UNIPROT:P80098 - FACTA Search

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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 dimensions of man-made mineral fiber whiskers are similar to those of some kinds of asbestos. Thus these mineral fibers raise the concern for potential health hazard for workers exposed in the occupational environments. This study was designed to define acute biological effects of intratracheally administered titanium dioxide whiskers (TO1) compared with nonfibrous titanium dioxide (TOP) and UICC amosite (Ams), and their relations to acute lung inflammation in rats. The observed geometric mean length (microm) and width (microm) and geometric standard deviation are: TO1(2.1[2.0], 0.14[1. 53]); Ams (4.3[3.3], 0.31[1.9]); and TOP (50 nm, 1-2 microm aggregates). Ten-week-old Wistar-Jcl male rats received a single tracheal injection of test materials at doses between 0.05 and 1.0 mg/rat. Control animals were injected with the same volume of saline. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected from rats on days 1, 3, and 7 after administration. In the group injected with TO1, total protein, cytokine-induced neutrophil chemoattractant (CINC)/growth-regulated gene product (GRO), interleukin (IL) 1beta, and tumor necrosis factor (TNF) alpha increased on day 1. Subsequently, total elastolytic activity and fucose levels in BAL increased by day 3. All parameters, except for fucose in BAL, recovered to the normal levels. Animals in the Ams group showed increased total protein and CINC/GRO and decreased total elastolytic activity in a dose-dependent manner on day 1. The fucose level increased on day 3 in the Ams group. All parameters returned to their control levels on day 7. Animals in the TOP group did not show significant changes any of parameters during the experimental period. Gene expression of TNF-alpha and monocyte chemoattractant protein (MCP) 3 in the lung increased dose-dependently in the animals treated with the three materials. The mRNAs for eotaxin and MIP-1alpha were overexpressed in the lung of animals treated with Ams and TO1, while RANTES mRNA was overexpressed dose-dependently in the lung of animals treated with Ams on day 1. Onset of inflammatory response was more rapid in the Ams group than the TO1 group. Recovery of the fucose level in BAL was slower in the TO1 group than in the Ams group, though we observed similar histopathological changes in the lung of animals with TO1 or Ams. We conclude that whisker-induced acute biological effects in the lung may be related to the shape of the whiskers and not to their chemical composition or surface crystal structure, showing biological effects similar to those of UICC amosite.
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PMID:Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats. 1038 Jan 63

The host response to Gram-negative LPS is characterized by an influx of inflammatory cells into host tissues, which is mediated, in part, by localized production of chemokines. The expression and function of chemokines in vivo appears to be highly selective, though the molecular mechanisms responsible are not well understood. All CXC (IFN-gamma-inducible protein (IP-10), macrophage inflammatory protein (MIP)-2, and KC) and CC (JE/monocyte chemoattractant protein (MCP)-1, MCP-5, MIP-1alpha, MIP-1beta, and RANTES) chemokine genes evaluated were sensitive to stimulation by LPS in vitro and in vivo. While IL-10 suppressed the expression of all LPS-induced chemokine genes evaluated in vitro, treatment with IFN-gamma selectively induced IP-10 and MCP-5 mRNAs, but inhibited LPS-induced MIP-2, KC, JE/MCP-1, MIP-1alpha, and MIP-1beta mRNA and/or protein. Like the response to IFN-gamma, LPS-mediated induction of IP-10 and MCP-5 was Stat1 dependent. Interestingly, only the IFN-gamma-mediated suppression of LPS-induced KC gene expression was IFN regulatory factor-2 dependent. Treatment of mice with LPS in vivo also induced high levels of chemokine mRNA in the liver and lung, with a concomitant increase in circulating protein. Hepatic expression of MIP-1alpha, MIP-1beta, RANTES, and MCP-5 mRNAs were dramatically reduced in Kupffer cell-depleted mice, while IP-10, KC, MIP-2, and MCP-1 were unaffected or enhanced. These findings indicate that selective regulation of chemokine expression in vivo may result from differential response of macrophages to pro- and antiinflammatory stimuli and to cell type-specific patterns of stimulus sensitivity. Moreover, the data suggest that individual chemokine genes are differentially regulated in response to LPS, suggesting unique roles during the sepsis cascade.
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PMID:Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo. 1041 57

The chemokine monocyte chemoattractant protein (MCP)-1 plays a role in regulating the lymphocyte and macrophage infiltrate in ovarian cancer, but macrophages also accumulate in necrotic areas of the tumors where there is little MCP-1 expression (Negus, R. P. M. et al., Am. J. Pathol. 1997. 150: 1723-1734). Necrotic regions are likely to be hypoxic. In this study we show that hypoxia inhibits MCP-1-induced migration of THP-1 monocytic cells and human macrophages. In contrast, lymphocytes from peripheral blood migrate normally to an MCP-1 gradient in hypoxic conditions. The inhibition of monocyte migration by hypoxia is rapid and reversible. At the exposure times studied (30-90 min) hypoxia does not affect expression of the MCP-1 receptor CCR2B and cells exposed to hypoxia still respond to MCP-1 with an elevation of intracellular calcium. Although hypoxia is known to modulate gene expression, the inhibition of migration reported here was not due to the production of soluble factors, and mRNA expression of macrophage migration inhibitory factor was unchanged. Hypoxia-induced inhibition of chemotaxis was not limited to MCP-1. Hypoxia also inhibited the chemotactic response to macrophage inflammatory protein-1alpha, RANTES and the chemoattractant N-formyl-met-leu-phe, but hypoxic cells were still able to phagocytose opsonized red blood cells. We suggest that inhibition of migration by hypoxia is not due to gene regulation but is a reflection of metabolic changes in the cell. Transient hypoxia may regulate the distribution of macrophages in tumors and other inflammatory conditions.
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PMID:Hypoxia inhibits macrophage migration. 1042 91

The relationship of expression of the C-C chemokines eotaxin, eotaxin 2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4 to the kinetics of infiltrating eosinophils, basophils, and other inflammatory cells was examined in allergen-induced, late-phase allergic reactions in the skin of human atopic subjects. EG2+ eosinophils peaked at 6 h and correlated significantly with eotaxin mRNA and protein, whereas declining eosinophils at 24 h correlated significantly with eotaxin-2 and MCP-4 mRNA. In contrast, no significant correlations were observed between BB1+ basophil infiltrates, which peaked at 24 h, and expression of eotaxin, eotaxin-2, RANTES, MCP-3, and MCP-4 or elastase+ neutrophils (6-h peak), CD3+ and CD4+ T cells (24 h), and CD68+ macrophages (72 h). Furthermore, 83% of eosinophils, 40% of basophils, and 1% of CD3+ cells expressed the eotaxin receptor CCR3, while eotaxin protein was expressed by 43% of macrophages, 81% of endothelial cells, and 6% of T cells (6%). These data suggest that 1) eotaxin has a role in the early 6-h recruitment of eosinophils, while eotaxin-2 and MCP-4 appear to be involved in later 24-h infiltration of these CCR3+ cells; 2) different mechanisms may guide the early vs late eosinophilia; and 3) other chemokines and receptors may be involved in basophil accumulation of allergic tissue reactions in human skin.
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PMID:C-C chemokines in allergen-induced late-phase cutaneous responses in atopic subjects: association of eotaxin with early 6-hour eosinophils, and of eotaxin-2 and monocyte chemoattractant protein-4 with the later 24-hour tissue eosinophilia, and relationship to basophils and other C-C chemokines (monocyte chemoattractant protein-3 and RANTES). 1049 Oct

Atopic (AA) and nonatopic (NAA) asthma are characterized by chronic inflammation and local tissue eosinophilia. Many C-C chemokines are potent eosinophil chemoattractants and act predominantly via the CCR3. We examined the expression of eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), MCP-4, and CCR3 in the bronchial mucosa from atopic (AA) and nonatopic (intrinsic; NAA) asthmatics and compared our findings with atopic (AC) and nonatopic nonasthmatic controls (NC). Cryostat sections were processed for immunohistochemistry (IHC), in situ hybridization (ISH), and double IHC/ISH. Compared with AC and NC, the numbers of EG2+ cells and the cells expressing mRNA for eotaxin, eotaxin-2, RANTES, MCP-3, MCP-4, and CCR3 were significantly increased in AA and NAA (p < 0.01). Nonsignificant differences in these variants were observed between AA and NAA and between AC and NC. Significant correlations between the cells expressing eotaxin or CCR3 and EG2+ eosinophils in the bronchial tissue were also observed for both AA (p < 0.01) and NAA (p = 0.01). Moreover, in the total asthmatic group (AA + NAA) there was a significant inverse correlation between the expression of eotaxin and that of the histamine PC20 (p < 0.05). Sequential IHC/ISH showed that cytokeratin+ epithelial cells, CD31+ endothelial cells, and CD68+ macrophages were the major sources of eotaxin, eotaxin-2, RANTES, MCP-3, and MCP-4. There was no significantly different distribution of cells expressing mRNA for these chemokines between atopic and nonatopic asthma. These findings suggest that multiple C-C chemokines, acting at least in part via CCR3, contribute to bronchial eosinophilia in both atopic and nonatopic asthma.
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PMID:Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. 1057 Mar 27

The human herpesvirus 6 (HHV-6) U51 gene defines a new family of betaherpesvirus-specific genes encoding multiple transmembrane glycoproteins with similarity to G protein-coupled receptors, in particular, human chemokine receptors. These are distinct from the HHV-6 U12 and HCMV US28 family. In vitro transcription and translation as well as transient cellular expression of U51 showed properties of a multiple transmembrane protein with a 30-kDa monomer as well as high m.w. aggregates or oligomers. Transient cellularly expressed U51 also appeared to form dimeric intermediates. Despite having only limited sequence similarity to chemokine receptors, U51 stably expressed in cell lines showed specific binding of the CC chemokine RANTES and competitive binding with other beta chemokines, such as eotaxin; monocyte chemoattractant protein 1, 3, and 4; as well as the HHV-8 chemokine vMIPII. In epithelial cells already secreting RANTES, U51 expression resulted in specific transcriptional down-regulation. This correlated with reduced secretion of RANTES protein into the culture supernatants. Regulation of RANTES levels may alter selective recruitment of circulating inflammatory cells that the virus can infect and thus could mediate the systemic spread of the virus from initial sites of infection in epithelia. Alternatively, chemokine regulation could modulate a protective inflammatory response to aid the spread of virus by immune evasion. Such mimicry, by viral proteins, of host receptors leading to down-regulation of chemokine expression is a novel immunomodulatory mechanism.
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PMID:RANTES binding and down-regulation by a novel human herpesvirus-6 beta chemokine receptor. 1067 75

Ischemia-reperfusion injury (IRI) is a major cause of renal dysfunction in both native kidneys and renal allografts. To broaden our understanding of the inflammatory mediators involved in IRI, we used multi-probe RNase protection assays to examine the expression of 26 different cytokine genes in a murine model of renal IRI. We observed that, in addition to up-regulation of IL-1beta and to a lesser extent TNF-alpha, IRI was associated with an intense and sustained up-regulation of three gp130-signaling cytokines, IL-6, IL-11, and leukemia inhibitory factor (LIF), as well as with up-regulation of the neutrophil chemotactic and activating mediator macrophage inflammatory protein (MIP)-2. Macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein (MCP)-1 were also moderately up-regulated after IRI, whereas mRNA levels of several other inflammatory mediators including IL-1alpha, IL-2, IL-4, interferon (IFN)-gamma, GM-CSF, and RANTES were minimally increased or remained undetectable. These findings identify MIP-2 as an attractive target for inhibition of leukocyte recruitment in renal IRI and also suggest a potentially novel role for gp130-mediated signals in IRI.
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PMID:Prominent and sustained up-regulation of gp130-signaling cytokines and the chemokine MIP-2 in murine renal ischemia-reperfusion injury. 1075 57

Chemokines may regulate the process of immune cell infiltration that is often found in pancreatic cancer. In this study, we investigated the secretion of the chemokines [interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and RANTES (regulated on activation, normal T cell expressed and secreted)] in human pancreatic cancer cell lines. The chemokine secretion in three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BxPC-3) was evaluated by enzyme-linked immunosorbent assay (ELISA) and Northern blot, and the activation of nuclear factor-kappaB (NF-kappaB) and NF-IL6 was assessed by an electrophoretic gel mobility shift assay (EMSA). Without any stimulation, IL-8 secretion was detected in all cell lines, and MCP-1 secretion was detected in PANC-1 and MIA PaCa-2 cells. However, RANTES secretion was not detected in all cells. The addition of IL-1beta and tumor necrosis factor (TNF)-alpha strongly enhanced IL-8, MCP-1, and RANTES secretion; these responses were observed at the mRNA level as well as at the protein level. IL-1beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-kappaB in PANC-1 cells, and the increase in chemokine mRNA expression correlated with NF-kappaB activation. The activation of NF-IL6 was modest. A blockade of NF-kappaB activation by TPCK markedly reduced the IL-1beta- and TNF-alpha-induced chemokine gene expression. Our findings indicate that chemokines are produced by pancreatic cancer cells, and suggest that these factors may contribute to the accumulation of tumor-associated immune cells. In addition, the transcriptional activation of chemokine genes in pancreatic cancer cells may be closely associated with NF-kappaB activation.
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PMID:The expression of chemokine genes correlates with nuclear factor-kappaB activation in human pancreatic cancer cell lines. 1088 30

Idiopathic pneumonia syndrome (IPS) is a significant complication following bone marrow transplantation (BMT). We have developed a murine model in which severe IPS is induced by pre-BMT conditioning and allogeneic T cells and is characterized by the recruitment of host monocytes and donor T cells into the lung by day 7 post-BMT. Chemokines regulate cellular recruitment and the migration of cells into inflammatory lesions. In this study, we examined the profiles of chemokines produced locally in the lung (parenchyma and bronchoalveolar lavage fluid) and systemically (serum) during the generation of IPS in the peri-BMT period. Protein and messenger RNA (mRNA) levels of CC chemokines (monocyte/lymphocyte attractants), especially monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, RANTES (regulated upon activation normal T-cell expressed and secreted), and C10, were preferentially induced in the lung by day 7 postallogeneic BMT. In addition, there was an increase in mRNA for IP-10 (a monocyte and Th1-cell chemoattractant). The CXC chemokines MIP-2 and KC, known neutrophil attractants, were moderately elevated. For the most part, these increases in chemokines were dependent on the coinfusion of allogeneic T cells with the BM inoculum. Ribonuclease protection assay and in situ hybridization analyses post-BMT showed that the lung was a major producer of MCP-1, a potent inducer of monocyte chemotaxis. Increases in MCP-1 levels in the lung preceded host APC influx whereas MIP-1alpha levels accompanied donor T-cell infiltration. In summary, we have shown that monocyte- and T-cell-attracting chemokines are associated with monocyte and T-cell recruitment during IPS.
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PMID:Induction of monocyte- and T-cell-attracting chemokines in the lung during the generation of idiopathic pneumonia syndrome following allogeneic murine bone marrow transplantation. 1091 Aug 93

Cytokines produced by activated macrophages and Th2 cells within the lung play a key role in asthma-associated airway inflammation. Additionally, recent studies suggest that the molecule CD40 modulates lung immune responses. Because airway epithelial cells can act as immune effector cells through the expression of inflammatory mediators, the epithelium is now considered important in the generation of asthma-associated inflammation. Therefore, the goal of the present study was to examine the effects of proinflammatory and Th2-derived cytokines on the function of CD40 in airway epithelia. The results show that airway epithelial cells express CD40 and that engagement of epithelial CD40 induces a significant increase in expression of the chemokines RANTES, monocyte chemoattractant protein (MCP-1), and IL-8 and the adhesion molecule ICAM-1. Cross-linking epithelial CD40 had no effect on expression of the adhesion molecule VCAM-1. The proinflammatory cytokines TNF-alpha and IL-1beta and the Th2-derived cytokines IL-4 and IL-13 modulated the positive effects of CD40 engagement on inflammatory mediator expression in airway epithelial cells. Importantly, CD40 ligation enhanced the sensitivity of airway epithelial cells to the effects of TNF-alpha and/or IL-1beta on expression of RANTES, MCP-1, IL-8, and VCAM-1. In contrast, neither IL-4 nor IL-13 modified the effects of CD40 engagement on the expression of RANTES, MCP-1, IL-8, or VCAM-1; however, both IL-4 and IL-13 attenuated the effects of CD40 cross-linking on ICAM-1 expression. Together, these findings suggest that interactions between CD40-responsive airway epithelial cells and CD40 ligand+ leukocytes, such as activated T cells, eosinophils, and mast cells, modulate asthma-associated airway inflammation.
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PMID:Proinflammatory and Th2-derived cytokines modulate CD40-mediated expression of inflammatory mediators in airway epithelia: implications for the role of epithelial CD40 in airway inflammation. 1092 9

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