Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chimeric receptors were prepared by exchanging the cytoplasmic region between leukemia inhibitory factor (LIF) receptor alpha subunit (gp190) and the other subunit-gp130 (190/130,130/190) and separately transduced into leukemia line HL-60 (to have the wild type subunit). The purpose is to investigate which subunit for activating MAPK p42/44 in leukemia cell while the cytoplasmic region homodimerization (190cyt-190cyt, 130cyt-130cyt) was induced by LIF. The results showed that MAPK p42/44 expression level after LIF stimulation 5 h was lower in the transformants with pED 130/190 (190cyt- 190cyt) (p < 0.01) and higher in the transformants with pED 190/130 (130cyt- 130cyt) (p < 0.05) than those in the parent cells. Meanwhile, MAPK p42/44 phosphorylation (Thr202/Tyr204) was ascended and the highest at 10 min in the 190/130 and descended in the 130/190. It suggests that gp130 activate MAPK p42/44 and gp190 indirectly regulate its expression and function. In order to analyses the relation of the subunit oligomerization and MAPK p42/44 we also prepared the recombination of the extracellular and transmembrane region of Fas and the cytoplasmic region of each LIFR subunit (Fas/190, Fas/130). After transduction into HL-60 with lipofection and induction by anti-Fas IgG, we found that MAPK p42/44 expression levels were lower in the Fas/190 than in the Fas/130 and parent cells (p < 0.01) and no difference between the Fas/130 and the wild type receptor. However, phospho-MAPK p42/44 were increased in the Fas/130 than the parent cells. It suggests that the oligomerization of the cytoplasmic regions of gp130 be potential to normally initiate MAPK p42/44 for the signal of HL-60 proliferation. We also determine that the separated oligomerization FasDD (no dimerization) can initiate the corresponding signal molecules, then regulate MAPK p42/44 expression and phosphorylation in leukemia cells.
 ...
PMID:Involving of the cytoplasmic region of leukemia inhibitory factor receptor alpha subunit, IL-6 related signal transducer-gp130 or fas death domain for MAPK p42/44 activation in HL-60 cell with LIF or anti-Fas IgG. 1126 54

The effects of the production of two closely related cytokines, oncostatin M (OSM) and leukaemia inhibitory factor (LIF), by astrocytoma cells were investigated using the stable cell line human U373-MG, which expressed and secreted both biologically active polypeptides. The expression of LIF by these cells caused resistance to this cytokine due to loss of the LIF receptor (LIFR), from the cell surface, suggesting its retention. In contrast, cells expressing OSM were stimulated by this cytokine, utilizing an autocrine mechanism, and possessed receptors for OSM, but not LIF, on the cell surface. In these cells the continuous up-regulation of OSM-induced gene expression was found even though the Janus kinase-signal transducer and activator of transcription ('JAK/STAT') pathway was almost exhausted due to long-term autocrine stimulation of the cells by OSM. The amount of LIFR was down-regulated in both LIF- and OSM-producing cells and this effect was not found in wild-type U373-MG cells treated with externally added cytokines. To investigate the mechanism of autocrine stimulation by OSM we constructed a stable cell line expressing a form of OSM that is retained in the endoplasmic reticulum (ER). This biologically active cytokine was not secreted, but was localized in the ER. In addition, it did not stimulate the astrocytoma cells in an autocrine manner. We conclude that expression of LIF causes resistance of astrocytoma cells to this cytokine, whereas expression of OSM leads to autocrine stimulation.
 ...
PMID:Differential effects of oncostatin M and leukaemia inhibitory factor expression in astrocytoma cells. 1128 16

Leukaemia Inhibitory Factor (LIF) is a multifunctional cytokine with an obligate role in the mouse in embryonic implantation. In this paper we demonstrate the existence of a functional LIF gene in the marsupial Sminthopsis crassicaudata, and the presence of LIF-related sequences in the monotreme Tachyglossus aculeatus (Australian echidna). Isolation of genomic and cDNA clones from S. crassicaudata, indicated that the LIF gene is highly conserved between marsupials and monotremes in terms of sequence and genomic organisation. Critical functional residues within the LIF sequence were also conserved including residues implicated in intracellular LIF activity, and in interaction with the receptor subunits LIFR and gp130. These findings suggest that the structure and biochemical function of the protein is likely to be conserved. Consistent with this, purified recombinant S. crassicaudata LIF interacted functionally with mouse receptor components and was sufficient for maintenance of mouse embryonic stem (ES) cells in the undifferentiated state. Conservation of LIF outside eutherians is intriguing given the markedly divergent reproductive strategies which include, for some marsupial species, embryonic diapause, and in monotremes, the absence of implantation. The availability of marsupial LIF probes provides an opportunity to investigate conservation of expression and function in these mammals.
 ...
PMID:Structure, sequence and function of a marsupial LIF gene: conservation of IL-6 family cytokines. 1143

Interleukin (IL)-6, leukaemia inhibitory factor (LIF) and IL-11 belong to the same family of cytokines whose receptors utilize gp130 as the signalling molecule. We have investigated the expression of the IL-11 receptor, IL-11Ralpha, protein in the human endometrium in vivo and the effects of IL-6, LIF and IL-11 on the production of metalloproteinases (MMPs) and cytokines by cultured endometrial epithelial and stromal cells. Immunostaining showed that IL-11Ralpha was expressed in both epithelial and stromal cells, with epithelial staining being more intense than stromal staining and little variation in staining in either compartment throughout the cycle. Incubation of both stromal and epithelial cells with IL-6, LIF and IL-11 had no effect on MMP-2, -7, -9, transforming growth factor (TGF)beta or IL-1beta production or cell growth. IL-6 and LIF also had no effect on tumour necrosis factor (TNF)alpha production, but IL-11 caused a dose-dependent decrease in TNFalpha production by epithelial cells. IL-6 receptor, LIF receptor and gp130 were all expressed by cultured stromal and epithelial cells, showing that the lack of effect is not due to lack of expression of the receptor components. The results show that although IL-6, LIF and IL-11 signal through the same molecule, they may have different effects in endometrial cells, suggesting the activation of different signalling pathways, which may ultimately be important in the control of endometrial function.
 ...
PMID:Expression of interleukin (IL)-11 receptor by the human endometrium in vivo and effects of IL-11, IL-6 and LIF on the production of MMP and cytokines by human endometrial cells in vitro. 1220 Apr 62

The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). IL-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.
 ...
PMID:Principles of interleukin (IL)-6-type cytokine signalling and its regulation. 1277 95

Variations in the expression of cytokines from the interleukin-6 (IL-6) family: ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF), and cardiotrophin 1 (CT-1) were studied during cardiac remodelling leading to left ventricular hypertrophy (LVH) in TGR(mRen2)27 rats at the age of 8 and 20 weeks. The cytokines mRNA levels within the free wall of the left ventricle were measured by semi-quantitative RT-PCR standardised with 18S. They were compared between heterozygous rats for the mRen2 transgene (TG+/-) and control rats (TG-/-). No significant difference was observed between results obtained at 8 and 20 weeks of age. At 20 weeks of age, TGR(mRen2)27 rats showed higher levels of mRNA LIF and IL-6 respectively by 52 and 55% compared to the control rats [LIF TG+/-: 3.17 +/- 0.21, TG-/-: 2.09 +/- 0.03; p < 0.001; n = 5; and IL-6 TG+/-: 1.53 +/- 0.13; TG-/-: 0.99 +/- 0.17; p < 0.05; n = 5]. By contrast, no variation of mRNAs levels of CT-1 and gp 130 genes was observed between control and transgenic rats. Concerning the cytokine receptors, the levels of mRNA for IL-6R did not vary while those of receptor subunits LIFR and CNTFR were decreased respectively by 48 and 42% in transgenic rats vs controls [LIFR TG+/-: 0.48 +/- 0.01; TG-/-: 0.92 +/- 0.08 p < 0.001; n = 5; and CNTFR TG+/-: 1.07 +/- 0.08; TG-/-: 1.85 +/- 0.18; p < 0.01; n = 5]. Therefore, these results show a specific pattern of activation of the cytokines pathway in the LVH of the TGR(mRen2)27 rat.
 ...
PMID:[Expression of cytokines and their receptors in left ventricular hypertrophy in TGR(mRen2)27 rats]. 1294 31

A chimeric receptor (130/190) containing the cytoplasmic region of leukemia inhibitory factor receptor alpha subunit (LIFRalpha, or gp190) and the extracellular transmembrane region of gp130 was generated. Expressed of the 130/190 chimera in HL-60 cells to induced the homodimerization of the cytoplasmic domains (190cyt-190cyt) with whole LIFRalpha subunit on HL-60 cells in response to LIF. Expression and activation of the signal transducer and activator of transcription factor-3 (Stat3) and inhibition of leukemia cell proliferation were evaluated in cells transfected with this chimeric molecule. Increased tyrosyl phosphorylation of Stat3 at Tyr705 was detected after 10 min LIF treatment in cells transfected with either the 130/190 or the wild type receptor. Cell proliferation was decreased upon LIF treatment in both cell types. However, expression of the C-terminal region of the cytoplasmic region of LIFRalpha subunit (190CT) in HL-60 cells resulted in lower levels of Stat3 phosphorylation induction by LIF and cell proliferation was unaffected. Immunohistochemical staining indicated an inverse correlation between Cdc25B expression and the levels of phospho-Stat3 in 190CT and 130/190 cells. Expression of CD15, a cell differentiation marker, was lower in 190CT than in 130/190 cells. Together, these results suggest that homodimerization of the 190 cytoplasmic region promotes the Tyr 705 phosphorylation, which correlates with the inhibition of proliferation and stimulation of differentiation in HL-60 cells. Our results also suggest a signal link between Stat3 and Cdc25B.
 ...
PMID:Molecular analysis of signaling events mediated by the cytoplasmic domain of leukemia inhibitory factor receptor alpha subunit. 1503 Jan 66

The cytokine receptor gp130 is the shared signalling subunit of the IL-6-type cytokines. Interleukin-6 (IL-6) signals through gp130 homodimers whereas leukaemia inhibitory factor (LIF) exerts its action through a heterodimer of gp130 and the LIF receptor (LIFR). Related haematopoietic receptors such as the erythropoietin receptor have been described as preformed dimers in the plasma membrane. Here we investigated gp130 homodimerization and heterodimerization with the LIFR by fluorescence resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC). We detected a FRET signal between YFP- and CFP-tagged gp130 at the plasma membrane of unstimulated cells that does not increase upon IL-6 stimulation. However, FRET between YFP-tagged gp130 and CFP-tagged LIFR considerably increased upon LIF stimulation. Using a BiFC approach that detects stable interactions we show that fluorescence complementation of gp130 constructs tagged with matching 'halves' of fluorescent proteins increases upon IL-6 stimulation. Taken together, these findings suggest that transient gp130 homodimers on the plasma membrane are stabilized by IL-6 whereas heterodimerization of gp130 with the LIFR is mainly triggered by the ligand. This view is supported by the observation that the simultaneous action of two IL-6 binding domains on two gp130 molecules is required to efficiently recruit a fluorescent IL-6 (YFP-IL-6) to the plasma membrane.
 ...
PMID:Dimerization of the cytokine receptors gp130 and LIFR analysed in single cells. 1625 48

Degeneration of axotomized GABAergic septohippocampal neurones has been shown to be enhanced in ciliary neurotrophic factor (CNTF)-deficient mice following fimbria-fornix transection (FFT), indicating a neuroprotective function of endogenous CNTF. Paradoxically, however, the cholinergic population of septohippocampal neurones was more resistant to axotomy in these mutants. As leukaemia inhibitory factor (LIF) has been identified as a potential neuroprotective factor for the cholinergic medial septum (MS) neurones, FFT-induced responses were compared in CNTF(-/-), LIF(-/-) and CNTF/LIF double knockout mice. In CNTF(-/-) mice, FFT-induced cholinergic degeneration was confirmed to be attenuated as compared with wildtype mice. The expression of both LIF and LIF receptor beta was increased in the MS providing a possible explanation for the enhanced neuronal resistance to FFT in these animals. However, ablation of the LIF gene also produced paradoxical effects; following FFT in LIF(-/-) mice no loss of GABAergic or cholinergic MS neurones was detectable during the first postlesional week, suggesting that other efficient neuroprotective mechanisms are activated in these animals. In fact, enhanced activation of astrocytes, a source of neurotrophic proteins, was indicated by increased up-regulation of glial fibrillary acidic protein and vimentin expression. In addition, mRNA levels for neurotrophin signalling components (e.g. nerve growth factor, p75(NTR)) were differentially regulated. The positive effect on axotomized cholinergic neurones seen in CNTF(-/-) and LIF(-/-) mice as well as the increased up-regulation of astrogliose markers was abolished in CNTF/LIF double knockout animals. Our results indicate that endogenous CNTF and LIF are involved in the regulation of neuronal survival following central nervous system lesion and are integrated into a network of neurotrophic signals that mutually influence their expression and function.
 ...
PMID:Altered neuronal responses and regulation of neurotrophic proteins in the medial septum following fimbria-fornix transection in CNTF- and leukaemia inhibitory factor-deficient mice. 1707 46

Leukaemia inhibitory factor (LIF) is a cytokine, which is associated with reproductive processes such as embryo development and implantation. The objectives of this study were to detect the presence of LIF receptor (LIFR) and glycoprotein 130 (gp 130) in the human Fallopian tube, endometrium and preimplantation embryo and to study the effect of mifepristone on the expression of LIFR and gp130 in the Fallopian tube. Twenty-two healthy fertile women received a single dose of 200 mg mifepristone or placebo immediately after ovulation (LH + 2). Biopsies were obtained from the Fallopian tubes during laparoscopic sterilization once between days LH + 4 and LH + 6 and from endometrium once between days LH + 6 and LH + 8. Preimplantation embryos were received from couples undergoing in vitro fertilization treatment. Immunohistochemistry was used to detect the presence of LIFR and gp130 in the Fallopian tube, endometrium and preimplantation embryo. Real-time PCR was used to study LIFR and gp130 expression in the Fallopian tube and endometrium. LIFR and gp130 were localized in the Fallopian tube, preimplantation embryo and endometrium. LIFR was more abundant in the Fallopian tube than in the endometrium. In the blastocyst, the staining of gp130 was mainly localized in the inner cell mass, whereas LIFR was expressed in all cells. The presence of LIFR and gp130 in the Fallopian tube and preimplantation embryo indicates a role for LIF in communication between the embryo and the Fallopian tube. Mifepristone did not affect the expression of LIFR and gp130 in the Fallopian tube, nor in the endometrium suggesting that progesterone might not be directly involved in the regulation of LIFR or gp130.
 ...
PMID:Leukaemia inhibitory factor receptor and gp130 in the human Fallopian tube and endometrium before and after mifepristone treatment and in the human preimplantation embryo. 1743 Sep 84


<< Previous 1 2 3 4 5 6 Next >>