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

The CD34 antigen is present at all differentiation stages of hematopoietic cells, from immature progenitor cells to committed precursor cells. In vivo, transplantation of CD34+ cells is sufficient to allow hematopoietic recovery after myeloablative chemotherapy, but a neutropenic period of 9-12 days still exists, even when hematopoietic growth factors are given posttransplantation. After ex vivo expansion cultures in the presence of cytokines, CD34+ cells can generate mature precursor cells in a stroma-free liquid culture system. This could lead to a shortening of the aplasia duration, but the persistence of primitive progenitor cells in the expanded CD34+ compartment remains to be demonstrated. In this study, CD34+ cells were isolated from eight peripheral blood (PB) and eight cord blood (CB) samples using either Isolex 50 (n = 6), Ceprate LC CD34 kit (n = 6), or Microcellector T-25 Stem Cell kit (n = 4). We have evaluated the functional potential of CD34+ cells after 7 days of ex vivo expansion culture in the presence of 500 UI/ml of interleukin-1 (IL-1), 10 ng/ml of IL-3, and 10 ng/ml of stem cell factor (SCF). The expansions of nucleated cells, granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive committed precursors, IL-1 + IL-3 + SCF + erythropoietin (EPO)-responsive multilineage progenitors, and 5-fluorouracil (5-FU)-resistant quiescent progenitor were 8-fold, 59-fold, 4.4-fold, and 2.2-fold, respectively. There was no significant difference in the amplification/expansion parameters between cultures initiated with CD34+ cells from PBSC or CB. Our data confirm that cytokine-mediated ex vivo expansion of blood CD34+ cells can produce large numbers of committed precursors and does not significantly affect the compartment containing more immature progenitors. Cytokine-mediated expansion could be of great interest in autologous transplantation to decrease the duration of marrow aplasia.
 ...
PMID:Expansion of blood CD34+ cells: committed precursor expansion does not affect immature hematopoietic progenitors. 913 45

To investigate the complex intra-articular immune activity in rheumatoid arthritis (RA), we analysed the expression of a wide range of cytokine mRNAs in synovial fluid cells from patients with rheumatoid arthritis. To minimize in vitro artefact, mRNA was rapidly extracted from synovial fluid leucocytes taken from single joints of seven patients and simultaneously from both knee joints of four patients. Expression of interleukin (IL) 1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) was detected using the reverse transcription/polymerase chain reaction. The expression of cytokines varied between patients. IFN-gamma mRNA was detected in 60% of the patients and IL-4 mRNA in 10%. Cytokine expression in both knees was very similar. These results suggest that T-cell activity in RA is detectable using sensitive techniques and that the intra-articular immunopathology of RA is systemically very similar.
 ...
PMID:Symmetrical synovial fluid cell cytokine messenger RNA expression in rheumatoid arthritis: analysis by reverse transcription/polymerase chain reaction. 913 23

The safety and efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as adjuvant therapy for interferon alpha (IFN-alpha) treatment has been evaluated in 20 non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. Adjuvant therapy with GM-CSF plus IFN-alpha was associated with less myelosuppression than with IFN-alpha alone (P < .01), although the rate of local adverse reactions increased. GM-CSF adjuvant therapy led to a 50% biochemical response (transaminase values within the normal range at therapy end) and to reductions in HCV RNA concentrations (median HCV RNA reduction of 99%, range 8-100%), which were similarly observed in single IFN-alpha recipients (median HCV RNA reduction of 91%, range 38-100%). However, HCV RNA became undetectable in three biochemical responders to the GM-CSF adjuvant therapy, but in only one biochemical non-responder to IFN-alpha alone. The use of GM-CSF as adjuvant therapy is safe and, although it has not improved the biochemical response, it might potentiate the virologic response to IFN-alpha treatment alone.
Cytokine 1996 Apr
PMID:Granulocyte-macrophage colony-stimulating factor as adjuvant therapy for factor as adjuvant therapy for interferon alpha treatment of chronic hepatitis C. 916 22

The aim of the present study was to investigate the patterns of cytokine production by T cell clones raised from in vivo activated synovial fluid (SF) mononuclear cells (MNC) of five patients with oligoarticular juvenile arthritis (JA). Freshly isolated SF T cells were cultured in vitro with low dose recombinant IL-2 and subsequently cloned by limiting dilution. Sixty-four clones were obtained from the five patients studied. Fifty-nine clones were TCR alpha/beta+, either CD4+ (n = 43) or CD8+ (n = 15). The remaining five clones were TCR gamma/delta+, CD4-, CD8-. Clone immunophenotypes differed in the individual patients. Forty-four T cell clones were stimulated with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) and supernatants tested for the presence of IL-2, IL-4, IL-5 and interferon-gamma (IFN-gamma) by ELISA or bioassays. Cytokine mRNA accumulation was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). Most of 44 clones tested released large amounts of IFN-gamma irrespective of the immunophenotype. Of these, 27 were classified as Th1-type and 17 as Th0-type based upon the IFN-gamma/IL-4 ratio in culture supernatants. Finally, when 10 representative T cell clones were tested for pro- and anti-inflammatory cytokines, gene expression by RT-PCR, all of them were found to express the granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha), IL-10 and transforming growth factor-beta 1 (TGF-beta1) genes, and half of them IL-6 and IL-8 mRNA. In conclusion, T cell clones, that represent the progeny of in vivo activated SF T cells from oligoarticular JA patients, display heterogeneous immunophenotypes, but all share the ability to produce large amounts of IFN-gamma, with a predominant Th1/Th0 pattern. The expression of pro- and anti-inflammatory cytokine genes in these clones suggests that in vivo activated SF T cells modulate joint inflammation in a complex fashion.
 ...
PMID:Synovial fluid T cell clones from oligoarticular juvenile arthritis patients display a prevalent Th1/Th0-type pattern of cytokine secretion irrespective of immunophenotype. 921 17

Vascular endothelial growth factor (VEGF) is a pleiotropic polypeptide that mediates endothelial-cell-specific responses such as induction of proliferation and vascular leakage. We examined the expression of VEGF messenger RNA (mRNA) and protein by human eosinophils in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5). Immunoreactive VEGF protein was detected in freshly isolated eosinophils by immunocytochemistry. Eosinophils spontaneously released VEGF protein in culture medium, and this release was upregulated by GM-CSF or IL-5. Freshly isolated eosinophils constitutively expressed VEGF mRNA. Although incubation of eosinophils in culture medium reduced steady-state VEGF mRNA levels, eosinophil VEGF mRNA levels were enhanced by GM-CSF and IL-5, and this enhancement was blocked by the transcription inhibitor actinomycin D. Analysis of alternatively spliced mRNA species revealed that eosinophils contained transcripts mainly encoding for the 121- and 165-amino-acid forms of VEGF. VEGF mRNA expression and VEGF release in cytokine-stimulated eosinophils were significantly reduced by treatment with a glucocorticosteroid, a protein-tyrosine kinase inhibitor, or a protein kinase C inhibitor. Cytokine-activated eosinophils may be an important source of a vascular permeability factor, namely VEGF, thus contributing to tissue edema formation at sites of allergic inflammation.
 ...
PMID:Expression of vascular endothelial growth factor by human eosinophils: upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5. 922 11

In this report, we studied the immunorestorative properties of subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with refractory solid tumours receiving second-line chemotherapy. Such patients exhibit abnormal immune responses in vivo and in vitro and, therefore, it was of interest to examine the effect of GM-CSF-induced immunomodulation on clinical response. We examined patients with primary malignant carcinomas (head and neck, n = 10; urogenital tract, n = 17; penis n = 6; colorectal, n = 8) who were treated with carboplatin (JM8), 300 ng/m2 on days 1 and 22, leucovorin (LV), 200 mg/m2 plus 5-fluoracil (5-FU), 500 mg/m2 on days 8, 15 and 29 and four cycles of daily injections with placebo or GM-CSF, 300 micrograms/day on days 3-6, 10-13, 17-20 and 24-27. Peripheral blood was collected from the patients one day after the end of each of the four-cycle injections with placebo or GM-CSF, namely on days 7, 14, 21 and 28. Peripheral blood mononuclear cells (PBMC) were tested in the autologous mixed lymphocyte reaction (AMLR) and for natural killer (NK) or lymphokine-activated killer (LAK) cell activity. Cytokine levels in serum were measured by immunoenzymatic (ELISA) assay. A total of 21 patients received a four-cycle regimen with GM-CSF (Group 1) and 20 were similarly treated with placebo (Group 2). All received standard chemotherapy as outlined above. Before GM-CSF treatment, all patients exhibited increased serum levels of interleukin-1 (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and prostaglandin E2 (PGE2) and decreased serum levels of IL-2. Cellular immune responses (AMLR, NK- and LAK-cytotoxicity) were also low in all patients. Five patients from Group 1 had a PR (partial response), 2 patients had CR (complete response), and 14 patients had stable disease. Seven patients from Group 2 showed progressive disease, 3 had a PR and 10 had stable disease. All immune parameters were significantly improved during treatment in Group 1 but remained unchanged or even deteriorated in Group 2. Administration of GM-CSF during treatment of cancer patients with conventional chemotherapeutic drugs results in a marked potentiation of deficient cellular immune responses in vitro and a change towards normalisation of cytokine serum levels. The results reported herein support the use of GM-CSF as immunopotentiator during chemotherapy, but more patients must be studied before definite conclusions can be drawn.
 ...
PMID:Granulocyte-macrophage colony-stimulating factor improves immunological parameters in patients with refractory solid tumours receiving second-line chemotherapy: correlation with clinical responses. 930 43

1. In this study, we observed the effects of RU 41740 (Biostim) on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-8 (IL-8) in human bronchial epithelial cells in vitro. 2. Cytokine production was assessed by enzyme-linked immunosorbent assay. 3. We report that epithelial cells spontaneously released both cytokines and that RU 41740 induced a significant increase in production of IL-8 and GM-CSF. 4. This is the first observation of a stimulatory effect of an immunostimulating compound used in humans on cytokine production by epithelial cells.
 ...
PMID:RU 41740 (Biostim) stimulates the production of granulocyte macrophage colony-stimulating factor and interleukin-8 by human bronchial epithelial cells in vitro. 930 5

The authors investigated the dependence on extracellular and intracellular free Ca2+ in the induction of apoptosis and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) by tumour necrosis factor (TNF) in a rat/mouse T cell hybridoma PC60 R55/R75, using the Ca2+ chelators EGTA and BAPTA/AM, respectively. TNF-induced apoptosis still occurred in the absence of free Ca2+, while GM-CSF production required the continuous presence of Ca2+. The latter was also true for GM-CSF production driven by interleukin 1 (IL-1). The dependence on Ca2+ in the induction of GM-CSF, but not of apoptosis, was further confirmed by the inhibition of TNF- or IL-1-induced cytokine production by cyclosporin A or FK506, drugs that block the Ca2+/calmodulin-dependent protein Ser/Thr phosphatase calcineurin. This differential requirement for Ca2+ illustrates the partial functional redundancy between TNF and IL-1, showing the activation of cytokine gene expression through a Ca(2+)-dependent activation of calcineurin, and a Ca(2+)-independent activation of apoptosis, exerted solely by TNF.
Cytokine 1997 Sep
PMID:Differential role of calcium in tumour necrosis factor-mediated apoptosis and secretion of granulocyte-macrophage colony-stimulating factor in a T cell hybridoma. 932 11

The human cell line, TF-1, was used to compare responses to interleukin 3 (IL-3), IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). TF-1 cells grew well in the presence of any one of the cytokines in early passages. However, the level of tyrosine phosphorylation was minimal in response to IL-5, and detection of a tyrosine phosphorylation signal required high concentrations of IL-5. When grown for longer periods of time in the presence of one of the cytokines, there were dramatic difference in the cells' responses. IL-3 or GM-CSF-grown cells showed only half of the original bioassay response to IL-5. However, cells grown in IL-5 alone kept the same response, and all cells showed the same response to IL-3 and GM-CSF. IL-5-grown cells also had an increased tyrosine phosphorylation signal, along with increased sensitivity to IL-5, yet there was no difference in an IL-5 bioassay. The relative level of detection of tyrosine phosphorylated JAK-2, STAT-5, SHC, and other substrates corresponded to the overall tyrosine phosphorylation signal. IL-5-grown cells had approximately 10-fold more IL-5 receptor alpha subunit message compared to IL-3-grown. These results suggest that response of TF-1 cells to IL-5 may be deceiving in that a good response in a bioassay can be observed with relatively little tyrosine phosphorylation, but an increase in tyrosine phosphorylation can be correlated with an increase in the expression of IL-5 receptor alpha subunit.
Cytokine 1997 Sep
PMID:Lack of correlation between growth of TF-1 cells and tyrosine phosphorylation signals in response to IL-3, IL-5 and GM-CSF. 932 13

Semi-quantitative, polymerase chain reaction (PCR) is used to uncover the patterns of cytokine transcription in the mouse thymus from day 14 to day 20 of gestation, a time period which includes many of the important events in thymic ontogeny. Interleukin 4 (IL-4), IL-7 and interferon gamma (IFN-gamma) mRNA is abundant from fetal day (Fd) 14-16, corresponding with the period of rapid proliferation of immature thymocytes in vivo. As the level of mRNA for these cytokines diminishes, the induction and increased expression of IL-3 and IL-2 occurs. The transcription of these cytokines correlates temporally with the period of proliferation-dependent phenotypic differentiation between Fd 16 and 20. The thymic epithelium (TE)-derived cytokines including IL-1alpha, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) begin to be transcribed between Fd 14-15 and show peak mRNA abundance from Fd 16-20. IL-5, tumour necrosis factor alpha (TNF-alpha) and LT (lymphotoxin or TNF-beta) constitute a fourth group of cytokines, along with the IL-4 receptor (IL-4R), which are transcribed at an even level throughout the fetal period. The IL-2 receptor beta chain (IL-2Rbeta) and IL-10 show abundant mRNA from Fd 14-20 and have a peak level of mRNA content on Fd 16. Taken together, these studies uncover complex, overlapping patterns of cytokine gene expression. The mRNA abundance and pattern of expression of each cytokine or cytokine receptor may indicate the relative contribution that it makes to different stages of fetal thymic ontogeny.
Cytokine 1997 Oct
PMID:Semi-quantitative polymerase chain reaction analysis of cytokine and cytokine receptor gene expression during thymic ontogeny. 934 2


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