Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate possible mechanisms of growth factor expression in acute myeloid leukemia, genes for granulocyte macrophage colony-stimulating factor (GM-CSF) were analyzed by Southern blots in 20 patients, for M-CSF in 13, for interleukin-6 (IL-6) in 14, for IL-6 receptor in 14 and for G-CSF in five patients. Only in one patient a complex rearrangement of the G-CSF gene with possible amplification was noted indicating rarity of direct alterations of growth factor genes in acute myelogenous leukemia (AML). Spontaneous m-RNA expression for GM-CSF was found in only one of 20 patients, and for IL-6 in eight of 11 patients. In vitro incubation of AML cells of eight patients with recombinant tumor necrosis factor for 24 hr revealed induction of GM-CSF m-RNA expression in three cases and GM-CSF protein expression in two of them. These data suggest that spontaneous GM-CSF production occurs rarely in AML and that monokines, such as tumor necrosis factor, may induce GM-CSF in AML cells. Therefore, interactions of AML cells with normal or malignant accessory cells may be important for autocrine stimulation in AML. Our data suggest that ectopic growth factor secretion is not the primary cause of generating AML but may contribute to progression of the disease. Alternatively, AML may represent a heterogenous group of leukemias with different etiology but similar phenotype.
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PMID:Mechanisms of growth factor expression in acute myeloid leukemia (AML). 219 15

The growth-promoting activities of interleukin-6 (IL-6) in combination with different factors were assessed in bone marrow (BM) cultures prepared from normal mice and from mice treated with 5-fluorouracil (5-FU). Effects on hematopoietic colony formation with respect to number, size, and cellular composition were evaluated. In agreement with previous reports, IL-6 acts synergistically with IL-3 to stimulate increased numbers of granulocyte/macrophage (GM) and multilineage colonies in day-2 and day-4 post-5-FU BM cultures. Furthermore, day 4 but not day 2 post-5-FU BM showed enhanced GM colony formation when stimulated with IL-6 plus interleukin-4 (IL-4) or granulocyte colony-stimulating factor (G-CSF). In contrast, IL-6 did not increase the number of colonies supported by M-CSF or GM-CSF. Nevertheless IL-6 interacted with all factors, including M-CSF and GM-CSF, to stimulate an increase in colony size. Many of these myeloid colonies attained a diameter of greater than or equal to 0.5 mm, suggesting they derive from high proliferative potential cells (HPP-CFC). The response of normal and day-8 post-5-FU BM containing high numbers of more mature progenitors was also assessed. We found IL-6 enhanced colony formation by lineage-restricted megakaryocytic and erythroid progenitors in the presence of IL-3 and IL-4 plus erythropoietin (Epo), respectively. The sum of these results shows that IL-6 interacts with a variety of factors to regulate the growth of progenitor cells at different stages of lineage commitment and maturation.
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PMID:Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells. 246 2

There are different types of myeloid leukemic cells that can be induced to differentiate to mature granulocytes or macrophages by different hematopoietic regulatory proteins. One type of leukemic clone can be induced to differentiate by recombinant macrophage and granulocyte differentiation-inducing protein-type 2 (MGI-2), which we have shown is Interleukin-6 (IL-6), and another type of leukemic clone can be differentiated by recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3. There was no subpopulation of growth factor-responsive or differentiation-defective cells before induction of differentiation in either type of clone. In both clones, induction of differentiation-induced requirement for a hematopoietic protein for cell viability. Viability of the cells was maintained by IL-6, IL-3, or macrophage colony-stimulating factor (M-CSF) but not by GM-CSF in the cells differentiated by IL-6, and by GM-CSF or IL-3 but not by IL-6 or M-CSF in the cells differentiated by GM-CSF or IL-3. The viable cells with a differentiated phenotype continued to multiply. In undifferentiated leukemic cells with no or few surface receptors for some of these proteins, there was an upregulation of the number of receptors during differentiation for the proteins to which the cells responded. But there were also differentiating leukemic cells with an upregulation of GM-CSF receptors although GM-CSF could not maintain the viability of the differentiating cells. The results indicate that induction of hormone responsiveness and upregulation of the hormone receptors can both occur in differentiating leukemic cells, and that the regulation of these two events can be separated.
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PMID:Induction of dependence on hematopoietic proteins for viability and receptor upregulation in differentiating myeloid leukemic cells. 254 28

The central feature of hemopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The entry into cell cycle of the dormant stem cells may be promoted by such factors as interleukin-1, interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). Once the stem cells leave G0 and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. While several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a random (stochastic) process. The proliferation of early hemopoietic progenitors requires the presence of interleukin-3 (IL-3), and the intermediate process appears to be supported by granulocyte/macrophage colony-stimulating factor (GM-CSF). Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as erythropoietin and G-CSF. Synthesis of a hemopoietic factor may take place in different cell types and is regulated by multiple factors. The physiological regulator of erythropoiesis is erythropoietin, which, by a feedback mechanism, provides fine control of erythrocyte production. Feedback mechanisms for leukocyte production have not been identified. It is possible that there is no feedback regulator of leukopoiesis. In this model, leukocyte production in the steady state is maintained at a genetically determined level. When an infection occurs, the bacterial lipopolysaccharides may augment the production of interleukin 1 alpha and beta, tumor necrosis factor, macrophage colony-stimulating factor, etc.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemopoietic stem cells: stochastic differentiation and humoral control of proliferation. 264 80

A variety of studies have shown that osteoclasts originate from bone marrow, but their exact progenitors and differentiation pathway remain unclear. The treatment of mice with a high dose of 5-fluorouracil (5-FU) results in an enrichment for primitive hematopoietic progenitors; using this procedure, we prepared a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro. When spleen cells from mice pretreated in vivo with 5-FU were cultured in the presence of methylcellulose medium containing recombinant interleukin-3 (rIL-3), small colonies consisting of blast cells with little sign of differentiation developed on day 7 of culture. We lifted these blast colonies, pooled them, and replated them as secondary methylcellulose cultures in the presence of rIL-3 and erythropoietin. Approximately 60% of the cells formed colonies comprising various combinations of neutrophils, macrophages, eosinophils, mast cells, megakaryocytes, and erythroblasts. We replated such blast cells into microtiter wells and cultured them in the presence of rIL-3 (100 U/mL) or recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) (100 U/mL) plus 1.25(OH)2D3 (10(-7) mol/L). Multinucleated cells appeared from day 14 of culture and approximately 100 giant cells per well were scored on day 21 of culture. Parathyroid hormone (1 U/mL) also induced the multinucleated cell formation. May-Grunwald-Giemsa staining revealed the large cells containing many nuclei in their cytoplasm, which is characteristic of bone-resorbing cells or osteoclasts. These cells showed a tartrate-resistant acid phosphatase (TRAP) activity. Calcitonin caused a striking shape change in these cells and suppressed the formation of multinucleated cells. Moreover, electron microscopy shows that these cells were able to resorb fetal calvariae. In the presence of r granulocyte-colony stimulating factor, r macrophage-colony stimulating factor, or r interleukin-6 plus 1.25(OH)2D3, formation of TRAP-positive multinucleated cells was lower compared with the support of rIL-3 or rGM-CSF. Mature macrophages collected from colonies did not form the multinucleated cells as described above, even in the presence of rIL-3 and 1.25(OH)2D3. Moreover, to exclude the possibility that osteoclasts generated from non-blast cells, we performed a cloning experiment from one isolated blast cell and demonstrated that single cells differentiate into osteoclasts or macrophages in the presence of rIL-3 with or without 1.25(OH)2D3. This system will provide a useful model for further analysis of osteoclast formation in vitro.
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PMID:Generation of osteoclasts from isolated hematopoietic progenitor cells. 266 99

An assay system was developed to measure feline hybridoma growth factor (HGF)/interleukin-6 (IL-6) activity in biological samples containing many kinds of cytokines by using the proliferation of the newly established mouse-rat hybridoma clone, B3B1. The proliferative response of this B3B1 clone was IL-6-specific, and could not be promoted by other cytokines including IL-1, IL-2, IL-3, and granulocyte-colony-stimulating factor (G-CSF). The anti-human B-cell stimulatory factor 2 (BSF-2)/IL-6 antiserum did not neutralize feline HGF/IL-6 activity in conditioned media prepared from feline con A-stimulated splenocytes and unstimulated alveolar macrophages, indicating antigenic differences between species. Feline HGF/IL-6 was eluted into the fractions corresponding to a molecular weight of 30,000-40,000 in gel filtration, and into the fractions at a salt concentration of 0.2-0.3 M NaCl in anion exchange chromatography. The physicochemical properties of feline HGF/IL-6 were slightly different from those of murine and human IL-6.
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PMID:Feline hybridoma growth factor/interleukin-6 activity. 268 91

The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.
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PMID:Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia. 304 49

A novel hemopoietic CSF has been identified in the medium conditioned by lectin-stimulated human T cells. The cDNA clone encoding this factor, isolated by functional expression cloning in monkey cos-1 cells, proved to be identical with the cDNA encoding the cytokine B cell stimulatory factor-2/IFN-beta 2, a factor now known as IL-6. In the murine system, IL-6 indirectly supports the formation of several different types of hemopoietic colonies, including those derived from early blast cells, and directly supports the proliferation of granulocyte/macrophage progenitors. These results expand the range of known target cells of IL-6 to include hemopoietic progenitors in addition to B cells, T cells, and fibroblasts and provide further evidence that this cytokine plays an important role within a network of interacting cytokines that regulates many different biologic responses.
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PMID:Stimulation of murine hemopoietic colony formation by human IL-6. 325 92

The mouse myeloid blood cell differentiation-inducing protein, macrophage and granulocyte inducer, type 2A (MGI-2A), was purified, and the amino acid sequence of a CNBr cleavage peptide (22 residues) was determined. This amino acid sequence is identical to the sequence found in positions 73 to 94 of mouse interleukin-6 (IL-6). Recombinant mouse IL-6 protein induces differentiation of mouse myeloid leukemic cells that are induced to differentiation by MGI-2, and monoclonal antimouse-MGI-2 antibody, which neutralizes MGI-2, also completely neutralizes this IL-6-induced differentiation. These results show that the major type of mouse myeloid differentiation-inducing protein (MGI-2A) and IL-6 are very similar and most likely identical proteins. Recombinant human IL-6 (also called interferon-beta 2 or B-cell differentiation factor), which shows only a 41% similarity to mouse IL-6, has 11 identical amino acid residues out of the 22 in the mouse MGI-2A peptide and also induces differentiation of the same myeloid leukemic cells.
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PMID:The myeloid blood cell differentiation-inducing protein MGI-2A is interleukin-6. 326 98

Interleukin-6 (IL-6, also known as B-cell stimulatory factor 2/interferon beta 2) was previously shown to support the proliferation of granulocyte/macrophage progenitors and indirectly support the formation of multilineage and blast cell colonies in cultures of spleen cells from normal mice. We report here that IL-3 and IL-6 act synergistically in support of the proliferation of murine multipotential progenitors in culture. The time course of total colony formation by spleen cells isolated from mice 4 days after injection of 5-fluorouracil (150 mg/kg) was significantly shortened in cultures containing both lymphokines relative to cultures supported by either of the two factors. Serial observations (mapping) of individual blast cell colonies in culture revealed that blast cell colonies emerged after random time intervals in the presence of IL-3. The average time of appearance in IL-6 alone was somewhat delayed, and in cultures containing both factors the appearance of multilineage blast cell colonies was significantly hastened relative to cultures grown in the presence of the individual lymphokines. In cultures of day-2 post-5-fluorouracil bone marrow cells, IL-6 failed to support colony formation; IL-3 alone supported the formation of a few granulocyte/macrophage colonies, but the combination of factors acted synergistically to yield multilineage and a variety of other types of colonies. In this system, IL-1 alpha also acted synergistically with IL-3, but the effect was smaller, and no multilineage colonies were seen. Together these results indicate that IL-3 and IL-6 act synergistically to support the proliferation of hemopoietic progenitors and that at least part of the effect results from a decrease in the G0 period of the individual stem cells.
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PMID:Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. 350 Nov 21


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