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

Interleukin-15 (IL-15) shares many biological functions with interleukin-2 (IL-2) due to common receptor components. IL-15 binds to the IL-2 receptor (IL-2R) beta-chain and the common gamma-chain receptor in addition to one other IL-15 binding receptor protein (IL-15R alpha). Both IL-2R beta- and gamma-chains are required to promote cell growth in hematopoietic cells. The colonic cryptlike epithelial cell line T84 contains the common gamma-chain but lacks the IL-2R beta-chain. We report IL-15R alpha-chain mRNA in T84 cells with the use of reverse transcriptase-polymerase chain reaction. T84 and normal colonic epithelial cells bind a FLAG-IL-15 fusion protein in immunoperoxidase and flow cytometric experiments. In addition, IL-15, but not IL-2, accelerates and enhances the development of transepithelial resistance across T84 monolayers in a dose-dependent fashion. We conclude that normal and T84 colonic epithelial cells express IL-15R alpha and are able to bind IL-15. IL-15 can deliver a nonproliferative functional signal in the absence of IL-2R beta-chain in T84 cells.
 ...
PMID:Interleukin-15 signals T84 colonic epithelial cells in the absence of the interleukin-2 receptor beta-chain. 917 31

It is known that there are some bidirectional interactions between the nervous and the immune systems via neurotransmitters and cytokines. To clarify whether any neurotransmitters modulate lymphocyte functions, we examined the effects of oxotremorine-M (Oxo-M) on interleukin-2 (IL-2) production in human peripheral blood lymphocytes by using enzyme-linked immunosorbent assays, Northern blot analyses, reverse transcriptase-polymerase chain reaction, and fluorescence-activated cell sorter. Pretreatment of cells with Oxo-M (10 nM to 10 microM) for 4-24 hr enhanced phytohemagglutinin (PHA)-induced IL-2 mRNA expression and markedly increased IL-2 production compared with those induced by PHA alone. Oxo-M alone did not affect IL-2 mRNA expression and IL-2 production. In CD3-positive T cells, pretreatment with Oxo-M for 24 hr enhanced PHA-induced IL-2 production. Furthermore, pretreatment with Oxo-M enhanced PHA-induced mRNA expression of the alpha and beta subunits of IL-2 receptors and DNA synthesis. Cytometric analysis showed Oxo-M treatment did not up-regulate expression of cell surface molecules such as CD3, CD2, CD4, CD8, and IL-2 receptors. These results suggest that activation of muscarinic receptors enhances T cell antigen receptor/CD3-induced IL-2 production.
 ...
PMID:Stimulatory roles of muscarinic acetylcholine receptors on T cell antigen receptor/CD3 complex-mediated interleukin-2 production in human peripheral blood lymphocytes. 918 67

Epstein-Barr virus (EBV) is a human lymphotropic virus whose main targets have traditionally been described as B lymphocytes and epithelial cells. Here we report the isolation and characterization of largely monoclonal transformed human T-cell lines infected by EBV. The transformed T cells expressed CD2, CD3, and either CD4 or CD8 surface molecules and more generally displayed the phenotype of naive T cells with a complete and clonal rearrangement of the T-cell receptor. None of the cell lines expressed B cells, natural killer, or myeloid antigens or had immunoglobulins genes rearrangement. They grew in the absence of growth factor; however, they all secreted interleukin-2 after mitogenic activation. Polymerase chain reaction (PCR) analysis showed the presence of EBV DNA in all these cell lines. Moreover, Southern blot analysis of one of these cell lines shows the presence of circular episomic EBV DNA, and by Northern blot or reverse transcriptase-PCR analysis, only the expression of Epstein-Barr nuclear antigen-1 (EBNA-1) and latent membrane protein-1 (LMP-1) genes was detected. Finally, the complete transformed phenotype of this T-cell line was shown by its injection into nude or recombination activating gene 2 (RAG2)-deficient mice that led to the formation of solid tumors.
 ...
PMID:Isolation and characterization of transformed human T-cell lines infected by Epstein-Barr virus. 919 76

Cytotoxic T lymphocytes and natural killer (NK) cells kill target cells by two main mechanisms, namely, the perforin/granzymes and the Fas ligand (Fas-L) pathways. The preferential activation of either of these two mechanisms by target cells is not known. This study examined whether various NK stimuli regulate preferentially the perforin/granzyme or the Fas pathways during the NK-cell-mediated cytotoxic reaction (NK-CMC). Purified peripheral-blood-derived NK cells were stimulated with interleukin-2 (IL-2), IL-12, or interferon alpha (IFN alpha) and their response was analyzed by the reverse transcriptase/polymerase chain reaction (RT-PCR) for NK-associated gene expression and by the 51Cr-release assay for cytotoxic function. RT-PCR data revealed that the perforin, granzyme A and granzyme B mRNAs were constitutively expressed in unstimulated NK cells and the level of perforin mRNA was augmented following activation. IL-2 enhanced the level of Fas-L mRNA in NK cells; however, the Fas-L level was much lower than that obtained in activated T cells. NK-CMC against Fas-sensitive cells was examined in the presence of neutralizing anti-(Fas antigen receptor) (Fas-R) antibody (ZB-4) or EGTA/Mg2+, which inhibits the perforin/granzyme pathway but not the Fas Fas-L interaction. The human colon adenocarcinoma HT-29 cells were sensitized to anti-Fas-R antibody (CH-11) cytotoxicity following treatment with IFN gamma. NK-CMC against untreated HT-29 cells was completely inhibited by EGTA/Mg2+ and was unaffected by ZB-4, while both EGTA/Mg2+ and ZB-4 partially inhibited NK-CMC against IFN gamma-treated HT-29 cells. Similar findings to those obtained with untreated NK cells were observed with NK cells stimulated with IL-2, IL-2 plus IL-12 or IFN alpha. In contrast to IFN gamma-treated HT-29 cells, the neutralizing anti-Fas antibody ZB-4 did not inhibit NK-CMC against Fas-sensitive U937, CEM or Jurkat tumor cells. These findings demonstrate that the Fas pathway is involved in NK-CMC against certain target cells but not all. Further, the data demonstrate that activation of NK cells by IL-2, IL-2 plus IL-12 or IFN alpha does not preferentially modulate the Fas-L-mediated killing by NK cells.
 ...
PMID:The participation of the Fas-mediated cytotoxic pathway by natural killer cells is tumor-cell-dependent. 924 63

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.
 ...
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 bovine interleukin-15 (IL-15) sequence was cloned from abomasal lymph node mRNA by enzymatic amplification of cDNA using human primers proximal to and including the translation start and stop sites. The open reading frame is 486 base pairs in length, and the proposed protein sequence shows 78.4% and 73.5% similarity with that predicted for the human and mouse sequences, respectively. Expressed and purified recombinant bovine IL-15 in the absence of the 48-amino acid leader sequence stimulated the proliferation of bovine lymphoblast cells at least 12-fold over background at maximum concentration levels. Competitive reverse transcriptase-polymerase chain reaction analysis showed constitutive levels of IL-15 mRNA within a broad range of tissues and cell types. Lipopolysaccharide addition to adherent lymph node populations caused moderate increases in IL-15 transcription, whereas the addition of phorbol 12-myristate 13-acetate and calcium ionophore failed to induce gene expression for this cytokine. Transcription of IL-15 was also downregulated in the presence of low concentrations of human recombinant interleukin-2.
 ...
PMID:Cloning and expression of bovine interleukin-15: analysis and modulation of transcription by exogenous stimulation. 928 28

It has been reported that the intrahepatic lymphocyte (IHL) population is somewhat differently constituted from lymphocytes in other lymphoid tissues. Staphylococcal enterotoxin B (SEB) is a superantigen which can induce T-cell tolerance in mice. The authors investigated the in vitro and in vivo responses of mouse IHL to SEB. An intravenous injection of SEB did not result in the augmentation of the proliferative response of IHL, while mesenteric and splenic lymphocytes (mLNC and SPC, respectively) had augmented responses. Interleukin-2 (IL-2) mRNA was clearly detected in mLNC and SPC by reverse transcriptase-polymerase chain reaction (RT-PCR) shortly after the administration of SEB, but it was scarcely expressed in IHL. The expression of CD25 (IL-2 receptor) was also augmented in mLNC and SPC in the early period, while it was not changed in IHL. These findings suggested that the time required for tolerance induction is different locally and that the loss of augmentation of IL-2 and IL-2 receptor production by IHL may be relevant to the rapid induction of T-cell tolerance in the liver.
 ...
PMID:A unique response to staphylococcal enterotoxin B by intrahepatic lymphocytes and its relevance to the induction of tolerance in the liver. 931 9

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.
 ...
PMID:FK-506 and cyclosporin A potentiate the IgE antibody production by contact sensitization with hapten in mice. 933 39

Granzyme B is a protein thought to play a pivotal role in the cytolytic functions of T cells. In view of this, the inducibility of this gene in freshly isolated T cells (T-TILs) infiltrating human renal cell carcinoma (RCC) in vitro was examined by using the reverse transcriptase-polymerase chain reaction (RT-PCR). A reduction in granzyme B messenger RNA (mRNA) expression in stimulated T-TILs from five of nine patients with RCC compared with autologous peripheral blood T cells was noted. The reduced expression was observed after multiple stimuli including anti-CD3 antibody, interleukin-2 (IL-2), and phytohemagglutinin (PHA). Because CD8+ T cells represent the predominant cytotoxic population, the ability of this cell population to express granzyme B mRNA after stimulation also was examined. When compared with CD8+ peripheral blood lymphocytes (T-PBLs) from patients with RCC and normal donors, the induction of granzyme B mRNA was reduced in CD8+ T-TILs. CD8+ T-TILs also had lower non-major histocompatibility complex (MHC)-restricted cytotoxic activity than did CD8+ T-PBLs against both Daudi cells and allogeneic RCC cell lines. These results show that in a subset of patients with RCC, depressed lytic activity of CD8+ TILs compared with CD8+ PBLs is present. Reduced granzyme B mRNA expression also was noted in selected patients.
 ...
PMID:Defective granzyme B gene expression and lytic response in T lymphocytes infiltrating human renal cell carcinoma. 940 54

To systematically elucidate the gene expression of inflammatory and immune modulators following middle cerebral artery occlusion (MCAO) in the rat, we studied interleukin-10 (IL-10) along with tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-2 (IL-2). Gene expression of these cytokines was studied ipsilateral and contralateral to the MCAO, with mRNA expression levels evaluated 2, 4, 6, 8 and 12 h following permanent MCAO by reverse transcriptase polymerase chain reaction (RT-PCR). In the ischemic hemisphere TNF-alpha and IL-1beta mRNA increased at 2 h following MCAO and peaked at 6 h, with IL-10 mRNA detected only at 6 h. Contralaterally, both TNF-alpha and IL-1beta mRNAs were expressed with a similar pattern to that in the ischemic hemisphere, but at lower levels, with no contralateral IL-10 expression. There was no difference in IL-2 gene expression between control and experimental animals in either hemisphere. These results demonstrate that IL-10 and TNF-alpha, IL-1beta gene expression is induced early following MCAO. The temporal profile of these cytokines is similar to that seen in sepsis, where TNF-alpha induces IL-10; subsequently IL-10 inhibits TNF-alpha expression. The similarity of the temporal profile of cytokine expression in sepsis and cerebral ischemia suggests that IL-10 should be studied as a potential inhibitor of TNF-alpha production in ischemic brain tissue. The factors inducing contralateral expression of the inflammatory cytokines, TNF-alpha and IL-1beta, along with the potential clinical significance of this remote cytokine gene expression, merit further study.
 ...
PMID:Gene expression of IL-10 in relationship to TNF-alpha, IL-1beta and IL-2 in the rat brain following middle cerebral artery occlusion. 941 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>