Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human monocyte chemoattractant protein (MCP)-1 encoded by the JE gene belongs to a family of low molecular weight secretory cytokines with monocyte-stimulating activity. JE transcripts are constitutively synthesized by normal and leukemic monocytes, as well as mesenchymal cells, including fibroblasts, vascular endothelial cells, and smooth muscle cells. Expression of MCP-1/JE is increased severalfold upon exposure of cells to recombinant human granulocyte-macrophage colony-stimulating factor but is down-regulated when cells are treated with lipopolysaccharide (LPS). Given the proinflammatory properties of MCP-1/JE, we have examined the modulatory effects of various antiinflammatory agents, including indomethacin, dexamethasone, cyclosporin A, and interleukin-4, on levels of MCP-1/JE transcripts either constitutively or inducibly expressed by human peripheral blood monocytes. Whereas indomethacin had no detectable effect on synthesis of MCP-1/JE transcripts and interleukin-4 treatment resulted in only a modest increase in steady state JE mRNA levels, exposure of monocytes to dexamethasone (DXS) led to a significant (2.5-10-fold) down-regulation of MCP-1/JE transcript levels. Studies examining the mechanism of down-regulation of JE mRNA by DXS indicated that DXS was acting transcriptionally and posttranscriptionally, by reducing the transcriptional rate of the MCP-1/JE gene and by destabilizing JE mRNA, a process requiring de novo RNA and protein synthesis. Although cyclosporin A by itself had no effect on synthesis of JE transcripts, it apparently relieved LPS-mediated down-regulation of JE transcript levels, by interfering with the destabilizing effect of LPS on JE mRNA. These results may provide new information regarding the action of antiinflammatory agents on synthesis of endogenous proinflammatory cytokines.
 ...
PMID:Effect of antiinflammatory agents on synthesis of MCP-1/JE transcripts by human blood monocytes. 138 39

The murine monocyte chemoattractant protein 1, JE/MCP-1, like its human counterpart monocyte chemotactic and activating factor (MCAF), attracts monocytes-macrophages to tumor tissues. In previous studies we reported that expression of the JE/MCP-1 gene in murine colon carcinoma cells reduced their tumorigenicity and suppressed their metastatic potential. We now demonstrate that the growth and metastasis of the renal adenocarcinoma cell line RENCA are reduced when it was admixed with syngeneic fibroblasts engineered to secrete the JE/MCP-1 cytokine before injection. Culture supernatants of JE/MCP-1-expressing cells plus lipopolysaccharide (LPS) synergistically activated tumoricidal properties in syngeneic macrophages against RENCA cells. This activity was blocked by anti-JE/MCP-1 antibody, indicating that JE/MCP-1 was involved in priming the macrophages to respond to LPS. Moreover, alveolar macrophages isolated shortly after iv injections of JE/MCP-1 transfected cells were cytotoxic to RENCA cells in vitro. Collectively, these data suggest that in addition to its chemotactic properties, JE/MCP-1 can synergize with bacterial endotoxins to activate macrophages, thus providing a rationale for the use of the JE/MCP-1 protein as a modality for treatment of metastasis.
 ...
PMID:Suppression of tumor growth and metastasis of murine renal adenocarcinoma by syngeneic fibroblasts genetically engineered to secrete the JE/MCP-1 cytokine. 755 38

The arrival of inflammatory phagocytic cells, namely neutrophils and mononuclear phagocytes, in the pleural space is a hallmark of pleural inflammation. It is probable that the temporal arrival of cells is mediated via the release of chemotactic cytokines by activated mesothelial cells. We hypothesized that human pleural mesothelial cells activated by bacterial endotoxin lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), or tumor necrosis factor-alpha (TNF-alpha) release cell-specific chemokines from the C-C and C-X-C family of chemokines, specifically monocyte chemoattractant protein 1 (MCP-1) and IL-8. We evaluated supernatants of stimulated mesothelial cells for biologic chemotactic activity for monocytes and neutrophils and quantitative antigenic protein levels for MCP-1 and IL-8. Expression of the proteins at mRNA level was tested via Northern blot analysis. We found that responses to LPS were significantly higher (P less than 0.05) than control supernatants of unstimulated mesothelial cells. Responses to IL-1 beta and TNF-alpha were significantly greater than those to LPS. Neutralization studies with specific rabbit anti-MCP-1 and IL-1 antibody demonstrated significant decreases in bioactivity for MCP-1 and IL-8, indicating that mesothelial cell-derived MCP-1 and IL-8 play a significant role in the chemotactic activity seen in stimulated mesothelial cell supernatants. On specific enzyme-linked immunosorbent assay testing, stimulated mesothelial cells produced significantly more MCP-1 and IL-8 when stimulated with IL-1 beta or TNF-alpha as compared to LPS. mRNA expression for MCP-1 peaked within 2 to 4 h following stimulation and was noted as early as 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pleural mesothelial cell expression of C-C (monocyte chemotactic peptide) and C-X-C (interleukin 8) chemokines. 776 22

The early atherosclerotic lesion is characterized by the migration of inflammatory cells, including monocytes, which may serve as a source of cytokines such as monocyte chemoattractant protein 1 (MCP-1), a homologue of mouse JE. We investigated the effect of MCP-1 on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. In Northern blot analysis, MCP-1/JE transcripts were not observed in unstimulated VSMC, but its expression was clearly observed by exposure to lipopolysaccharide (1 micrograms/ml) for 6 h. Human recombinant MCP-1 inhibited the uptake of [3H]thymidine by VSMC cultured in 0.5% fetal bovine serum (FBS) containing Dulbecco's modified Eagle's medium (DMEM) in a dose-dependent manner. The inhibitory effect of MCP-1 on the growth of VSMC was also confirmed by a change in cell counts. The antiproliferative effect of MCP-1 was significantly blocked in the presence of an anti-MCP-1 antibody. MCP-1-induced inhibition of [3H]thymidine uptake was not affected in the presence of indomethacin (1 micrograms/ml) or NG-monomethyl-L-arginine (0.1 mM), and MCP-1 showed no effect on 6-ketoprostaglandin F1 alpha, guanosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphate syntheses in VSMC. These results indicate that MCP-1 inhibits the proliferation of VSMC in vitro and that its effect is independent of prostaglandin or nitric oxide generation.
 ...
PMID:Monocyte chemoattractant protein 1 inhibits growth of rat vascular smooth muscle cells. 790 Aug 56

Neutrophils are the predominant leukocyte population in acute inflammation. Granulomatous inflammation such as tuberculosis is a specific type of chronic inflammation characterized by the predominant accumulation of macrophages. To clarify the mechanism of cellular recruitment in inflammation, the expression of chemokines, interleukin-8 and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein 1 (MCP-1), was examined in human blood monocytes in response to lipopolysaccharide of Escherichia coli, which could induce acute inflammation, or purified protein derivative (PPD) or Mycobacterium tuberculosis, which could provoke chronic inflammation. Monocytes stimulated with PPD or M. tuberculosis expressed low levels of antigenic interleukin-8 but high levels of MCAF/MCP-1 compared with monocytes stimulated with lipopolysaccharide. Northern blot analysis showed the early induction of interleukin-8 mRNA and the delayed expression of MCAF/MCP-1 mRNA in response to PPD or M. tuberculosis. Thus, the disparate expression of chemokines may contribute to the cellular recruitment in acute and chronic inflammations.
 ...
PMID:Selective expression of monocyte chemotactic and activating factor/monocyte chemoattractant protein 1 in human blood monocytes by Mycobacterium tuberculosis. 796 19

Lipopolysaccharide, a potent pro-inflammatory constituent of bacterial cell walls, is capable of promoting glomerular inflammation, by both activating circulating inflammatory cells and local interactions with renal parenchymal cells. We sought to determine whether lipopolysaccharide was capable of promoting glomerular inflammation by directly stimulating mesangial cell production of monocyte chemoattractant protein 1, a recently described cytokine capable of eliciting recruitment of mononuclear phagocytes into inflammatory foci. Northern hybridization analysis revealed dose and time-dependent induction of mRNA coding for monocyte chemoattractant protein 1 in quiescent rat mesangial cells treated with lipopolysaccharide. Lipopolysaccharide-elicited induction of monocyte chemoattractant protein mRNA was detectable after 1 hour and persisted for at least 30 hours. Media isolated from rat mesangial cell cultures stimulated by lipopolysaccharide possessed monocyte chemotactic activity that was detectable at 8 hours and peaked at 24 hours; an antimonocyte chemoattractant protein antibody blocked 87% of this chemotactic activity. We suggest that lipopolysaccharide, released from bacterial cell walls, promotes glomerular inflammation by stimulating mesangial cell production of monocyte chemoattractant protein 1.
 ...
PMID:Lipopolysaccharide induces monocyte chemoattractant protein production by rat mesangial cells. 803 94

C/EBP-related proteins 2 and 3 (CRP2 and CRP3) are differentially expressed by P388 lymphoblasts and their derivative P388D1(IL1) macrophages. We have ectopically expressed CRP2, the predominant CRP in macrophages, in P388 lymphoblasts. The expression of CRP2 is sufficient to confer the lipopolysaccharide (LPS)-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to lymphoblasts, which normally do not display LPS induction of inflammatory cytokines. Consistent with these findings, the expression of CRP2 antisense RNA blocks the LPS induction of IL-6 expression in P388D1(IL1) macrophages. This work clearly establishes the essential role of CRP2 in the induction of cytokine genes by LPS. Additionally, these data add MCP-1 to the list of cytokines showing an involvement of CRP2 in their expression.
 ...
PMID:C/EBP-related protein 2 confers lipopolysaccharide-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to a lymphoblastic cell line. 804 85

Using a rat lung organ culture system, we analyzed the role of monocyte chemoattractant protein 1 (MCP 1) in leukocyte to lung adhesive interactions and monocyte-mediated lung injury. Quantitative leukocyte to lung adhesive interactions were examined using an adaptation of the Woodruff-Stamper frozen section binding assay. Pretreatment of organ cultures with recombinant human tumor necrosis factor (rhTNF alpha) resulted in a protein synthesis-dependent increase in the adhesiveness of lung tissue for peripheral blood monocytes. Adhesion of monocytes to lung tissue was not increased above baseline after 7 hours but increased more than twofold by 24 hours and persisted through 48 hours. Binding of monocyte to lung tissue was further increased when recombinant rat MCP 1 was added to monocyte suspensions immediately before being layered onto lung sections derived from either TNF alpha-treated or untreated organ cultures. Addition of antibody directed against rat CD11b/c resulted in a moderate reduction in monocyte binding. TNF or lipopolysaccharide-induced activation of mononuclear cells in the presence of [3H]leucine-labeled organ cultures resulted in lung injury as assessed by radioisotope release. Mononuclear cell-mediated organ culture injury could be partially inhibited with anti-rat MCP 1 antibody, anti-rat CD11b/c antibody, or antioxidants including catalase and deferoxamine. Anti-MCP 1 and anti-CD11b/c increased the absolute numbers of monocytes that could be retrieved from monocyte-lung co-cultures while catalase and deferoxamine did not. In vitro studies revealed that isolated rat peripheral blood monocytes produce O2- in response to MCP 1. These data provide a functional correlate for recent in vitro studies which suggest that MCP 1 may mediate leukocyte adhesive processes by up-regulating beta 2 integrin expression on monocytes. This study provides evidence that monocytes activated by MCP 1 can damage lung tissue through an oxidant-mediated mechanism. Monocyte chemoattractant protein 1 may participate in the pathogenesis of monocyte-mediated lung injury by modulating inflammatory cell adhesion as well as through monocyte activation.
 ...
PMID:Analysis of monocyte chemoattractant protein 1-mediated lung injury using rat lung organ cultures. 810 96

Endogenous lipopolysaccharide has been implicated as a cofactor in the hepatocellular injury and death resulting from toxic liver injury. To prevent this lipopolysaccharide-induced injury and to further understand the mechanism of this effect, an anti-lipopolysaccharide antibody was administered to rats in which toxic hepatocellular injury was induced. Rats were given the hepatotoxin galactosamine together with an isotypic control antibody B55 or the anti-lipopolysaccharide antibody E5. E5 treatment resulted in reductions of serum AST levels of 43% at 36 hr (p < 0.02) and 60% at 48 hr (NS) after galactosamine administration. These decreases in AST values were accompanied by diminished histological evidence of injury and inflammation. In carbon tetrachloride-induced liver injury, E5 similarly reduced serum AST levels at 36 and 48 hr by 47% (p < 0.04) and 54% (p < 0.03), respectively. E5 treatment was equally effective in reducing AST levels 48 hr after administration of carbon tetrachloride, whether the initial dose of antibody was given 1 hr before or 3 or 6 hr after the administration of this toxin. To understand the mechanism of this E5 effect, the activation of the toxic cytokine tumor necrosis factor-alpha and the chemotactic cytokine monocyte chemoattractant protein 1 was examined by Northern-blot analysis of RNA from rat livers after galactosamine-induced injury and treatment with B55 or E5. Despite E5's efficacy in reducing hepatocellular damage, E5 treatment did not affect the timing or magnitude of tumor necrosis factor-alpha or monocyte chemoattractant protein 1 activation during galactosamine-induced injury.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration. 817 53

The present study shows that monocyte chemotactic activity in crevicular fluids increases with severity of the disease and that a monocyte chemoattractant, monocyte chemoattractant protein 1 (MCP-1), is expressed as the predominant cytokine of gingival tissues and their fibroblasts treated with Porphyromonas (Bacteroides) gingivalis lipopolysaccharide (P-LPS). High monocyte chemotactic activity in the crevicular fluids was neutralized significantly by antiserum specific for the JE/MCP-1 protein. Marked expression of the MCP-1 gene was observed in the gingival tissues of all adult periodontal patients tested, but not in those of healthy subjects. Monocyte chemotactic activity was observed in culture supernatants of human normal gingival tissues treated with P-LPS, and the chemotactic activity increased in a dose-related manner. Expression of MCP-1 in P-LPS-treated human gingival fibroblasts was further examined. P-LPS induced the MCP-1 gene expression in a dose- and treatment time-dependent manner. The MCP-1 gene product in the culture supernatant was detected as two forms with molecular masses of 11,000 and 15,000 Da by immunoprecipitation with the specific antiserum. The MCP-1 gene expression was induced in the fibroblasts treated with interleukin-1 beta and tumor necrosis factor alpha, but not with interleukin-6. These results suggest that gingival fibroblasts can participate in monocyte recruitment in gingival tissues of adult periodontal patients via the MCP-1 gene product and that MCP-1 plays an important role in the inflammatory reaction in the disease.
 ...
PMID:Expression of monocyte chemoattractant protein 1 (MCP-1) in adult periodontal disease: increased monocyte chemotactic activity in crevicular fluids and induction of MCP-1 expression in gingival tissues. 822 96


1 2 3 4 5 6 7 8 9 10 Next >>