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)

Cytokines are believed to play a critical role as mediators between the oviduct and the developing embryo. A synchronous development of embryo and endometrium is essential to successful implantation. It seems to be beneficial for embryo development to rest for some time in the Fallopian tube. Expression of cytokines in the human Fallopian tube and the effect of mifepristone were investigated. Fourteen women with regular menstrual cycles and proven fertility, admitted to the hospital for tubal ligation, were randomly allocated to control or treatment groups. Mifepristone 200 mg was given on day LH+2. Surgery was performed on day LH+3 to LH+5. Biopsies were obtained from the ampullar and isthmic regions of the tubes. Expression of interleukin 8 (IL-8), tumour necrosis factor alpha (TNFalpha), transforming growth factor beta (TGFbeta) and leukaemia inhibitory factor (LIF) was analysed using immunohistochemistry. All cytokines except IL-8 showed the same staining intensity both in the ampullar and isthmic region, while IL-8 was more pronounced in the ampullar region in both epithelial and stromal cells. Exposure to mifepristone made the spatial difference in IL-8 disappear and increased the expression of TNFalpha in the epithelium of the isthmus, but had no effect on the expression of TGFbeta1 or LIF. Changes in cytokine expression in the Fallopian tube are likely to influence embryo development, which could contribute to the contraceptive effect of mifepristone.
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PMID:Effect of mifepristone on the expression of cytokines in the human Fallopian tube. 1512 76

Proteasome inhibition has become a target for antitumour and anti-inflammatory therapy. The present study investigated the influence of cysteine proteinase and proteasome inhibitors on chemokine production in lung epithelial cells and monocytic cells. The lung carcinoma cell lines A549, SK-MES, NCI-H727, virus-transformed bronchial epithelial cell line BEAS-2B, primary lung epithelial cells, and the acute monocytic leukaemia cell lines Mono-Mac-6 and THP-1 were incubated with proteasome (N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN), beta-lactone) or cysteine proteinase inhibitor (L-trans-Epoxysuccinyl-Leu-3-methylbutylamide-ethyl ester) and the influence on chemokine production (interleukin-8: IL-8, monocyte chemoattractant protein-1, RANTES) was quantified at protein and mRNA levels. Inhibition of proteasome activity by ALLN and beta-lactone resulted in significantly increased IL-8 secretion (5- to 22-fold). Cysteine proteinase inhibitors did not influence chemokine production. The simultaneous rise in IL-8 mRNA was caused by an increased half-life of mRNA and increased RNA synthesis. Moreover, analysis of transcription factor activation revealed induction of activator protein-1 (c-Jun) activity by proteasome inhibition, whereas nuclear factor-kappaB (p50 and p65) was not activated. The significant increase in IL-8 production after proteasome inhibition was also observed in primary lung epithelial cells and in monocytic cells. In addition, the secreted IL-8 was biologically active as shown by the neutrophil chemotaxis assay. In conclusion, it was shown that proteasome inhibitors stimulate interleukin-8 secretion in lung epithelial cells and monocytic cells, thus recruiting neutrophils.
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PMID:Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells. 1529 3

To study the early stages of development from stem cells of the CD56+ cell population [which includes natural killer (NK) cells], granulocyte-colony stimulating factor-mobilized peripheral blood CD34+ cells from healthy donors were sorted to >99% purity and cultured in the presence of stem cell factor and interleukin (IL)-2. After 3 weeks in culture, the majority of cells acquired CD33, with or without human leukocyte antigen-DR and CD14. In 20 stem cell donors tested, 8.7 +/- 8.8% of cells were CD56+. Two major CD56+ subsets were identified: CD56(bright), mainly CD33- cells (7+/-10%, n=11) with large, granular lymphocyte morphology, and CD56dim, mainly CD33+ (2.5+/-2, n=11) cells with macrophage morphology. The CD56bright population had cytoplasmic granzyme A but lacked killer inhibitory receptor, suggesting they were immature NK cells. The CD56dim, CD33+, population lacked NK markers. They may represent a minor subset of normal monocytes at a developmental stage comparable with the rare CD56+ CD33+ hybrid myeloid/NK cell leukemia. Consistent with a monocyte nature, CD56dimCD33+ proliferated and produced a variety of cytokines upon lipopolysaccharide stimulation, including IL-8, IL-6, monocyte chemoattractant protein-1, and macrophage-derived chemokine but not interferon-gamma. In a short-term cytotoxicity assay, they failed to kill but powerfully inhibited the proliferation of the NK-resistant cell line P815. The generation of CD56+ cells was negatively regulated by hyaluronic acid and IL-4, indicating that extracellular matrix may play an important role in the commitment of CD34+ cells into CD56 myeloid and lymphoid lineages.
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PMID:G-CSF-mobilized CD34+ cells cultured in interleukin-2 and stem cell factor generate a phenotypically novel monocyte. 1534 23

Benzene toxicity is considered to be elicited by its metabolites and phenolic metabolites of benzene are known to induce apoptosis in leukemia cells in culture and in human bone marrow progenitor cells. One potential mechanism of apoptosis induced by benzene metabolites that has not been examined is the production of pro-apoptotic cytokines such as endothelial IL-8 from endothelial cells in bone marrow stroma. In this study, we utilized HL-60 cells which are known to produce the endothelial form of IL-8 (eIL-8) and human bone marrow endothelial cells (HBMEC) as model systems. Hydroquinone (HQ), Catechol (Cat) and benzenetriol (BT) all induced eIL-8 production and apoptosis in HL-60 cells. HQ induced a marked 50-70 fold stimulation of eIL-8 levels and HL-60 cells were shown to have the eIL-8 receptor, CXCR1 thus enabling an autocrine pathway of apoptosis. However, treatment with recombinant eIL-8 failed to induce apoptosis in HL-60 cells as previously reported and antibodies to either IL-8 or CXCR1 did not significantly abrogate benzene metabolite-induced apoptosis. HQ and Cat but not BT also induced stimulation of eIL-8 production in HBMEC. These data demonstrate that although metabolites of benzene induce marked stimulation of eIL-8, this is unlikely to be responsible for apoptosis induced in HL-60 cells. Our data also demonstrates that phenolic metabolites of benzene stimulate the production of eIL-8 from HBMEC suggesting that higher levels of endothelial-derived cytokines may occur in bone marrow after benzene exposure.
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PMID:Stimulation of endothelial IL-8 (eIL-8) production and apoptosis by phenolic metabolites of benzene in HL-60 cells and human bone marrow endothelial cells. 1558 39

Acute graft-versus-host disease (GVHD) is a primary T-cell-mediated complication of allogeneic hematopoietic stem cell transplantation (HSCT), occurring when donor-derived T cells are stimulated by host antigen-presenting cells (APCs), enhanced by proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha. Recent data indicate that besides differences in major histocompatibility and minor histocompatibility antigens, cytokine gene polymorphisms have a predictive value for the complication of GVHD. Patients with a high anti-inflammatory IL-10 production have been demonstrated to be protected from GVHD while patients with high TNF-alpha serum levels were more at risk for GVHD. Pharmacological immunosuppression for GVHD prophylaxis and therapy, including unspecific approaches with corticosteroids or methotrexate (MTX), as well as more specific therapy with cyclosporin A (CsA), tacrolimus (FK506), sirolimus, mycophenolate mofetil (MMF), antithymocyte globulin (ATG), and monoclonal antibodies (MAbs) directed against CD3, CD25, CD52, cytotoxic T-lymphocyte antigen (CTLA)-4, CD40 ligand, or TNF-alpha, have been proven to be effective. Recent data on novel techniques to selectively deplete alloreactive T cells by removal, destruction, or anergy induction while preserving leukemia-specific T-cell clones suggest a clinical benefit from these approaches. Gene-modified T cells that can selectively be depleted and CD4(+)CD25(+) regulatory T cells are under investigation for their ability to modulate alloreactivity after HSCT. With a better understanding of the immunopathogenesis of acute GVHD and the technical improvement of recently described therapeutic approaches, such as removal of naive T cells, selection of Th2 cells, suicide gene transduced T cells, and adoptive transfer of regulatory T cells, the use of alloreactivity as a treatment modality may be expanded to nonhematological disease entities such as solid tumors or autoimmune disorders.
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PMID:Immunopathogenesis of acute graft-versus-host disease: implications for novel preventive and therapeutic strategies. 1544 32

Benzene toxicity is considered to be elicited by its metabolites and phenolic metabolites of benzene are known to induce apoptosis in leukemia cells in culture and in human bone marrow progenitor cells. One potential mechanism of apoptosis induced by benzene metabolites that has not been examined is the production of pro-apoptotic cytokines such as endothelial IL-8 from endothelial cells in bone marrow stroma. In this study, we utilized HL-60 cells which are known to produce the endothelial form of IL-8 (elL-8) and human bone marrow endothelial cells (HBMEC) as model systems. Hydroquinone (HQ), Catechol (Cat) and benzenetriol (BT) all induced eIL-8 production and apoptosis in HL-60 cells. HQ induced a marked 50-70-fold stimulation of eIL-8 levels and HL-60 cells were shown to have the eIL-8 receptor, CXCR I thus enabling an autocrine pathway of apoptosis. However, treatment with recombinant elL-8 failed to induce apoptosis in HL-60 cells as previously reported and antibodies to either IL-8 or CXCRI did not significantly abrogate benzene metabolite-induced apoptosis. HQ and Cat but not BT also induced stimulation of elL-8 production in HBMEC. These data demonstrate that although metabolites of benzene induce marked stimulation of eIL-8, this is unlikely to be responsible for apoptosis induced in HL-60 cells. Our data also demonstrates that phenolic metabolites of benzene stimulate the production of eIL-8 from HBMEC suggesting that higher levels of endothelial-derived cytokines may occur in bone marrow after benzene exposure.
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PMID:Stimulation of endothelial IL-8 (eIL-8) production and apoptosis by phenolic metabolites of benzene in HL-60 cells and human bone marrow endothelial cells. 1535 18

Roots of Astragalus species are used to treat leukemia and for wound healing in Turkish folk medicine. In order to evaluate this information, the effect of 13 cycloartane- and 1 oleanan-type triterpene saponins isolated from Turkish species (Astragalus brachypterus, Astragalus cephalotes, Astragalus microcephalus, and Astragalus trojanus), as well as methanol extracts from the roots of three Astragalus species (Astragalus cephalotes, Astragalus oleifolius and Astragalus trojanus) were studied. Cytokine concentrations of interleukins IL-1beta, IL-8 and TNF-alpha after bacterial lipopolysaccharide (LPS) and IL-2, IL-4 and INF-gamma after phorbolacetate (PHA) stimulation were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. All triterpene saponins tested in the present study showed a prominent IL-2 inducing activity between 35.9% and 139.6%. Among the extracts the highest score was obtained for Astragalus oleifolius (141.2%). Glycosides of 20,24-epoxy and 20,25-epoxy cycloartanes showed higher IL-2 inducing activity than those of acyclic-cycloartane derivatives as well as aglycone of 20,24-epoxy cycloartanes, cycloastrogenol. Especially the activity of Astragaloside VII, a tridesmosidic glycoside of cycloastrogenol, was the most remarkable. The oleanan-type triterpene saponin also showed a prominent IL-2 inducing activity. IL-2 is a cytokine produced by activated T cells, which has shown powerful immunostimulatory and antineoplastic properties. Accordingly, the IL-2 inducing activity of the triterpene saponins might be the mechanism involved in order to explain the immunomodulatory and anticancer effects of Astragalus species.
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PMID:Effects of triterpene saponins from Astragalus species on in vitro cytokine release. 1558 52

Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disease often associated with autoimmune disorders such as rheumatoid arthritis. High levels of soluble Fas ligand have been implicated in development of chronic neutropenia. However, a comprehensive analysis of constitutive chemokine and lymphokine production in LGL leukemia has not previously been reported. Here, we utilized RNase protection assays and enzyme-linked immunosorbent assays (ELISAs) to address this question. RANTES, IL-8, MIP-1alpha, MIP-1beta, IL-1beta, IL-10, IL-12 p35, IL-18, IFN-gamma and IL-1Ra were the cytokine transcripts expressed in elevated levels from RNA of peripheral blood mononuclear cells of LGL leukemia patients. Confirmatory ELISAs indicated that sera from LGL leukemia patients have elevated levels of RANTES, MIP-1beta, IL-18, and to a lesser extent IL-8 and IL-1Ra. This pattern of cytokine upregulation is similar to that seen in some chronic infections or in autoimmune diseases, thus characterizing LGL leukemia as a proinflammatory disorder.
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PMID:Constitutive production of proinflammatory cytokines RANTES, MIP-1beta and IL-18 characterizes LGL leukemia. 1564 40

Nude rats bearing the LC-6-JCK human lung cancer xenograft displayed cancer-associated wasting syndrome in addition to humoral hypercalcemia of malignancy. In these rats, not only PTHrP but also several other human proinflammatory cytokines, such as IL-6, leukemia-inducing factor, IL-8, IL-5 and IL-11, were secreted to the bloodstream. Proinflammatory cytokines induce acute-phase reactions, as evidenced by a decrease of serum albumin and an increase in alpha1-acid glycoprotein. Tumor resection abolished the production of proinflammatory cytokines and improved acute-phase reactions, whereas anti-PTHrP antibody affected neither proinflammatory cytokine production nor acute-phase reactions. Nevertheless, tumor resection and administration of anti-PTHrP antibody similarly and markedly attenuated not only hypercalcemia but also loss of fat, muscle and body weight. Body weight gain by anti-PTHrP antibody was associated with increased food consumption; increased body weight from anti-PTHrP antibody was observed when animals were freely fed but not when they were given the same feeding as those that received only vehicle. Furthermore, nude rats bearing LC-6-JCK showed reduced locomotor activity, less eating and drinking and low blood phosphorus; and anti-PTHrP antibody restored them. Although alendronate, a bisphosphonate drug, decreased blood calcium, it affected neither locomotor activity nor serum phosphorus level. These results indicate that PTHrP represses physical activity and energy metabolism independently of hypercalcemia and proinflammatory cytokine actions and that deregulation of such physiologic activities and functions by PTHrP is at least in part involved in PTHrP-induced wasting syndrome.
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PMID:Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. 1580 Sep 41

In patients with chronic myeloid leukemia (CML) who do not reach a (near) complete cytogenetic response, the disease progresses over several years from an indolent, chronic phase into a rapidly fatal blast crisis. Events that are responsible for this transformation process are largely unknown. To identify changes in gene expression that occurred during the course of the disease, we performed cDNA subtraction on sequentially stored peripheral blood mononuclear cell pellets, collected throughout the course of disease of a single CML patient. In total, 32 differentially expressed sequences were identified, of which 27 corresponded to known genes. On quantitative PCR, eight of these genes, YWHAZ, GAS2, IL8, IL6, PBEF1, CCL4, SAT and MMRN, showed comparable differential expression in additional CML patient samples. This set of genes can be considered as a starting point for further research on causes of disease transformation in CML and may lead to new targets in the treatment of resistant CML.
Leukemia 2005 Jun
PMID:Identification of genes potentially involved in disease transformation of CML. 1581 27


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