Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines are now considered as constitutive factors of the brain. Some of them are involved in the mechanism regulating lineage commitment and cellular differentiation of the central nervous system (CNS). We describe here the analysis of gene expression in cortex and hippocampus, of interleukin-1 alpha (IL1), interleukin-2 (IL2), interleukin-6 (IL6), macrophage-colony stimulating factor-1 (MCSF) and monocyte chemoattractant protein-1 (MCP1) in fetal (day 18 of gestation; G18), newborn (postnatal day 2; P2), young (postnatal day 21; P21) and adult rat using the reverse transcriptase-polymerase chain reaction (RT-PCR). IL6 and MCP1 mRNA presented distinct patterns of expression levels: IL6 mRNA level is most highly expressed in the embryonic cortex, whereas MCP1 is expressed at a maximal level in the postnatal day 2 cortical area. In the hippocampus, IL6 is most expressed at the adult stage and MCP1 exhibits an equal level of expression from day two to the adult stage. However, under our experimental conditions, IL1 alpha, IL2 and MCSF mRNA were not observed. Thus, certain cytokine genes, each with a specific pattern, are expressed in the rat CNS in adult and during ontogenesis. These observations suggest that cytokines might be involved as regulating factors promoting CNS development.
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PMID:Developmental expression of cytokine genes in the cortex and hippocampus of the rat central nervous system. 780 81

Chemoattractant cytokines, the chemokines, play an important role in early events of inflammation at the site of tissue damage. We examined the expression of mRNA and the protein products of two such chemokines; i.e. monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the ischemic brain tissue following middle cerebral artery occlusion (MCAo). The mRNA transcripts of MCP-1 and MIP-1 alpha were detected by Northern hybridization and reverse transcriptase polymerase chain reaction (RT/PCR), respectively, and the anatomic distribution of specific proteins was analyzed by immunohistochemistry. We found that MCP-1 mRNA was not expressed in the brains of normal rats or rats sacrificed 2 h after MCAo. 6 h after the induction of cerebral ischemia, weak expression of both mRNAs was detected in the ischemic tissue. mRNAs were expressed up to 48 h, and were markedly attenuated at 96 h. In the rats subjected to MCA occlusion, MCP-1 immunoreactivity was diffusely expressed and localized to the ischemic area, and was most intense at 48 h after MCA occlusion. Endothelial cells and macrophage-like cells expressed MCP-1 protein in the ischemic brain. The distribution and morphology of MIP-1 alpha immunoreactive cells were identical with activated astrocytes. We conclude that MCP-1 and MIP-1 alpha mRNAs and proteins are induced after cerebral ischemia in the rat. They may have a role in promoting inflammatory and/or repair processes in the ischemic brain, possibly by attracting or modulating inflammatory cells in the ischemic area.
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PMID:Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. 786 Jul 8

Central nervous system (CNS) expression of two chemokine mRNAs, encoding monocyte chemoattractant protein-1 (MCP-1) and IFN-gamma-inducible protein (IP-10), was previously shown to be closely related to the onset of clinical signs of murine experimental autoimmune encephalomyelitis (EAE). Chemokine mRNAs accumulated in a striking, transient burst within astrocytes, near inflammatory leukocyte infiltrates. It remained unclear if chemokines functioned to initiate leukocyte entry into CNS tissues, or to amplify the intrathecal inflammatory reaction. To address this issue, we determined the expression of chemokine mRNAs at the earliest evidence of CNS immune-mediated inflammation. For these experiments, mice were sacrificed in pairs at varying times after immunization. Only one member of each pair was symptomatic for EAE at the time of sacrifice. Symptom presence correlated well with histological inflammation at the time of sacrifice. RNA was prepared from two CNS sites, brain and spinal cord, and expression of chemokine mRNAs was analyzed by a sensitive and quantitative reverse transcriptase/polymerase chain reaction dot-blot hybridization assay. CNS expressions of MCP-1 and IP-10 gene were correlated tightly with histological inflammation; indeed, chemokine expression was never detected in the absence of leukocyte infiltrates. In situ hybridizations showed that astrocytes expressed chemokine transcripts. These findings provide new information about mechanisms controlling chemokine mRNA expression during immune-mediated inflammation in EAE and are consistent with a role for chemokines as amplifiers of CNS inflammatory reactions.
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PMID:Central nervous system chemokine mRNA accumulation follows initial leukocyte entry at the onset of acute murine experimental autoimmune encephalomyelitis. 890 49

Blocking CD28-B7 T-cell costimulation by CTLA4Ig induces tolerance to rat renal allografts and inhibits Th1, but spares Th2, cytokines. We now report on the mechanisms of CD28-B7 blockade in this model. Lymphocytes from CTLA4Ig-treated animals showed significant reduction of mixed lymphocyte response, as well as antidonor cytotoxic T-cell effector function, as compared with rejecting controls. Flow cytometry studies on sera of renal allograft recipients showed complete inhibition of antidonor humoral responses by CTLA4Ig. Analysis by reverse transcriptase-polymerase chain reaction and immunohistology showed that intragraft macrophage products, monocyte chemoattractant protein-1 and inducible nitric oxide synthase, were reduced by CTLA4Ig therapy. Immunohistologic studies also showed reduced intragraft macrophage infiltration and decreased staining for the fibrogenic and mitogenic growth factor, transforming growth factor-beta. These results indicate that CD28-B7 blockade inhibits cell-mediated and humoral immune responses, and suggest that strategies targeting T-cell costimulation may provide a novel approach to prevent chronic allograft rejection.
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PMID:CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft model: inhibition of cell-mediated and humoral immune responses in vivo. 899 Mar 93

Two forms of the monocyte chemoattractant protein-1 receptors (the type A monocyte chemoattractant protein 1 (MCP-1) receptor CCR-2A and the type B MCP-1 receptor (CCR-2B) have been recently cloned and found to differ only in their terminal carboxyl tails. Here, we report that the two isoforms are alternatively spliced variants of a single MCP-1 receptor gene. Sequencing of the gene revealed that the 47-amino acid carboxyl tail of CCR2B was located in the same exon as the seven transmembrane domains of the receptor, and the 61-amino acid tail of CCR2A was in a downstream exon. Examination of freshly isolated human monocytes by reverse transcriptase-polymerase chain reaction revealed that CCR2B was the predominant isoform and that message levels of both CCR2A and CCR2B decreased as the monocytes differentiated into macrophages. In stably transfected cell lines, CCR2B trafficked well to the cell surface, but CCR2A was found predominantly in the cytoplasm. Equilibrium binding studies revealed that those CCR2A receptors that successfully trafficked to the cell surface bound MCP-1 with high affinity (Kd = 310 pM), similar to CCR2B. In signaling studies, both CCR2A and CCR2B mediated agonist-dependent calcium mobilization, as well as inhibition of adenylyl cyclase. Creation of chimeras between CCR2A and the human thrombin receptor revealed that the cytoplasmic retention of CCR2A was due to its terminal carboxyl tail. Progressive truncation of the carboxyl tail indicated that a cytoplasmic retention signal(s) was located between residues 316 and 349. These data indicate that the alternatively spliced form of the human MCP-1 receptor (CCR2A) binds MCP-1 with high affinity and is a functional receptor and that expression at the cell surface is controlled by amino acid sequences located in the terminal carboxyl tail.
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PMID:Organization and differential expression of the human monocyte chemoattractant protein 1 receptor gene. Evidence for the role of the carboxyl-terminal tail in receptor trafficking. 899

CGN is a rapidly progressive glomerular disease. Monocytes/macrophages are frequently observed in glomeruli in cases of CGN and they are considered to play a crucial role in the pathogenesis of this disease. We described previously the glomerular expression of monocyte chemoattractant protein-1 (MCP-1), which is a potent chemoattractant for monocytes and a member of CC chemokine family, in an experimental model of CGN. In the present study we investigated the expression of mRNAs for other CC chemokines, namely, MCP-3, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, RANTES and TCA3, all of which are chemotactic for monocytes, in the CGN model. First, we established a reverse transcriptase-polymerase chain reaction (RT-PCR) method by which mRNA for each of the CC chemokines could be amplified separately, and then we measured the levels of the expression of mRNAs for the chemokines in diseased glomeruli at several time points after induction of CGN. The mRNAs for all CC chemokines examined were expressed in glomeruli of rats with CGN. Moreover, induction of the gene expression of MIP-1alpha and MIP-1beta seemed to occur earlier than that of the others. CC chemokines may contribute to the recruitment and activation of monocytes in CGN, and each individual CC chemokine may play an overlapping but distinct role in the pathogenesis of this disease.
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PMID:Gene expression of CC chemokines in experimental crescentic glomerulonephritis (CGN). 921 37

1. Intraperitoneal (i.p.) injection of murine recombinant IL-1beta (mrIL-1beta) produced a dose-dependent (0.5-50 ng) and time-related (0.5-2 h) secretion of murine monocyte chemoattractant protein-1 (mMCP-1; 3-4 ng per cavity) in the lavage fluids. MCP-1 mRNA could also be detected in the cell pellets by reverse transcriptase-polymerase chain reaction (RT-PCR). 2. MCP-1 levels were reduced by more than 90% by co-administration of IL-1 receptor antagonist (10 microg) (n=6, P<0.05). In contrast, an IL-1 mutant with low affinity for IL-1 receptor type I, termed yIL-1betadelta4 (50 ng), produced only a modest release of the chemokine. Treatment of mice with dexamethasone (DEX) (approximately 1 mg kg(-1) s.c.) reduced mrIL-1beta-induced mMCP-1 gene expression (apparent total inhibition) and protein release in the lavage fluids (approximately 40% reduction; n=10; P<0.05). Drastic reductions in the numbers of residential macrophages or mast cells did not modify the levels of mMCP-1 recovered in the lavage fluids. 3. Injection of mrIL-1beta produced neutrophil accumulation into the peritoneal cavities (maximal at 4 h with 1.42+/-0.15 x 10(6) cells per mouse). Co-injection of a specific polyclonal antibody against mMCP-1 reduced this process by more than 50% (n=6; P<0.05). In conclusion, we studied the mechanisms leading to the specific release of the CC chemokine mMCP-1 after in vivo administration of mrIL-1beta.
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PMID:Investigation of the functional role played by the chemokine monocyte chemoattractant protein-1 in interleukin-1-induced murine peritonitis. 978 4

To isolate the interferon-inducible protein 10 (IP-10) receptor gene, we searched for cells that respond to IP-10. Among several human and murine T cell lines, only CTLL2 cells ( a murine cytotoxic T cell line) responded to IP-10 with transient elevation of intracellular Ca2+. The murine IP-10 receptor gene has been cloned from cDNA derived from CTLL2 cells using the reverse transcriptase-polymerase chain reaction protocol with two degenerate primers corresponding to conserved regions of chemokine receptors. The cDNA encoding the murine IP-10 receptor has an open reading frame of 1101 bp corresponding to a protein of 367 amino acids that exhibits 86 % identity with the human IP-10 receptor. It mediates Ca2+ mobilization in response to IP-10, but does not recognize other rodent chemokines, including GRO, RANTES, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha). Northern blot analysis revealed that murine IP-10 and its receptor mRNA were constitutively expressed in the spleen and thymus from normal mouse, while IP-10 and its receptor mRNA were derived from stromal cells and lymphocytes in both tissues, respectively. In vivo treatment with concanavalin A (Con A) for 12 hrs revealed that splenocytes significantly induce IP-10 receptor mRNA expression and show a good chemotactic response to IP-10. Therefore, it is supposed that IP-10 and its receptor are important for lymphocyte trafficking to lymphoid organs and that the IP-10 receptor on lymphocytes is rapidly inducible on inflammation or in immunological events.
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PMID:Cloning of the murine interferon-inducible protein 10 (IP-10) receptor and its specific expression in lymphoid organs. 979 Sep 4

Lymphoepithelioma-like carcinoma (LELC) of the lung is a recently recognized primary non-small cell lung carcinoma with distinct clinicopathological features and an aetiological association with Epstein-Barr virus (EBV) infection. The tumour consists of clusters and sheets of poorly or undifferentiated tumour cells in close association with numerous mononuclear inflammatory cells, including a rich component of tumour-associated macrophages (TAMs). To investigate the molecular mechanism leading to the TAM-rich stroma, the expression of a monocyte-specific chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1), was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH), and the presence of TAMs was demonstrated by immunohistochemistry in nine LELCs. The results were compared with those found in 17 conventional non-small cell lung carcinomas. RT-PCR showed specific MCP-1 amplification in both LELCs and non-LELCs, but ISH demonstrated a unique and extensive expression of MCP-1 transcripts by the tumour cells of LELCs only, while TAMs, stromal fibroblasts, and endothelial cells formed the major source of MCP-1 in non-LELCs. TAMs in LELCs were more abundant and showed a close topographical relationship with the MCP-1-expressing tumour cells. The results indicate that tumour cell expression of MCP-1 in LELCs is an important mechanism contributing to their distinctive morphological features. This is the first study that demonstrates the in vivo upregulation of a monocyte-specific chemokine by EBV-related carcinomas, illustrating an interesting aspect of tumour biology in EBV-related neoplasms.
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PMID:Monocyte chemoattractant protein-1 (MCP-1) expression in primary lymphoepithelioma-like carcinomas (LELCs) of the lung. 1020 85

In human chorionic villi, numerous macrophages, so-called Hofbauer cells, are located adjacent to trophoblasts. To determine the role of the macrophages in the proliferation and differentiation of trophoblasts, cytotrophoblast cells were cultured in serum-free culture-conditioned media of villous macrophages (VMCM), peritoneal macrophages (PMCM), and villous fibroblasts (VFCM). In VMCM, proliferation of cytotrophoblast cells was detected at 24 h by immunocytochemistry with Ki-67-antibody. A large number (P < 0.001) of multinucleated syncytia was formed in VMCM. In VMCM, cytotrophoblast cell fusion was completed by 96 h, which coincided with the peak of hCG secretion and initiation of human placental lactogen (hPL) release. Levels of hCG (P < 0.001) and hPL (P < 0. 001) secretion from syncytial cells were significantly higher in VMCM than in PMCM or in VFCM. Concentrations of macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) analyzed by ELISA were greater in VMCM than in PMCM or in VFCM, whereas monocyte chemoattractant protein-1 (MCP-1) concentration was high in PMCM. The expression patterns of M-CSF, VEGF, and MCP-1 in villous macrophages and peritoneal macrophages by reverse transcriptase-polymerase chain reaction were similar to their secretion patterns. Thus, villous macrophages have a greater ability to stimulate hCG and hPL secretion than do peritoneal macrophages. This study suggests that macrophages within the villous stroma may stimulate the growth and differentiation of trophoblasts through their secreted substances.
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PMID:Human villous macrophage-conditioned media enhance human trophoblast growth and differentiation in vitro. 1072 80


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