisthesis thus remains uncertain with the recent rejection of Premarket Approval (PMA status by the FDA (April 2009. Further investigation of its treatment success and immunological consequences appears warranted to establish FDA approval for its use in its current form.Keywords: osteogenic protein-1, bone morphogenetic protein-7, spinal fusion

  13. Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, Jeremy D., E-mail: jwilbur@msg.ucsf.edu [Graduate Program in Biophysics, University of California, San Francisco, California 94143 (United States); Hwang, Peter K. [Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 (United States); Brodsky, Frances M. [The G. W. Hooper Foundation, Departments of Microbiology and Immunology and of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 94143 (United States); Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 (United States); Fletterick, Robert J. [Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 (United States); Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 (United States); Graduate Program in Biophysics, University of California, San Francisco, California 94143 (United States)

    2010-03-01

    Variable packing interaction related to the conformational flexibility within the huntingtin-interacting protein 1 coiled coil domain. Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington’s disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coil domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.

  14. Effect of cannabinoid receptor 2 on body weight, blood lipids and inflammatory factor in obese mice%大麻素受体2对肥胖小鼠体质量、血脂及炎症因子的影响

    Institute of Scientific and Technical Information of China (English)

    陈彦; 陈刚; 余惠珍; 吴冰; 许桂平

    2014-01-01

    目的 研究大麻素受体2(type 2 cannabinoid receptor,CB2受体)对肥胖小鼠体质量、血甘油三酯(triglyceride,TG)、肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)和单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)的影响.方法 20只雄性小鼠随机分为正常组(N组,n=4)、肥胖组(n=16),分别给予普通饲料和高脂饲料喂养6周,成功制作肥胖小鼠模型.再将肥胖组小鼠随机分为4组:模型组(S组,n=4)、CB2激动剂JWH-133干预组(J组,n=4)、CB2拮抗剂AM-630干预组(A组,n=4)、JWH-133+ AM-630干预组(AJ组,n=4).N组、S组腹腔内注射生理盐水,10 mg/kg,1次/天,共28 d;J、A、AJ组分别腹腔内注射JWH-133、AM-630、JWH-133+AM-630,10 mg/kg,1次/天,共28 d.药物干预前后测定小鼠的体质量、血TG、TNF-α、MCP-1水平.结果 给药第4周J组小鼠体质量、血TG、TNF-α、MCP-1水平均显著高于S组,A组上述指标均显著低于S组(P<0.05),AJ组指标与S组对比差异无统计学意义.结论 CB2受体在肥胖发病机制中起重要作用.激活CB2受体会增加肥胖小鼠体质量、血TG、TNF-α、MCP-1水平,抑制CB2受体会减低肥胖小鼠体质量、血TG、TNF-α、MCP-1水平.

  15. Effects of mycophenolate mofetil, valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan; CHEN Bing; HOU Xiang-hua; GUAN Guang-ju; LIU Gang; LIU Hai-ying; LI Xue-gang

    2007-01-01

    Background Podocyte has inflammatory role in the development of diabetic nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury in streptozotocin-induced diabetic rats. Angiotensin Ⅱ receptor blocker (ARB), another renal protecting agent, can decrease podocyte loss in DN. In this study, we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) and nephrin to evaluate podocyte's role in inflammatory reaction in DN, observe and compare the effect of MMF alone and in combination with valsartan, on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats.Methods Diabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ (65 mg/kg). The successfully induced diabetic rats were randomly divided into four groups: diabetes without treatment group (DM), valsartan treated group (DMV), MMF treated group (DMM), and combined therapy group (DMVM). Normal rats of the same sibling were chosen as control (NC). At the end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the ratio of kidney weight/body weight (RWK/B) were measured. The rats were sacrificed for the observation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels were detected by semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used to detect the mRNA levels of nephrin and MCP-1.Results Compared with group NC, serum glucose level, 24-hour UP and RWK/B in group DM were significantly higher (P<0.01), and the nephrin mRNA level in DM group was significantly lower (P<0.05). The nephrin mRNA expression levels in group DMV, DMM and DMVM were all higher than that of DM group (P<0.05) and no significant differences were found among the three treatment groups (P>0.05). Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour UP and

  16. Anti-atherosclerotic effects of sitagliptin in patients with type 2 diabetes mellitus

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    Omoto S

    2015-07-01

    Full Text Available Seitaro Omoto,1 Takehito Taniura,2 Tohru Nishizawa,3 Takeshi Tamaki,3 Akira Shouzu,4 Shosaku Nomura3 1Division of Internal Medicine, Korigaoka Yukeikai Hospital, 2Division of Internal Medicine, Daiwa Hospital, 3First Department of Internal Medicine, Kansai Medical University, 4Division of Internal Medicine, Saiseikai Izuo Hospital, Osaka, Japan Background: Advanced glycation end products, selectins, and adiponectin play important roles in the development of atherosclerosis in individuals with diabetes. Sitagliptin has been shown to reduce the concentration of glycated hemoglobin in diabetic patients. However, its effects on soluble receptor for advanced glycation end products (sRAGEs, selectins, and adiponectin in these patients are poorly understood. This study was conducted to assess the effects of sitagliptin on the circulating levels of sRAGEs, monocyte chemoattractant protein-1 (MCP-1, selectins, and adiponectin in patients with type 2 diabetes. Methods: Diabetic patients eligible for sitagliptin monotherapy or combination therapy (eg, sitagliptin plus a sulfonylurea were administered sitagliptin (50 mg/day for 6 months. Levels of soluble P-selectin (sP-selectin, soluble E-selectin (sE-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1, MCP-1, sRAGEs, and adiponectin were measured by ELISA at baseline and after 3 and 6 months of treatment. Results: At baseline, the levels of MCP-1, sP-selectin, sE-selectin, and sVCAM-1 were higher and the level of adiponectin was lower in diabetic patients than in nondiabetic patients. Sitagliptin therapy for 3 and 6 months significantly reduced plasma levels of sP-selectin, sE-selectin, sVCAM-1, and MCP-1 relative to baseline, while significantly increasing adiponectin levels. sRAGEs did not exhibit a statistical significance, although there was an increasing tendency. Furthermore, the reductions in sP-selectin, sE-selectin, sVCAM-1, and MCP-1 during sitagliptin therapy were significantly greater

  17. Makorin Ring Finger Protein 1 as Adjunctive Marker in Liquid-based Cervical Cytology.

    Science.gov (United States)

    Lee, Maria; Chang, Min Young; Shin, Ha-Yeon; Shin, Eunah; Hong, Sun Won; Kim, Kyung-Mi; Chay, Doo Byung; Cho, Hanbyoul; Kim, Jae-Hoon

    2016-01-01

    To assess the utility of makorin ring finger protein 1 (MKRN1) as a marker of cervical pathology.A PROspective specimen collection and retrospective Blinded Evaluation study was conducted. Liquid-based cytology samples were collected from 187 women, embedding all residuals as cell blocks for immunohistochemical staining of MKRN1 and P16 . Results of liquid-based cervical cytology, immunostained cell block sections, and human papillomavirus (HPV) hybrid capture (with real-time polymerase chain reaction) were analyzed. Clinical outcomes were analyzed overall and in subsets of specimens yielding atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions.Makorin ring finger protein 1 positivity and grades (1-3) of cervical intraepithelial neoplasia (CIN) increased in tandem (CIN1, 32.4%; CIN2, 60.0%; and CIN3, 80.0%), reaching 92.3% in invasive cancer. Sensitivity, specificity, positive predictive value, and negative predictive value in detecting CIN2+ via MKRN1 were 73.8%, 76.8%, 75.6%, and 75.0%, respectively. The performance of liquid-based cytology was poorer by comparison (61.3%, 69.5%, 66.2%, and 64.8%, respectively), and HPV assay (versus MKRN1 immunohistochemical staining) displayed lower specificity (67.7%). Combined HPV + MKRN1 testing proved highest in sensitivity, specificity, positive predictive value, and negative predictive value (71.8%, 85.5%, 82.3%, and 76.5%, respectively), whereas corresponding values for cytology + HPV (60.6%, 81.8%, 75.4%, and 69.2%) and cytology + MKRN1 (58.8%, 84.1%, 78.3%, and 67.7%) were all similar. In instances of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions, the HPV + MKRN1 combination performed best by above measures (100%, 72.7%, 73.9%, and 100%), followed by cytology + MKRN1 (100%, 50.0%, 60.7%, and 100%).Makorin ring finger protein 1 displayed greater sensitivity and specificity than liquid-based cytology and

  18. Hyperexcitable neurons and altered non-neuronal cells in the compressed spinal ganglion.

    Science.gov (United States)

    LaMotte, Robert H; Ma, Chao

    2008-10-25

    The cell body or soma in the dosal root ganglion (DRG) is normally excitable and this excitability can increase and persist after an injury of peripheral sensory neurons. In a rat model of radicular pain, an intraforaminal implantation of a rod that chronically compressed the lumbar DRG ("CCD" model) resulted in neuronal somal hyperexcitability and spontaneous activity that was accompanied by hyperalgesia in the ipsilateral hind paw. By the 5th day after onset of CCD, there was a novel upregulation in neuronal expression of the chemokine, monocyte chemoattractant protein-1 (MCP-1 or CCL2) and also its receptor, CCR2. The neurons developed, in response to topically applied MCP-1, an excitatory response that they normally do not have. CCD also activated non-neuronal cells including, for example, the endothelial cells as evidenced by angiogenesis in the form of an increased number of capillaries in the DRG after 7 days. A working hypothesis is that the CCD induced changes in neurons and non-neuronal cells that may act together to promote the survival of the injured tissue. The release of ligands such as CCL2, in addition to possibly activating nociceptive neurons (maintaining the pain), may also act to preserve injured cells in the face of ischemia and hypoxia, for example, by promoting angiogenesis. Thus, somal hyperexcitability, as often said of inflammation, may represent a double edged sword.

  19. Combined Microencapsulated Islet Transplantation and Revascularization of Aortorenal Bypass in a Diabetic Nephropathy Rat Model

    Directory of Open Access Journals (Sweden)

    Yunqiang He

    2016-01-01

    Full Text Available Objective. Revascularization of aortorenal bypass is a preferred technique for renal artery stenosis (RAS in diabetic nephropathy (DN patients. Restenosis of graft vessels also should be considered in patients lacking good control of blood glucose. In this study, we explored a combined strategy to prevent the recurrence of RAS in the DN rat model. Methods. A model of DN was established by intraperitoneal injection of streptozotocin. Rats were divided into 4 groups: SR group, MIT group, Com group, and the untreated group. The levels of blood glucose and urine protein were measured, and changes in renal pathology were observed. The expression of monocyte chemoattractant protein-1 (MCP-1 in graft vessels was assessed by immunohistochemical staining. Histopathological staining was performed to assess the pathological changes of glomeruli and tubules. Results. The levels of urine protein and the expression of MCP-1 in graft vessels were decreased after islet transplantation. The injury of glomerular basement membrane and podocytes was significantly ameliorated. Conclusions. The combined strategy of revascularization and microencapsulated islet transplantation had multiple protective effects on diabetic nephropathy, including preventing atherosclerosis in the graft vessels and alleviating injury to the glomerular filtration barrier. This combined strategy may be helpful for DN patients with RAS.

  20. Hyperexcitable neurons and altered non-neuronal cells in the compressed spinal ganglion

    Institute of Scientific and Technical Information of China (English)

    Robert H. LaMotte; Chao MA

    2008-01-01

    The cell body or soma in the dosal root ganglion (DRG) is normally excitable and this excitability can increase and persist after an injury of peripheral sensory neurons. In a rat model of radicular pain, an intraforaminal implantation of a rod that chronically compressed the lumbar DRG ("CCD" model) resulted in neuronal somal hyperexcitability and spontaneous activity that was accom-panied by hyperalgesia in the ipsilateral hind paw. By the 5th day after onset of CCD, there was a novel upregulation in neuronal expression of the chemokine, monocyte chemoattractant protein-1 (MCP- 1 or CCL2) and also its receptor, CCR2. The neurons developed, in response to topically applied MCP-1, an excitatory response that they normally do not have. CCD also activated non-neuronal cells including, for example, the endothelial cells as evidenced by angiogenesis in the form of an increased number of capillaries in the DRG after 7 days. A working hypothesis is that the CCD induced changes in neurons and non-neuronal cells that may act together to promote the survival of the injured tissue. The release of ligands such as CCL2, in addition to possibly activating nociceptive neurons (maintaining the pain), may also act to preserve injured cells in the face of ischemia and hypoxia, for example, by promoting angiogenesis. Thus, somal hyperexcitability, as often said of inflammation, may represent a double edged sword.

  1. High-Mobility Group Box-1 Induces Decreased Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in the Diabetic Retina

    Directory of Open Access Journals (Sweden)

    Ahmed M. Abu El-Asrar

    2013-01-01

    Full Text Available To test the hypothesis that brain-derived neurotrophic factor-(BDNF- mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1 in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE, soluble intercellular adhesion molecule-1 (sICAM-1, monocyte chemoattractant protein-1 (MCP-1, and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.

  2. Smooth muscle cells influence monocyte response to LDL as well as their adhesion and transmigration in a coculture model of the arterial wall.

    Science.gov (United States)

    Kinard, F; Jaworski, K; Sergent-Engelen, T; Goldstein, D; Van Veldhoven, P P; Holvoet, P; Trouet, A; Schneider, Y J; Remacle, C

    2001-01-01

    We investigated the possible interference of smooth muscle cells with monocyte response to LDL as well as with their adhesion and transmigration in a coculture of porcine endothelial and smooth muscle cells. Lysophosphatidylcholine (LPC), a component of oxidized LDL (oxLDL), stimulated the adhesion of THP-1 cells to endothelial cells both in mono- and in coculture with smooth muscle cells. When THP-1 cells were incubated with endothelial cells in the presence of copper oxLDL, their adhesion was increased, but only in coculture. The addition of sodium nitroprusside (SNP) together with oxLDL markedly increased the adhesion of THP-1 cells in coculture. Close proximity between endothelial and smooth muscle cells was necessary to observe that effect. Furthermore, this increase in adhesion of THP-1 cells can, at least in part, be attributed to the augmented production of monocyte chemoattractant protein-1 (MCP-1) observed in coculture under the influence of oxLDL and SNP. The passage of THP-1 cells through the coculture was stimulated by MCP-1 and LPC. These results show that physical contacts or close proximity between endothelial and smooth muscle cells play a key role in the adhesion of monocytes and their infiltration into the intima in response to oxLDL.

  3. Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation.

    Science.gov (United States)

    Fukuda, Kazuki; Matsumura, Takeshi; Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko; Nakao, Saya; Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji; Kawada, Teruo; Nishikawa, Takeshi; Araki, Eiichi

    2015-01-30

    The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe(-/-) mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe(-/-) mice. In conclusion, statins mediate anti-atherogenic effects through PPARγ activation in SMCs. These effects of statins on SMCs may be beneficial for the prevention of atherosclerosis.

  4. Force-Induced H2S by PDLSCs Modifies Osteoclastic Activity during Tooth Movement.

    Science.gov (United States)

    Liu, F; Wen, F; He, D; Liu, D; Yang, R; Wang, X; Yan, Y; Liu, Y; Kou, X; Zhou, Y

    2017-02-01

    Hydrogen sulfide (H2S), a gasotransmitter, has been recently linked to mesenchymal stem cell (MSC) function and bone homeostasis. Periodontal ligament stem cells (PDLSCs) are the main MSCs in PDL, which respond to mechanical force to induce physiological activities during orthodontic tooth movement (OTM). However, it is unknown whether mechanical force might induce endogenous H2S production by PDLSCs to regulate alveolar bone homeostasis. Here, we used a mouse OTM model to demonstrate that orthodontic force-induced endogenous H2S production in PDL tissue was associated with macrophage accumulation and osteoclastic activity in alveolar bone. Then, we showed that mechanical force application induced cystathionine β-synthase (CBS) expression and endogenous H2S production by PDLSCs. Moreover, blocking endogenous H2S or systemically increasing H2S levels could decrease or enhance force-induced osteoclastic activities to control tooth movement. We further revealed how force-induced H2S production by PDLSCs contributed to the secretion of monocyte chemoattractant protein-1 (MCP-1) and the expression of receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) system by PDLSCs. The secretion and expression of these factors controlled macrophage migration and osteoclast differentiation. This study demonstrated that PDLSCs produced H2S to respond to and transduce force signals. Force-induced gasotransmitter H2S production in PDLSCs therefore regulated osteoclastic activities in alveolar bone and controlled the OTM process through the MCP-1 secretion and RANKL/OPG system.

  5. The RhoA/ROCK Pathway Ameliorates Adhesion and Inflammatory Infiltration Induced by AGEs in Glomerular Endothelial Cells.

    Science.gov (United States)

    Rao, Jialing; Ye, Zengchun; Tang, Hua; Wang, Cheng; Peng, Hui; Lai, Weiyan; Li, Yin; Huang, Wanbing; Lou, Tanqi

    2017-01-05

    A recent study demonstrated that advanced glycation end products (AGEs) play a role in monocyte infiltration in mesangial areas in diabetic nephropathy. The Ras homolog gene family, member A Rho kinase (RhoA/ROCK) pathway plays a role in regulating cell migration. We hypothesized that the RhoA/ROCK pathway affects adhesion and inflammation in endothelial cells induced by AGEs. Rat glomerular endothelial cells (rGECs) were cultured with AGEs (80 μg/ml) in vitro. The ROCK inhibitor Y27632 (10 nmol/l) and ROCK1-siRNA were used to inhibit ROCK. We investigated levels of the intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein1 (MCP-1) in rGECs. Db/db mice were used as a diabetes model and received Fasudil (10 mg/kg/d, n = 6) via intraperitoneal injection for 12 weeks. We found that AGEs increased the expression of ICAM-1 and MCP-1 in rGECs, and the RhoA/ROCK pathway inhibitor Y27632 depressed the release of adhesion molecules. Moreover, blocking the RhoA/ROCK pathway ameliorated macrophage transfer to the endothelium. Reduced expression of adhesion molecules and amelioration of inflammatory cell infiltration in the glomerulus were observed in db/db mice treated with Fasudil. The RhoA/ROCK pathway plays a role in adhesion molecule expression and inflammatory cell infiltration in glomerular endothelial cells induced by AGEs.

  6. A bioengineered drug-Eluting scaffold accelerated cutaneous wound healing In diabetic mice.

    Science.gov (United States)

    Yin, Hao; Ding, Guoshan; Shi, Xiaoming; Guo, Wenyuan; Ni, Zhijia; Fu, Hong; Fu, Zhiren

    2016-09-01

    Hyperglycemia in diabetic patients can greatly hinder the wound healing process. In this study we investigated if the engagement of F4/80(+) murine macrophages could accelerate the cutaneous wound healing in streptozotocin induced diabetic mice. To facilitate the engagement of macrophages, we engineered a drug-eluting electrospun scaffold with a payload of monocyte chemoattractant protein-1 (MCP-1). MCP-1 could be readily released from the scaffold within 3 days. The electrospun scaffold showed no cytotoxic effects on human keratinocytes in vitro. Full-thickness excisional cutaneous wound was created in diabetic mice. The wound fully recovered within 10 days in mice treated with the drug-eluting scaffold. In contrast, the wound took 14 days to fully recover in control groups. The use of drug-eluting scaffold also improved the re-epithelialization. Furthermore, we observed a larger population of F4/80(+) macrophages in the wound bed of mice treated with drug-eluting scaffolds on day 3. This marked increase of macrophages in the wound bed could have contributed to the accelerated wound healing. Our study shed new light on an immuno-engineering solution for wound healing management in diabetic patients.

  7. Trikatu, an herbal compound ameliorates rheumatoid arthritis by the suppression of inflammatory immune responses in rats with adjuvant-induced arthritis and on cultured fibroblast like synoviocytes via the inhibition of the NFκB signaling pathway.

    Science.gov (United States)

    Doss, Hari Madhuri; Ganesan, Ramamoorthi; Rasool, Mahaboobkhan

    2016-10-25

    The present study was designed to investigate the potential therapeutic effect of trikatu, an herbal compound and its underlying molecular mechanism in rats with adjuvant-induced arthritis (AIA). Our results indicate that trikatu (1000 mg/kg/b.wt. oral) administration suppressed the production of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1) and downregulated the mRNA expression levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17, MCP-1, receptor activator of nuclear factor kappa B ligand (RANKL), cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS)) and transcription factors (nuclear factor kappa B 65 (NFкB-p65) and activator protein-1 (AP-1)) in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats. Consistently, the protein expression of NFкB-p65, IL-17, TNF-α, COX-2, and RANKL was also dramatically reduced in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats by trikatu treatment. In addition, trikatu suppressed the expression and phosphorylation of NFкB-p65 similar to the Bay 11-7082 (NFкB inhibitor) in cultured AIA-fibroblast like synoviocytes. Furthermore, trikatu alleviated the histopathology of joint of arthritic rats. Overall, these data highlights that trikatu could be a promising alternative modality for the possible treatment of rheumatoid arthritis and other inflammatory diseases.

  8. Effect of Sipjeondaebo-tang on cancer-induced anorexia and cachexia in CT-26 tumor-bearing mice.

    Science.gov (United States)

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

    2014-01-01

    Cancer-associated anorexia and cachexia are a multifactorial condition described by a loss of body weight and muscle with anorexia, asthenia, and anemia. Moreover, they correlate with a high mortality rate, poor response to chemotherapy, poor performance status, and poor quality of life. Cancer cachexia is regulated by proinflammatory cytokines such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor- α (TNF- α). In addition, glucagon like peptide-1 (GIP-1), peptide YY (PYY), ghrelin, and leptin plays a crucial role in food intake. In this study, we investigated the therapeutic effects of one of the traditional herbal medicines, Sipjeondaebo-tang (Juzen-taiho-to in Japanese; SJDBT), on cancer anorexia and cachexia in a fundamental mouse cancer anorexia/cachexia model, CT-26 tumor-bearing mice. SJDBT was more significantly effective in a treatment model where it was treated after anorexia and cachexia than in a prevention model where it was treated before anorexia and cachexia on the basis of parameters such as weights of muscles and whole body and food intakes. Moreover, SJDBT inhibited a production of IL-6, MCP-1, PYY, and GLP-1 and ameliorated cancer-induced anemia. Therefore, our in vivo studies provide evidence on the role of SJDBT in cancer-associated anorexia and cachexia, thereby suggesting that SJDBT may be useful for treating cancer-associated anorexia and cachexia.

  9. Cryoglobulins as Potential Triggers of Inflammation in Schizophrenia

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    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.

  10. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10

    Directory of Open Access Journals (Sweden)

    Soojin Park

    2016-01-01

    Full Text Available Epidemiological and experimental evidence support health risks associated with the exposure to airborne particulate matter with a diameter of <10 μM (PM10. PM10 stimulates the production of reactive oxygen species (ROS and inflammatory mediators. Thus, we assumed that natural antioxidants might provide health benefits attenuating hazardous effects of PM10. In the present study, we examined the effects of pomegranate peel extract (PPE on THP-1 monocytic cells exposed to PM10. PM10 induced cytotoxicity and the production of ROS. It also increased the expression and secretion of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and monocyte chemoattractant protein-1 (MCP-1, and cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1. PPE at 10–100 μg mL−1 attenuated the production of ROS and the expression of TNF-α, IL-1β, MCP-1, and ICAM-1, but not VCAM-1, in THP-1 cells stimulated by PM10 (100 μg mL−1. PPE also attenuated the adhesion of PM10-stimulated THP-1 cells to EA.hy926 endothelial cells. PPE constituents, punicalagin and ellagic acid, attenuated PM10-induced monocyte adhesion to endothelial cells, and punicalagin was less cytotoxic compared to ellagic acid. The present study suggests that PPE and punicalagin may be useful in alleviating inflammatory reactions due to particulate matter.

  11. Combination of Medicinal Herbs KIOM-79 Reduces Advanced Glycation End Product Accumulation and the Expression of Inflammatory Factors in the Aorta of Zucker Diabetic Fatty Rats

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    Eunjin Sohn

    2011-01-01

    Full Text Available Previous studies have reported that KIOM-79 shows a strong inhibitory effect on AGE formation and inhibited a proinflammatory state in a murine macrophage cell line. In the present study, we investigated the effect of KIOM-79 on AGE accumulation and vascular inflammation in the aorta of Zucker diabetic fatty (ZDF rats, a commonly used model of type 2 diabetes. Seven-week-old male ZDF rats were treated with KIOM-79 (50 mg/kg once a day orally for 13 weeks. We examined the dissected aortas for AGE accumulation, expression of the receptor for AGEs (RAGE, and the expression of proinflammatory factors, including monocyte chemoattractant protein-1 (MCP-1, vascular endothelial growth factor (VEGF, and vascular adhesion molecule-1 (VCAM-1. Nuclear factor-kappaB (NF-κB and inducible nitric oxide synthase (iNOS were also measured by Southwestern histochemistry, electrophoretic mobility shift assay (EMSA, and immunohistochemistry, respectively. KIOM-79 markedly reduced the accumulation of AGEs and the expression of RAGE in the aorta. We also found that KIOM-79 attenuated the expression of inflammatory factors including NF-κB, MCP-1, VEGF, VCAM-1, and iNOS in the aortas of ZDF rats. These data suggest that KIOM-79 may prevent or retard the development of inflammation in diabetic vascular disease.

  12. Association of NFKB1 gene polymorphism (rs28362491) with levels of inflammatory biomarkers and susceptibility to diabetic nephropathy in Asian Indians

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    Gautam, Amar; Gupta, Stuti; Mehndiratta, Mohit; Sharma, Mohini; Singh, Kalpana; Kalra, Om P; Agarwal, Sunil; Gambhir, Jasvinder K

    2017-01-01

    AIM To investigate the association of NFKB1 gene -94 ATTG insertion/deletion (rs28362491) polymorphism with inflammatory markers and risk of diabetic nephropathy in Asian Indians. METHODS A total of 300 subjects were recruited (100 each), normoglycemic, (NG); type 2 diabetes mellitus (T2DM) without any complications (DM) and T2DM with diabetic nephropathy [DM-chronic renal disease (CRD)]. Analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism and ELISA. Pearson’s correlation, analysis of variance and logistic regression were used for statistical analysis. RESULTS The allelic frequencies of -94 ATTG insertion/deletion were 0.655/0.345 (NG), 0.62/0.38 (DM) and 0.775/0.225 (DM-CRD). The -94 ATTG ins allele was associated with significantly increased levels of urinary monocyte chemoattractant protein-1 (uMCP-1); uMCP-1 (P = 0.026) and plasma tumor necrosis factor-alpha (TNF-α); TNF-α (P = 0.030) and almost doubled the risk of diabetic nephropathy (OR = 1.91, 95%CI: 1.080-3.386, P = 0.025). CONCLUSION -94 ATTG ins/ins polymorphism might be associated with increased risk of developing nephropathy in Asian Indian subjects with diabetes mellitus. PMID:28265344

  13. Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

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    Mones M. Abu Shady

    2015-08-01

    Full Text Available OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27. Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb, erythrocyte sedimentation rate (ESR, and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a, interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p 0.05. Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05.CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

  14. Cryptotanshinone inhibits TNF-α-induced early atherogenic events in vitro.

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    Ahmad, Zuraini; Ng, Chin Theng; Fong, Lai Yen; Bakar, Nurul Ain Abu; Hussain, Nor Hayuti Mohd; Ang, Kok Pian; Ee, Gwendoline Cheng Lian; Hakim, Muhammad Nazrul

    2016-05-01

    Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. Salvia miltiorrhiza (danshen) is a traditional Chinese medicine that has been effectively used to treat cardiovascular disease. Cryptotanshinone (CTS), a major lipophilic compound isolated from S. miltiorrhiza, has been reported to possess cardioprotective effects. However, the anti-atherogenic effects of CTS, particularly on tumor necrosis factor-α (TNF-α)-induced endothelial cell activation, are still unclear. This study aimed to determine the effect of CTS on TNF-α-induced increased endothelial permeability, monocyte adhesion, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), monocyte chemoattractant protein 1 (MCP-1) and impaired nitric oxide production in human umbilical vein endothelial cells (HUVECs), all of which are early events occurring in atherogenesis. We showed that CTS significantly suppressed TNF-α-induced increased endothelial permeability, monocyte adhesion, sICAM-1, sVCAM-1 and MCP-1, and restored nitric oxide production. These observations suggest that CTS possesses anti-inflammatory properties and could be a promising treatment for the prevention of cytokine-induced early atherogenesis.

  15. Crocetin Inhibits Lipopolysaccharide-Induced Inflammatory Response in Human Umbilical Vein Endothelial Cells

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    Lei Song

    2016-11-01

    Full Text Available Background/Aim: Crocetin is a readily bioavailable and bioactive compound extracted from Saffron. Previous studies indicated its various biomedical properties including antioxidant and anti-coagulation potencies. However, its effect on inflammation, notably within the cardiovascular system, has not been investigated yet. In the present study, we utilized human umbilical vein endothelial cell (HUVEC to elucidate the effect of Crocetin on vascular inflammation. Methods: Cell viability and toxicity were evaluated by MTT and Lactate dehydrogenase (LDH assay, respectively. Pro-inflammatory chemokine Monocyte Chemoattractant Protein-1 (MCP-1 and Interleukin-8 (IL-8 expressions were determined by RT-PCR and ELISA. With fluorescence labeled U937 cells, we examined immune cell adhesion to the inflamed HUVEC in vitro, which was further confirmed by the H&E staining in the murine subcutaneous endothelium in vivo. Results: Upon Lipopolysaccharide (LPS-induced inflammatory response in HUVECs, Crocetin ameliorated cell cytotoxicity, suppressed MCP-1 and IL-8 expressions through blocking NF-κB p65 signaling transduction. Moreover, Crocetin inhibited immune cells adhesion and infiltration to inflamed endothelium, which is a key step in inflammatory vascular injury. Conclusions: These findings suggest that Crocetin, a natural herb extract, is a potent suppressor of vascular endothelial inflammation.

  16. Inhibitory effect of chlorophyllin on the Propionibacterium acnes-induced chemokine expression.

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    Kang, Mi-Sun; Kim, Jin-Hee; Shin, Boo-Ahn; Lee, Hyun-Chul; Kim, Youn-Shin; Lim, Hae-Soon; Oh, Jong-Suk

    2013-12-01

    Chlorophyllin (CHL), a chlorophyll-derivative, exhibits several beneficial properties, including antibacterial, antioxidant, and anticancer activities. However, its antibacterial and anti-inflammatory activities against Propionibacterium acnes have not been described. The antibacterial activity of this compound was evaluated in vitro using the broth microdilution method. CHL had an inhibitory effect on the growth of P. acnes (MIC = 100 μM). In a real-time reverse transcription-polymerase chain reaction and an enzyme-linked immunosorbent assay, CHL significantly decreased interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner, decreasing both mRNA and protein levels for these chemokines in THP-1 cells indicating the anti-inflammatory effects of it. To investigate the molecular mechanisms underlying the anti-inflammatory properties of CHL in THP-1 cells stimulated by P. acnes, we used western blotting to analyze the effect of CHL on activation of the nuclear factor (NF)-κB. CHL inhibited P. acnes-induced IL-8 and MCP-1 production via blockade of NF-κB activation in THP-1 cells. Therefore, based on these results, we suggest that CHL is a useful agent to control the growth of P. acnes involved in acne inflammation and prevent acne.

  17. Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats.

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    Legette, Leecole L; Luna, Arlyn Y Moreno; Reed, Ralph L; Miranda, Cristobal L; Bobe, Gerd; Proteau, Rosita R; Stevens, Jan F

    2013-07-01

    Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (pxanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome.

  18. Lipopolysaccharide induced inflammation in the perivascular space in lungs

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    Pabst Reinhard

    2008-07-01

    Full Text Available Abstract Background Lipopolysaccharide (LPS contained in tobacco smoke and a variety of environmental and occupational dusts is a toxic agent causing lung inflammation characterized by migration of neutrophils and monocytes into alveoli. Although migration of inflammatory cells into alveoli of LPS-treated rats is well characterized, the dynamics of their accumulation in the perivascular space (PVS leading to a perivascular inflammation (PVI of pulmonary arteries is not well described. Methods Therefore, we investigated migration of neutrophils and monocytes into PVS in lungs of male Sprague-Dawley rats treated intratracheally with E. coli LPS and euthanized after 1, 6, 12, 24 and 36 hours. Control rats were treated with endotoxin-free saline. H&E stained slides were made and immunohistochemistry was performed using a monocyte marker and the chemokine Monocyte-Chemoattractant-Protein-1 (MCP-1. Computer-assisted microscopy was performed to count infiltrating cells. Results Surprisingly, the periarterial infiltration was not a constant finding in each animal although LPS-induced alveolitis was present. A clear tendency was observed that neutrophils were appearing in the PVS first within 6 hours after LPS application and were decreasing at later time points. In contrast, mononuclear cell infiltration was observed after 24 hours. In addition, MCP-1 expression was present in perivascular capillaries, arteries and the epithelium. Conclusion PVI might be a certain lung reaction pattern in the defense to infectious attacks.

  19. Anti-inflammatory effects of limonene from yuzu (Citrus junos Tanaka) essential oil on eosinophils.

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    Hirota, Ryoji; Roger, Ngatu Nlandu; Nakamura, Hiroyuki; Song, Hee-Sun; Sawamura, Masayoshi; Suganuma, Narufumi

    2010-04-01

    Yuzu (Citrus junos Tanaka) has been used as a traditional medicine in Japan. We investigated in vitro anti-inflammatory effects of limonene from yuzu peel on human eosinophilic leukemia HL-60 clone 15 cells. To examine anti-inflammatory effects of limonene on the cells, we measured the level of reactive oxygen species (ROS), monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF) kappa B, and p38 mitogen-activated protein kinase (MAPK). We found that low concentration of limonene (7.34 mmol/L) inhibited the production of ROS for eotaxin-stimulated HL-60 clone 15 cells. 14.68 mmol/L concentration of limonene diminished MCP-1 production via NF-kappa B activation comparable to the addition of the proteasomal inhibitor MG132. In addition, it inhibited cell chemotaxis in a p38 MAPK dependent manner similar to the adding of SB203580. These results suggest that limonene may have potential anti-inflammatory efficacy for the treatment of bronchial asthma by inhibiting cytokines, ROS production, and inactivating eosinophil migration.

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

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    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.