Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied cytokine expression by the human bladder carcinoma cell line 5637 using a cDNA-PCR procedure. Transcripts for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, tumor-necrosis factor-alpha (TNF-alpha), and TNF-beta were constitutively present, whereas IL-3, IL-4, IL-5, and IL-9 mRNA sequences could not be detected. This expression pattern was not altered after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation (4 and 8 h) of 5637 cells. Relative expression levels of cytokines were assessed by limiting dilution of the cDNA pool. This procedure proved to be a semiquantitative technique when compared to Northern blot analysis.
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PMID:Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. 188 17

We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.
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PMID:Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. 188 23

The biological effects of recombinant hematopoietic factors, which are considered to stimulate megakaryocytopoiesis in vitro or in vivo, were studied utilizing purified rat megakaryocytes. Recombinant human erythropoietin (rhEPO), recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), and recombinant murine interleukin 3 (rmIL-3) stimulated both [3H]thymidine and [3H]leucine incorporation into purified rat megakaryocytes. In contrast, recombinant human interleukin 6 (rhIL-6) did not stimulate [3H]thymidine uptake but did increase [3H]leucine incorporation into purified rat megakaryocytes. These in vitro data suggest that DNA synthesis in megakaryocytes may be regulated by EPO, GM-CSF, and IL-3, and that protein synthesis is stimulated by EPO, GM-CSF, IL-3, and IL-6 in vitro.
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PMID:Biological effects of recombinant erythropoietin, granulocyte-macrophage colony-stimulating factor, interleukin 3, and interleukin 6 on purified rat megakaryocytes. 189 46

Purified recombinant human (rhu) interleukin (IL)-1 alpha, rhuIL-6, iron saturated lactoferrin (LF), and T-lymphocytes were assessed for their effects on the survival of granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid (erythroid burst-forming units, BFU-E) progenitor cells from human low-density (LD) and nonadherent LD T-lymphocyte-depleted (NALT-) bone marrow (BM) cells. Colony-stimulating factor (CSF) deprivation studies showed that 10 ng/ml IL-1 alpha could promote the survival of CFU-GM and BFU-E from NALT- BM cells. Concentrations of 1 ng/ml IL-1 alpha and 1-100 ng/ml IL-6 alone could not promote progenitor cell survival from NALT- BM cells; however, concentrations of 1 ng/ml each of IL-1 alpha and IL-6 could synergize to promote the survival of CFU-GM but not of BFU-E. The combination of these low concentrations of IL-1 alpha and IL-6 could, however, support the survival of BFU-E in the presence of purified T-lymphocytes. LF could decrease the survival of CFU-GM and BFU-E from LD but not from NALT- BM cells, apparently due to the inhibition of IL-1 release from monocytes in this cell population. The suppressive effect of LF on the survival of those progenitor cells was abolished by concentrations of 10 ng/ml IL-1 alpha or 1 ng/ml each of IL-1 alpha and IL-6. These results demonstrate that the survival of human marrow CFU-GM and BFU-E can be influenced by IL-1, IL-6, LF, and T-lymphocytes.
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PMID:Influence of T-lymphocytes and lactoferrin on the survival-promoting effects of IL-1 and IL-6 on human bone marrow granulocyte-macrophage and erythroid progenitor cells. 189 56

Oligonucleotide primer pairs specific for interleukins (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, and IL-6, as well as for granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA/cDNA were synthesized in order to detect cytokine transcripts by reverse transcription and subsequent polymerase chain reaction (RT/PCR). Analysis of RNA preparations of the human bladder carcinoma cell line 5637 by this methodology reveals expression of mRNAs for IL-1 alpha, IL-1 beta, IL-6, G-CSF, M-CSF, and for GM-CSF, whereas mRNAs for IL-2, IL-3, IL-4, and IL-5 are not detectable. These results are in agreement with data obtained by classical methods. Thus, for the cytokines IL-2, IL-3, IL-4, and IL-5, it was not possible to detect a phenomenon described as 'illegitimate transcription,' defined as the low level transcription of any gene in any cell type. This finding is of importance for the applicability of mRNA phenotyping employing RT/PCR for the determination of mRNA expression patterns. For M-CSF mRNA detection, two oligonucleotide primer pairs had to be used to distinguish between the alpha-(pcCSF17) and beta-splicing forms and to overcome the problem of non-amplification of a larger fragment in the presence of a competing smaller one, defined here as 'incomplete positivity.' For G-CSF, IL-4, IL-2, and IL-5, RT/PCR reveals two fragments. Restriction enzyme analysis of the additional fragments suggests that they may arise from alternative splicing events. For G-CSF and IL-4, exons 3 and 2 seem to be spliced out, respectively. The additional fragments for IL-2 and IL-5 RT/PCR have not yet been further characterized, but the size of the fragments makes it seem probable that exons 2 and 3 are spliced out for IL-2 and IL-5, respectively. The biological role of these alternative mRNAs has yet to be determined.
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PMID:Rapid and sensitive mRNA phenotyping for interleukins (IL-1 to IL-6) and colony-stimulating factors (G-CSF, M-CSF, and GM-CSF) by reverse transcription and subsequent polymerase chain reaction. 189 64

We have isolated the genomic sequence of human interleukin-9 (IL-9) based on its sequence homology with a human IL-9 cDNA isolated from human T-cell leukemia virus (HTLV)-I-transformed T cells by expression cloning. The entire genomic sequence has been determined and the gene consists of five exons and four introns. The human IL-9 gene is mapped to the long arm of human chromosome 5 at band 5q31-32, a region found to be deleted in a number of patients with acquired 5q- abnormalities and hematologic disorders. Several blocks of transcriptional control sequences have been identified at the 5'-flanking region of the human IL-9 gene that may play an important role in the control of IL-9 gene expression. The 5'-regulatory region of the human IL-9 gene also contains sequences identified in the 5'-flanking regions of other cytokine genes mapped to the long arm of human chromosome 5, including IL-3, IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor and other T-cell growth factor genes including IL-2 and IL-6. The IL-9 gene is constitutively expressed in the HTLV-I-transformed human T cells and the expression of IL-9 in these cells can be further induced by 12-O-tetradecanoyl phorbol 13-acetate. Transient transfection analysis using the plasmid containing the 5'-flanking region of IL-9 gene upstream from the firefly luciferase ciferase report gene indicated that the 0.9-kb Smal-Sacl fragment of the IL-9 gene contains sequences required for the constitutive and activated expression of IL-9 gene in HTLV-I-transformed cells. These results will now allow us to study the regulatory mechanism of IL-9 gene expression in normal and leukemic human T cells.
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PMID:Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells. 190 Dec 33

We assessed the effect of interleukin-9 (IL-9) on clonogenic maturation and cell-cycle status of hematopoietic progenitors of fetal (umbilical cord blood) and adult (bone marrow) origin. As a single agent IL-9 supported, in a concentration-dependent fashion, maturation of burst-forming units-erythroid (BFU-E) of adult and fetal origin. However, only 1/3 the number of adult BFU-E colonies developed, as did in response to granulocyte-macrophage colony-stimulating factor (GM-CSF), and only 1/6 the number developed as did in response to IL-3. In contrast, the effect of IL-9 on fetal BFU-E colonies was equal to that of GM-CSF and IL-3. Synergistic effects of IL-9 with low concentrations (0.1 ng/mL) of GM-CSF and IL-3 were seen on adult BFU-E colony formation, but no effect was apparent at higher concentrations (1.0 ng/mL). In contrast, using fetal cells, synergistic effects of IL-9 with low and high concentrations of GM-CSF and IL-3 were apparent. Addition of IL-9 to plates containing fetal cells plus GM-CSF and IL-3 not only resulted in more BFU-E colonies, but also in more multicentered (greater than or equal to 10 individual centers) colonies, and more cells per colony. IL-9 had a wider spectrum of action on progenitors of fetal origin than on progenitors of adult origin, supporting the generation of fetal multipotent colony-forming unit (CFU)-Mix and CFU-GM colonies. Incubation with IL-9 did not accelerate cycling of adult or fetal BFU-E, CFU-Mix, or CFU-GM to the extent observed after incubation with IL-6. Thus, IL-9 primarily supported maturation of erythroid progenitors of adult origin, and its addition to plates containing GM-CSF and IL-3 (1.0 ng/mL) did not result in maturation of additional clones. In contrast, IL-9 had a wider spectrum of action on fetal progenitors and, when combined with IL-3 and GM-CSF, resulted in clonogenic maturation of progenitors that did not undergo maturation after stimulation with IL-3 and GM-CSF.
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PMID:Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors. 190 74

We investigated the effects of several cytokines on HLA-DR expression in cultured fibroblasts derived from retroocular connective tissue and pretibial and abdominal skin of patients with Graves' ophthalmopathy (GO) and pretibial dermopathy (PTD), as well as from normal individuals. We hypothesized that differences in response to cytokines between fibroblasts from various anatomical areas might play a role in the site-selective involvement of the extrathyroidal manifestations of Graves' disease. HLA-DR expression in fibroblasts was quantitated by scanning densitometry of whole cell lysates subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Direct immunofluorescence of cell monolayers was also performed. We hypothesize that unique characteristics of these fibroblasts may play a role in GO and PTD. Cultured retroocular, pretibial, and abdominal fibroblasts from patients with Graves' disease as well as from normal individuals did not express HLA-DR spontaneously. Treatment in vitro with interferon-gamma (IFN gamma; 100 U/mL) for 5 days induced HLA-DR by 50- to 80-fold (P less than 0.0001) in fibroblasts from all sites and subjects studied. However, IFN gamma-induced HLA-DR expression was significantly greater in retroocular (P less than 0.005) and pretibial (P less than 0.0005) fibroblasts from patients with GO and PTD than in fibroblasts obtained from the same anatomical sites of normal individuals. Further, retroocular and pretibial fibroblasts from patients with GO and PTD responded to IFN gamma more vigorously than did abdominal fibroblasts from these same patients (P less than 0.0001). IFN gamma-induced HLA-DR expression was enhanced by concomitant treatment with tumor necrosis factor-alpha (100 U/mL). In contrast, treatment of retroocular fibroblasts with transforming growth factor-beta (10 ng/mL), epidermal growth factor (1 ng/mL), or interleukin-6 (IL-6; 100 U/mL) significantly attenuated IFN gamma-induced HLA-DR reactivity by 40-59% (P less than 0.05). Incubation of retroocular fibroblasts with tumor necrosis factor-alpha, IL-1 alpha (10 U/mL), IL-2 (10 U/mL), IL-6, granulocyte-macrophage colony-stimulating factor (100 U/mL), epidermal growth factor, and transforming growth factor-beta alone did not affect HLA-DR expression. These results indicate that several cytokines can influence HLA-DR expression in cultured fibroblasts. The enhanced induction of HLA-DR by IFN gamma in retroocular and pretibial fibroblasts compared with that in abdominal fibroblasts may partially explain the selective involvement of the retroocular connective tissue and pretibial skin in fully expressed Graves disease.
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PMID:Increased induction of HLA-DR by interferon-gamma in cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial dermopathy. 190 94

Interleukin-4 (IL-4) is a T-cell-derived cytokine that regulates induction of proliferation of resting B cells and acts on various other immunocompetent cells, such as monocytes/macrophages and mast cells, as well as hematopoietic progenitor cells. On hematopoietic progenitor cells, cooperation with another cytokine (such as granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, IL-3, or IL-6) is required to render the cells responsive to IL-4. The present study was undertaken to determine if such an interaction entails induction of IL-4 receptor (IL-4R) expression. Using the murine myeloid leukemia M1 cell line and mature, bone marrow (BM)-derived macrophages, we investigated whether IL-4R expression can be induced during differentiation. We detected no high-affinity IL-4R on the surface of either cell, but with exposure to IL-6 a significant induction of IL-4R was measured on both cell types by fluorescence-activated cell sorter analysis. This increase in IL-4R was first noted 6 hours after exposure of the cells to IL-6 and continued to increase up to 48 hours. By RNase protection analysis we found that the expression of IL-4R mRNA also appeared within 6 hours, continuing to increase up to 48 hours. Nuclear run-on assays showed that this increase in steady-state level of IL-4R mRNA results from a transcriptional activation of the IL-4R gene. These data suggest that regulation of IL-4R expression by IL-6 is under transcriptional control.
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PMID:Regulation of interleukin-4 receptors on murine myeloid progenitor cells by interleukin-6. 191 57

Philadelphia chromosome1 positive (Ph1) chronic myelogenous leukemia (CML) is characterized by metamorphosis of the chronic phase to blastic crisis. However, cellular events associated with this transition are poorly understood. To examine the possible participation of hematopoietic growth factors in this process, we studied growth factor expression in adherent layers of bone marrows derived from CML Ph1 patients in various stages of the disease. Interleukin-1 beta (IL-1 beta) and IL-6 mRNA were expressed in five of six patients, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in one of six patients with myeloid/undifferentiated blast crisis. In addition, leukemia inhibitory factor (LIF) expression was increased in four of six patients with myeloid/undifferentiated blast crisis phase of the disease. IL-1 beta was also detected in bone marrow adherent layer conditioned medium from two of these patients. These results were in sharp contrast to the lack of detectable levels of uninduced IL-1 beta, IL-6, and GM-CSF mRNA, in samples derived from 4 patients in lymphoid blastic crisis, 3 in accelerated, and 11 in chronic phases of the disease, or from normal controls. The possibility of a paracrine loop formation, whereby the adherent layers representing the bone marrow stroma are induced to express hematopoietic growth factors, was supported by our finding IL-1 beta mRNA expression in the leukemic blast cells in three of four studied patients in blast crisis and IL-1 beta protein production in seven of eight patients studied. Finally, coculturing CML blast crisis cells onto pre-established adherent layers induced the expression of both IL-1 beta and IL-6 genes. From this preliminary study, it appears that abnormal expression of growth factors is a common event with CML Ph1 progression. We hypothesize that IL-1 beta generated by the transformed malignant clone stimulates the marrow stroma to produce various growth factors, and that this process may play a role in disease progression.
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PMID:Alteration in bone marrow adherent layer growth factor expression: a novel mechanism of chronic myelogenous leukemia progression. 193 51


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