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

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)
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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.
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PMID:Monocyte chemoattractant protein 1 inhibits growth of rat vascular smooth muscle cells. 790 Aug 56

Infiltration of mononuclear cells is an early pathological finding in human and experimental atherosclerosis. However, the cellular and molecular basis for cell infiltration is incompletely understood. While the intercellular adhesion molecule-1 (ICAM-1) is expressed on endothelial cells and promotes the adhesion of mononuclear cells, there is little information on the expression of ICAM-1 on vascular smooth muscle cells (SMC). In this study, we investigated the expression of ICAM-1 on cultured rat SMC and its regulation by pro-inflammatory cytokines, interleukin 1 alpha (IL-1 alpha), interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1). In immunohistochemical staining, ICAM-1 molecules were constitutively expressed on the surface of SMC. In flow cytometric and ELISA analyses, ICAM-1 molecule expression on SMC was significantly upregulated by IL-1 alpha and MCP-1, but not by IL-6, in a dose-dependent manner. The effects of IL-1 alpha and MCP-1 were observed as early as 4 h. In Northern blot analysis, ICAM-1 mRNA was slightly detectable in unstimulated SMC, but its expression was clearly observed following exposure to IL-1 alpha or MCP-1. These results suggest that ICAM-1 on SMC, as well as on endothelial cells, could participate in the focal accumulation of mononuclear cells in human atherosclerotic lesions.
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PMID:Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by pro-inflammatory cytokines. 790 95

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.
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PMID:Selective expression of monocyte chemotactic and activating factor/monocyte chemoattractant protein 1 in human blood monocytes by Mycobacterium tuberculosis. 796 19

We reported previously that a synthetic peptide (RS-83277) derived from human C-reactive protein (CRP) augmented human monocyte/macrophage tumoricidal activity and cytokine production. RS-83287, a synthetic peptide derived from a different CRP site, was ineffective. Because chemoattractant properties have been attributed to some CRP-derived peptides, we hypothesized that RS-83277, in addition to activating effects, might promote human monocyte chemotaxis. Results indicated that neither CRP peptide RS-83277 nor RS-83287 was, itself, a chemoattractant. RS-83277, but not RS-83287, however, elicited time-dependent production of monocyte chemoattractant activity in conditioned media (CM) of cultured human mononuclear leukocytes and purified, adherent monocytes (MO). CM from nonadherent MO contained no activity, indicating that adherence was required for monocyte response. Monocyte chemoattractant activity was dose-dependent and was removed by treatment with immobilized antibody to human monocyte chemoattractant protein 1 (MCP-1) but not by irrelevant IgG. These results indicate that a specific peptide segment of CRP acts upon human adherent monocytes to promote production of the autocrine chemotactic and activating factor MCP-1. Data suggest that degraded CRP represents a complex source of biologically active peptides which, among other effects, may amplify monocyte recruitment to sites of injury.
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PMID:Human monocytes produce monocyte chemoattractant protein 1 (MCP-1) in response to a synthetic peptide derived from C-reactive protein. 799 30

From an expression library in lambda UniZAP, derived from porcine corpus luteum (CL), a clone lambda MCP9 was detected by hybridization with a porcine MCP-1 specific probe. A pBluescriptSK-derivative pMCP9 was generated from lambda MCP9 by in vivo excision and was shown to contain an open reading frame (ORF) encoding a protein highly homologous to bovine monocyte chemoattractant protein-2 (MCP-2). Comparison of amino acid sequences of known MCPs identified the protein encoded by pMCP9 as porcine MPC-2. The 3' untranslated region of pMCP9 was completed by 3' RACE. Northern analysis using RNA from porcine luteal cells and probes specific for porcine MCP-1 and MCP-2 revealed that porcine luteal cells express both MCPs. According to Southern analysis MCP-2, like MCP-1, is specified by a single copy gene.
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PMID:Porcine luteal cells express monocyte chemoattractant protein-2 (MCP-2): analysis by cDNA cloning and northern analysis. 799 15

Activated synoviocytes are major effector cells in the pathogenesis of rheumatoid arthritis (RA) because of their capacity to secrete a variety of inflammatory mediators. Among these mediators, the chemotactic proteins monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8) are likely to contribute to the recruitment of inflammatory cells into the arthritic joint. We examined the effects of anti-rheumatic drugs on the MCP-1 and IL-8 production by cultured RA synoviocytes exposed to pro-inflammatory agonists. Both chemotactic cytokines were quantified by specific enzyme-linked immunosorbent assays (ELISA), and found to accumulate in the culture supernatants. Although the time course of formation was similar, the yield of IL-8 was three to 10-fold higher than that of MCP-1. Non-steroidal anti-inflammatory drugs inhibited the synthesis of prostaglandins, but did not influence the production and release of both chemotactic cytokines. Of three disease-modifying drugs tested, dexamethasone and gold sodium thiomalate (GST) inhibited the production of IL-8 and MCP-1, while methotrexate (MTX) was inactive. Dexamethasone reduced the production of MCP-1 and IL-8 by 20-65% and 60-80%, respectively, whilst GST inhibited MCP-1 and IL-8 synthesis in suboptimally, but not in optimally stimulated synoviocytes. Taken together, these results show that the production of MCP-1 and IL-8 is similarly affected by anti-rheumatic drugs and that dexamethasone is the most potent inhibitor suggesting that part of the anti-rheumatic action of glucocorticoids is due to prevention of accumulation of chemotactic cytokines acting on neutrophils and monocytes.
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PMID:Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes. Effects of anti-rheumatic drugs. 803 99

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.
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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.
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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.
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PMID:Analysis of monocyte chemoattractant protein 1-mediated lung injury using rat lung organ cultures. 810 96


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