Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-11 is a stromal cells derived cytokine which stimulates the proliferation of primitive haemopoietic progenitor cells. For this paper we have studied the constitutive expression of IL-11 mRNA in a panel of wellknown leukaemic cell lines and samples from AML patients at diagnosis. Moreover, the same cellular populations were evaluated for their proliferative response to recombinant-human-(r-hu). IL-11 alone and combined with r-hu-IL-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and stem cell factor (SCF, c-kit ligand). The colony-forming ability of HL60, K562, KG1 cells and eight fresh AML cell populations was assessed by a clonogenic assay in methylcellulose. In eight additional AML cases the number of S-phase leukaemic cells induced by IL-11 was determined by the bromodeoxyuridine (BRDU) incorporation assay after 3d of liquid culture. IL-11, as single cytokine, did not stimulate the colony formation of the three myeloid cell lines under serum-containing and serum-free conditions. In contrast, the proliferation of the leukaemic cells in response to IL-3, GM-CSF and SCF was enhanced by co-incubation with IL-11, and this effect was reversed in blocking experiments by the anti-IL-11 Moab. When tested on primary AML samples, IL-11 alone showed little, if any, proliferative activity. However, it increased the IL-3-dependent blast colony formation in eight out of eight cases and GM-CSF in seven cases. IL-11 also augmented synergistically the number of CFU-L stimulated by SCF in seven cases. A combination of three factors (IL-11, SCF and IL-3) yielded optimal colony formation. The BRDU studies showed the significant increase of AML cells in S-phase when IL-11 was combined with SCF, whereas the two CSF had no activity on their own. Positive interaction was also observed when IL-11 was added to IL-3 supplemented cultures in five out of eight cases tested. Reverse transcriptase-polymerase chain reaction amplification (RT-PCR) demonstrated the constitutive expression of IL-11 mRNA in all the cell lines and 11/12 AML samples studied at diagnosis. These results indicate that IL-11 is expressed in leukaemic myeloid cells and that their proliferation is regulated by the cytokine which acts as a synergistic factor.
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PMID:Interleukin-11 (IL-11) acts as a synergistic factor for the proliferation of human myeloid leukaemic cells. 854 68

Nontransformed stromal colony-derived cell lines (CDCLs) consist of a pure stromal cell population that differentiates following a vascular smooth muscle cell repertoire, and whose in vivo counterpart is that of myoid cells found in adult and fetal human bone marrow cords. We studied the cytokine expression by reverse-transcriptase polymerase chain reaction (RT-PCR) from pooled fast-growing clones from 10 different bone marrow samples. RT-PCR indicated that 30 cytokines (out of 42 studied) were expressed by CDCLs (20 after medium renewal and hydrocortisone renewal, three after addition of interleukin I beta (IL-1 beta) and seven in only part of the CDCL layers examined). The cytokines expressed comprised mediators known to be involved in the maintenance of early and late hematopoiesis (IL-1 alpha and IL-beta, IL-6, IL-7, IL-8, IL-11 and IL-13; colony-stimulating factors, thrombopoietin, erythropoietin, stem cell factor, fit 3-ligand, hepatocyte cell growth factor, tumor necrosis factor alpha, leukemia inhibitory factor, transforming growth factors beta 1 and beta 3; and macrophage inflammatory protein 1 alpha), angiogenic factors (fibroblast growth factors 1 and 2, vascular endothelial growth factor) and mediators whose usual target (and source) is the connective tissue-forming cells (platelet-derived growth factor A, epidermal growth factor, transforming growth factors alpha and beta 2, oncostatin M and insulin-like growth factor 1), or neuronal cells (nerve growth factor). The cytokines not expressed were lymphokines (IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and IL-12 and interferon gamma) or mediators synthesized by macrophages (inhibin, activin, platelet-derived growth factor B, and IL-1 receptor antagonist). This study complements the description of the phenotype of the myoid cells, confirming that these cells are the marrow connective tissue-forming cells; moreover, this work suggests that stromal control of hematopoiesis is multifactorial and that myoid cells are involved in the control of marrow angiogenesis and innervation.
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PMID:The broad spectrum of cytokine gene expression by myoid cells from the human marrow microenvironment. 909 Jul 90

Activated macrophage-conditioned medium (M-CM) induces megakaryocytic differentiation of HIMeg-1 cells. The megakaryocytic differentiation activity (MDA) is proteinaceous since it is susceptible to treatments by proteinases, heat, and reducing agents. MDA is not thrombopoietin (TPO) since (1) TPO alone or in conjunction with several other recombinant cytokines fails to induce any degree of HIMeg-1 cell differentiation; and (2) a neutralizing antibody against TPO or an antibody against the extracellular domain of c-mpl is unable to abolish M-CM-induced CD41 expression on HIMeg-1 cells. Reverse transcriptase-mediated polymerase chain reaction shows that HIMeg-1 cells express c-mpl but not TPO. Additional neutralizing antibody studies suggest that MDA is not one of the cytokines known to induce some degree of megakaryopoiesis in vitro or in vivo including interleukin 3 (IL-3), IL-6, IL-11, granulocyte-macrophage colony-stimulating factor, erythropoietin, or stem cell factor. On the other hand, MDA appears to be a combination of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha), since neutralizing antibodies against these two cytokines completely abolish MDA-induced CD41 expression. In addition, either recombinant human IFN-gamma or TNF-alpha alone is capable of inducing CD41 and CD42 expression on HIMeg-1 cells. In combination, IFN-gamma and TNF-alpha induce a maximal level of CD41 and CD42 expression which is also accompanied by an increase in cell size and DNA ploidy level. Thus, our studies indicate that IFN-gamma/TNF-alpha is capable of inducing megakaryocytic differentiation of the HIMeg-1 cell line and that HIMeg-1 is a good system for studying the molecular mechanism mediating megakaryocytic differentiation.
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PMID:Megakaryocytic differentiation of HIMeg-1 cells induced by interferon gamma and tumour necrosis factor alpha but not by thrombopoietin. 987 25

Earlier, we described a stromal cell-free two-step clonal culture system in which murine primitive lymphohematopoietic progenitors produce myeloid and B-lymphoid lineage cells. In the same culture T-cell potential of the progenitors was maintained. We now report that, in addition to myeloid and B-lymphoid cells, putative T-cell progenitors are also produced in culture. Lineage-negative (Lin-) Ly-6A/E+ c-kit+ bone marrow cells from 5-fluorouracil-treated mice were cultured in methylcellulose in the presence of SF (Steel factor), interleukin (IL)-11, and IL-7, and the resulting primary colonies were picked and pooled. When injected into severe combined immune deficiency (scid) mice, the pooled cells reconstituted the T-cell compartment of the scid mice earlier than freshly prepared primitive marrow cells. This reconstitution activity of the pooled primary colony cells was enriched in the Ly-6A/E+ and FcgammaRII/III-/low cell fractions. Reverse transcriptase-polymerase chain reaction (RT-PCR) and DNA-PCR analyses showed that some of the primary colony cells are differentiated sufficiently to express messenger RNA (mRNA) of T-cell receptor (TCR) beta-chain and pre-TCR alpha (pTalpha) and, although not frequently, to perform Dbeta-Jbeta rearrangement of the TCR gene. Micromanipulation studies confirmed the clonal origin of myeloid lineage cells and the cells positive for the T-cell-specific transcripts and D-J rearrangement of TCR beta-chain. These results suggested that, in the presence of SF, IL-11, and IL-7, primitive lymphohematopoietic progenitors differentiate toward T-cell lineage in addition to myeloid and B-cell lineages.
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PMID:Differentiation in culture of murine primitive lymphohematopoietic progenitors toward T-cell lineage. 1036 Nov 16

Several cytokines have been found to play a role in the pathogenesis of B-CLL. In the present study using reverse-transcriptase polymerase chain reaction (RT-PCR), FACS analysis and immunofluorescence we have shown the constitutive expression of IL-11 and IL-11R alpha in B-chronic lymphocytic leukemia (B-CLL). The expression level of IL-11R alpha in B-CLL cells is much higher than in PBL of normal donors. Recombinant human IL-11 (rhIL-11) activates B-CLL cells, leading to morphologic alterations of the cells and increase in cell number and size. Short-term cultivation in the presence of rhIL-11 did not lead to quantitative changes in the ratio of the living vs apoptotic and dead cells. However, in contrast to rhIL-6, pretreatment with rhIL-11, did not cause B-CLL cells to be resistant to the action of dexamethasone. These data suggest an essential role for the IL-11/IL11 R alpha system in the pathogenesis of the malignant B-CLL cells.
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PMID:Over-expression of the functional interleukin-11 alpha receptor in the development of B-cell chronic lymphocytic leukemia. 1169 7