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Myeloid Growth Factors in the Lung
Published in Jason Kelley, Cytokines of the Lung, 2022
Jack Gauldie, Manel Jordana, Gerald Cox
Although some mast cell lines can express IL-3 (Plaut et al., 1989), the apparently predominant source for this cytokine is activated helper T cells (Fung et al., 1984; Arai et al., 1990). Interleukin-3 is a pluripotent hematopoietic stem cell factor that stimulates multilineage colony formation in vitro from bone marrow cells (Ottman et al., 1989). This stimulation appears to be functional at the very early stages of stem cell differentiation, but the stimulation of mast cell growth is restricted to the murine cytokine, whereas human IL-3 stimulates basophil differentiation in vivo in primates (Mayer et al., 1989).
Quantitative Assays for Human Hemopoietic Progenitor Cells
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
Heather J. Sutherland, Allen C. Eaves, Connie J. Eaves
Most of the other factors now known to have hemopoietic colony-stimulating activity have been called interleukins, because they are produced by one type of leukocyte and act on another. One of these that has been intensively studied is interleukin-3 (IL-3). It is also known by a variety of other names, including “multi-CSF”, because of its potent stimulating effects on the early stages of erythroid colony development from primitive erythroid cells, as well as on pluripotent cells and precursors of other lineages.54 Now that many factors are available as recombinant, purified reagents, it is clear that most can act on a much broader range of target cell populations than originally anticipated. For example, GM-CSF and IL-3 show extensive, although not complete, overlap on the types of cells they can stimulate,55,56 and G-CSF can stimulate primitive pluripotent cells, as well as later progenitors that mature into granulocytes.57 Other glycoprotein molecules with CSF activity on human or murine myeloid progenitors include IL-5,58,59 IL-6,60 IL-7,61 IL-9,62 IL-10,63 and IL-11.64 In addition, the ability of various factors to synergize in stimulating various aspects of myelopoiesis in vitro, has revealed the importance of testing combinations of factors which may not alone appear to have much effect. IL-1, IL-4, IL-6, IL-7, IL-11, and the ligand for c-kit are examples of factors known to participate in such synergisms.34,57
The Autacoid Functions of Adenosine in Asthma
Published in Devendra K. Agrawal, Robert G. Townley, Inflammatory Cells and Mediators in Bronchial Asthma, 2020
R. Polosa, M. K. Church, S. T. Holgate
In interleukin-3-driven bone marrow-derived mast cells of mice, Marquardt et al.68 have confirmed the enhancing effect of adenosine on IgE-stimulated mediator release via an interaction through A2 receptors. This activity was limited to the release of preformed β-hexosaminidase), but not newly generated, mediators such as prostaglandin D2 (PGD2) and leukotriene B4 (LTB4). The selective enhancement of mast cell degranulation aligns with the observation in atopic and nonatopic asthmatic subjects that selective histamine H1-receptor antagonists terfenadine and astemizole almost totally inhibit bronchoconstriction induced by inhaled AMP.21,69 Bronchoconstriction provoked by AMP (and by implication adenosine) in non-atopic asthmatics is also inhibited by terfenadine21 indicating that, in this variant of asthma, adenosine also may serve to augment preformed mediator release from mast cells. Using potent inhibitors of cyclooxygenase such as flurbiprofen and indomethacin, some evidence for a contribution of contractile prostaglandins to the response has also been found.70,71
Gene expression profiles and cytokine environments determine the in vitro proliferation and expansion capacities of human hematopoietic stem and progenitor cells
Published in Hematology, 2022
Roberto Dircio-Maldonado, Rosario Castro-Oropeza, Patricia Flores-Guzman, Alberto Cedro-Tanda, Fredy Omar Beltran-Anaya, Alfredo Hidalgo-Miranda, Hector Mayani
HSCs, MPCs and EPCs were cultured in liquid suspension cultures, in order to assess their proliferation and expansion potentials. Proliferation was defined as the capacity of a primitive cell to divide and give rise to new cells, regardless of their lineage and maturation stage. Expansion was defined as the capacity of a primitive cell to divide and give rise to new primitive cells, biologically similar to the initial cell. Each one of the cell populations obtained was resuspended in Serum-Free Expansion Medium (StemSpan™ SFEM; STI). The culture medium was supplemented with different combinations of the following recombinant hematopoietic cytokines: Thrombopoietin (TPO), FLT-3-ligand (FL), Stem Cell Factor (SCF), Interleukin-3 (IL-3), IL-6, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), G-CSF, and erythropoietin (EPO). All cytokines were purchased from R&D (Minneapolis, MN) and were added at 10 ng/ml; except for EPO, which was added at 3 IU/ml. Cells were cultured in 24-well tissue culture plates at 37°C in an atmosphere of 5% CO2 in air, at a concentration of 5 × 103 cells/ml/well. After 5 days of culture, cells were harvested from the wells, counted, and analyzed for progenitor cell content. Secondary cultures were initiated with 5–10 × 104 nucleated cells. Cultures were processed in this manner every 5 days.
mmu-miR-199a-5p regulates CYP2B10 through repression of E4BP4 in mouse AML-12 hepatocytes
Published in Xenobiotica, 2021
Shujing Ren, Guanghui Sun, Zhengping Wu, Yanke Lin, Shuai Wang, Dong Dong, Pei Yu, Haiyan Huang, Baojian Wu
E4BP4 (adenovirus E4 promoter-binding protein), also known as NFIL3 (nuclear-factor interleukin 3 regulated), is a transcriptional repressor that regulates gene transcription by binding to a specific DNA sequence called D-box (Mitsui et al. 2001). E4BP4 is distributed in various tissues including the liver, intestine, and kidney (Nishimura and Tanaka 2001). It plays an important role in immune responses such as interleukin-3-mediated pre-B lymphocyte survival (Ikushima et al. 1997; Male et al. 2012). E4BP4 is also regarded as a component of the circadian clock and regulates circadian rhythms by inhibiting the expression of PER1 and PER2 (Ohno et al. 2007). It is thus not surprising that E4BP4 has been identified as an important circadian regulator of drug-eliminating genes and pharmacokinetics. For instance, E4BP4 plays a role in the circadian regulation of hepatic CYP enzymes such as CYP3A11 (Tong et al. 2019). E4BP4 regulates CES enzymes by inhibiting the transrepression activity of REV-ERBα, thereby affecting the metabolism and pharmacokinetics of CES substrates (Zhao et al. 2018).
Pre-clinical development of a novel CD3-CD123 bispecific T-cell engager using cross-over dual-variable domain (CODV) format for acute myeloid leukemia (AML) treatment
Published in OncoImmunology, 2021
Hélène Bonnevaux, Stephane Guerif, Jana Albrecht, Erwan Jouannot, Thibaud De Gallier, Christian Beil, Christian Lange, Wulf Dirk Leuschner, Marion Schneider, Cendrine Lemoine, Anne Caron, Céline Amara, Cédric Barrière, Justine Siavellis, Valérie Bardet, Ernesto Luna, Pankaj Agrawal, Donald R. Drake, Ercole Rao, Peter Wonerow, Chantal Carrez, Véronique Blanc, Karl Hsu, Dmitri Wiederschain, Paula G. Fraenkel, Angéla Virone-Oddos
Evidence from in vitro and in vivo models suggests AML may derive from leukemic stem cells (LSCs) that give rise to leukemic blasts, and persistence of LSCs is hypothesized to cause relapse after an initial remission.6–8 Thus, eradication of LSCs becomes an important therapeutic goal. CD123, the surface interleukin-3 (IL-3) receptor alpha chain, is expressed in normal hematopoietic cells and stimulates cell proliferation in response to IL-3. Interestingly, CD123 is very frequently overexpressed in AML blasts and LSCs;9–14 indeed, it is 1 of only 7 transcripts in the AML gene expression signature that is overexpressed in leukemic blasts compared with normal hematopoietic cells from healthy controls.15 The majority of the AML cells from human patients expresses IL-3 receptors and proliferates when cultured in the presence of IL-3.16,17 In most patients, CD123 is strongly expressed in LSCs and blasts, regardless of their cytogenetic or mutational profile.18 High expression of CD123 on blast cells at diagnosis correlates with a higher blast count, a lower rate of complete response (36% vs 70%; P < .05), and a shorter median duration of complete response.17–19 Thus, CD123 represents an attractive therapeutic target in patients with AML.20