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 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.
J Interferon Cytokine Res 1995 Jul
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

Cytotoxic action of leukocytes may be involved in the pathogenesis of inflammatory heart muscle disorders. We investigated the expression of rat leukocyte chemotactic cytokines--cytokine induced neutrophil chemoattractant (CINC) and JE--in cultured neonatal rat cardiac myocytes; CINC belongs to the interleukin 8 (IL-8) family and JE is a homologue of human monocyte chemoattractant protein 1 (MCP-1). In Northern blot analysis, CINC and JE transcripts were not clearly observed in unstimulated rat cardiac myocytes. However, their expression was clearly observed after exposure to tumour necrosis factor-alpha (TNF-alpha; 100 U/ml) for 2-6 h. We then evaluated IL-8 and MCP-1 mRNA expression in human endomyocardial biopsy specimens from seven patients with idiopathic dilated cardiomyopathy by polymerase chain reaction analysis. Both IL-8 and MCP-1 mRNA transcripts were recognized in all patients studied. These results show for the first time that leukocyte chemotactic cytokines, IL-8 and MCP-1, are expressed in myocardial tissue, which might contribute to the pathogenesis of inflammatory heart muscle disorders.
Cytokine 1995 Apr
PMID:Expression of leukocyte chemotactic cytokines in myocardial tissue. 764 Mar 50

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.
Cytokine 1994 Mar
PMID:Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes. Effects of anti-rheumatic drugs. 803 99

We have isolated a cDNA (NC28) transcribed from a mRNA which is transiently induced in U937 promonocytic cells by PMA and super-induced by cycloheximide. NC28 cDNA encodes a new member of the chemokine family, MCP-3, recently purified from MG-63 osteosarcoma cells by Van Damme et al. [1]. The MCP-3 protein sequence shows 74% identity with human monocyte chemoattractant protein 1 (MCP-1) and, like MCP-1, recombinant MCP-3 protein shows chemotactic activity for monocytes but not for neutrophils. However the secreted MCP-3 protein differs from MCP-1 in being N-glycosylated. The 3' noncoding regions of MCP-3 and MCP-1 mRNAs are more diverged (44%), allowing specific cDNA probes to be made, and indicating that the two genes are evolutionarily distant. Sequence comparisons of the 3' noncoding regions suggest that MCP-3 may be the human homologue of the mouse MARC gene [2], and that MCP-1 and MCP-3 genes arose by a gene duplication event before the mammalian radiation. Both MCP-1 and MCP-3 mRNAs are expressed by PBMC, principally by monocytes, with MCP-1 mRNA being expressed at levels 2-4 times that of MCP-3 mRNA. However, while MCP-1 mRNA is also expressed at high levels in fibroblast or astrocytoma cell lines after IL-1 and TNF stimulation, MCP-3 mRNA is expressed only at very low levels in these cells. The cellular origin of MCP-3 is thus more restricted than that of MCP-1. In our experiments on PBMC, LPS is not a consistent inducer of MCP-1 and MCP-3 mRNAs. In some experiments, it actually decreases levels of these two mRNAs, while concomitantly increasing IL-6 and TNF-alpha mRNA levels. Levels of MCP-1 and MCP-3 mRNAs in PBMC are both increased by IFN-gamma, although IL-6 mRNA is not induced. They are also increased by PHA-P and are decreased, in most cases, by IL-13 [3]. MCP-1 and MCP-3 mRNAs are thus co-ordinately regulated in monocytes in response to a number of inducing or inhibitory agents, in a manner differing in several respects from that of other monokines such as IL-6.
Eur Cytokine Netw
PMID:Molecular cloning of the MCP-3 chemokine gene and regulation of its expression. 831 76

The cDNA encoding human monocyte chemotactic protein 3 (hMCP-3) was cloned in pHIL-S1, a vector designed for inducible secreted heterologous expression in the methylotrophic yeast Pichia pastoris. After transformation of P. pastoris by electroporation, several clones with the human MCP-3 gene integrated at the alcohol oxidase (AOX-1) locus were isolated. One of these clones (M30) expressed the mature MCP-3 protein with three additional amino acids at its NH2 terminus as a secretion product in the supernatant. The recombinant protein comigrated on SDS-PAGE and cross-reacted immunologically with synthetic hMCP-3. Intermediate-scale production in shake flasks was obtained at expression levels of approximately 1 mg per liter. The recombinant mutant MCP-3 was purified to homogeneity by adsorption on silicic acid, affinity chromatography on heparin-Sepharose, and reversed-phase HPLC. At the amino terminus of the purified recombinant protein, the presence of the additional sequence Arg-Glu-Phe was confirmed by direct protein sequence analysis. The recombinant hMCP-3 mutein was not glycosylated, as evidenced by deglycosylation experiments and by mass spectrometry. In analogy with MCP-1, the amino terminus of MCP-3 is crucial for its agonistic effect on receptive cells. At concentrations up to 3.5 micrograms/ml, the recombinant mutein was not active in vitro as a chemotactic factor for monocytes. However, the mutant MCP-3 acted as an MCP-3 receptor antagonist in a competition chemotaxis assay at 100- to 1000-fold excess over the synthetic MCP-3 agonist. It might thus be a useful tool to study antagonism of MCP-3 action in vitro and in disease models of cancer and inflammation.
J Interferon Cytokine Res 1995 Nov
PMID:Expression of a human mutant monocyte chemotactic protein 3 in Pichia pastoris and characterization as an MCP-3 receptor antagonist. 859 Mar 7

The mechanism by which specific immunotherapy exerts its beneficial effect remains unclear. Chemokines are implicated in inflammatory and allergic diseases, in particular via their ability to induce histamine release from basophils, a potential early target of rush venom immunotherapy (RVIT), In this study, the authors evaluated ex vivo regulated upon activation normal T-cell expressed and secreted (RANTES), interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) production and mRNA expression by mononuclear cells (MNC) from nine patients undergoing a 3.5-h ultra rush treatment, before treatment at Day 0 (D0), at the end of the 3.5-h of the rush at Day 4h (D4h), at Day 15 (D15) and Day 45 (D45) after treatment. Increased RANTES release and mRNA expression were observed in 24-h culture of peripheral blood MNC collected at D4h. This was followed by a decrease in the production of RANTES, IL-8 and MCP-1, 45 days after initiation of RVIT. The same pattern was observed after in vitro venom stimulation of MNC. At the mRNA level, similar profiles were observed except for IL-8 mRNA which inversely increased during RVIT. These results suggest that RVIT is associated with a general decrease in chemokines which may explain, in part, the clinical efficacy of specific immunotherapy.
Cytokine 1998 Sep
PMID:Early modifications of chemokine production and mRNA expression during rush venom immunotherapy. 977 Mar 32

The cytotoxic action of leukocytes may be a most probable cause of cardiac myocyte damage seen in chronic myocarditis and dilated cardiomyopathy (DCM). The migration and tissue infiltration of leukocytes is regulated by chemotactic cytokines. Recently, the presence of monocyte chemoattractant protein 1 (MCP-1) messenger RNA has been demonstrated in endomyocardial biopsy tissue obtained from patients with DCM. This chemokine could contribute to enhanced leukocyte recruitment and activation resulting in chronic damage of cardiomyocytes. Accordingly, we sought to determine whether the severity of left ventricular dysfunction in DCM is associated with quantitative alterations of MCP-1 messenger RNA and MCP-1 protein in endomyocardial biopsy tissue. A group of DCM patients with low to moderate impairment of left ventricular function (ejection fraction 45.3+/-2.3%, n=7) was compared to patients with severe left ventricular dysfunction (ejection fraction 25.5+/-3.1%, n=7). MCP-1 messenger RNA expression was determined by quantitative polymerase chain reaction. MCP-1 protein and the presence of infiltrating inflammatory cells were detected by immunohistochemistry. DCM patients with severe left ventricular dysfunction showed a 2.35 fold higher MCP-1 messenger RNA expression when compared to DCM patients with less severe dysfunction (P=0.0229). Positive immunohistochemical staining for MCP-1 was found in all seven patients with severe left ventricular dysfunction and was particularly distinct within the cardiac interstitum. In five of seven patients with less severe systolic dysfunction, MCP-1 protein was found, but was less pronounced and distributed in patchy interstitial areas, close to intramyocardial vessels. Furthermore, there was a consistent trend toward a higher infiltration of inflammatory cells in DCM patients with lower ejection fraction. In conclusion, MCP-1 is dynamically regulated in DCM related deterioration of left ventricular function. This mechanism might contribute to myocyte damage via infiltrated and activated monocytes.
Cytokine 1998 Oct
PMID:Monocyte chemoattractant protein 1 (MCP-1) gene expression in dilated cardiomyopathy. 981 26

Asthma is considered a Th2-like disease, characterized by locally increased levels of interleukin (IL) 4. The bronchial epithelium plays an important role in the initiation and perpetuation of inflammatory reactions within the airways. However, little is known about the presence of IL-4 receptors on human bronchial epithelial cells, or the effects of IL-4 on these cells. In this report, definitive evidence of IL-4 receptor expression on human bronchial epithelial cells using several methods is presented. IL-4 receptor expression on human bronchial epithelial cells in vivo was demonstrated using in situ hybridization and immunohistochemistry. No difference in IL-4 receptor protein expression was observed between bronchial biopsies of healthy subjects compared to allergic asthmatics. Cultured human bronchial epithelial cells also expressed IL-4 receptor mRNA and protein (as determined by RT-PCR analysis and flow cytometry, respectively). IL-4 receptor protein expression by bronchial epithelial cells could be increased by stimulation with PMA+calcium ionophore, whereas IL-1beta and IL-6 decreased IL-4 receptor expression. A cyclic AMP analogue and IL-4 had no effect. Finally, it is shown that the IL-4 receptor is functionally active as IL-4 stimulates the release of IL-8, monocyte chemoattractant protein 1, and particularly IL-1 receptor antagonist by human bronchial epithelial cells. It is concluded that human bronchial epithelial cells express IL-4 receptors both in vivo and in vitro. Stimulation of human bronchial epithelial cells by IL-4 may result in the release of both pro- and anti-inflammatory mediators known to be upregulated in asthmatic airways.
Cytokine 1998 Oct
PMID:Interleukin 4 receptors on human bronchial epithelial cells. An in vivo and in vitro analysis of expression and function. 981 35

Reactive oxygen species can directly damage tissue. In this setting, amplification of tissue damage also occurs through infiltration of inflammatory cells either acutely or chronically. Several recent studies suggest that reactive oxygen species stimulate production of certain chemokines, which are potent chemoattractants for inflammatory cells. In the present study, we examined whether oxidants, generated by the combination of xanthine and xanthine oxidase (X/XO), alter chemokine production by monocytes and U937 cells. Our findings demonstrate that X/XO stimulates monocytes, but not U937 cells, to produce increased amounts of interleukin-8 (IL-8) and monocyte chemoattractant protein. This effect is attenuated by pretreatment with dimethylsulfoxide (DMSO), a scavenger of hydroxyl radicals, but is not affected by superoxide dismutase or catalase. In contrast, X/XO-induced cytotoxicity, evidenced by lactate dehydrogenase release, is mediated primarily by hydrogen peroxide, as catalase reverses this effect. Finally, exposure to X/XO causes an increase in nuclear factor kappa B (NF-kappaB), and this effect is attenuated by DMSO. These studies suggest that reactive oxygen species can induce production of molecules that amplify inflammation through attraction of inflammatory cells. It appears the hydroxyl radical is the principal oxidant species involved in stimulation of chemokine production.
J Interferon Cytokine Res 1999 Jul
PMID:Modulation of monocyte chemokine production and nuclear factor kappa B activity by oxidants. 1045 47


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