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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone tissue is continually being remodelled according to physiological circumstances. Two main cell populations (osteoblasts and osteoclasts) are involved in this process, and cellular activities (including cell differentiation) are modulated by hormones, cytokines and growth factors. Within the last 20 years, many factors involved in bone tissue metabolism have been found to be closely related to the inflammatory process. More recently, a cytokine family sharing a common signal transducer (gp130) had been identified, which appears to be a key factor in bone remodelling. This family includes interleukin 6, interleukin 11, oncostatin M, leukaemia inhibitory factor, ciliary neurotrophic factor and cardiotrophin-1. This paper provides an exhaustive review of recent knowledge on the involvement of gp130 cytokine family in bone cell (osteoblast, osteoclast, etc.) differentiation/activation and in osteoarticular pathologies.
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PMID:gp130 Cytokine family and bone cells. 1102 60

Recent investigations of the cytokine network surrounding myeloma cells have disclosed the importance of gp130-related cytokines including interleukin (IL)-6 for myeloma cell survival and proliferation, identification of IL-10 as a growth factor for myeloma cells, the close relationship between IL-10 and the receptors for gp130-related cytokines, and the growth enhancement effect of IL-11 and IL-7 on myeloma cells. In this study, IL-10 production was observed in three out of seven human myeloma cell lines examined and five (including three producing lines) out of 10 lines exhibited mRNA expression of IL-10. The IL-10 mRNA expression was also enhanced in approximately one third of primary specimens, whereas the IL-10 receptor (R) expression was not changed compared with that of normal component marrow controls. However, reverse transcription-polymerase chain reaction (RT-PCR) assay of various cytokines and their receptors showed no particular association with IL-10-producing myeloma lines compared with non-producing lines. Supplementing exogenous IL-10 or neutralization of the IL-10 signal by anti-IL-10 monoclonal antibody (mAb) in a culture conditions did not significantly affect myeloma cell growth regardless of expression of IL-10 or its receptor (IL-10R). However, supplement of anti-IL-10 mAb caused upregulation of certain genes such as IL-11, leukaemia inhibitory factor receptor (LIFR) and syndecan-1 in IL-10R-expressing cell lines. These findings indicate that the cytokine network surrounding myeloma cells is complicated and variable. In addition, IL-10 may modify this network and the cellular biological properties of myeloma cells rather than cell proliferation.
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PMID:Expression and production of interleukin 10 in human myeloma cell lines. 1112 45

Deregulated expression of the myc-family of oncogenes in hematopoietic and other cell types plays an important role in tumorigenesis, and results in increased proliferative potential and block of cellular differentiation. We have previously shown that IFN-gamma restores phorbol ester-induced differentiation and cell cycle arrest in v-myc transformed human U-937 monoblasts. To investigate whether other cytokine signals could also abrogate such a block, IL-1, IL-3, IL-4, IL-6, IL-7, IL-10, IL-11, LIF, oncostatin M, M-CSF, G-CSF and GM-CSF, and TGFbeta1, TNF-alpha, IFN-alpha were examined. We show that GM-CSF and IL-6, in combination with the phorbol ester 12-O-tetradecanoyl-phorbol acetate (TPA), restored differentiation and cell cycle arrest. In contrast, treatment by TGFbeta1 +/- TPA resulted in an efficient G1/G0 arrest, but did not appear to induce terminal differentiation. Restoration of differentiation and cell cycle arrest was accomplished despite maintained expression of the v-Myc protein. Our results show that the cytokine-induced signals reduced Myc-dependent transcription of an artificial target promoter/reporter gene construct, correlating in most, but not all, cases with decreased association of v- and c-Myc with its essential partner, Max. Thus, cytokine-induced signals may counteract the activity of deregulated Myc, and contribute to the normalization of differentiation, arrest in the G1/G0 phase of the cell cycle, or both.
Leukemia 2001 Feb
PMID:Cytokine-induced restoration of differentiation and cell cycle arrest in v-Myc transformed U-937 monoblasts correlates with reduced Myc activity. 1123 37

The rat pituitary cell line, MtT/SM, has the characteristics of somatomammotrophs. The cells secrete both prolactin (PRL) and growth hormone (GH). We examined the effects of cytokines such as leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), oncostatin M and interleukin 11 on the secretion of these hormones by the cells. These cytokines stimulate proliferation of the cells and inhibit the secretion of PRL by 70-80% and that of GH by 50%. They induce tyrosine phosphorylation of STAT3 in the cells. The cells containing PRL or GH decreased at 48 h after treatment of the cells with LIF or IL-6. These results suggest that the LIF/IL-6 family of cytokines inhibits the functions of mammotrophs and somatotrophs in the pituitary gland.
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PMID:Leukaemia inhibitory factor and interleukin 6 inhibit secretion of prolactin and growth hormone by rat pituitary MtT/SM cells. 1144 19

The interleukins function as intercellular hormones, possessing the ability to alter the activity of a target cell population. Interleukin-4, secreted by activated T-cells, has shown antitumor activity in vitro against multiple myelomas, lymphoma, chronic myelomonocytic leukemia, and some solid tumors. Early promising clinical studies have shown the efficacy of IL-4 in decreasing the malignant lymphocyte count and in normalizing hematologic parameters in patients with CLL and in inducing transient clinical responses in patients with non-Hodgkin's lymphoma. Interleukin-6 possesses immunomodulating properties including enhancement of NK cell activity and induction of cytotoxic T-cell activity. IL-6 has shown antitumor activity in mice injected with weakly immunogenic syngeneic tumors and has been shown to inhibit in vitro human breast carcinoma and leukemia/lymphoma proliferation through a direct tumor inhibitory effect. Clinical studies investigating the antitumor activity of IL-6 are currently in phase II clinical trials. IL-6 and IL-11 have demonstrated thrombopoietic enhancing activity in primate models and early clinical trials. These agents have a potential application in ameliorating the thrombocytopenia associated with myeloablative chemotherapy. Yet to enter clinical trials, IL-12 has been shown to enhance the lytic activity of nonspecific NK/LAK cells and appears to be more efficient than IL-2 or IFN's in enhancing NK cytotoxicity. IL-12 has also been shown to enhance specific allogeneic human CTL responses and to induce the secretion of IFN-gamma from both resting and activated T and NK cells. In summary, these interleukins are now promising agents under investigation as effective treatment strategies in the oncologic setting.
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PMID:A Review of the New Cytokines: IL-4, IL-6, IL-11, and IL-12. 1183 74

The development of cancer cachexia has been linked to cytokines related to interleukin6 (IL-6). We examined the kinetics of IL-6, IL-11, oncostatinM (OSM) and leukaemia inhibitory factor (LIF) induction in the splenocytes of tumour-bearing mice. Using a lung carcinoma line, which grows in C57BL/6J mice, we observed that when the tumour grew and cachexia was observed, the splenocytes produced IL-6, IL-11, and OSM, but not LIF. Cytokine expression was observed within 1 week (day 3 for IL-6 and IL-11, and day 1 for OSM) of administration of tumour cells, and was observed in splenocytes without tumour metastases to the spleen. Cytokine expression preceded cachexia (determined by changes in serum triglyceride levels and decrease in epididymal fat-pad weights) development by over 1 week. Exogenous administration of IL-11 resulted in the accelerated onset of cachexia, compared to control protein treatment, but without an effect on the tumour burden. In vivo treatment with a neutralizing dose of anti-OSM antibody inhibited the triglyceride dysregulation only until the synthesis of IL-6 and IL-11 began in the spleen (day 3). Afterward, IL-6 and IL-11 induced lipid catabolism in the absence of functional OSM. We conclude from the data described above that cachexia developed due to a systemic cytokine response induced by a tumour burden, and that IL-6-like cytokines contributed independently to lipid hypercatabolism in the aetiology of cancer cachexia.
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PMID:Cancer cachexia is mediated in part by the induction of IL-6-like cytokines from the spleen. 1188 29

Interleukin (IL)-6-type cytokines are multifunctional proteins involved in cardiac hypertrophy and myocardial protection. Recent studies, performed on animal models, report the production of these cytokines by heart. The aim of this study was to analyse the capacity of myocytes and fibroblasts isolated from human atrium to secrete IL-6, leukaemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), IL-11, oncostatin M (OSM), ciliary neurotrophic factor (CNTF) and the soluble receptor subunits sIL-6R and sgp130 during primary culture. We detected LIF, IL-11, sgp130 and a large amount of IL-6, but not OSM, CT-1, CNTF nor IL-6R in these culture supernatants. Both cardiomyocytes and fibroblasts are able to spontaneously produce IL-6. The increase of IL-6 production all along the culture period appears to be the consequence of fibroblast proliferation and gp130 stimulation. This is the first demonstration that human cardiac cells are able to secrete IL-6, but also LIF and IL-11 in vitro. These cytokines could be involved in an autocrine and/or a paracrine networks regulating myocardial cyto-protection, hypertrophy and fibrosis.
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PMID:Secretion of IL-6, IL-11 and LIF by human cardiomyocytes in primary culture. 1212 42

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.
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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

Acute graft-versus-host disease (aGVHD) is the major complication of allogeneic stem cell transplantation (allo-HSCT), significantly limits the application of the therapy. Current evidence suggests that dysregulated cytokine production is responsible for many manifestations of aGVHD. The mechanisms have been most clearly delineated in mouse models, detailed analysis of human tissue is required. Monitoring serum levels of cytokine sIL-2R, TNF-alpha and IFN-gamma after transplantation or cytokine gene expression before transplantation can predict prognossis of aGVHD. GVHD have graft-versus-leukemia (GVL) effect, and GVL can be seperated from GVHD. IL-2, IL-12, IL-11, KGF and G-CSF could possess the roles of reducing GVHD while preserving GVL.
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PMID:[Roles of Cytokines in Acute Graft-Versus-Host Disease] 1257 74

To study the biological role of human cultured bone marrow mesenchymal stem cell (BM-MSC) in hematopoiesis by investigation of its expression of multiple hematopoietic growth factors, RT-PCR was used to analyze the expression of SCF, Flt3-ligand, TPO, LIF, G-CSF, GM-CSF, IL-3, IL-6 and IL-11 at mRNA level for human BM-MSC from healthy donors and patients with leukemia and lymphoma. BM-MSC were incubated with or without hydrocortison (HC). The results clearly showed that the cultured BM-MSC expressed mRNA of SCF, Flt3-ligand, TPO, LIF, IL-6 and IL-11 at passages 3 up to 15, but did not express G-CSF, GM-CSF and IL-3. The same expression pattern of above cytokines was seen also for the patient's BM-MSC. HC was able to induce BM-MSC to express G-CSF but not to express GM-CSF. BM-MSC seemed not to change morphologically after incubation with HC for up to 21 days. In conclusion, both normal and patient BM-MSC should be potential to promote hematopoiesis according to their expression of multiple hematopoietic cytokines, and HC is able to induce hematopoietic growth factor expression.
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PMID:[Human bone marrow mesenchymal stem cells express multiple hematopoietic growth factors]. 1274 29


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