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)

Experimental infection of non-human primates with simian malaria parasites offers a controlled system to study malarial immunity. Plasmodium cynomolgi (P. vivax-like) and P. knowlesi (P. falciparum-like) infections in the rhesus monkey were used as a model to test the hypothesis that initial acute infection stimulates type 1/pro-inflammatory cytokine expression followed by a gradual type 2/anti-inflammatory response upon re-infection. This study analyzed cytokine gene expression (interleukin-12, interferon-gamma, tumor necrosis factor-alpha = type 1; interleukin-4, interleukin-10 = type 2) using a semi-quantitative reverse transcriptase-polymerase chain reaction in monkeys infected with each of the parasites (three per group). Clinicoparasitologic and serologic parameters were also monitored. Monkeys were re-infected to assess whether enhanced immunity could increase parasite clearance. The immune response to P. cynomolgi infection in rhesus monkeys seemed to be mediated by anti-parasite, pro-inflammatory responses during primary infection with a transition to protective type 2 responses after repeat infection. The immune responses to P. knowlesi infection were more varied. Anti-inflammatory responses were more prevalent during primary infection. Repeat infection stimulated a wide variety of responses; most included expression of tumor necrosis factor-alpha, a cytokine that has been associated with inflammatory and host-destructive effects (weight loss, fever, anemia). These observations further confirmed that the simian malaria/rhesus monkey model is well suited for studies on the regulation of immunity to acute Plasmodium infection.
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PMID:Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium knowlesi infections. 1251 48

Stimulation of immune cells by antigens triggers changes in the transcription of genes encoding cytokines and other proteins; these changes in gene expression are part of the normal immune response. Previous studies have provided evidence that biotin status may affect secretion of cytokines by immune cells. Here we determined whether biotin supplementation affects gene expression in human immune cells. Peripheral blood mononuclear cells were isolated from healthy adults before and after supplementation with 8.8 micro mol biotin/d for 21 d. Cells were cultured ex vivo with concanavalin A for 21 h to simulate stimulation with antigens. Expression of genes that play roles in cytokine metabolism, cell proliferation, signal transduction, stress response, apoptosis and biotin homeostasis was quantified by using DNA microarrays and reverse transcriptase-polymerase chain reaction. The abundance of mRNA encoding interferon-gamma, interleukin-1beta, and 3-methylcrotonyl-CoA carboxylase was 4.3, 5.6 and 8.9 times greater, respectively, after supplementation with biotin compared with before supplementation. In contrast, the abundance of mRNA encoding interleukin-4 was 6.8 times greater before supplementation than after supplementation. These data suggest that biotin supplementation affects gene expression in human immune cells. Effects of biotin on gene expression are likely to modulate the response of immune cells to antigens.
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PMID:Biotin supplementation increases expression of genes encoding interferon-gamma, interleukin-1beta, and 3-methylcrotonyl-CoA carboxylase, and decreases expression of the gene encoding interleukin-4 in human peripheral blood mononuclear cells. 1261 42

Tissue structural cells are known in some situations to play a role in the presentation of antigen and in immunoregulation. We assessed the expression of B7 homologs, known to be involved in antigen presentation and lymphocyte costimulation, in human airway epithelial cells. Flow cytometry performed on the airway epithelial cell line BEAS-2B, as well as primary bronchial epithelial cells (PBEC), showed that B7-H2 was constitutively expressed on both BEAS-2B and PBEC, whereas B7-1 and B7-2 were undetectable on either epithelial cell type. B7-H2 expression was confirmed by Western blot using a specific antibody. Stimulation with various cytokines, including tumor necrosis factor-alpha, interferon-gamma, and interleukin-4, slightly downregulated B7-H2 expression detected by flow cytometry, but did not significantly alter the apparent level of protein as assessed by Western blotting. Northern blotting detected mRNA for B7-H2 and B7-1, but not B7-2. B7-H2 was cloned from BEAS-2B cells and the sequence verified. Expression of B7-H2 mRNA was detected by real-time reverse transcriptase-polymerase chain reaction in PBEC from three independent donors. Immunohistochemical analysis of airway derived from autopsies revealed expression of B7-H2 in human airway epithelial cells. These results demonstrate that airway epithelial cells express the costimulatory molecule B7-H2, and suggest the possibility that B7-H2 may participate in antigen presentation by epithelial cells.
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PMID:Expression of the costimulatory molecule B7-H2 (inducible costimulator ligand) by human airway epithelial cells. 1270 12

Serum response factor (SRF) is a transcription factor essential for smooth muscle (SM) myogenesis. Its role in myofibroblast differentiation is, however, unknown. We studied the expression and the localization of SRF in bleomycin-induced pulmonary fibrosis, where myofibroblasts are abundant. We found that SRF levels were upregulated in bleomycin-exposed mouse lungs mainly due to de novo synthesis of SRFDelta5, a less myogenic SRF isoform. Before myofibroblast differentiation, SRF/SRFDelta5 was immunolocalized mostly in the cytoplasm of scattered fibroblasts at lesion sites. With the development of myofibroblasts, however, SRF/SRFDelta5 was found in myofibroblast nuclei. cDNA array analysis showed that SRFDelta5 and SRF induced expression of transforming growth factor-beta1, a critical factor in myofibroblast differentiation. This was accompanied by de novo expression of several inflammatory cell-specific mRNAs. The latter was confirmed by reverse transcriptase-polymerase chain reaction. Treatment of lung fibroblasts with tumor necrosis factor-alpha, which is produced early in the bleomycin model, induced SRFDelta5 expression and SRF/SRFDelta5 cytoplasmic accumulation, whereas addition of transforming growth factor-beta1 caused SRF/SRFDelta5 nuclear translocation followed by SM alpha-actin synthesis. Interleukin-4, another cytokine involved in myofibroblast differentiation, did not affect SRF or induce SRFDelta5 expression. Our studies therefore suggested a new mechanism whereby SRF and SRFDelta5 contribute to the emergence of myofibroblasts in lung injury and fibrosis.
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PMID:Involvement of serum response factor isoforms in myofibroblast differentiation during bleomycin-induced lung injury. 1277 47

The in vivo effects of IL-18 on bone metabolism were investigated by histopathology in IL-18 transgenic mice. Deformed cortical bone and decreased turnover rate of lumbar trabecular bone are consistent with increased expression of IFN-gamma and IL-18 in the bone marrow. Interleukin (IL)-18 has been demonstrated to inhibit osteoclastogenesis in an in vitro co-culture system. We investigated the effects of IL-18 overexpression on bone metabolism by comparing bone characteristics in male IL-18 transgenic (TG) mice, which secrete mature murine IL-18 from their B- and T-cells, and their wildtype littermates (WT). Histopathological analysis revealed that the cortical bone of the femur was thinner and more deformed in IL-18 TG mice. Bone histomorphometry showed that the cortical bone area of the mid-diaphysis of the femur and the trabecular bone volume of the lumbar vertebrae were significantly reduced in IL-18 TG mice. IL-18 TG mice also exhibited significantly fewer osteoclasts and a reduced bone formation rate in the trabecular bones of their lumbar vertebrae. Real-time reverse transcriptase-polymerase chain reaction amplification of bone marrow cell mRNA revealed that interferon (IFN)-gamma mRNA expression was significantly increased, whereas IL-4 mRNA expression was significantly reduced, in IL-18 TG mice. However, the expression ratio of receptor activator of NFkappaB ligand and osteoprotegerin mRNA was not significantly altered. Thus, deformed cortical bone and a decreased turnover rate of lumbar trabecular bone are characteristic of IL-18 TG mice, and these features might be associated with the increased expression of IFN-gamma and IL-18 in the bone marrow.
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PMID:Bone malformations in interleukin-18 transgenic mice. 1281 49

Telomerase, the reverse transcriptase that maintains telomere DNA, is usually undetectable in most adult tissues but is positive in embryonic tissues and in cancers. In addition, freshly islolated or in vitro-activated lymphocytes were shown to express high levels of telomerase activity, although its expression in myeloid cells including dendritic cells (DCs) is largely unknown. Here, we investigated telomerase activity during the differentiation and maturation process of DCs. In vitro culture of bone marrow (BM) cells with granulocyte macrophage-colony stimulating factor and interleukin-4 induced a dramatic increase of telomerase activity accompanied with their differentiation into DCs. Furthermore, stimulation with microbial components such as lipopolysaccharide (LPS), which triggers maturation of DCs, augmented the activity. In vivo responses of telomerase activity were also observed in splenic DCs by injection of LPS intraperitoneally. It is interesting that in old mice, telomerase activity of splenic DCs was significantly higher than young mice but rather decreased after LPS stimulation. By measuring expression of cell-surface activation markers, splenic DCs of old mice responded poorly to LPS stimulation. Such poor responses to LPS were also observed in BM-derived DCs. These different features of DCs between young and old mice may contribute to a pathogenesis to microbial infections.
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PMID:Dramatic increase of telomerase activity during dendritic cell differentiation and maturation. 1288 44

Sputum examination is being increasingly used as a non-invasive method for the study of airway inflammation. However, the technical applications of sputum are still limited because of the small number of cells recovered. In attempt to extend applications of sputum examinations, we developed and standardised, the reverse transcriptase-polymerase chain reaction (RT-PCR), a sensitive and specific technique of detection of mRNA, in induced sputum samples. Total RNA were extracted from samples containing as few as 50 to 80,000 cells, using a phenol-chloroform extraction method. RT-PCR was successfully tested on beta-actin, interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and tumour necrosis factor-beta (TGF-beta) genes. This protocol provides a simple technique to extract total RNA from a few number of induced sputum cells. It permits the semi-quantitatively study of cytokine gene expression in airways with simple means.
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PMID:Study of cytokine gene expression in small cell samples: use in induced sputum. 1297 86

Type 1 diabetes is an autoimmune disease with an inflammatory process directed against the beta cells in pancreas. This investigation aimed at studying the immune response during the first 3 months after the diagnosis of type 1 diabetes, with focus on the balance of T-helper 1 (Th1)- and Th2-like cytokines, produced spontaneously and in response to relevant autoantigens. Peripheral blood mononuclear cells (PBMCs) were collected from type 1 diabetic children (10-17 years) at 5, 20, 35 and 90 days after diagnosis. Expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-gamma, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD(65))-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. Spontaneous and antigen-induced expression and secretion of cytokines were low at the diagnosis of type 1 diabetes. During the first month, after diagnosis, the GAD(65)-peptide caused an increased ratio of IFN-gamma/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-gamma (P = 0.07). Expression of IFN-gamma mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. Thus, duration after diagnosis as well as metabolic state should be carefully considered both in studies of the pathogenesis of type 1 diabetes and in immune intervention studies at onset.
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PMID:Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes. 1514 63

Insemination elicits inflammatory changes in female reproductive tissues, but whether this results in immunological priming to paternal antigens or influences pregnancy outcome is not clear. We have evaluated indices of lymphocyte activation in lymph nodes draining the uterus following allogeneic mating in mice and have investigated the significance of sperm and plasma constituents of semen in the response. At 4 days after mating, there was a 1b7-fold increase in the cellularity of the para-aortic lymph node (PALN) compared with virgin controls. PALN lymphocytes were principally T and B lymphocytes, with smaller populations of CD3(+) B220(lo), NK1.1(+) CD3(-) (NK) and NK1.1(+) CD3(+) (NKT) cells. CD69 expression indicative of activation was increased after mating and was most evident in CD3(+) and NK1.1(+) cells. Synthesis of cytokines including interleukin-2, interleukin-4 and interferon-gamma was elevated in CD3(+) PALN cells after exposure to semen, as assessed by intracellular cytokine fluorescence-activated cell sorting, immunohistochemistry and quantitative reverse transcriptase polymerase chain reaction. Matings with vasectomized males indicated that the lymphocyte activation occurs independently of sperm. However, in contrast, males from which seminal vesicle glands were surgically removed failed to stimulate PALN cell proliferation or cytokine synthesis. Adoptive transfer experiments using radiolabelled lymphocytes from mated mice showed that lymphocytes activated at insemination home to embryo implantation sites in the uterus as well as other mucosal tissues and lymph nodes. These findings indicate that activation and expansion of female lymphocyte populations occurs after mating, and is triggered by constituents of seminal plasma derived from the seminal vesicle glands. Moreover, lymphocytes activated at insemination may help mediate maternal tolerance of the conceptus in the implantation site.
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PMID:Semen activates the female immune response during early pregnancy in mice. 1514 72

Interleukin-4 (IL-4)-mediated pro-oxidative and pro-inflammatory vascular environments have been implicated in the pathogenesis of atherosclerosis. The cellular and molecular regulatory mechanisms underlying this process, however, are not fully understood. In the present study, we employed GeneChip microarray analysis to investigate global gene expression patterns in human vascular endothelial cells after treatment with IL-4. Our results showed that mRNA levels of a total of 106 genes were significantly up-regulated and 41 genes significantly down-regulated with more than a 2-fold change. The majority of these genes are critically involved in the regulation of inflammatory responses, apoptosis, signal transduction, transcription factors, and metabolism; functions of the remaining genes are unknown. The changes in gene expression of selected genes related to inflammatory reactions, such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6), were verified by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses. IL-4 treatment also significantly increased the adherence of inflammatory cells to endothelial cell monolayers in a dose-dependent manner. These results may help determine the molecular mechanisms of action of IL-4 in human vascular endothelium. In addition, a better understanding of IL-4-induced vascular injury at the level of gene expression could lead to the identification of new therapeutic strategies for atherosclerosis.
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PMID:Gene expression profile in interleukin-4-stimulated human vascular endothelial cells. 1550 79


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