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Zhongjie Sun - One of the best experts on this subject based on the ideXlab platform.
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klotho gene deficiency causes salt sensitive hypertension via Monocyte Chemotactic Protein 1 cc chemokine receptor 2 mediated inflammation
Journal of The American Society of Nephrology, 2015Co-Authors: Xiaoli Zhou, Kai Chen, Han Lei, Zhongjie SunAbstract:Klotho ( KL ) is a newly discovered aging suppressor gene. In mice, the KL gene extends the lifespan when overexpressed and shortens the lifespan when disrupted. This study investigated if KL deficiency affects BP and salt sensitivity using KL mutant heterozygous (+/−) mice and wild-type (WT) mice (9 weeks of age, 16 mice per group). Notably, systolic BP in KL(+/−) mice began to increase at the age of 15 weeks, reached a peak level at the age of 17 weeks, and remained elevated thereafter, whereas systolic BP remained consistent in WT mice. High salt (HS) intake further increased BP in KL(+/−) mice but did not affect BP in WT mice. Blockade of CC chemokine receptor 2 (CCR2), involved in Monocyte chemotaxis, by a specific CCR2 antagonist (INCB3284) abolished the HS-induced increase in BP in KL(+/−) mice. Furthermore, HS loading substantially increased the expression of Monocyte Chemotactic Protein-1 and the infiltration of macrophages and T cells in kidneys in KL(+/−) mice, and treatment with INCB3284 abolished these effects. Treatment of KL(+/−) mice with INCB3284 also attenuated the increased renal expressions of serum glucocorticoid-regulated kinase 1, thiazide-sensitive NaCl cotransporter, and ATP synthase β along with the renal structural damage and functional impairment induced by HS loading. In conclusion, KL deficiency caused salt-sensitive hypertension and renal damage by CCR2-mediated inflammation.
Alberto Mantovani - One of the best experts on this subject based on the ideXlab platform.
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elevated cerebrospinal fluid levels of Monocyte Chemotactic Protein 1 correlate with hiv 1 encephalitis and local viral replication
AIDS, 1998Co-Authors: Paola Cinque, Silvano Sozzani, Manuela Mengozzi, Luca Vago, Valter Torri, Daniela Ceresa, Elisa Vicenzi, Pietro Transidico, Ambrogio Vagani, Alberto MantovaniAbstract:OBJECTIVE To investigate whether the CC-chemokine Monocyte Chemotactic Protein (MCP)-1 could play a role in the pathogenesis of HIV infection of the central nervous system. This hypothesis was suggested by previous observations, including our finding of elevated cerebrospinal fluid (CSF) levels of this chemokine in patients with cytomegalovirus (CMV) encephalitis. DESIGN AND METHODS CSF levels of MCP-1 were determined in 37 HIV-infected patients with neurological symptoms, and were compared with both the presence and severity of HIV-1 encephalitis at post-mortem examination and CSF HIV RNA levels. MCP-1 production by Monocyte-derived macrophages was tested after in vitro infection of these cells by HIV. RESULTS CSF MCP-1 levels were significantly higher in patients with (median, 4.99 ng/ml) than in those without (median, 1.72 ng/ml) HIV encephalitis. Elevated CSF MCP-1 concentrations were also found in patients with CMV encephalitis and with concomitant HIV and CMV encephalitis (median, 3.14 and 4.23 ng/ml, respectively). HIV encephalitis was strongly associated with high CSF MCP-1 levels (P = 0.002), which were also correlated to high HIV-1 RNA levels in the CSF (P = 0.007), but not to plasma viraemia. In vitro, productive HIV-1 infection of Monocyte-derived macrophages upregulated the secretion of MCP-1. CONCLUSIONS Taken together, these in vivo and in vitro findings support a model whereby HIV encephalitis is sustained by virus replication in microglial cells, a process amplified by recruitment of mononuclear cells via HIV-induced MCP-1.
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expression of Monocyte Chemotactic Protein 3 in human Monocytes exposed to the mycobacterial cell wall component lipoarabinomannan
Cytokine, 1997Co-Authors: Valerie Vouretcraviari, Guido Poli, Salvatore Cenzuales, Alberto MantovaniAbstract:Abstract Monocyte Chemotactic Protein-3 (MCP-3) is a C–C chemokine which interacts with the CCR1, CCR2 (MCP-1) and CCR3 receptors and has a distinct spectrum of action. The present study was designed to assess whether mycobacterial components were able to induce expression and production of MCP-3 in human Monocytes. Mycobacterial lipoarabinomannan (LAM) induced expression of MCP-3 mRNA in human peripheral blood mononuclear cells. The non-mannose-capped version of lipoarabinomannan (AraLAM) was considerably more potent than the mannose-capped version ManLAM or the simpler version phosphatidylinositol mannoside (PLM). Among mononuclear cells, Monocytes were responsible for LAM-induced MCP-3 mRNA expression. Whole mycobacteria ( Mycobacterium bovis BCG) strongly induced MCP-3 expression. Pretreatment with actinomycin D abolished LAM-induced MCP-3 expression, whereas cycloheximide only partially reduced the expression. LAM-induced MCP-3 expression was associated with the production of immunoreactive PTX3. Interleukin 10 (IL-10) and IL-13 inhibited the induction of MCP-3 by LAM. Thus mycobacterial cell wall components induced expression of MCP-3 in human Monocytes. MCP-3, a chemokine active on mononuclear phagocytes, NK cells, T cells and dendritic cells, may be relevant to the induction and expression of immunity against mycobacteria.
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induction of natural killer cell migration by Monocyte Chemotactic Protein 1 2 and 3
European Journal of Immunology, 1994Co-Authors: Paola Allavena, Jo Van Damme, Giancarlo Bianchi, Dan Zhou, Petr Jilek, Silvano Sozzani, Alberto MantovaniAbstract:Under certain physiological and pathological conditions, naturall killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C-C chemokine, Monocyte Chemotactic Protein-1 (MCP-1). MCP-1 induced migration across filters of interleukin (IL)-2-activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP-1 receptor on NK cells indicated that the Chemotactic response to MCP-1 was blocked by pre-treatment of cells with Bordetella pertussis toxin, and MCP-1 but not IL-8 displaced 125I-labeled MCP-1 from IL-2-activated NK cells. The related chemokines MCP-2 and MCP-3 were also active – though less potent – attractants for activated NK cells. Thus the spectrum of action of MCP-1, -2 and -3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.
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expression of Monocyte Chemotactic Protein and interleukin 8 by cytokine activated human vascular smooth muscle cells
Arteriosclerosis Thrombosis and Vascular Biology, 1991Co-Authors: Ji Ming Wang, Antonio Sica, Giuseppe Peri, Sabine Walter, Ines Martin Padura, Peter Libby, Miroslav Ceska, Ivan J D Lindley, Francesco Colotta, Alberto MantovaniAbstract:The present study was designed to investigate the capacity of human vascular smooth muscle cells (SMCs) to produce a cytokine Chemotactic for Monocytes (Monocyte Chemotactic Protein [MCP]) and by way of comparison, a related polypeptide activator of neutrophils (known as interleukin-8 [IL-8] or neutrophil activating Protein-1 [NAP-1]. On exposure to IL-1, SMCs released high levels of Chemotactic activity for Monocytes, which could be removed by absorption with anti-MCP antibodies. MCP production by activated SMCs was comparable to that of IL-1-stimulated umbilical vein endothelial cells. Activated SMCs released appreciable levels of IL-8, as determined by a specific enzyme-linked immunosorbent assay, but little Chemotactic activity for neutrophils. IL-1-treated SMCs expressed high levels of both MCP and IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumor necrosis factor and bacterial lipopolysaccharide but not IL-6 also induced MCP and IL-8 gene expression in SMCs. Nuclear runoff analysis revealed that IL-1 augmented transcription of the MCP and IL-8 genes. The capacity of SMCs to produce a cytokine (MCP) that recruits and activates circulating mononuclear phagocytes may be of considerable importance in the pathogenesis of vascular diseases (e.g., vasculitis and atherosclerosis) that are characterized by Monocyte infiltration of the vessel wall.
Ali Akoum - One of the best experts on this subject based on the ideXlab platform.
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spontaneous and stimulated secretion of Monocyte Chemotactic Protein 1 and macrophage migration inhibitory factor by peritoneal macrophages in women with and without endometriosis
Fertility and Sterility, 2002Co-Authors: Ali Akoum, Jihong Kong, Christine N Metz, Marie Claude BeaumontAbstract:Abstract Objective: To assess spontaneous and stimulated secretion of Monocyte Chemotactic Protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF) by peritoneal macrophages in women with and without endometriosis. Design: Macrophages were isolated from the peritoneal fluid and cultured for different periods of time (6, 20, and 44 hours) without any stimulation to determine spontaneous secretion of MCP-1 and MIF. Macrophages were also exposed to 1 μg/mL lipopolysaccharide for 6 hours to evaluate the stimulated secretion of these cytokines. Setting: Gynecology clinic and human reproduction research laboratory. Patient(s): Twelve fertile women and 11 women with endometriosis. Intervention(s): Peritoneal fluid obtained at laparoscopy. Main Outcome Measure(s): Monocyte Chemotactic Protein-1 and MIF concentrations in the culture medium using ELISA. Result(s): Peritoneal macrophages of women with endometriosis demonstrated an increased capacity to secrete MCP-1 either spontaneously or after stimulation with lipopolysaccharide. They also showed a marked tendency for an increased secretion of MIF, but no statistically significant difference was found. Conclusion(s): Monocyte Chemotactic Protein-1 and MIF production by peritoneal macrophages may contribute to paracrine and autocrine activation and to macrophage accumulation in the peritoneal cavity of women with endometriosis. These mechanisms may exacerbate peritoneal inflammation and favor the growth of endometrial implants.
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effect of hormonal agents on Monocyte Chemotactic Protein 1 expression by endometrial epithelial cells of women with endometriosis
Fertility and Sterility, 2000Co-Authors: Annie Boucher, Andre Lemay, Ali AkoumAbstract:Abstract Objective: To assess whether hormonal agents used in the medical treatment of endometriosis, such as danazol and GnRH agonist, exert direct regulatory action on Monocyte Chemotactic Protein-1 (MCP-1) expression by endometrial epithelial cells. Design: Primary cultures of epithelial cells isolated from human endometrium were exposed to different concentrations of cytokines and steroid hormone analogs. Expression of MCP-1 was analyzed at the levels of Protein and messenger RNA. Setting: Gynecology clinic and laboratory of endocrinology of reproduction. Patient(s): Women presenting for infertility or pelvic pain in whom endometriosis was diagnosed by using laparoscopy. Intervention(s): Endometrial tissue biopsy performed at laparoscopy. Main Outcome Measure(s): Secretion of MCP-1 Protein was measured by using enzyme-linked immunosorbent assay, and mRNA steady-state levels were measured by performing Northern blot analysis. Result(s): Buserelin acetate, a GnRH agonist (0.1–10 ng/mL), had no significant effect on MCP-1 expression, whereas danazol (10 −7 –10 −5 M), a testosterone analog, and dexamethasone, an anti-inflammatory glucocorticoid hormone (10 −12 –10 −6 M), showed a direct and a dose-dependent inhibitory effect on MCP-1 expression. This effect occurred at the level of Protein and mRNA. Conclusion(s): The findings of the study may affect understanding of the mechanisms by which hormonal treatments act on endometriosis and influence its clinical manifestations.
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increased Monocyte Chemotactic Protein 1 level and activity in the peripheral blood of women with endometriosis
American Journal of Obstetrics and Gynecology, 1996Co-Authors: Ali Akoum, Andre Lemay, Shaun R Mccoll, Isabelle Paradis, Rodolphe MaheuxAbstract:Abstract OBJECTIVE: Our purpose was to evaluate Monocyte Chemotactic Protein-1 in the peripheral blood of women with and without endometriosis. STUDY DESIGN: Fifty-seven patients with endometriosis at laparoscopy done for infertility and pelvic pain were compared with 44 fertile women with no evidence of endometriosis at tubal ligation by laparoscopy. Monocyte Chemotactic Protein-1 concentration in the plasma was determined by enzyme-linked immunosorbent assay and its biologic activity was evaluated by measuring Monocyte chemotaxis with use of a human histiocytic cell line (U937). RESULTS: Monocyte Chemotactic Protein-1 concentrations (median and range of values) found in the plasma were higher in patients with endometriosis (163, 0 to 788 pg/ml) than in normal controls (0, 0 to 355 pg/ml). This elevation was significant only in the minimal stage of endometriosis (revised American Fertility Society stage I). However, increased Chemotactic activity (mean number of migrating cells/mm 2 ± SEM) was found in the stages I (1240 ± 141), II (519 ± 30), and III-IV (523 ± 23) of the disease compared with normal controls (205 ± 20). A total of 35% to 44% of this activity was inhibited in the presence of an antibody specific to Monocyte Chemotactic Protein-1. CONCLUSION: Endometriosis is associated with increased level and activity of Monocyte Chemotactic Protein-1 in the peripheral blood. The elevation and activation of this cytokine could play a relevant role in the immunoinflammatory process associated with the disease. (Am J Obstet Gynecol 1996;175:1620-5.)
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cytokine induced secretion of Monocyte Chemotactic Protein 1 by human endometriotic cells in culture
American Journal of Obstetrics and Gynecology, 1995Co-Authors: Ali Akoum, Andre Lemay, C Brunet, Jacques HebertAbstract:Abstract OBJECTIVE: Local secretion of Chemotactic factors could contribute to the attraction of macrophages into the peritoneal cavity of women wiht endometriosis. The purpose of this study was to investigate the ability of endometriotic cells to produce Monocyte Chemotactic and activating Protein-1 in response to interleukin-1β and tumor necrosis factor-α, which are found in elevated levels in the peritoneal fluid of patients with endometriosis. STUDY DESIGN: Cultures of fibroblasts-like and epithelial cells isolated from endometriotic tissue were incubated with different concentrations of cytokines for varying periods of time. The de novo secretion of Monocyte Chemotactic Protein-1 in the culture supernants was analyzed by immunoprecipitation and electrophoresis after metabolic labeling with sulfur 35-labeled cysteine RESULTS: The incubation of endometriotic fibroblast-like cells with interleukin-1β and tumor necrosis factor-α resulted in a time- and dose-dependent release of Monocyte Chemotactic Protein-1 into the culure supernatant. Coincubation of the cells with tumor necrosis factor-α and interferon gamma resulted in a synergistic and dose-dependent increase of the Monocyte Chemotactic Protein-1 secretion, whereas interferon gamma alone had no significant effect. Preliminary results indicate that Monocyte Chemotactic Protein-1 is also produced by endometriotic epithelial cells in response to the same cytokines. CONCLUSIONS: Cytokine-stimulated endometriotic cells synthesize and secrete Monocyte Chemotactic Protein-1 in culture, and they may play a relevant role in the recruitment of macrophages to the peritoneal cavity of patients by the local production of Chemotactic factors.
Marcus Thelen - One of the best experts on this subject based on the ideXlab platform.
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Monocyte Chemotactic Protein 4 mcp 4 a novel structural and functional analogue of mcp 3 and eotaxin
Journal of Experimental Medicine, 1996Co-Authors: Mariagrazia Uguccioni, S H Lima, Gianni Garotta, Beatrice Dewald, Ulf Forssmann, Pius Loetscher, H Li, Y Li, Barbara Kreider, Marcus ThelenAbstract:A novel human CC chemokine complementary DNA was identified in a library constructed from human fetal RNA, cloned into a baculovirus vector, and expressed in Sf9 insect cells. The mature recombinant Protein that was released had the NH2-terminal sequence pyro-QPDALNVPSTC...and consisted of 75 amino acids. Minor amounts of two variants of 77 and 82 residues (NH2 termini: LAQPDA...and FNPQGLAQPDA...) were released as well. The novel chemokine was designated Monocyte Chemotactic Protein 4 (MCP-4) and the variants were designated (LA)MCP-4 and (FNPQGLA)MCP-4. MCP-4 shares the pyroglutamic acidproline NH2-terminal motif and 56-61% sequence identity with the three known Monocyte Chemotactic Proteins and is 60% identical to eotaxin. It has marked functional similarities to MCP-3 and eotaxin. Like MCP-3, MCP-4 is a chemoattractant of high efficacy for Monocytes and T lymphocytes. On these cells, it binds to receptors that recognize MCP-1, MCP-3, and RANTES. On eosinophils, MCP-4 has similar efficacy and potency as MCP-3, RANTES, and cotaxin. It shares receptors with eotaxin and shows full cross-desensitization with this cosinophil-selective chemokine. Of the two variants, only (LA)MCP-4 could be purified in sufficient quantities for testing and was found to be at least 30-fold less potent than MCP-4 itself. This suggests that the 75-residue form with the characteristic NH2 terminus of an MCP is the biologically relevant species.
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Monocyte Chemotactic Protein 4 mcp 4 a novel structural and functional analogue of mcp 3 and eotaxin
Journal of Experimental Medicine, 1996Co-Authors: Mariagrazia Uguccioni, S H Lima, Gianni Garotta, Beatrice Dewald, Ulf Forssmann, Pius Loetscher, H Li, Y Li, Barbara Kreider, Marcus ThelenAbstract:A novel human CC chemokine complementary DNA was identified in a library constructed from human fetal RNA, cloned into a baculovirus vector, and expressed in Sf9 insect cells. The mature recombinant Protein that was released had the NH2-terminal sequence pyro-QPDALNVPSTC...and consisted of 75 amino acids. Minor amounts of two variants of 77 and 82 residues (NH2 termini: LAQPDA...and FNPQGLAQPDA...) were released as well. The novel chemokine was designated Monocyte Chemotactic Protein 4 (MCP-4) and the variants were designated (LA)MCP-4 and (FNPQGLA)MCP-4. MCP-4 shares the pyroglutamic acidproline NH2-terminal motif and 56-61% sequence identity with the three known Monocyte Chemotactic Proteins and is 60% identical to eotaxin. It has marked functional similarities to MCP-3 and eotaxin. Like MCP-3, MCP-4 is a chemoattractant of high efficacy for Monocytes and T lymphocytes. On these cells, it binds to receptors that recognize MCP-1, MCP-3, and RANTES. On eosinophils, MCP-4 has similar efficacy and potency as MCP-3, RANTES, and cotaxin. It shares receptors with eotaxin and shows full cross-desensitization with this cosinophil-selective chemokine. Of the two variants, only (LA)MCP-4 could be purified in sufficient quantities for testing and was found to be at least 30-fold less potent than MCP-4 itself. This suggests that the 75-residue form with the characteristic NH2 terminus of an MCP is the biologically relevant species.
Suresh Mahalingam - One of the best experts on this subject based on the ideXlab platform.
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protection from arthritis and myositis in a mouse model of acute chikungunya virus disease by bindarit an inhibitor of Monocyte Chemotactic Protein 1 synthesis
The Journal of Infectious Diseases, 2011Co-Authors: Angelo Guglielmotti, Nestor E Rulli, Michael S Rolph, Anon Srikiatkhachorn, Surapee Anantapreecha, Suresh MahalingamAbstract:Chikungunya virus (CHIKV) is associated with outbreaks of infectious rheumatic disease in humans. Using a mouse model of CHIKV arthritis and myositis, we show that tumor necrosis factor-a, interferon-?, and Monocyte Chemotactic Protein 1 (MCP-1) were dramatically induced in tissues from infected mice. The same factors were detected in the serum of patients with CHIKV-induced polyarthralgia and polyarthritis, with MCP-1 levels being particularly elevated. Bindarit (MCP inhibitor) treatment ameliorated CHIKV disease in mice. Histological analysis of muscle and joint tissues showed a reduction in inflammatory infiltrate in infected mice treated with bindarit. These results suggest that bindarit may be useful in treating CHIKV-induced arthritides in humans.