Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncostatin M was found to stimulate the IL-6-addicted hybridoma line B9. Leukaemia inhibitory factor did not stimulate proliferation of this line. Both of these factors bind to the gp130 of the IL-6 receptor. In another cell line that is stimulated by LIF (DA.1), neither IL-6 nor oncostatin M stimulated proliferation. Previously it had been thought that the gp130 alone is sufficient to bind ligand and transduce signal and that oncostatin M could bind to and activate the LIF receptor, but these data show this is not always the case. Mice primed with Pristane were found to have IL-6 in their sera and peritoneal fluid only at a few time points following Pristane treatment; this was determined by IL-6-specific ELISA. When the same samples were analysed on IL-6-addicted B9 cells, stimulatory activity was found at all time points. When the Pristane-primed samples were assayed for oncostatin M activity in the A375 melanoma assay, there was oncostatin M activity at various time points. IL-6 did not have activity on the A375 cells. These data indicate that oncostatin M play a role in the generation of plasmacytoma in vivo.
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PMID:Oncostatin M stimulates proliferation in B9 hybridoma cells: potential role of oncostatin M in plasmacytoma development. 803 97

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, acute-phase reaction and haematopoiesis (for reviews see refs 1, 2). In vitro, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and interleukin-11 display overlapping activities with IL-6. This functional redundancy may be explained by the interactions of specific binding receptors with a common signal-transducing receptor (gp130) (for reviews see refs 3, 4). To elucidate the unique function of IL-6 in vivo, we have disrupted the IL-6 gene by homologous recombination. IL-6-deficient mice develop normally. They fail to control efficiently vaccinia virus and infection with Listeria monocytogenes, a facultative intracellular bacterium. The T-cell-dependent antibody response against vesicular stomatitis virus is impaired. Further, the inflammatory acute-phase response after tissue damage or infection is severely compromised, whereas it is only moderately affected after challenge with lipopolysaccharide. We conclude that IL-6 production induced by injury or infection is an important in vivo SOS signal which coordinates activities of liver cells, macrophages and lymphocytes.
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PMID:Impaired immune and acute-phase responses in interleukin-6-deficient mice. 812 68

Differentiation induction in murine M1 leukemia cells by interleukin 6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) is postulated to occur via a common receptor chain, gp130. In this study, growth factor-induced differentiation of M1 cells was accompanied by a late and persistent decrease in levels of mRNA and protein for a helix-loop-helix transcription factor, the SCL gene product. To evaluate whether reduced SCL expression was instrumental in monocyte differentiation, an SCL cDNA expression vector was introduced into M1 cells to obtain cell lines in which overexpression of SCL mRNA and protein was enforced. This resulted in a reduction in cells differentiating in response to LIF and OSM but not in response to IL-6. Scatchard analysis indicated that both parental and SCL-transfected cell lines exhibited similar receptor numbers and receptor affinities for LIF, OSM, and IL-6, suggesting that the differential responsiveness was not due to selective receptor down-modulation. Thus, these data implicate SCL in monocytic differentiation and provide evidence for differential receptor signaling pathways despite utilization of a common gp130 subunit by all three receptors.
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PMID:The SCL gene product is regulated by and differentially regulates cytokine responses during myeloid leukemic cell differentiation. 835 96

Leukemia-inhibitory factor (LIF) and oncostatin M (OSM) are members of a family of structurally similar growth factors presenting overlapping and specific functions. Although the genes coding for IL-6, CSF3 and CNTF are scattered in the human and mouse genome, human LIF and OSM genes have conserved synteny in the course of evolution. Through isolation of a YAC and a cosmid clone containing both LIF and OSM we demonstrate that the two genes are linked in tandem on human chromosome 22q12, separated by 16 kilobases of intervening genomic DNA and transcribed in the same head-to-tail orientation. The close physical linkage between LIF and OSM genes brings new evidence of their evolutionary relationship.
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PMID:Tandem linkage of genes coding for leukemia inhibitory factor (LIF) and oncostatin M (OSM) on human chromosome 22. 840 48

Using fluorescence in situ hybridization, a cosmid clone containing the gene for oncostatin M (OSM) was mapped to human chromosome 22q12, placing the OSM gene in the same chromosome band as the leukemia-inhibitory factor gene (LIF). The location of the OSM gene was determined relative to the t(11;22)(q24;q12) of Ewing's sarcoma and found to be distal to the translocation breakpoint on chromosome 22. Analysis of physical distances by pulsed-field gel electrophoresis demonstrated further that the two genes lie within 500 kb of each other.
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PMID:Localization of the human oncostatin M gene (OSM) to chromosome 22q12, distal to the Ewing's sarcoma breakpoint. 842 53

The acute phase response is defined as a large number of diverse reactions which attempt to adjust the organism to the effects of stress/injury. It is now clear that there is a complex interaction between the cytokines with interleukin-6 predominant, but also involving interleukin-1, tumor necrosis factor and a group of recently described cytokines including as well interleukin-11, leukaemia inhibitory factor and oncostatin M all of which influence the levels of acute phase proteins. In clinical practice, C reactive protein (CRP) is frequently used as marker of the acute-phase response. It has a short half-life and consequently it is a sensitive measure of cytokine-induced protein synthesis. In rheumatoid arthritis (RA) the rate appearance of bony erosions in the early phase of the disease correlated with the mean serum concentration of CRP in some studies. A recent study examining the rate of spinal trabecular bone loss in the first year of rheumatoid disease found a strong correlation between bone loss and serum CRP concentrations. It appears that CRP concentrations reflect the level of "systemic osteoclast-activating factor" and are, therefore, a good measure of the general catabolic state of the patient. Many would now consider that persistently elevated serum CRP in patients with RA is in itself an indication for immunosuppressive therapy.
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PMID:[Usefulness of the determination of C reactive protein and other acute phase proteins in rheumatoid arthritis]. 853 81

The cytokines interleukin (IL)-6, IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitor factor (LIF), oncostatin M (OSM) and probably the recently cloned cytokine cardiotrophin-1, signal, in combination with their specific receptors, through the common signal transducer gp130. Here, we report that the signaling activities of IL-6, IL-11, CNTF and OSM/LIF can be specifically blocked by different anti-gp130 monoclonal antibodies (mAb). Furthermore, we found two mAb, B-P8 and B-S12, which directly activate gp130 independently of the presence of cytokines or their receptors. This agonistic activity includes induction of cytokine-dependent cell proliferation and stimulation of acute-phase protein synthesis in liver cells. Compared to B-P8 mAb, the B-S12 mAb exhibited the strongest agonistic activity, while both mAb are synergistic in their action. This activity could not be blocked by inhibiting mAb against IL-6 and the IL-6 receptor. In contrast to F(ab')2 of B-S12 which still could activate gp130, Fab fragments completely lost their agonistic activity. Activation by tyrosine phosphorylation of the transcription factors Stat1 and APRF/Stat3 was also induced by B-S12 and B-P8, suggesting that both mAb induce homodimerization of gp130. Since hematopoietic stem cells express gp130 on their plasma membrane, it was anticipated that the agonistic anti-gp130 mAb could stimulate the proliferation of these stem cells. Indeed, B-S12 and B-P8 were able to stimulate CD34+ cells. In summary, our data show for the first time that mAb against gp130 can specifically block the action of distinct IL-6-type cytokines that signal through gp130. Such mAb might be of great value for therapeutic applications in diseases where a single cytokine action needs to be inhibited. In addition, the agonistic gp130 mAb may be used as growth factors for maintenance and expansion of stem cells prior to grafting.
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PMID:Interleukin-6 signal transducer gp130 has specific binding sites for different cytokines as determined by antagonistic and agonistic anti-gp130 monoclonal antibodies. 856 40

A consensus regarding myeloma cell growth factor responsiveness and ability to produce autocrine interleukin (IL)-6 has not yet been obtained. In this study, we have established three new human myeloma cell lines (DP-6, KAS-6/1 and KP-6) from patients with aggressive disease. Extensive characterization of these cell lines revealed considerable heterogeneity at several levels. Growth factor responsiveness was initially addressed. Although the potent myeloma cell growth factor, IL-6, induced the proliferation and allowed for the expansion of all three cell lines, a panel of other cytokines elicited heterogeneous responses in each cell line. IL-3, IL-10, IL-11, insulin-like growth factor-I and tumor necrosis factor-alpha also stimulated DNA synthesis in all three cell lines; however, the magnitude of the response was generally lower than that observed in cultures containing IL-6. Transforming growth factor-beta, by contrast, uniformly inhibited the growth of all three cell lines. IL-1alpha and IL-1beta induced the proliferation of the DP-6 cells, but had minimal effects on the KAS-6/1 and KP-6 cells. Interferon (IFN)-alpha stimulated DNA synthesis in the KAS-6/1 cells, but inhibited the proliferation of the DP-6 and KP-6 cells. By comparison, IFN-gamma induced the growth of the KAS-6/1 and DP-6 cells, but inhibited the KP-6 cells. The gp130-associated cytokines, IL-11, leukemia inhibitory factor and oncostatin M, stimulated the growth of the KAS-6/1 cells, but had minimal effects on the DP-6 and KP-6 cells. The cell lines were also analyzed for IL-6 expression. RT-PCR analysis demonstrated that all three cell lines expressed IL-6 mRNA. However, when culture supernatants were tested using a sensitive IL-6 ELISA or IL-6 bioassay only the DP-6 and KP-6 cells were shown to be secreting biologically active IL-6. In summary, although all three of these cell lines were established from myeloma patients, the heterogeneity observed between these cell lines was considerable and may reflect, as well as provide tools to study, the heterogeneity observed in clinical disease.
Leukemia 1996 May
PMID:Establishment and characterization of three myeloma cell lines that demonstrate variable cytokine responses and abilities to produce autocrine interleukin-6. 865 85

The expression of transcripts of cytokines of the interleukin-6 (IL-6) family has been examined in human breast tumors, breast cancer cell lines, and adipose stromal cells, by means of reverse transcription polymerase chain reaction amplification. Of the six breast tumor samples examined, all expressed transcripts encoding IL-6 and Leukemia Inhibitory Factor (LIF). Four of the samples also expressed transcripts for oncostatin M (OSM) and IL-11, and three expressed the IL-6 receptor. Adipose stromal cells expressed IL-6, IL-11 and LIF, but not the IL-6 receptor, consistent with previous conclusions that IL-6 activity in these cells required addition of IL-6 soluble receptor. In the case of T47D cells, expression of IL-11 protein was confirmed by immunotitration. Moreover, in these cells, expression of IL-11 transcripts was induced 3-fold by addition of estradiol to the culture medium. These results add credence to our previous proposal that breast cancer development is regulated in part by local autocrine and paracrine mechanisms via epithelial/mesenchymal interactions, in which estrogen produced by stromal cells surrounding the tumor acts to stimulate the production of growth factors and cytokines by the tumor cells. Some of these may act to stimulate further the growth and development of the tumor, while these or other factors may act on the surrounding mesenchymal cells in a paracrine fashion to stimulate aromatase expression in the presence of glucocorticoids. Thus, a positive feedback loop is established which leads to the development and growth of the tumor.
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PMID:Expression of transcripts of interleukin-6 and related cytokines by human breast tumors, breast cancer cells, and adipose stromal cells. 873 8

Ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), oncostatin M (OSM), interleukin-6 (IL-6), and interleukin-11 (IL-11) are structurally and functionally related cytokines. We compared their survival-promoting activities on embryonic chick and newborn rat dorsal root ganglion (DRG) neurones. Human CNTF showed the well known trophic effect on both chick and rat DRG neurones. Human and murine LIF and, at unphysiologically high doses, human OSM were trophic for rat neurones, but failed to promote chick DRG cell survival. Human IL-11, murine IL-6 and human IL-6 did not improve chick or rat DRG neurone survival; soluble human IL-6 receptor alpha did not increase sensitivity to human IL-6. Thus, human CNTF as well as murine and human LIF had special neurotrophic properties compared with other related cytokines.
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PMID:Human CNTF and related cytokines: effects on DRG neurone survival. 874 40


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