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 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.
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PMID:Effect of antiinflammatory agents on synthesis of MCP-1/JE transcripts by human blood monocytes. 138 39

CC chemokines constitute a novel class of cytokines that attract and activate monocytes and lymphocytes, as well as basophil and eosinophil leukocytes, with distinct target cell profiles, and are believed to be involved in the regulation of different types of inflammation. The action of the recently identified monocyte chemotactic protein 3 (MCP-3) on human basophil and eosinophil function was studied and compared with that of other CC chemokines. In basophils, MCP-3, MCP-1, RANTES, and macrophage inflammatory protein (MIP)-1 alpha all induced cytosolic-free calcium concentration ([Ca2+]i) changes and, with different efficacies, chemotaxis (RANTES = MCP-3 >> MCP-1 > MIP-1 alpha), histamine release (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha), and leukotriene C4 formation, after IL-3 pretreatment (MCP-1 = MCP-3 >> RANTES > MIP-1 alpha). Thus, MCP-3 was as effective as MCP-1 as an inducer of mediator release, and as effective as RANTES as a stimulus of basophil migration. In contrast to MCP-1, MCP-3 was also a stimulus for eosinophils, and induced [Ca2+]i changes and chemotaxis as effectively as RANTES, which is the most potent chemotactic cytokine for these cells. Desensitization of the transient changes in [Ca2+]i was used to assess receptor usage. In basophils, stimulation with MCP-3 prevented responsiveness to MCP-1 and RANTES, but not to MIP-1 alpha. No single CC chemokine (except for MCP-3 itself) affected the response to MCP-3, however, which was prevented only when the cells were prestimulated with both MCP-1 and RANTES. In eosinophils, by contrast, cross-desensitization between RANTES and MCP-3 was obtained. RANTES and to a lesser extent MCP-3 also desensitized eosinophils toward MIP-1 alpha. The desensitization data suggest the existence of three chemokine receptors: (a) a MCP-1 receptor expressed on basophils but not eosinophils that is activated by MCP-1 and MCP-3; (b) a RANTES receptor in basophils and eosinophils that is activated by RANTES and MCP-3; and (c) a MIP-1 alpha receptor that is activated by MIP-1 alpha, RANTES and, more weakly, by MCP-3. This study shows that MCP-3 combines the properties of RANTES, a powerful chemoattractant, and MCP-1, a highly effective stimulus of mediator release, and thus has a particularly broad range of activities toward both human basophil and eosinophil leukocytes.
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PMID:Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine. 750 12

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.
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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

Chronic rejection, the most important cause of long-term graft failure, is thought to result from both alloantigen-dependent and -independent factors. To examine these influences, cytokine dynamics were assessed by semiquantitative competitive reverse transcriptase-PCR and by immunohistology in an established rat model of chronic rejection lf renal allografts. Isograft controls develop morphologic and immunohistologic changes that are similar to renal allograft changes, although quantitatively less intense and at a delayed speed; these are thought to occur secondary to antigen-independent events. Sequential cytokine expression was determined throughout the process. During an early reversible allograft rejection episode, both T-cell associated [interleukin (IL) 2, IL-2 receptor, IL-4, and interferon gamma] and macrophage (IL-1 alpha, tumor necrosis factor alpha, and IL-6) products were up-regulated despite transient immunosuppression. RANTES (regulated upon activation, normal T-cell expressed and secreted) peaked at 2 weeks; intercellular adhesion molecule (ICAM-1) was maximally expressed at 6 weeks. Macrophage products such as monocyte chemoattractant protein (MCP-1) increased dramatically (to 10 times), presaging intense peak macrophage infiltration at 16 weeks. In contrast, in isografts, ICAM-1 peaked at 24 weeks. MCP-1 was maximally expressed at 52 weeks, commensurate with a progressive increase in infiltrating macrophages. Cytokine expression in the spleen of allograft and isograft recipients was insignificant. We conclude that chronic rejection of kidney allografts in rats is predominantly a local macrophage-dependent event with intense up-regulation of macrophage products such as MCP-1, IL-6, and inducible nitric oxide synthase. The cytokine expression in isografts emphasizes the contribution of antigen-independent events. The dynamics of RANTES expression between early and late phases of chronic rejection suggest a key role in mediating the events of the chronic process.
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PMID:Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1. 756 6

The tissue macrophage plays a prominent role in wound repair, yet the parameters that influence macrophage migration into the wound bed are not well understood. To better understand the process of macrophage recruitment, the production of JE, the murine homologue of monocyte chemoattractant protein 1(JE/MCP-1), was examined in a murine model of dermal wound repair. High levels of JE/MCP-1 mRNA were found in dermal punch wounds at 12 hours and 1 day (24 hours) after wounding; mRNA levels slowly decreased to undetectable by day 21. In situ hybridization analysis of wounds revealed that JE/MCP-1 was predominantly expressed by monocytic and macrophage-like cells, as well as by occasional fibroblasts and other interstitial cells. To correlate JE/MCP-1 production with macrophage migration, macrophage infiltration into the wound bed was quantitated. The number of macrophages within the wound increased to a maximum at day 3 (11.3 +/- 4.5 macrophages per high power field), began to decrease at day 5 (4.8 +/- 1.9 macrophages per high power field), and reached near base line at day 10 (3.0 +/- 1.1 macrophages per high power field). The results demonstrate that JE/MCP-1 production within wounds is closely linked to the time course and distribution of macrophage infiltration, with maximal JE/MCP-1 mRNA levels occurring 1 to 2 days before maximal macrophage infiltration. The results support a role for JE/MCP-1 in the recruitment of wound macrophages and suggest that macrophages, through the production of JE/MCP-1, may sustain the recruitment of additional monocytes and macrophages into sites of injury.
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PMID:Modulation of JE/MCP-1 expression in dermal wound repair. 771 54

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

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

The expression of the monocyte chemoattractant protein (MCP-1), a member of the chemokine family of low molecular weight cytokines, was assessed by immunohistochemistry in bronchial biopsies from 12 asthmatic and 12 normal subjects. Both a monoclonal antibody (F9) and a polyclonal antibody were employed to detect MCP-1, while the mouse myeloma protein (MOPC21) was used as a negative control. Strong positive reactions for MCP-1 were seen in the bronchial epithelium. Subepithelial macrophages, blood vessels, and bronchial smooth muscle were also stained. Hue-saturation-intensity color image analysis was used to quantify reactions of the monoclonal antibody in the epithelial and subepithelial layers. With the monoclonal antibody, asthmatic biopsies showed 51.8 +/- 3.7% (mean +/- SEM) of the epithelium staining positively, whereas normal subjects reacted much less, with 6.4 +/- 1.9% of the epithelium staining (P < 0.0001); there was no overlap between the two groups. Likewise, staining was increased in the subepithelium of asthmatic airway biopsies, with 11.5 +/- 3.1% and 2.0 +/- 1.0% staining positively in asthmatic and normal subepithelium, respectively, (P < 0.002). There was a significant correlation between staining of the epithelium and subepithelium (r = 0.77, P < 0.001). The polyclonal anti-MCP-1 antibody also gave strong reactions in the epithelium and subepithelium, with 34.0 +/- 7.8% of the asthmatic and 1.6 +/- 1.0% of the normal bronchial epithelium staining positively (P < 0.0001). These increased levels of MCP-1 in the asthmatic airways suggest that they may play a role in macrophage recruitment and activation and thereby contribute to the inflammatory pathology of bronchial asthma.
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PMID:Increased expression of the monocyte chemoattractant protein-1 in bronchial tissue from asthmatic subjects. 811 Apr 69

Malignant human papillomavirus type 18 (HPV18)-positive cervical carcinoma cells can be reverted to a nonmalignant phenotype by generation of somatic cell hybrids with normal human fibroblasts. Although nontumorigenic hybrids, their tumorigenic segregants, and the parental HeLa cells have similar in vitro properties, inoculation only of nontumorigenic cells into nude mice results in a selective suppression of HPV18 transcription which precedes cessation of cellular growth. Our present study, aimed at understanding the differential regulation in vitro and in vivo, shows that the JE gene, encoding the monocyte chemoattractant protein (MCP-1), is expressed only in nontumorigenic hybrids. Although the gene, including its regulatory region, is intact, no JE (MCP-1) mRNA is detected in the tumorigenic segregants and in other malignant HPV-positive cervical carcinoma cell lines. Tests of several monocyte-derived cytokines showed that only tumor necrosis factor alpha strongly induces the JE (MCP-1) gene in nontumorigenic cells and that this is accompanied by a dose-dependent reduction of HPV transcription. The JE (MCP-1) up-regulation occurs within 2 h and does not require de novo protein synthesis. The response to tumor necrosis factor alpha seems to be mediated by an NF-kappa B-related mechanism, since the induction can be completely abrogated by pretreating the cells with an antioxidant such as pyrrolidine dithiocarbamate. Interestingly, cocultivation of nonmalignant hybrids with monocyte-enriched fractions from human peripheral blood also results in an induction of the JE (MCP-1) gene and a concomitant suppression of HPV18 transcription. Neither effect is observed in malignant cells. These data suggest that JE (MCP-1) may play a pivotal role in the intercellular communication by triggering an intracellular pathway which negatively interferes with viral transcription in HPV-positive nontumorigenic cells.
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PMID:Differential regulation of the JE gene encoding the monocyte chemoattractant protein (MCP-1) in cervical carcinoma cells and derived hybrids. 813 98

The chemokines are a large group of cytokines that are recognized to be important mediators of inflammation. In this study we show that the human mast cell leukemia line HMC-1 is a source of multiple chemokines, including I-309, monocyte chemoattractant protein 1, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, RANTES, and interleukin-8. I-309 and MCP-1 transcripts are expressed at low levels in unstimulated HMC-1. However, phorbol ester treatment up-regulates these and other chemokine transcript levels and also up-regulates chemokine protein synthesis and secretion. Induction of chemokine transcripts in HMC-1 requires de novo protein synthesis. We compared the effects of anti-inflammatory glucocorticoids on the expression of chemokine genes in HMC-1 to their effects in activated T-cells. We find that methyl-prednisolone reduces MCP-1 but not other chemokine transcripts in HMC-1, even though there are distinct and more general effects on chemokine transcripts in activated T-cells. These effects are attributed to inhibition of transcription rather than transcript stability. Our results suggest that human mast cells may be a source of multiple chemokines, that glucocorticoids may inhibit the expression of only a subset of these chemokines, and that mast cells and T-cell chemokine expression may occur via distinct regulatory pathways.
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PMID:Expression of multiple chemokine genes by a human mast cell leukemia. 818 67


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