Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
 30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antitumoral macrophages (MAK) were obtained by the culture of human mononuclear cells in hydrophobic bags. From one cytapheresis, up to 10(9) mature macrophages could be purified by elutriation after one week of culture in IMDM medium in the presence of 2% human AB serum. These MAK cells were used for adoptive treatment in metastatic cancer patient with no dose-limiting toxicity. The present study aimed to improve the average MAK yield by addition of GM-CSF and of dihydroxy-cholecalciferol. The differentiated macrophages obtained presented higher antitumoral functionality in response to rh-IFN gamma than in their absence. These MAK presented all the differentiation antigens of cytotoxic macrophages compared to MAK cells differentiated in standard medium. They killed human tumor targets effectively in vitro at a low (1/1) effector/tumor ratio; furthermore, the antitumoral activity reached by MAK cells after IFN gamma activation appeared to be stabilized for several days.
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PMID:Production of human macrophages with potent antitumor properties (MAK) by culture of monocytes in the presence of GM-CSF and 1,25-dihydroxy vitamin D3. 129 73

The measurement of cytokine mRNA levels is of fundamental importance in the understanding of diverse pathological states. We present a simplification of a polymerase chain reaction-based technique which permits the simultaneous measurement of up to 20 cytokine mRNAs, together with those of several other cellular products, including beta 2-microglobulin and beta-actin. The technique makes use of internal standards bearing multiple PCR primer sites which are identical to those on the mRNAs to be assayed. Known quantities of the standards are added to the cellular RNA and the mixture is co-reverse transcribed and co-amplified. The simplifications described here are based on the fact that each pair of amplicons accumulates in a constant ratio even in the plateau phase of amplification. As a result, no preliminary experiments to determine the limits of the exponential phase of amplification are necessary; the same number of cycles may be chosen for all the mRNAs to be measured, whatever their level in the mixture might be; pipetting errors are avoided since all calculations are based upon the relative quantities of co-amplified material. Here we illustrate the method through a quantitative study of the expression of cytokine mRNAs in U373 human astrocytoma cells before and after stimulation with IL-1 beta. Quantitation was carried out either by incorporating radioactivity in the amplicons or by fluorescence measurements after propidium iodide staining. Only very low numbers of transcripts for IL-6, IL-8, CSF-1, MCP-1 and either Gro alpha or Gro beta were detectable in unstimulated cells. The levels of these cytokine mRNAs increased dramatically following IL-1 beta stimulation and, in addition, transcription of IL-1 beta, TNF alpha, GM-CSF, G-CSF, Gro gamma and MCP-1, some of which have not previously been detected in U373, was initiated in the stimulated cells. At the same time we found that transcripts for IL-2, IL-3, IL-4, IL-5, IFN gamma, huMlP1 alpha and huMlP1 beta were totally absent in this cell line. These results suggest a potentially important role for astrocytes in the local amplification of inflammatory responses in the brain.
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PMID:Simultaneous quantitation of cytokine mRNAs in interleukin-1 beta stimulated U373 human astrocytoma cells by a polymerisation chain reaction method involving co-amplification with an internal multi-specific control. 129 3

Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases.
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PMID:Therapeutic aspects of myelodysplastic syndromes in chronic phase. 131 Jan 27

Fc receptors (FcR) are of importance in immune and inflammatory reactions. FcR expression as mRNA and surface protein was therefore examined in the myelomonocytic cell line, U937, after stimulation with phorbol ester (PMA), in the presence of seven different cytokines (interferon-gamma [IFN gamma], IFN alpha, granulocyte-macrophage colony-stimulating factor [GM-CSF], tumour necrosis factor-alpha [TNF alpha], TNF beta, interleukin-beta [IL-1 beta], IL-2) or dexamethasone. HLA class I and CD11b expression were also examined. Cell surface expression of FcRI and II was measured by flow cytometry using monoclonal antibodies, and the mRNA of FcRII was measured with cDNA or oligonucleotide probes. The major findings were: PMA increased cell surface FcRI, FcRII and CD11b, but decreased HLA; PMA caused a fivefold increase in all three FcRII RNA transcripts (2.5, 1.5 and 0.9 kb) in Northern analysis; IFN gamma, IFN alpha and GM-CSF increased the expression of FcRI and II, and there was no effect with IL-1 beta, IL-2, TNF alpha or TNF beta (only GM-CSF increased the expression of CD11b); all cytokines further increased FcRI and FcRII expression in the presence of PMA; HLA expression was also increased in the presence of PMA, IFN alpha and IFN gamma; dexamethasone reduced the levels of FcRI and II in cells stimulated with PMA with or without cytokines. Thus stimulatory agents and cytokines can alter the expression of surface Fc gamma R and mRNA encoding FcRI or II, providing potential control mechanisms for the modulation of these receptors in inflammatory responses.
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PMID:Effects of PMA, cytokines and dexamethasone on the expression of cell surface Fc receptors and mRNA in U937 cells. 135 19

The conference, organized by Profs. Mitrou, Bergmann (Frankfurt), Huber (Mainz) and Niederle (Leverkusen), concentrated almost exclusively on the role of cytokines in cancer. The majority of presentations concerned IFN-alpha, IL 2 or TNF-alpha, but G-CSF, GM-CSF, IL 4, IL 10 and TGF-beta were not neglected. Presentations achieved a laudable balance between basic science and clinically oriented studies. The present report emphasizes the clinical aspects; proceedings of the entire meeting will be published by S. Karger AG, Basel.
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PMID:The role of cytokines in tumor immunotherapy. Report on the 2nd Frankfurt International Cytokine Symposium 25-27 June 1992, Frankfurter Hof, Frankfurt, Germany. 136 64

Human alloreactive T lymphocyte clones derived from cells invading a rejected kidney allograft, were analyzed for their ability to transcribe eleven cytokine genes under phorbol ester (PMA) plus calcium ionophore (CaI A 23187) stimulation. In addition to the positive signal previously obtained for IL-2 transcripts, strong specific patterns were seen with cytoplasmic dot hybridizations for IFN gamma and GM-CSF mRNAs in all the 17 clones screened. For the remaining transcripts (IL-3, IL-4, IL-5, IL-6, TNF alpha, LT, M-CSF and HILDA/LIF), these techniques proved to be inadequate. Northern-blots were therefore performed on three clones exhibiting different phenotypes (CD4+ CD8- non cytotoxic, CD4+ CD8- cytotoxic and CD4- CD8+ cytotoxic). Positive specific signal with the eleven probes could be obtained. Nevertheless, the IL-6 message was found only in the helper clone and the TNF alpha transcript appeared at a later time point compared to the other cytokine messages (its maximum expression was observed around 24 hours post-stimulation). In conclusion, we demonstrate that under PMA+CaI activation, one clone is able to simultaneously transcribe at least eleven lymphokine genes. Except, perhaps for IL-6, the pattern of lymphokine transcription did not permit us to distinguish between different lymphocyte subsets.
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PMID:Simultaneous transcription of eleven cytokines in human alloreactive T lymphocyte clones after stimulation by phorbol ester and A23187. 136 87

In order to elucidate the role of keratinocytes (KCs) in the induction of contact sensitivity, we applied various contact sensitizers [2,4-dinitrofluorobenzene (DNFB), urushiol, 3-n-pentadecylcatechol (PDC), 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone)] and tolerizing compounds [2,4-dinitrothiocyanobenzene (DNTB), 5-methyl-3-n-pentadecyl-catechol (5-Me-PDC)] onto the earskin of non-sensitized Balb/c mice. In addition, we applied croton oil as a non-sensitizing, but stimulatory agent. Cytokine production was demonstrated by Northern blot hybridization of the total cellular RNA extracted from epidermal cells depleted by Langerhans cells and Thy 1+ dendritic cells using radiolabeled DNA probes encoding for the murine cytokines IL-1 alpha, -2, -3, -4, TNF alpha, IFN tau, GM-CSF and G-CSF. From all cytokines tested, TNF alpha and IL-1 alpha were markedly increased upon in vivo stimulation with contact sensitizers and also after application of croton oil. Both light and electron microscopic immunostaining with a polyclonal and monoclonal antibody demonstrated the presence of TNF alpha in the epidermis. This staining was most pronounced in KCs of the suprabasal epidermis upon application of contact sensitizers or croton oil, but not with tolerizing analogues. Using a functional assay significantly more TNF alpha was found in the supernatants of KCs treated in vitro with DNFB or LPS than with DNTB. GM-CSF was found in untreated epidermis as well as in stimulated cells. The results suggest that the sensitizing properties of contact sensitizers may partly be dependent on their ability to induce proinflammatory mediators. The induction and release of TNF alpha and IL-1 alpha in KCs by contact sensitizers may play an important role in the early response to immunogenic or inflammatory signals in vivo, whereby tolerance induction seems to be less dependent on these cytokines.
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PMID:Induction of inflammatory cytokines in murine keratinocytes upon in vivo stimulation with contact sensitizers and tolerizing analogues. 136 8

New experimental findings on the mutual regulation of growth, differentiation and function of human blood cells by growth factors offer the opportunity to use these factors in the treatment of haematological diseases. The hitherto known growth factors are divided into four basic groups: 1. haematopoietic growth factors proper [multi-CSF (IL-3), GM-CSF, G-CSF, M-CSF, erythropoietin, lymphopoietin (IL-7) and megakaryopoietin (IL-11)], 2. cytokines (IL-1 to IL-11, TFN)., 3. other growth factors (PDGF, FGF, MGF) and 4. so-called negative regulators of haematopoiesis (IFN, MIP, TGF beta and IL-10), some of which support the differentiation of stem cells. Before growth factors can be routinely used in clinical work, it is essential to acquire closer knowledge of their interrelations, the activity of their receptors and natural or acquired inhibitors in vivo.
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PMID:[Growth factors in hematology]. 136 11

The CD20 molecule is a unique phosphoprotein exclusively expressed on B cells during most stages of B cell ontogeny. We here report that rIL-4 down-regulates the expression of CD20 with anti-Leu-16 mAb (clone L27) on both unstimulated and anti-mu preactivated normal and leukemic B cells. None of the other recombinant lymphokines tested (IL-1, IL-2, IL-3, IL-6, IFN-alpha, and IFN-gamma, granulocyte/macrophage-CSF, transforming growth factor-beta, TNF-alpha, and lymphotoxin) decreased CD20 expression. Incubation of unstimulated or anti-mu preactivated B cells with IL-4 did not affect the steady state CD20 mRNA, suggesting that IL-4 exerted its effect mainly at a nontranscriptional level. Hence, IL-4 selectively down-regulates the CD20 epitope recognized by clone L27 without affecting seven other different epitopes, indicating that IL-4 acts by modifying the conformation of the CD20 molecule rather than by inhibiting its production or inducing its internalization. IL-4 most likely utilizes a protein kinase C-independent signal transduction pathway to modify CD20 molecule inasmuch as staurosporine, an inhibitor of protein kinase C, antagonizes phorbol esters (PMA) but not IL-4-induced CD20 down-regulation. In contrast, anti-CD40 mAb reverses the IL-4 but not the PMA inhibitory effect on CD20 expression. Given that CD20 may be part of a Ca2+ ion channel and plays a role in B cell activation and proliferation, it is proposed that the ability of anti-CD40 mAb to maintain the CD20 molecule in a given epitopic configuration on IL-4-stimulated B cells may be related to the long term proliferation of normal B cells that are strictly dependent on the presence of IL-4 and cross-linked anti-CD40 mAb for their continuous growth.
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PMID:IL-4 induces conformational change of CD20 antigen via a protein kinase C-independent pathway. Antagonistic effect of anti-CD40 monoclonal antibody. 137 68

To determine the role of germline epsilon transcription in IgE synthesis, the effects of cytokines on germline epsilon RNA synthesis in IL-4 dependent epsilon switching in B cells was investigated. Induction of germline epsilon transcription in highly purified B cells seems to be a specific property of IL-4, since none of the other cytokines tested [IL-1 alpha, beta, IL-2, IL-3, IL-5, IL-6, IL-7, IL-9, IL-10, G-CSF, GM-CSF, M-CSF, IFN-gamma, IFN-alpha, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta] were effective. TGF-beta, IFN-gamma, and IFN-alpha inhibit IL-4 dependent IgE synthesis, but only TGF-beta blocked germline epsilon RNA synthesis in purified B cells, indicating that this may be the mechanism by which TGF-beta inhibits IgE synthesis, and that IFN-gamma and IFN-alpha act on other stages of the regulatory process resulting in IgE production. IL-5, IL-6, and TNF-alpha enhance IL-4 dependent IgE synthesis, but only TNF-alpha enhanced IL-4 induced germline epsilon RNA synthesis. Finally, anti-CD40 mAbs and the non-IL-4 producing CD4+ T cell clone A3, which in the presence of IL-4 induce IgE synthesis by purified B cells, both strongly enhanced germline epsilon transcription. These data, together with the observation that epsilon switching in cultures initiated with single sIgM+, sIgE- B cells in all instances was preceded by germline epsilon RNA synthesis, indicate that there is a strong relationship between germline epsilon transcription and IgE synthesis.
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PMID:Modulation of IL-4 induced germline epsilon RNA synthesis in human B cells by tumor necrosis factor-alpha, anti-CD40 monoclonal antibodies or transforming growth factor-beta correlates with levels of IgE production. 137 45


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