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)

According to the 'aberrant HLA expression' hypothesis, endocrine autoimmunity is driven by presentation of self antigens by target cells over-expressing HLA molecules. In autoimmune thyroid diseases (AITD), thyroid follicular cells (thyrocytes) over-express HLA class I and HLA class II molecules. Since efficient presentation of endogenous peptides via class I requires transporters that translocate endogenous peptides from the cytoplasm to the endoplasmic reticulum, i.e. transporters associated with antigen processing (TAP) -1 and -2, the capability of thyrocytes to express TAP and whether TAP is hyperexpressed in AITD glands are issues relevant to the above hypothesis. Results from immunofluorescence and Northern blotting studies on primary thyrocyte cultures and on a thyroid cell line demonstrate that thyrocytes express constitutively TAP-1 at a low level, and that this expression is readily induced by interferon-gamma (IFN-gamma) and to a lesser extent by IFN-alpha. In AITD, but not in non-autoimmune glands, thyrocytes hyperexpress TAP-1, as demonstrated by both immunohistopathology and flow cytometry. The cytokine pattern does not bear, as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), a clear relationship with TAP-1 expression. These results have broad implications and suggest that the core concept of the 'aberrant HLA expression' hypothesis of endocrine autoimmunity could be incorporated in the currently prevailing view of 'autoimmunity by breach of peripheral tolerance'.
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PMID:Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity: a contributing factor to the breach of tolerance to thyroid antigens? 921 31

Two monoclonal antibodies (MAb), HB65A (IgG2a) and HB86A (IgGI), recognize a unique cell surface molecule on equine T-lymphocytes. The molecule, designated EqWC4, identified by these MAbs is present on a subpopulation of CD4+ equine lymphocytes (6.3-10.2% of Arabian lymphocytes CD4+ WC4+) and a smaller population of CD8+ lymphocytes (0.5% to 1.2% of Arabian lymphocytes CD8+ WC4+). EqWC4 is absent from B-lymphocytes, granulocytes, and macrophages. Both MAbs bound to a 46-kDa protein following immunoprecipitation reactions with lysates of surface labeled thymocytes. Immunoaffinity purification using HB65A yielded two molecules of 46 kDa and 52 kDa under reducing conditions and a third 92-kDa molecule was present in nonreduced conditions. Activation by mitogen did not increase expression of EqWC4 on equine lymphocytes. Lymphocytes from Arabian, Pony, and Thoroughbred breeds showed a common distribution of EqWC4 among leukocytes. However, there were significantly fewer Pony lymphocytes bound to HB65A and HB86A when compared to Arabian and Thoroughbred breeds. Using reverse transcriptase-polymerase chain reaction (RT-PCR), magnetically enriched populations (to 80% of cells isolated) of EqWC4+ lymphocytes expressed a cytokine RNA profile dominated by -interleukin2 (IL-2) and interferon-gamma (IFN-gamma) for unstimulated cells. Upon mitogen stimulation, IL-4 was also expressed at low levels while the IL-2 levels decreased and the IFN-gamma levels increased relative to unstimulated cells. EqWC4 is similar to CD28 in molecular weight and its formation of dimers and could therefore be the equine orthologue. However, because of the differences in CD28 expression, EqWC4 probably represents a previously uncharacterized equine lymphocyte marker.
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PMID:Cytokine RNA expression in an equine CD4+ subset differentiated by expression of a novel 46-kDa surface protein. 922 25

Macrophages and polymorphonuclear cells (PMN) play a major role as cells primarily responsive to microbial biological response modifiers (BRM). Although much attention has been given to macrophages, PMN have been relatively underinvestigated. We have recently studied the responses of PMN from HIV- and HIV+ subjects after stimulation with a powerful immunomodulatory fraction from the cell wall of Candida albicans (MP-F2) and compared this to bacterial lipopolysaccharide (LPS). Both cytokine patterns and PMN anticandidal activity were investigated. MP-F2, like LPS, was an active inducer of interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-1 beta production by PMN and monocytes from all subjects. IL-12 was also produced by MP-F2-stimulated PMN in the presence of interferon-gamma (IFN-gamma). PMN from HIV+ subjects showed increased in vitro expression of TNF-alpha and IL-6 genes as determined by semiquantitative reverse transcriptase-polymerase chain reaction. In all subjects, cytokine gene expression was strongly stimulated by MP-F2 or LPS and inhibited by IL-10. Production of IL-6 and TNF-alpha protein (measured by ELISA) was higher in PMN from HIV+ subjects in at least one of the conditions tested (unstimulated or stimulated by LPS or MP-F2). However, the amount of the C-X-C chemokine IL-8 was equal in PMN from HIV- and HIV+ subjects. PMN from HIV+ subjects were at least as active in inhibiting candide growth as PMN from HIV- controls. In both groups PMN were equally stimulated by MP-F2 and LPS. Only in severely neutropenic subjects was there some reduction in the anticandidal activity but not in cytokine responses. When appropriately stimulated by microbial BRM, PMN are active producers of pro-inflammatory and immunomodulatory cytokines. This production is not only totally preserved in HIV+ subjects but may be higher than in PMN from HIV- subjects and may be coupled with an efficient anticandida activity. We suggest that during common bacterial or fungal infections PMN may contribute to the dysregulated production of inflammatory cytokines in AIDS patients.
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PMID:Possible participation of polymorphonuclear cells stimulated by microbial immunomodulators in the dysregulated cytokine patterns of AIDS patients. 922 94

This review considers the potential reduction of embryo mortality in vitro and in vivo in ruminants. Data on cytokines provided by different fields of reproductive immunology and biology were collated. Because of the crucial importance of the local interactions between the embryo and its dam, the expression of growth-factor and cytokine genes was analysed in the embryo proper, trophoblast, oviduct and endometrium by reverse transcriptase polymerase chain reaction in sheep and in cattle during the pre- and periimplantation periods. Many deleterious cytokines, such as tumour necrosis factor-alpha, interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and beneficial cytokines, such as transforming growth factor-beta, leukaemia inhibiting factor, colony-stimulating factor-1 (CSF-1), granulocyte-macrophage CSF, IL-1, IL-3, IL-4, IL-6, IL-10 and IFN-tau appeared to be involved in embryo survival in ruminants and other species. Their administration is efficient in a murine experimental model (CBA/J x DBA/2) of embryonic and fetal mortality. For instance, recombinant ovine IFN-tau (roIFN-tau) injected at the moment of implantation drastically reduces embryonic mortality in this model. In ruminants, roIFN-tau and recombinant bovine IFN-tau are very efficient in maintaining progesterone luteal secretion in cyclic animals. The involvement of IFN-tau in the mechanisms of maternal pregnancy recognition are particularly detailed in relation to inhibition of 13,14 dihydro-15-keto-prostaglandin F2 alpha (PGFM) pulses and oxytocin uterine receptivity. A synthetic model of the anti-luteolytic effects of IFN-tau on the endometrial cell is proposed. Finally, the particular potential of serum pregnancy-specific proteins (PSPs: PSPB, PSP60, pregnancy-associated glycoprotein) for monitoring embryo survival, with examples given for cattle and sheep is underlined.
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PMID:Recent developments and potentialities for reducing embryo mortality in ruminants: the role of IFN-tau and other cytokines in early pregnancy. 926 83

The reasons why severe allergic reactions to bee and wasp stings develop in only a small portion of exposed individuals are incompletely understood, but differences in T cell responses to venom antigens comparing allergic and non-allergic individuals are likely to be important. To identify such differences, venom-induced proliferative responses and cytokine mRNA production by blood mononuclear cells from Vespula venom-allergic patients and non-allergic individuals were compared. Mononuclear cells from most venom-allergic patients proliferated in response to alkylated Vespula venom (7275 +/- 8387 ct/min, n = 19), and the extent of proliferation was greater for patients with a history of multiple prior stings and those with high levels of venom-specific IgE. Although mononuclear cells from non-allergic subjects showed little or no proliferation in response to venom (926 +/- 711 ct/min, n = 8), production of mRNAs coding for IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma) in response to Vespula venom by cells from non-allergic subjects was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), indicating that these individuals had been previously sensitized to venom antigens. In contrast to the Th0 cytokine mRNA profile observed for non-allergic individuals, venom-allergic patients released a more restricted profile of cytokines following stimulation with venom. Only IFN-gamma mRNA expression was detected in all individuals evaluated, whereas IL-2 mRNA was not detected during the first 48 h of stimulation, and T cells from only one of three venom-allergic individuals produced detectable IL-4 or IL-5 mRNA. The difference in cytokine profiles observed comparing venom-allergic patients and non-allergic controls could not be attributed to intrinsic differences in T cells from these individuals, because polyclonal stimulation with phorbol myristate acetate (PMA) + ionophore induced similar cytokine mRNA profiles in the two groups. These studies demonstrate clear differences in the T cell responses of venom-allergic subjects, that may contribute to the development of severe allergic reactions in these individuals.
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PMID:Characterization of proliferative responses and cytokine mRNA profiles induced by Vespula venom in patients with severe reactions to wasp stings. 927 31

Five repeated topical applications of 2,4-dinitrofluorobenzene to the ears of BALB/c mice resulted in contact dermatitis on the ears as well as significant elevation in dinitrophenol-specific IgE antibody and total IgE in the serum. FK-506 and cyclosporin A inhibited the development of contact dermatitis in terms of skin thickness and histopathological changes of skin lesions. On the contrary, these two drugs potentiated dinitrophenol-specific and total IgE antibody production without affecting IgG and IgM levels in serum. The expression of interferon-gamma mRNA in reverse transcriptase-polymerase chain reaction in the ear was inhibited by FK-506 and cyclosporin A. The expression of interleukin-4 mRNA, germline C epsilon and productive C epsilon in the auricular lymph node was not affected by these two drugs. Contrary to the above in vivo findings, the immunosuppressors, FK-506 and cyclosporin A, inhibited the production of interferon-gamma and interleukin-2 by cultured Th1 cells (1E10.H2 cells) and of interleukin-4 and -5 by Th2 cells (D10.G4.1 cells) in vitro. These results indicated that FK-506 and cyclosporin A selectively inhibited the Th1 cell-mediated contact dermatitis and potentiated the Th2 cell-mediated IgE antibody production in vivo. This potentiation is probably due to the down-regulation of interferon-gamma production by Th1 cells after the treatment with these drugs. However, because FK-506 and cyclosporin A inhibited the production of cytokines by both Th1 and Th2 cells in vitro and these two immunosuppressors showed higher selectivity toward inhibiting Th1 cell-mediated reactions by limitations in vivo experiments.
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PMID:FK-506 and cyclosporin A potentiate the IgE antibody production by contact sensitization with hapten in mice. 933 39

The Fas antigen is a cell surface receptor that, when engaged by Fas ligand or specific agonistic antibodies, triggers apoptosis. The effect of an agonistic monoclonal antibody to mouse Fas antigen (Fas mAb, clone J02) on the viability of cells from dispersed mouse corpora lutea (CL cultures) was tested. Cultures were prepared by enzymatic digestion of CL from day 4-7 pseudopregnant mice. Cultures were pretreated with 0, 1, 10, 100, or 1000 U/ml murine interferon-gamma (IFN) at 72 h of culture. IFN has been shown to increase Fas antigen expression in a number of cell types. At 96 h (time zero), cultures were treated with Fas mAb or IgG. By 4 h after Fas mAb treatment, discrete homogeneous patches of cells within the cultures showed characteristic signs of apoptosis, including blebbing of cell membranes, detachment, and disappearance from the culture. CL cultures contain luteal, stromal, and endothelial cells; fibroblasts; and surface epithelial cells (OSE). Cells dying in response to Fas mAb were identified as OSE. Affected cells had the cobblestone appearance and distinct nuclei typical of epithelial cells. Unlike luteal cells, OSE did not stain with the lipophilic dye, Nile red. The cells did not stain with acetylated low density lipoprotein conjugated to the fluorescent marker octadecyl indocarbocyanine, a marker for endothelial cells and monocytes. Cells in patches stained positively for cytokeratin, a marker for epithelial cells. Fas-mediated cytotoxicity was quantified by counting the number of cells present in discrete patches of OSE 0 and 8 h after Fas mAb treatment. Fas mAb treatment had no effect in cultures pretreated with 0 or 1 U/ml IFN, but induced significant death of OSE in cultures pretreated with 10, 100, and 1000 U/ml IFN (37 +/- 11%, 54 +/- 18%, and 60 +/- 11%, respectively). There was no apparent effect of Fas mAb on other cell types within the CL cultures. To confirm that cells dying in response to Fas mAb were OSE, experiments were also performed on enriched cultures of OSE prepared by enzymatic digestion of the outer surface of the ovary. In enriched OSE cultures pretreated with 200 U/ml IFN, there was 44% killing in response to Fas mAb, whereas in cells not pretreated with IFN, there was no effect. In situ fluorescent end labeling of DNA in CL cultures indicated that treatment with IFN and Fas mAb induced DNA fragmentation in OSE typical of apoptosis. Immunocytochemistry of CL cultures indicated that Fas antigen was expressed in OSE pretreated with IFN. Quantitative reverse transcriptase-PCR showed that IFN pretreatment increased Fas antigen messenger RNA levels 2.3-fold in enriched cultures of OSE. In summary, OSE in CL cultures and enriched cultures of OSE undergo apoptosis in response to Fas mAb when pretreated with IFN. In vivo, OSE undergo programmed cell death before ovulation and rapidly proliferate to repair the surface of the ovulatory follicle after ovulation. Most ovarian cancers are derived from the OSE. The results have implications for both normal ovarian function and oncogenesis in the ovary.
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PMID:Fas antigen-mediated apoptosis of ovarian surface epithelial cells. 934 78

Since the discovery of its involvement in the pathogenesis of simian immunodeficiency virus infection, the role of macaque monkey interferon-gamma (IFNgamma) has been a focus of particular interest. The purpose of this study was to express bioactive recombinant monkey IFNgamma, as well as clone cynomolgus monkey IFNgamma cDNA. The isolation of a cDNA encoding cynomolgus monkey IFNgamma was performed using a reverse transcriptase polymerase chain reaction-based strategy with activated monkey lymphocyte cDNA as templates. Cynomolgus monkey IFNgamma consists of 165 amino acids including a putative signal sequence and has 94, 60 and 39% identity to human, bovine and murine homolgues, respectively. Monkey IFNgamma cDNA was highly expressed as three distinct secreted proteins by a recombinant baculovirus system. The secreted proteins were revealed to have antiviral activity up to 10(8) units/ml characteristic of authentic IFNgamma by a bioassay of a cytopathic effect reduction assay.
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PMID:Molecular cloning and expression of cynomolgus monkey interferon-gamma cDNA. 936 3

We explored expression and possible function of interferon-gamma (IFN-gamma) in cultured fetal (E15) rat dorsal root ganglion neurons combining whole cell patch-clamp electrophysiology with single cell reverse transcriptase polymerase chain reaction and confocal laser immunocytochemistry. Morphologically, we located IFN-gamma protein in the cytoplasm of the neurons in culture as well as in situ during peri- and postnatal development. Transcripts for classic IFN-gamma and for its receptor were determined in probes of cytoplasm sampled from individual cultured neurons, which had been identified by patch clamp electrophysiology. In addition, the cultured neurons expressed both chains of the IFN-gamma receptor. Locally produced IFN-gamma acts back on its cellular source. Phosphorylation and nuclear translocation of the IFN-inducible transcriptional factor STAT1 as well as IFN-gamma-dependent expression of major histocompatibility complex class I molecules on the neuronal membrane were noted in untreated cultures. However, both processes were substantially blocked in the presence of antibodies neutralizing IFN-gamma. Our findings indicate a role of IFN-gamma in autocrine regulation of sensory neurons.
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PMID:Interferon gamma gene expression in sensory neurons: evidence for autocrine gene regulation. 939 71

Nitric oxide (NO) is suggested to play a role in mediating pulmonary injury. However, interspecies differences appear to exist in the ability of alveolar macrophages (AM) to express the inducible nitric oxide synthase (iNOS) and to generate NO. The purpose of this study was to compare iNOS expression and NO production by rat, hamster, monkey, and human AM using the identical experimental conditions in vitro. As AM donors, CD rats, Syrian golden hamsters, cynomolgus monkeys, and nonsmoking, healthy human volunteers were used. The AM were obtained by bronchoalveolar lavage and stimulated in vitro with various concentrations and combinations of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). The oxidation product of NO, nitrite, was measured in the AM supernatant by the Griess reaction. The expression of iNOS in AM was detected using immunocytochemistry and immunoblotting. The expression of iNOS mRNA was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rat AM, stimulated with either LPS or IFN-gamma, produced nitrite in a time- and dose-dependent manner. Combination of LPS and IFN-gamma resulted in a significantly enhanced nitrite formation. However, none of the treatments was able to induce hamster, monkey, or human AM to release measurable amounts of nitrite. Whereas expression of iNOS protein was only detected in stimulated rat AM, expression of iNOS mRNA was found in unstimulated and stimulated rat AM, slightly in stimulated hamster AM, but not in monkey and human AM. In conclusion, our findings point to distinct regulatory mechanisms of the NO pathway in AM from these four different species.
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PMID:Expression of inducible nitric oxide synthase and formation of nitric oxide by alveolar macrophages: an interspecies comparison. 940 Jul 41


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