Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

In this study we tested whether the pattern of cytokines expressed by human carcinomas could account for a different in vivo recruitment of leukocyte subpopulations as a part of the anti-tumor immune response. Two carcinoma cell lines, SK-OV-3 ovary carcinoma and CALU-3 lung carcinoma, were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence and ELISA for the expression and in vitro production of cytokines with chemotactic, proinflammatory and growth-stimulating activity. Although both cell lines displayed a constitutive expression of granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage-CSF (GM-CSF), M-CSF, interleukin (IL-) 1 alpha and IL-8, only CALU-3 cell line expressed IL-10, RANTES (Regulated upon Activation, Normal T Expressed and Secreted) and monocyte-activating protein (MCP)-1. MCP-1 and IL-8 were detected by immunohistochemistry on sections from tumors xenografted in nude mice. To analyze whether the tumor-released cytokines modulate leukocytes in tumor infiltration, we studied the distribution of human peripheral blood leukocytes injected in the proximity of SK-OV-3 and of CALU-3 tumor xenografts. While SK-OV-3 was unable to recruit human leukocytes and appeared to be barely infiltrated by murine CD45+ cells, CALU-3 appeared to be rapidly and heavily infiltrated by human leukocytes which induced tumor necrosis within 18-24 hr.
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PMID:An in vivo model to compare human leukocyte infiltration in carcinoma xenografts producing different chemokines. 766 28

The myocardial ischemia and reperfusion injury is caused by the re-introduction of coronary circulation in ischemic myocardial tissues. A number of experiments demonstrate that immunological response such as adherence of neutrophils to endothelial cells play a critical role in reperfusion injury. In this paper, the effect of global ischemia and reperfusion on the expression of cytokine genes by myocardial tissues as well as cell adhesion molecules by neutrophils were studied by using Langendorff model. Cardiac dysfunction and immunological response in 25 min global ischemia at 37.5 degrees C followed by 60 min reperfusion were studied in isolated rat heart perfused with blood supplied from support rat (Langendorff model). Cardiac functions were measured with a left intraventricular balloon. The mean post-experimental reduction of the left ventricular end-systolic pressure were 87.5 +/- 1.6% of pre-experimental level in the control perfusion group and 55.5 +/- 5.8% in the reperfusion group. Immunofluorescence flow cytometry showed that ischemia and reperfusion injury did not affect the expression of adhesion molecules on neutrophils which were isolated from perfused blood samples. Cytokine gene expression was analyzed by direct analysis of mRNA obtained from the blood-perfused, isolated rat heart. The level of expression of the cytokine genes was assessed using semiquantitative reverse transcriptase-polymerase chain reaction (semiquantitative RT-PCR). IL-6, IL-8, IFN-gamma, TNF-alpha were expressed in normal heart tissue at low level and were upregulated following ischemia and reperfusion. IL-1 beta, MCP-1 and IL-1 receptor antagonist were not expressed at detectable level in normal heart but were induced following global ischemia. IL-1 alpha was not expressed at detectable level in normal heart but was induced following reperfusion of the ischemic heart. Histological examination of myocardial tissue from the reperfusion group revealed no evidence of myocardial necrosis. Only a mild interstitial edema as well as weak focal hemorrhage was detected after reperfusion of ischemic hearts. These results suggest that there is a process which causes early stage of post-ischemic myocardial dysfunction without involving myocardial necrosis nor infiltration of inflammatory cells.
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PMID:[Cardiac dysfunction and endogenous cytokines in global ischemia and reperfusion injury]. 811 7

Constitutive expression of mRNAs for GRO alpha, GRO beta, GRO gamma, and MCP-1, belonging to the chemokine family of 8- to 10-kDa cytokines with chemotactic properties for granulocytes and monocytes, has been identified in freshly isolated human nasal and bronchial epithelium, and in bronchoalveolar macrophages (AM). Expression of GRO alpha, GRO gamma, and MCP-1, but not GRO beta, was found in airway epithelial cells. AM expressed all three GRO genes in addition to MCP-1. On reverse transcription, chemokine mRNAs yielded 0.5-30 cDNA molecules/cell, depending on the chemokine and cell type, as determined by a semiquantitative reverse transcriptase-polymerase chain reaction technique. When chemokine mRNA expression in AM and bronchial epithelium from healthy nonatopic individuals was compared, AM expressed more GRO alpha, but similar levels of GRO gamma, MCP-1, and interleukin-8 (IL-8), as in the bronchial epithelial cells. Modulation of chemokine expression by tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml) or endotoxin [lipopolysaccharide (LPS), 100 ng/ml] exposure was studied in primary nasal epithelial cell and alveolar macrophage cultures. In epithelial cells, LPS did not induce chemokine expression but GRO alpha, IL-8, and MCP-1 were upregulated approximately 100-fold by TNF alpha; GRO gamma expression was elevated only 1.5- to 4-fold. In AM cultures, all three GROs were strongly induced by LPS with peak mRNA expression 24 h after stimulation (approximately 50- to 100-fold increase compared with control cultures). MCP-1 mRNA expression, on the other hand, was not increased by LPS in AM. GRO protein was present in supernatants of stimulated epithelial cells and AM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Constitutive and stimulated MCP-1, GRO alpha, beta, and gamma expression in human airway epithelium and bronchoalveolar macrophages. 816 97

Previous studies demonstrated the involvement of astrocytes in the development of astrogliosis, a condition in which these cells undergo proliferation and hypertrophy. To examine whether astrocytes could migrate into lesions, we tested the influence of the murine chemokines MCP-1, KC, TCA3, and MIP-1 beta on migration of cultured neonatal mouse astrocytes. Subnanomolar concentrations of MCP-1 and KC were active chemoattractants indicating that these molecules were effective at physiologic concentrations. Specificity of MCP-1 was demonstrated by antibody inhibition and by the finding that the chemokine MIP-1 beta failed to induce astrocyte migration. The migratory responses were sensitive to pertussis toxin; this finding is consistent with involvement of G protein-coupled receptors. To examine the receptors for these chemokines further, we cloned the mouse homolog of the human MCP-1 receptor from a mouse peritoneal exudate cell cDNA library. The gene had 78% nucleotide sequence homology with the human MCP-1 receptor (the nucleotide sequence of clone 1 encoding the mouse MCP-1 receptor can be obtained from the GenBank database, accession number U56819). However, reverse transcriptase-polymerase chain reaction (RT-PCR) failed to detect message for either the MCP-1 or KC receptors in astrocytes. The combined data suggest that mouse astrocytes use novel receptors to recognize these chemokines.
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PMID:Mouse astrocytes respond to the chemokines MCP-1 and KC, but reverse transcriptase-polymerase chain reaction does not detect mRNA for the KC or new MCP-1 receptor. 887 98

Chemokines are small proteins that selectively activate and recruit leukocytes to sites of inflammation. Several of them, including the CC chemokines RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and the CXC chemokines IL-8, GRO-alpha, ENA-78 have been identified in rheumatoid synovium, implicating a potential role for these molecules in rheumatoid arthritis. We have investigated the expression patterns of CC chemokine receptors in the joints of mice with collagen-induced arthritis, a model for human rheumatoid arthritis. In addition, we have investigated the incidence and severity of arthritis in mice receiving administration of MetRANTES, a modified chemokine which is a nanomolar antagonist of certain CC chemokine receptors. The mRNA expression pattern of the chemokines and their receptors in the joints of arthritic mice was investigated using reverse transcriptase-PCR and in situ hybridization. An upregulation of the CC chemokine receptors mCCR1, mCCR2; mCCR3 and mCCR5 was found in the joints from arthritic mice, compared to control animals. In addition, injections of MetRANTES reduced the incidence of disease in a dose dependent manner. Furthermore, in MetRANTES-treated mice that did develop arthritis a significantly lower severity of disease was observed compared with control animals. Our data clearly demonstrate a role for CC chemokines and their receptors in inflammatory joint destruction and support the use of chemokine receptor antagonists as potential tools to control inflammatory diseases such as rheumatoid arthritis.
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PMID:Effect of a CC chemokine receptor antagonist on collagen induced arthritis in DBA/1 mice. 923 36

Recent data suggest that mast cells (MC) are involved in the regulation of leukocyte accumulation in inflammatory reactions. In this study, expression of leukocyte-chemotactic peptides (chemokines) in purified human lung MC (n = 16) and a human mast cell line, HMC-1, was analyzed. Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) showed baseline expression of monocyte chemoattractant protein (MCP)-1 mRNA in unstimulated MC. Exposure of MC to recombinant stem cell factor (rhSCF, 100 ng/mL) or anti-IgE (10 microgram/mL) was followed by a substantial increase in expression of MCP-1 mRNA. Neither unstimulated nor stem cell factor (SCF )-stimulated lung MC expressed transcripts for interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, or RANTES by Northern blotting. The mast cell line HMC-1, which contains a mutated and intrinsically activated SCF-receptor, was found to express high levels of MCP-1 mRNA in a constitutive manner. Exposure of HMC-1 cells to rhSCF resulted in upregulation of MCP-1 mRNA expression, and de novo expression of MIP-1beta mRNA. The SCF-induced upregulation of MCP-1 mRNA in lung MC and HMC-1 was accompanied by an increase in immunologically detectable MCP-1 in cell supernatants (sup) (lung MC [<98%], control medium, 1 hour: 159 +/- 27 v SCF, 100 ng/mL, 1 hour: 398 +/- 46 pg/mL/10(6) cells; HMC-1: control, 1 hour: 894 +/- 116 v SCF, 1 hour: 1,536 +/- 265 pg/mL/10(6)). IgE-dependent activation was also followed by MCP-1 release from MC. MC-sup and HMC-1-sup induced chemotaxis in blood monocytes (Mo) (control: 100% +/- 12% v 2-hour-MC-sup: 463% +/- 38% v HMC-1-sup: 532% +/- 12%), and a monoclonal antibody (MoAb) to MCP-1 (but not MoAb to IL-8) inhibited Mo-chemotaxis induced by MC-sup or HMC-1-sup (39% to 55% inhibition, P < .05). In summary, our study identifies MCP-1 as the predominant CC-chemokine produced and released in human lung MC. MCP-1 may be a crucial mediator in inflammatory reactions associated with MC activation and accumulation of MCP-1-responsive leukocytes.
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PMID:The c-kit ligand stem cell factor and anti-IgE promote expression of monocyte chemoattractant protein-1 in human lung mast cells. 937 54

Traumatic injury to the brain initiates multiple interrelated processes that involve parenchymal, vascular, and infiltrating inflammatory cells. Nitric oxide (NO) and chemokines have been implicated as regulators of the central nervous system injury response. Following a cryogenic lesion of the cerebral cortex in mice, mRNA for NO synthase (NOS)-2 was detected by reverse transcriptase polymerase chain reaction ipsilaterally 12 h after injury and persisted for 2 weeks. While mRNA was also detected contralaterally, the time course of expression was shorter (1 week). By immunohistochemistry, NOS-2 protein was initially detected ipsilaterally 12 h after injury in infiltrating inflammatory cells. Astroglial cells expressed NOS-2 from 24 to 72 h after injury. The expression of monocyte chemoattractant protein (MCP-1) mRNA peaked at 6 h on the lesion side, remained for 24 h and then declined by 48 h. On the unlesioned side, MCP-1 mRNA was expressed to a much lesser extent and had declined by 24 h. The up-regulation of MCP-1 was relatively specific as a closely related mRNA encoding IP-10 was not significantly increased. These findings implicate a role for NOS-2 and MCP-1 as potential regulators of cellular events following cryogenic cerebral trauma.
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PMID:Expression of monocyte chemoattractant protein (MCP-1) and nitric oxide synthase-2 following cerebral trauma. 945 27

The major target organ of systemic infection with the intracellular bacterium Listeria monocytogenes is the liver, to where inflammatory leukocytes are rapidly recruited. We determined by reverse transcriptase polymerase chain reaction the early chemokine response in the liver after systemic infection of mice with listeriae, and in parallel compared chemokine release from macrophages and hepatocytic cells in vitro. Murine bone marrow-derived macrophages (BMM) grown in fetal calf serum-supplemented medium were used as macrophages and the TIB75 cell line as hepatocytic cells. Within 1-3 hours, gene expression of monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha, MIP-2, KC, and interferon-gamma inducible protein-10 (IP-10) was upregulated in liver tissue of infected mice. BMM infected in vitro with L. monocytogenes showed a generalized chemokine response, and readily released MCP-1, MIP-1 alpha, MIP-2, and KC, as measured by enzyme-linked immunosorbent assay. In contrast, the chemokine response of hepatocytic cells was more restricted, and infection induced MCP-1 and KC, but not MIP-2 and MIP-1 alpha. Interferon gamma enhanced chemokine release from hepatocytic cells, but unexpectedly had either no or a negative effect on chemokine secretion by BMM cultured in serum-supplemented medium. Listeriolysin (Hly)-negative avirulent listeriae as well as listeriae killed by heat or gentamycin initiated a similar chemokine response in BMM and hepatocytic cells as did wild-type L. monocytogenes. Stimulation of hepatocytic cells with the monokines, tumor necrosis factor alpha and interleukin (IL-)1 alpha, but not IL-6, augmented liberation of chemokines. Together, our data demonstrate an early hepatic chemokine response to L. monocytogenes in murine listeriosis. Probably, not only macrophages but also parenchymal cells participate in chemokine production.
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PMID:Macrophages and hepatocytic cells as chemokine producers in murine listeriosis. 971 70

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


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