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)

The basophilic leukaemia cell line KU812 can be induced to differentiate into basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line. KU812 cells express affinity receptors for IgE, produce histamine and tryptase and have the capacity for IgE-mediated histamine release. In this study we have examined the cytokines, produced by the Mo cell line, which are responsible for the observed differentiation-inducing effect in the KU812 cell line. It was shown that interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced differentiation in the KU812 cells and that these cytokines were responsible for the differentiation-inducing effect of the Mo supernatant. Other cytokines tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and IL-6 after 3 days cultivation with conditioned media from the Mo T-cell line. Untreated cells showed no detectable levels of TNF-alpha or IL-6 receptors indicating induction of these receptors during differentiation. Spontaneous differentiation was shown to occur under serum-free conditions which may be the result of endogenous IL-6 production through an autocrine loop. The activity of TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to the respective cytokine.
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PMID:TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell line KU812. 813 23

We have examined whether activation of MAP kinases [or extracellular signal-regulated kinases (ERKs)] is required for the survival of rat sympathetic neurons by comparing the actions of three survival factors whose survival-promoting actions can be blocked by neutralizing Fab fragments to p21 ras (Nobes and Tolkovsky, 1995, Eur. J. Neurosci., 7, 344-350), nerve growth factor (NGF), the cytokines ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF), and the cyclic AMP analogue 4-(8-chlorophenylthio)cAMP (CPTcAMP). NGF-induced survival was accompanied by an intense (15- to 30-fold) and steady (> 24 h) activation of p44 and p42 ERKs which waned rapidly (t1/2 approximately 30 min) upon NGF withdrawal. However, concentrations of NGF that induced a weak (4- to 5-fold) stimulation of the ERKs were not sufficient to maintain long-term survival. Moreover, prolonged and intense stimulation of the ERKs by NGF for up to 15.5 h was unable to confer long-term survival, since withdrawal of NGF after this time resulted in neuronal death that was kinetically indistinguishable from the death of neurons that had not been exposed to NGF. By contrast, CNTF and LIF continued to support survival for up to 3 days after eliciting only transient (< 30 min and 1 h respectively) activation of p44 and p42 ERKs, while CPTcAMP induced survival for several days without any measurable activation of the ERKs. Taken together, these data suggest that ERK activation per se is neither necessary nor sufficient for survival and that alternative pathways exist for effecting long-term survival of rat sympathetic neurons.
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PMID:Activation of p44 and p42 MAP kinases is not essential for the survival of rat sympathetic neurons. 854 72

The Fas/Apo-1 molecule is a member of tumor necrosis factor/nerve growth factor (TNF/NGF) receptor family and is able to induce apoptosis in various type of malignant cells, including most of the human leukemia T-cells. We previously demonstrated that the Fas-resistant variants may exist in highly Fas-sensitive human leukemia T-cell lines. The surface expression of Fas antigen was unchanged in the variant cells, suggesting the requirement of the cytoplasmic mechanism to exert apoptosis. In the present study, we examined the changes in cytoplasmic proteins of the Fas-sensitive and Fas-resistant cells after stimulation with anti-Fas antibody, 2D1. In Western blotting analysis, we found that the stimulation of Fas-sensitive cells with 2D1, but not resistant variants, induced a repression of cyclin-dependent kinases (cdks), p34cdc2 and p33cdk2, along with apoptosis. There was no alteration in the expression of bcl-2, HSP70, HSP90, and cyclin proteins examined. This observation seemed specific to Fas-mediated apoptosis, because calcium ionophore A23187 or sodium azide failed to repress the expression of cdks. These results indicate that the specific depletion of cdks, most likely due to proteolysis, may play a role in Fas-mediated apoptosis.
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PMID:Selective depletion of cyclin-dependent kinases is associated with Fas-mediated apoptosis in human leukemia T-cell lines. 878 21

This study demonstrates the localization and regulation of a novel neuropeptide of 33 amino acids, secretoneurin (SN), in the rat superior cervical ganglion. Gel filtration chromatography of ganglion proteins followed by a specific radioimmunoassay revealed that SN is the predominant cleavage product of secretogranin II, a member of the chromogranin/secretogranin protein family, in adult ganglia. SN was detected within the majority of nerve endings surrounding postganglionic neurons that were identified by the presence of synaptophysin and, in part, colocalized leu-encephalin. Applying immuno-electronmicroscopy, SN was localized to large dense core vesicles of neuronal and small intensely fluorescent (SIF) cells. In situ hybridization revealed the presence of secretogranin II mRNA in postganglionic neurons and, to a lesser extent, in SIF cells. One week after transection of the postganglionic branches SN levels were not significantly altered; however, a decrease of secretogranin II mRNA was observed in postganglionic neurons but not in SIF cells. After decentralization of the ganglion, SN-immunoreactive nerve terminals disappeared and intraganglionic SN levels were reduced by 70%, indicating the preganglionic origin of SN-positive nerve fibres and varicosities. Secretogranin II mRNA was slightly reduced under this condition. Combined axotomy and decentralization further diminished intraganglionic secretogranin II mRNA, although peptide levels increased significantly above control values under these conditions. Double-labelling immunofluorescence with antibodies against the somatodendritic marker microtubule-associated protein 2 (MAP2) revealed that the increase in SN immunoreactivity was due to an accumulation of SN in axonal processes of postganglionic neurons. SN immunoreactivity was also detected in dissociated neonatal superior cervical ganglion cultures and increased significantly upon treatment with nerve growth factor, the survival and differentiation factor of sympathetic neurons during perinatal development. Co-culture with non-neuronal cells or addition of leukaemia inhibitory factor, a cytokine known to stimulate synthesis of various peptides after nerve transection, did not influence SN immunoreactivity. Therefore, since no fixed relationship between SN and any of the known neuropeptides or neurotransmitters expressed in sympathetic neurons was observed, the expression of this novel peptide appears to be independently regulated.
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PMID:Localization and axotomy-induced regulation of the peptide secretoneurin in the rat superior cervical ganglion. 892 Dec 86

To explore the potential involvement of neurotrophins in the actions of retinoic acid (RA) on leukaemia differentiation, we examined the ability of RA to regulate the expression of neurotrophins and Trk receptors in several leukaemia cell lines. Expression of TrkA was dramatically induced by RA at both the mRNA and protein level in leukaemia cell lines K562 and KG-1. Furthermore, while no expression of trkB and trkC was detected, constitutive expression of nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 could be detected in leukemia cells. Our findings suggested that NGF/trkA may potentially be involved in the RA-induced differentiation of leukemia cells.
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PMID:Induction of TrkA receptor by retinoic acid in leukaemia cell lines. 917 86

Sciatic sensory afferents that retrogradely transport and accumulate leukaemia inhibitory factor (LIF) within their soma were characterized in the adult rat in vivo. Twenty-four percent of neurons within the L4 and L5 dorsal root ganglia accumulated biotinylated LIF following intraneural injection of the cytokine into the sciatic nerve. Labelled cell bodies were predominantly of small diameter (20.1 +/- 0.5 microm). Retrograde transport was eliminated by excess unlabelled LIF but not by the related cytokines, ciliary-derived neurotrophic factor (CNTF) and interleukin-6 (IL-6). Double labelling revealed that the majority (81%) of LIF-accumulating neurons were immunopositive for CGRP and 34% were immunopositive for the cell surface glycoconjugate IB4. Sixty-two percent of LIF-accumulating neurons were immunopositive for trkA. Our results demonstrate a group of small-diameter sensory neurons that retrogradely transport LIF, comprising cells that constitutively express neuropeptides and those likely to be peptide-deficient. LIF-accumulating neurons expressing trkA are also potentially responsive to nerve growth factor. It is likely that the LIF-accumulating neurons described in this study are nociceptive in function.
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PMID:Leukaemia inhibitory factor is retrogradely transported by a distinct population of adult rat sensory neurons: co-localization with trkA and other neurochemical markers. 921 8

Sensory neurons isolated from dorsal root ganglia of postnatal mice were analysed for cell surface p75, using fluorescent antibody staining with flow cytometry. They were found to follow a single bell-shaped distribution of p75 level, with no discrete group of p75-negative neurons. Sensory neurons were then separated by fluorescence-activated cell sorting into high- and low-p75 populations, consisting of cells within the highest and lowest 15th percentiles, respectively, of p75 expression levels. The sorted neurons were tested for trkA staining. All high-p75 neurons were positive for trkA, while many low-p75 cells were negative for trkA. The sorted neurons were placed in culture, and their survival in the absence and presence of various neurotrophins was measured. Low-p75 cells were found to have enhanced survival in the absence of neurotrophins, while cells with high p75 levels had reduced survival, compared to the overall population. Almost all high-p75 neurons were rescued with nerve growth factor, whereas less than half of the low-p75 cells were rescued. The slope of the dose response to nerve growth factor did not differ markedly between high- and low-p75 cells. High-p75, but not low-p75, neurons were responsive to neurotrophin-3. There was only a small response to either brain-derived neurotrophic factor or neurotrophin-4 in both high- and low-p75 neurons. All low-p75 neurons, and 68% of high-p75 neurons, survived in the presence of ciliary neurotrophic factor. These results, while consistent with our hypothesis that p75 may act as a death factor in postnatal sensory neurons, also imply a role for p75 in the modulation of trk responsiveness to neurotrophins. They also indicate overlapping neurotrophin responses in sensory neurons, especially in those with high p75 levels. A large proportion of low-p75 cells were not responsive to any of the nerve growth factor-related neurotrophins, suggesting an important role for cytokines such as ciliary neurotrophic factor and leukaemia inhibitor factor in the survival of sensory neurons.
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PMID:Rescue of dorsal root sensory neurons by nerve growth factor and neurotrophin-3, but not brain-derived neurotrophic factor or neurotrophin-4, is dependent on the level of the p75 neurotrophin receptor. 968 65

We investigated putative roles of transforming growth factor (TGF)-beta expressed in peripheral ganglia in the regulation of neuronal cell survival during the period of ontogenetic neuron death (OD). The chick ciliary ganglion (CG), where OD occurs between embryonic days (E) 6 and 10, was employed as a model system. We show that CG neurons (E8) are immunoreactive (ir) for TGF-beta2 and -beta3 as well as the TGF-beta receptor TbetaR-II, but are not ir for TGF-beta1. Ciliary neurotrophic factor (CNTF) and fibroblast growth factor (FGF)-2, established neurotrophic molecules for CG neurons, up-regulate TGF-beta3 mRNA and TGF-beta biological activity in cultures of E8 CG neurons. None of the TGF-beta isoforms--beta1, beta2, or beta3--has a trophic, survival-promoting effect on cultured CG neurons. However, all isoforms enhance CG neuron survival mediated by CNTF or FGF-2, significantly and over a wide range of concentrations. In combination with the neurotrophins (NT) nerve growth factor (NGF) and NT-3, which are not neurotrophic for CG neurons, TGF-beta significantly promotes CG neuron survival. However, TGF-beta does not act synergistically with the neuropoietic cytokines oncostatin M, leukemia inhibiting factor, or interleukin-6. Immunoneutralization of endogenous TGF-beta released from CG neurons using an antibody to TGF-beta1/-beta2/-beta3 significantly reduces the potency of CNTF or FGF-2 to promote CG neuron survival. The blocking effect of the anti-pan-TGF-beta antibody could be rescued by adding exogenous TGF-beta. Together, these data suggest that para-/autocrine TGF-beta signaling has an important effect on the regulation of neuron survival in a model system of peripheral neurons.
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PMID:TGF-beta regulates the survival of ciliary ganglionic neurons synergistically with ciliary neurotrophic factor and neurotrophins. 985 58

Culture media from rat basophilic leukemia cells (RBL-2H3) induced the neurite outgrowth of rat pheochromocytoma PC12 cells, a model system for neuronal differentiation. The extension of the neurite outgrowth was dependent on the culture time of RBL-2H3 cells in the DMEM medium. The DMEM medium conditioned by RBL-2H3 cells for 48 h induced neurite outgrowth of PC12 cells significantly. The neurite extension was much higher than that by medium containing 1 ng/ml nerve growth factor (NGF) but was rather lower than that by medium containing 10 or 50 ng/ml NGF. The neurite extension by 50 ng/ml NGF was completely suppressed by excess anti-NGF antibody (1-1.5 microg/ml), while the extension by culture medium conditioned by RBL-2H3 cells for 48 h was not completely suppressed in the presence of the same amount of anti-NGF antibody. The neurite extension by the culture medium of RBL-2H3 cells was also suppressed by anti-interleukin (IL)-6 antibody (1 microg/ml), although IL-6 itself (20 units) could scarcely induce the neurite outgrowth of PC12 cells. This suggests that IL-6 in the culture medium of RBL-2H3 cells could be effective in inducing the neurite extension in cooperation with NGF. In the presence of an excess of both anti-NGF and anti-IL-6 antibodies, the culture medium of RBL-2H3 cells induced the neurite extension of PC12 cells. This suggests that the action of the various factors from RBL-2H3 cells may be synergistic as far as the neurite outgrowth of PC12 cells is concerned.
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PMID:Soluble factors from rat basophilic leukemia (RBL-2H3) cells stimulated cooperatively the neurite outgrowth of PC12 cells. 988 36

Transection of the fimbria-fornix leads to retrograde degeneration of axotomized septal cholinergic neurons as manifested by loss of choline acetyltransferase and low-affinity nerve growth factor receptor (p75NGFR) immunoreactivity. Nerve growth factor administered into cerebral ventricles at the time of axotomy can prevent these changes, while ciliary neurotrophic factor can prevent the loss of p75NGFR immunostaining. Leukaemia inhibitory factor shares structural homologies with ciliary neurotrophic factor and has similar actions in the nervous system. Both proteins share the same signalling pathways, which involve the interleukin-6 transducing receptor components leukaemia inhibitory factor receptor beta and gp130. In this study, we compared the effects of leukaemia inhibitory factor, ciliary neurotrophic factor and nerve growth factor, administered into cerebral ventricles, on p75NGFR and choline acetyltransferase immunoreactivity in septal neurons after fimbria-fornix transection. We found that leukaemia inhibitory factor, like ciliary neurotrophic factor, prevents the loss of p75NGFR-stained medial septal neurons after fimbria-fornix axotomy, without maintaining choline acetyltransferase expression in these neurons. In addition, p75NGFR-immunostained neurons had significantly smaller mean diameter after axotomy in leukaemia inhibitory factor- and ciliary neurotrophic factor-treated animals as compared with either nerve growth factor-treated or unlesioned animals. These findings suggest that both leukaemia inhibitory factor and ciliary neurotrophic factor can prevent the axotomy-induced cell death of septal cholinergic neurons, but that, in contrast to nerve growth factor, these growth factors do not maintain the expression of choline acetyltransferase or the normal neuronal size of these injured neurons.
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PMID:Leukaemia inhibitory factor prevents loss of p75-nerve growth factor receptor immunoreactivity in medial septal neurons following fimbria-fornix lesions. 1036 99


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