Abstract：
:It is known that inadequate erythropoietin (EPO) production contributes to the pathogenesis of anemia of inflammation, although the exact molecular mechanism is unknown. Aryl hydrocarbon receptor (AhR) may compete with hypoxia-inducible factor 2α (HIF-2α), the master regulator of EPO production, for binding with HIF-1β. The effect of kynurenine, an endogenous AhR activator that increases in inflammation, on EPO and hepcidin production was evaluated. HepG2 cells were treated with the hypoxia mimetic CoCl2, kynurenine, the AhR inhibitor CH223191, and combinations of these. EPO and hepcidin production was measured with enzyme-linked immunosorbent assay. HIF-2α and CYP1A1 levels, a transcriptional target of AhR, were assessed by Western blotting. CoCl2 increased EPO production and decreased hepcidin and CYP1A1. Kynurenine exerted the opposite effects. Wherever CH223191 was added, the inhibitor overcorrected kynurenine-induced alterations in both the presence and the absence of CoCl2. Also, treatment with CH223191 alone increased EPO and decreased hepcidin, indicating that there is a degree of constitutive AhR activation, possibly by other endogenous AhR activators. In conclusion, kynurenine, by competing with HIF-2α, may contribute to anemia of inflammation by decreasing EPO and increasing hepcidin production. The fact that inactivation of AhR alone induces EPO makes this transcription factor a potential therapeutic target in situations that require increased EPO.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Eleftheriadis T,Pissas G,Antoniadi G,Liakopoulos V,Stefanidis Idoi
10.1016/j.exphem.2015.08.010subject
Has Abstractpub_date
2016-01-01 00:00:00pages
60-7.e1issue
1eissn
0301-472Xissn
1873-2399pii
S0301-472X(15)00631-1journal_volume
44pub_type
杂志文章abstract：OBJECTIVE:Resveratrol (3,4',5,-trihydroxystilbene, RV), an ingredient of wine, is an inhibitor of the proliferation-linked enzyme ribonucleotide reductase (RR) and shows a broad spectrum of cytotoxic effects against human cancer cells. In order to enhance these effects, we introduced additional hydroxyl moieties into t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.05.018
更新日期：2006-10-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine IL-15 in patients transplanted with autologous peripheral blood progenitor cells (PBPC) for hematologic mali...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00747-0
更新日期：2001-12-01 00:00:00
abstract：:Clonality studies can establish the single-cell origin of tumors and thus differentiate clonal malignant and premalignant processes from reactive polyclonal processes. Detection of clonal cells may be based on direct tracking of cell lineage-specific sequences or disease-specific somatic mutations identifying the clon...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.01.013
更新日期：2020-03-01 00:00:00
abstract：:Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.08.003
更新日期：2016-11-01 00:00:00
abstract：:Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed agai...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 00:00:00
abstract：:Rats made transiently neutropenic by intra-arterial administration of vinblastine (3 mg/kg) and infected with E. coli (6.02+/-0.45 X 10(8), per animal) have a mortality rate of 90% within 48 h post infection. Multiple transfusions of large numbers of granulocytes (harvested from Deca-Durabolin treated donor rats) prot...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:The long-term effects of a maximum tolerated dose of doxorubicin (ADR) (10 mg/kg, LD10/60) on the recovery of the hematopoietic compartments of the femoral marrow from radiation (450 rad) were investigated over a 32-week interval using a mouse model. Comparative radiation response curves, estimating hematopoietic prol...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
abstract：:Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Dendritic cells (DC) are recognized as the most potent antigen-presenting cells with the ability to stimulate naive resting T cells and to initiate primary immune responses. Encouraging results in vaccination studies in animal models and the development of protocols to generate sufficient numbers of human DC for clini...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/s0301-472x(01)00730-5
更新日期：2001-11-01 00:00:00
abstract：:Phagocytic cells are characterized by their ability to generate superoxide anions upon activation by appropriate stimuli. UM384, a myelomonocytic cell line, was shown to be defective in this oxidase activity as measured by nitroblue tetrazolium or cytochrome c reduction. Cytochrome b558, a unique pigment present in ph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：OBJECTIVE:Several transducing molecules, including JAK2, STAT5, MAP kinases, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are activated by interaction between erythropoietin (EPO) and the EPO receptor. The aim of this was to examine the relative involvement of PI3K in the development of glycoph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00868-8
更新日期：2002-09-01 00:00:00
abstract：:Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) is a (deoxy)guanosine triphosphate (dGTP/GTP)-activated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase involved in cellular dNTP homoeostasis. Mutations in SAMHD1 have been associated with the hyperinflammatory disease Ai...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2017.05.001
更新日期：2017-08-01 00:00:00
abstract：:Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：OBJECTIVE:Use of a trifunctional bispecific antibody (trAb) given concomitantly with allogeneic cell therapy to achieve an anti tumor effect without graft-vs-host disease (GVHD). MATERIALS AND METHODS:A trAb-directed against murine CD3 and human epithelial cell adhesion molecule (EpCAM) (BiLu), was given alone or conc...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.03.005
更新日期：2008-08-01 00:00:00
abstract：:Our previous studies suggested that a defect in the hemopoietic microenvironment of bone marrow occurred in the anemia of chronic inflammatory disease. We examined the in vivo hemopoietic and marrow stromal cell (MSC) response of shielded marrow to 5000 rad leg-irradiation (5000 rad LI), the in vitro growth of BFUE, C...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-04-01 00:00:00
abstract：OBJECTIVE:Activating mutations in FLT3 are known to be a frequent transforming event in acute myeloid leukemia. Small molecule-inhibitor therapy targeting the FLT3 kinase is, therefore, an attractive strategy. FLT3 kinase inhibitors, such as PKC412, have already entered clinical trials. Even though results are encourag...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.07.008
更新日期：2007-10-01 00:00:00
abstract：:Mantle cell lymphoma (MCL) affects approximately 4500 patients/year in the US and demonstrates a male to female ratio of approximately 4:1. While the pathobiology underlying this ratio is unknown, the hematopoietic system is characterized by sex-related differences in androgen receptor (AR) expression, leading us to h...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2017.01.001
更新日期：2017-05-01 00:00:00
abstract：:Mds1-Evi1 (also known as Prdm3) and Prdm16 are two highly related zinc finger transcription factors that, within the hematopoietic system, are both expressed primarily in hematopoietic stem cells (HSCs). Our laboratory previously found that constitutive Mds1-Evi1 knockout mice are viable, but their HSCs are unable to ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2020.04.010
更新日期：2020-05-01 00:00:00
abstract：OBJECTIVE:To examine the possibility of adoptive cellular immunotherapy such as donor lymphocyte infusion using ex vivo expanded cord blood (CBL) lymphocytes, the potential expansion ability of CBL lymphocytes and the function of expanded CBL lymphocytes were evaluated. MATERIALS AND METHODS:Mononuclear cell fractions...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00776-2
更新日期：2002-04-01 00:00:00
abstract：:Hematopoiesis in continuous bone marrow culture is dependent upon close-range interaction between hematopoietic cells and marrow-derived adherent cells. The latter have been shown to include a significant proportion of fibroblastic elements, synthesizing the attachment protein fibronectin. The role of fibronectin in c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-02-01 00:00:00
abstract：:We compared the cell division behavior of CD34(-) and CD34(+) (CD33/CD38/CD71)-negative (Lin(-)) CD133(+) cord blood cells stimulated with the cytokines Flt3-ligand, stem cell factor, and thrombopoietin. Within a 4-day time frame, Lin(-)CD34(-) CD133(+) (CD34(-)) cells underwent more cell divisions in serum-free cultu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.05.016
更新日期：2007-09-01 00:00:00
abstract：:Data in this report determined the effect of a single injection of recombinant interleukin 1 alpha (rIL-1) prior to irradiation of B6D2F1 mice on the recovery of colony-forming cells (CFC) at early and late times after sublethal and lethal doses of radiation. Injection of rIL-1 promoted an earlier recovery of mature c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:The present studies evaluated effects of recombinant human (rhu) and murine (rmu) flt3 ligand (flt3-L) on colony formation by subsets of myeloid stem and progenitor cells present in low-density (LD) and cell-sorted CD34 hu cord blood (CB) and bone marrow (BM) cells and unseparated mu BM cells. By itself, flt3-L had we...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：OBJECTIVE:Excessive apoptosis may have a role in the ineffective hematopoiesis and cytopenias observed in myelodysplastic syndromes. The goals of this study were 1) to quantify apoptosis in patients with "early stage" myelodysplasia [including patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), RA...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00179-x
更新日期：2000-07-01 00:00:00
abstract：:The concept that mesenchymal stromal cells (MSCs), a component of the hematopoietic microenvironment, can be a target for alloreactive effector cells in the context of graft-vs-host disease has not been investigated in detail. Mixed lymphocyte reaction (MLR) supernatant was used to mimic the inflammatory milieu induce...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.07.011
更新日期：2012-11-01 00:00:00
abstract：OBJECTIVE:TGF-beta1 is a powerful inhibitor of erythropoiesis. However, its mechanisms of action are not fully elucidated yet at the cellular level. In this work we have studied the effects of TGF-beta on UT-7 cell survival, proliferation and differentiation. MATERIALS AND METHODS:UT-7 cell line is strictly dependent ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00155-1
更新日期：2000-03-01 00:00:00
abstract：:Activation of the N-ras gene via coding region mutations has been previously documented in 25% of patients with acute myeloid leukemia (AML). Since overexpression of normal N-ras is also transforming in vitro, the N-ras promoter of AML patients was analyzed for the presence of promoter mutations that may affect expres...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:Despite its growing use as a marker of proliferation, the relationship between expression of the nuclear antigen Ki67 and other indices of proliferation in acute myelogenous leukemia (AML) has not been elucidated. In this study, short-term primary suspension cultures of human AML bone marrow cells were used to compare...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：OBJECTIVE:The advantage of recipient hematopoiesis over that of xenogeneic donors poses a fundamental obstacle to the induction of xenograft tolerance through mixed hematopoietic chimerism. Here we explore the role of beta1 integrins in maintenance of human vs porcine hematopoiesis within a human hematopoietic environm...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.11.011
更新日期：2005-03-01 00:00:00
