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)

JE is a member of the family of "immediate early" genes induced by growth factors and cytokines. JE encodes a low molecular weight secretory glycoprotein analogous to the human monocyte chemoattractant protein, MCP-1. JE and MCP-1 proteins are thought to play an important role in inflammation and in the recruitment of monocyte/macrophages to the vessel wall during the development of atherosclerosis. We have previously reported that the induction of JE in rat aortic smooth muscle cells (SMC) was specific to platelet-derived growth factor (PDGF) and was not seen with other growth agonists. Using a luciferase reporter system and transient transfection assays of rat aortic SMC, we now report the identification of a region in the proximal rat JE promoter that is responsive to PDGF but not to other growth factors (angiotensin II and alpha-thrombin) or cytokines (interleukin 1-beta and tumor necrosis factor-alpha). The full response to PDGF (approximately 6-fold) requires the cooperative activity of two potentially novel cis-acting elements, at positions -146 to -128 and -84 to -59. While each element produces a different pattern in electrophoretic mobility shift assays, they appear to bind the same PDGF-responsive species. Further analysis of these regions should provide important insights into PDGF-specific responses in vascular SMC.
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PMID:Platelet-derived growth factor-specific regulation of the JE promoter in rat aortic smooth muscle cells. 973

Astrocytes constitute a part of the blood-brain barrier. Chemokine expression by astrocytes may contribute to leucocyte infiltration within the central nervous system (CNS) during inflammation. To investigate factor(s) regulating chemokine expression by astrocytes, we studied the induction of beta-chemokine mRNA expression in adult rat astrocytes. Astrocyte-derived monocyte chemoattractant protein- (MCP-1), RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta mRNA were induced by interferon-gamma (IFN-gamma). Tumour necrosis factor-alpha (TNF-alpha) induced MCP-1, RANTES and MIP-1beta mRNA expression, and lipopolysaccharide (LPS) induced MCP-1, MIP-1alpha and MIP-1beta mRNA expression in astrocytes. LPS-induced MCP-1, MIP-1alpha and MIP-1beta mRNA expression by astrocytes was antagonized by transforming growth factor (TGF)-beta1 and interleukin (IL)-10. TGF-beta1 and IL-10 also down-regulated MCP-1 and RANTES mRNA expression induced by TNF-alpha. IL-10, but not TGF-beta1, inhibited MIP-1beta mRNA expression induced by TNF-alpha. The results of this in vitro study suggest that beta-chemokine mRNA expression by adult rat astrocytes can be induced by LPS or proinflammatory cytokines, while regulatory cytokines, such as TGF-beta1 and IL-10, down-regulate astrocyte-derived beta-family chemokine mRNA expression induced by LPS, IFN-gamma and TNF-alpha. Further study of CNS chemokines will enhance our understanding of leucocyte recruitment to the CNS and suggest therapeutic strategies for neurological disorders.
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PMID:Regulation of beta-chemokine mRNA expression in adult rat astrocytes by lipopolysaccharide, proinflammatory and immunoregulatory cytokines. 982 59

Recent studies support the concept that pulmonary granulomatous inflammation directed by interferon (IFN)-gamma, interleukin (IL)-12, and nitric oxide usually resolves in the absence of fibrosis. To determine whether nitric oxide participates in modulating the fibrotic response during the development of pulmonary granulomas in response to purified protein derivative (PPD), mice presensitized to PPD received daily intraperitoneal injections of N(G)-nitro-D-arginine-methyl ester (D-NAME), N(G)-nitro-L-arginine-methyl ester (L-NAME), or aminoguanidine after delivery of PPD-coated beads to the lungs. Eight days later, morphometric analysis of lung granulomas revealed that L-NAME-treated mice when challenged with PPD in vitro for 36 hours had the largest pulmonary granulomas and the greatest collagen deposition among the treated groups. In addition, equivalent numbers of dispersed lung cells from L-NAME- and aminoguanidine-treated mice produced significantly higher levels of IL-4, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1alpha and significantly lower levels of eotaxin compared with D-NAME-treated mice. Cultures of dispersed lung cells from L-NAME-treated mice also produced significantly more IL-10 and less IL-12 compared with similar numbers of dispersed lung cells from D-NAME-treated mice. Cultures of isolated lung fibroblasts from L-NAME-treated mice expressed higher levels of C-C chemokine receptor 2 (CCR2) and CCR3 mRNA and contained less MCP-1 and eotaxin protein than a similar number of fibroblasts from D-NAME-treated mice. Thus, nitric oxide appears to regulate the deposition of extracellular matrix in lung granulomas through the modulation of the cytokine and chemokine profile of these lesions. Alterations in the cytokine, chemokine, and procollagen profile of this lesion may be a direct effect of nitric oxide on the pulmonary fibroblast and provide an important signal for regulating fibroblast activity during the evolution of chronic lung disease.
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PMID:Collagen deposition in a non-fibrotic lung granuloma model after nitric oxide inhibition. 984 76

CD68 is a myelomonocytic marker identified in human dermal macrophages. Although the existence of CD68 + dendritic epidermal cells has been reported, their characteristics have not been well elucidated. Cutaneous lymphocyte-associated antigen (CLA) is a homing receptor of cutaneous inflammatory T cells. Our recent report suggested that CLA was a homing molecule of CD1a+ Langerhans cells (LC) in the skin. In the present study we tested whether CD68 and CLA+ dendritic epidermal cells were present in skin specimens of normal skin and diseased skin such as lichen planus (LP), psoriasis vulgaris (PS), discoid lupus erythematosus (DLE), basal cell epithelioma (BCE), squamous cell carcinoma (SCC), irritated seborrheic keratosis (iSK), and Bowen's disease (BD). CD68+ dendritic epidermal cells were identified in normal skin and consisted of half the population of CD1a+ LC. These data indicate that CD68+ dendritic epidermal cells constitute a subpopulation of CD1a+ LC. CLA was expressed on a small percentage of CD68+ dendritic epidermal cells in normal skin. A remarkably increased number of CD68+ dendritic epidermal cells and upregulation of CLA on CD68+ dendritic epidermal cells were observed in diseased skin. The percentage of CLA+ cells among all CD68+ dendritic epidermal cells was less than that of CLA+ cells among all CD1a+ LC in diseased skin. The percentage of CLA+ cells among all CD68+ dendritic dermal cells was much less than that of CLA+ cells among all CD1a+ dendritic dermal cells. In normal skin, the epidermis showed minimal expression of monocyte chemoattractant protein (MCP)-1 and TGF-beta2, and no expression of TGF-beta1. In diseased skin, the epidermis showed elevated, but still moderate immunoreactivity for MCP-1. Slightly enhanced immunoreactivity for TGF-beta2, but not for TGF-beta1, was observed in the epidermis of diseased skin. Increased epidermal MCP-1 immunohistochemical staining was associated with the increased number of CD68 dendritic epidermal cells. These data suggest the possibility that MCP-1 secretion from the epidermis can affect the migration of CD68; Cutaneous lymphocyte-associated antigen; Monocyte chemoattractant protein-1; TAF-beta.
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PMID:Increased numbers of CD68 antigen positive dendritic epidermal cells and upregulation of CLA (cutaneous lymphocyte-associated antigen) expression on these cells in various skin diseases. 986 49

Mononuclear cell (MNC) infiltration of the salivary and lacrimal glands is a major feature in Sjogren's syndrome (SS) and its animal model, murine autoimmune sialoadenitis (MAS). To investigate factors that influence selective infiltration by MNC of submandibular glands in young and adult MRL/lpr mice with MAS, expression of mRNA encoding the beta-chemokines monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and regulated upon activation, normal T-cell expressed and secreted (RANTES) was investigated by in situ hybridization. MCP-1 protein production was also evaluated by immunohistochemistry. Young mice with MAS showed an early up-regulation of mRNA expression for MCP-1, MIP-1beta and RANTES, while MIP-1alpha mRNA expression was not affected. Adult mice with MAS showed a further up-regulation of mRNA expression for MCP-1, MIP-1beta and RANTES, and a remarkably strong up-regulation for MIP-1alpha. Immunohistochemistry revealed that MCP-1 protein production paralleled MCP-1 mRNA expression in both young and adult mice. These observations implicate MCP-1, MIP-1beta and RANTES as potential chemokines in induction of MAS, and MCP-1, MIP-1beta, RANTES and prominently MIP-1alpha in progression and perturbation of MAS.
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PMID:Coordinate up-regulation of the beta-chemokine subfamily in autoimmune sialoadenitis of MRL/lpr mice. 987 96

The pathology of multiple sclerosis (MS) is characterized by breakdown of the blood-brain barrier (BBB), accompanied by infiltration of macrophages and T lymphocytes into the central nervous system (CNS). The migration of these cells into the CNS parenchyma may be partly regulated by chemokines. The aim of this study was therefore to investigate the cellular localization of the potent monocyte- and T-cell-attracting chemokine monocyte chemoattractant protein (MCP)-1 by immunohistochemistry on postmortem brain tissue from MS and normal control cases. Brain tissue samples of six MS patients and four patients without a history of brain disease were neuropathologically classified according to characteristic (immuno)histochemical staining patterns. Frozen tissue sections of active demyelinating MS lesions, chronic active demyelinating MS lesions, and normal control brain were immunohistochemically stained with a monoclonal antibody directed against MCP-1. In active demyelinating MS lesions as well as in chronic active MS lesions, reactive hypertrophic astrocytes were strongly immunoreactive for MCP-1, whereas perivascular and parenchymal foamy macrophages did not express MCP-1 protein. These results suggest a significant role for the beta-chemokine MCP-1, synthesized in vivo by reactive hypertrophic astrocytes, in the recruitment and activation of myelin-degrading macrophages and thereby contributing to the evolution of MS lesions.
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PMID:Expression of MCP-1 by reactive astrocytes in demyelinating multiple sclerosis lesions. 991 17

Differential chemokine production by colonic epithelial cells is thought to contribute to the characteristic increased infiltration of selected population of leukocytes cells in inflammatory bowel disease. We have previously demonstrated that IL-13 enhances IL-1alpha-induced IL-8 secretion by the colonic epithelial cell line HT-29. We have now explored the C-C chemokine expression and modulation in this system. The combination of TNF-alpha and IFN-gamma was the minimal stimulation required for regulated on activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein (MCP-1) mRNA expression and secretion by HT-29 cells. The same stimulation induced a stronger IL-8 mRNA expression and secretion. Pretreatment with IL-13 or IL-4, reduced significantly the RANTES, and MCP-1, but not IL-8 mRNA expression and secretion. In contrast, IL-10 had no effect on either MCP-1, or RANTES, or IL-8 generation. Pretreatment of HT-29 cells with wortmannin suggested that the IL-13-induced inhibition of C-C chemokine expression is via activation of a wortmannin-sensitive phosphatidylinositol 3-kinase. These data demonstrate that colonic epithelial cell chemokine production can be differentially regulated by T cell-derived cytokines and suggest an interplay between epithelial cells and T lymphocytes potentially important in the intestinal inflammation.
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PMID:C-X-C and C-C chemokine expression and secretion by the human colonic epithelial cell line, HT-29: differential effect of T lymphocyte-derived cytokines. 1006 68

Bone marrow-derived macrophages (BMM) comprise a population of quiescent cells which can be activated by defined signals. Here, we directly compare the release of chemokines and monokines by BMM raised either in serum-supplemented or in serum-free medium in response to Listeria monocytogenes EGD or Mycobacterium bovis BCG infection. We focused on this issue because there have been several controversial reports on the production of cytokines by BMM due to different in vitro culture conditions. Culture in serum-supplemented medium primed BMM for release of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-12, but had no effect on macrophage inflammatory protein (MIP)-1alpha and tumor necrosis factor (TNF)-alpha production in response to L. monocytogenes infection. After challenge infection with M. bovis, BMM raised and stimulated in serum-supplemented medium secreted higher levels of MCP-1, MIP-1alpha, IL-6, and TNF-alpha but not of IL-12 as compared to BMM cultured and infected in a serum-free medium. The effects of serum could be partially mimicked by interferon-gamma. Because the serum components responsible for BMM priming are undefined, BMM cultured under serum-free conditions provide an appropriate cell population for defining macrophage activating signals.
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PMID:Effect of fetal calf serum on cytokine release by bone marrow-derived macrophages during infection with intracellular bacteria. 1008

Gut-derived lipopolysaccharide (LPS) may contribute to hepatocellular necrosis in alcoholic hepatitis through neutrophil sequestration in hepatic sinusoids. It is well known that the female has a greater susceptibility to alcoholic liver injury than the male. The aim of the present study was to investigate the effect of long-term ethanol consumption on ability of the liver to produce cytokine-induced neutrophil chemoattractant-1 (CINC-1), the most potent neutrophil-chemokine in rats, after LPS administration. Furthermore, we aimed to evaluate the gender difference in this ability. Male and female rats were pair-fed a liquid diet containing 36% of the total calories as ethanol or dextrose for 6 to 8 weeks. They were given LPS intravenously, and chemokine mRNA expression in the liver was evaluated after 2 and 6 hr. To study the organ or chemokine specificity, CINC-1 mRNA expression in the spleen and monocyte chemoattractant protein (MCP)-1 mRNA level were also determined. Serum ALT activity started to increase between 2 and 6 hr. Female rats fed an ethanol diet showed significantly higher ALT activity 6 hr after LPS injection than the male rats. CINC-1 mRNA expressions in the liver after 2 and 6 hr were significantly higher in the ethanol-fed group, compared with the pair-fed control. Female rats fed an ethanol diet showed a significantly higher level of CINC-1 mRNA in the liver than the male rats 2 hr after LPS injection. CINC-1 levels in the liver homogenates paralleled closely its mRNA expression, whereas its concentrations in sera did not correlate with those in the liver. Neither CINC-1 mRNA expression in the spleen nor MCP-1 mRNA expression in the liver was affected by ethanol feeding or gender. An additional experiment using the gonadectomized rats fed an ethanol diet showed that gonadectomy totally abolished the gender difference in CINC-1 mRNA of the liver. We conclude that CINC-1 induction in the liver may be responsible for LPS-induced hepatitis in the ethanol-fed rats, and that the difference in ability to produce CINC-1 between males and females is one important factor that may partly account for the gender difference of alcoholic liver disease.
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PMID:Effect of long-term ethanol consumption on ability to produce cytokine-induced neutrophil chemoattractant-1 in the rat liver and its gender difference. 1023 81

Chemokines are a group of inducible, locally acting proinflammatory cytokines which have been implicated in the pathogenesis of a variety of diseases. Important members of the group include monocyte chemoattractant protein (MCP)-1, -2, -3, macrophage inhibitory protein (MIP)-1alpha, -1beta and RANTES (regulated upon activation, normal T expressed and secreted). To facilitate further investigation of the human chemokines, we have constructed a novel multispecific competitor fragment containing primer binding sites for the CC-chemokines MCP-1, MCP-2, MCP-3, MIP-1alpha, MIP-1beta and RANTES, the CXC-chemokines MIP-2alpha, MIP-2beta as well as for the housekeeping gene beta-actin. Using this competitor fragment we can demonstrate reliable semiquantitation of reverse transcribed chemokine mRNAs. The assay should be useful for further studies, in particular for the semiquantitation of chemokine mRNA species from small cell or tissue specimens.
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PMID:Semiquantitation of human chemokine mRNA levels with a newly constructed multispecific competitor fragment. 1035 7


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