REVIEW Interleukin-3 Receptor in Acute Leukemia

Total Page:16

File Type:pdf, Size:1020Kb

REVIEW Interleukin-3 Receptor in Acute Leukemia Leukemia (2004) 18, 219–226 & 2004 Nature Publishing Group All rights reserved 0887-6924/04 $25.00 www.nature.com/leu REVIEW Interleukin-3 receptor in acute leukemia U Testa1, R Riccioni1, D Diverio2, A Rossini1, F Lo Coco3 and C Peschle1 1Department of Hematology and Oncology, Istituto Superiore di Sanita`, Viale Regina Elena 299, Rome, Italy; 2Dipartimento di Biotecnologie Cellulari, Universita` ‘‘La Sapienza’’, Rome, Italy; and 3Cattedra e Divisione di Ematologia, Universita` Tor Vergata, Ospedale S Eugenio, Rome, Italy Recent studies indicate that abnormalities of the interleukin-3 Several lines of evidence have indicated that AML1/ETO is receptor (IL-3R) are frequently observed in acute myeloid insufficient by itself to induce leukemia, but instead alters the leukemias (AMLs) and may contribute to the proliferative advantage of leukemic blasts. This review analyzes the self-renewal capacities of hematopoietic stem cells, resulting in evidences indicating that the IL-3R represents one of the target the formation of a preleukemic population that lacks a great 5 molecules involved in the stimulation of proliferation of AMLs, growth advantage. For the development of an overt leukemic and the overexpression of the IL-3Ra chain may represent one condition, AML1/ETO-induced effects must be associated with of the mechanisms contributing to the development of a highly the effects of secondary mutations that cooperate with the malignant leukemic phenotype. Furthermore, there is evidence primary mutation and ultimately result in a growth advantage that the IL-3Ra is a marker of leukemic stem cells, at variance 6,7 with normal stem cells that are IL-3RaÀ. Finally, the IL-3R may and in a block of cell differentiation. In line with these represent an important target for the development of new findings, a high frequency of NRAS and c-kit mutations have þ antileukemic drugs. been observed in AML patients with AML1/ETO leukemias. Leukemia (2004) 18, 219–226. doi:10.1038/sj.leu.2403224 Therefore, it was proposed that fusion proteins encoding Published online 4 December 2003 hybrid transcription factors require genetic complementation Keywords: leukemia; growth factors; interleukins; proliferation; with mutant or activated kinases. Activated kinases could differentiation interfere with the cell cycle and complement the differentia- tion-blocking activity of chimeric transcription factors. This model is supported also by additional important observations: (a) fusion proteins, such as BCR/ABL or TEL/AML1 or AML1/ The current model on the pathogenesis of acute myeloid ETO, are found in normal subjects at a frequency about 100 leukemias (AMLs) 8,9 times the corresponding leukemia rates, thus indicating that their presence in few hemopoietic cells is per se not sufficient Several lines of experimental evidence suggest that multiple for the development of a leukemic condition; (b) the analysis of mechanisms are involved in the genesis of human tumors and, the clonal relationship of concordant leukemia in identical particularly, of AMLs.1,2 Among these different pathogenetic mozygotic twins strongly argues in favor of a parental in utero mechanisms, the occurrence of chromosomic translocations 10 origin of pediatric leukemias. with consequent generation of fusion genes and corresponding In the recent years several genes have been identified, fusion proteins play a major role in the genesis of these diseases. mutated or abnormally expressed in AML, that confer a Stem cells are the main target for these key genetic events in proliferative survival advantage to leukemic blasts. These genes acute leukemias. The major contribution of fusion proteins, such are characterized by their involvement in the control of cell as PML/RARa, AML1/ETO, AML1/Evi1 or CBFb/SMMHC, con- proliferation. Thus, the hemopoietic receptor tyrosine kinase sists in the capacity to block the differentiation process at a Flt3 is constitutively activated in 30–35% of cases of AML, as a specific stage (reviewed in Tenen).3 Studies in transgenic mice consequence of internal tandem-repeat mutations in the harboring the fusion gene in their genome clearly indicate that juxtamembrane domain, or activating loop mutations (reviewed the simple expression of this gene in hemopoietic cells greatly 11 in Gilliland and Griffin). Similarly, Flt3 is frequently over- contributes to the differentiation block and, in some cases, also 12 expressed in secondary, therapy-related AMLs and in lympho- in part to the proliferative stimulation, but per se is not sufficient 13 4 blastic leukemia with MLL rearrangements and with for the development of a leukemic condition. This conclusion 14 hyperdiplody. Finally 5–10% of patients with myelodysplasia is directly supported by several experimental models, such as have mutations of the Flt3 gene. The occurrence of a significant transgenic animals expressing the PML/RARa fusion gene: these association between the presence of Flt3 mutations in AML and animals, in spite a high expression of the transgene, need 1–2 the number of blast cells strongly indicates that the mutated years before the development of leukemia. This time is required receptor induces a proliferative biologic effect in leukemic for the acquisition in hemopoietic cells of additional mutations, blasts. Activating loop mutations have been identified in the mainly occurring at the level of genes involved in the control of hematopoietic receptor tyrosine kinase c-kit in 5% of AML cell proliferation, whose alterations are required for tumor 15 cases. Furthermore, activating loop mutations in RAS family development. Interestingly, similar observations have been also members, mainly NRAS and KRAS, have been identified in 15– made in M2 leukemias associated with the t(8;21) translocation 16 25% of cases. It was estimated that mutations of some and the consequent formation of the AML1/ETO fusion protein. components of the receptor tyrosine kinase pathway (including Flt3, c-kit, VEGFRs, c-fms and RAS) occur in 450% of AML Correspondence: Dr U Testa, Department of Hematology and patients. Oncology, Istituto Superiore di Sanita`, Viale Regina Elena 299, 00161 Rome, Italy; Fax: þ 39 064 938 7087; E-mail: [email protected] Recent studies indicate that abnormalities of the interleukin-3 Received 22 July 2003; accepted 15 October 2003; Published online receptor (IL-3R) are frequently observed in AMLs and may 4 December 2003 contribute to the proliferative advantage of leukemic blasts.17 IL-3R in acute leukemia U Testa et al 220 This review will analyze the evidences indicating that the IL-3R GM-CSFR acquired biologic activity on cell differentiation and may represent one of the target molecules involved in the losted its activity on cell proliferation of FDPC-mix cells.23 stimulation of proliferation in AMLs and particularly, that its According to these observations, it was suggested that IL-3 overexpression may represent one of the mechanisms involved exerts its biologic activities mostly at the level of the control of in the pathogenesis of a highly malignant leukemic phenotype. proliferation of hemopoietic progenitors, while the predominant This review will not cover the basic physiology of the IL-3R, as effect of GM-CSF is on the differentiation of these cells. well as the signal transduction pathways induced by the The analysis of the signal transduction pathways triggered by activation of this receptor since this topic was covered by an IL-3R activation is out the scope of the present review, and the excellent review, recently published on this journal.18 reader is referred to an excellent review recently published on this journal.18 Here, only a brief summary of this process is briefly oultined. After ligand binding, the IL-3R/GM-CSFR bc Basic background becomes phosphorylated, and through the recruitment of adaptor proteins such as Shc, Grb2, and Sos activates the Ras Normal hematopoiesis is a multistep process in which lineage signaling pathway. The activated Ras pathway in turn stimulates development occurs as a consequence of the initial stochastic Raf followed by the downstream induction of the MAPK differentiation of pluripotent stem cells with the generation of pathway related to ERK1 and ERK2, linked to increased multipotent hemopoietic progenitors and the subsequent differ- expression of the transcription factors c-fos and c-jun. The entiation along the different hemopoietic lineages of these cells activation of the MAPK pathway is not restricted only to ERK1 under the ordered effects of a number of growth factors. These and ERK2, but involves also p38, and JNK/SAPK. Another very growth factors may be classified according to the level of their important transduction pathway induced during the activation biological action as early-acting hemopoietic growth factors of the IL-3R is represented by the phosphatidylinositol 3-kinase (HGFs), multilineage HGFs and late-acting HGFs. The prototype (PI-3K)/AKT pathway: the p85 subunit of PI3 K associates with of multilineage HGF is represented by IL-3. the bc of the activated IL-3R at the level of phosphorylated Ser- The main biologic activity of IL-3 is exerted at the level of the 585,24 recruits PKB/AKT by phosphorylation of its serine progenitor compartment, where this cytokine stimulates the residues and transmits several survival signals. Ultimately, these survival and proliferation of multipotent cells; particularly, IL-3 various transcription pathways influence in a specific way gene stimulates the development of multilineage colonies from transcription activating
Recommended publications
  • Evolutionary Divergence and Functions of the Human Interleukin (IL) Gene Family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W
    UPDATE ON GENE COMPLETIONS AND ANNOTATIONS Evolutionary divergence and functions of the human interleukin (IL) gene family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W. Nebert3* and Vasilis Vasiliou1 1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA 2Department of Clinical Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA 3Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267–0056, USA *Correspondence to: Tel: þ1 513 821 4664; Fax: þ1 513 558 0925; E-mail: [email protected]; [email protected] Date received (in revised form): 22nd September 2010 Abstract Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term ‘interleukin’ (IL) has been used to describe a group of cytokines with complex immunomodulatory functions — including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host’s immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type.
    [Show full text]
  • IL-1/IL-3 Gene Therapy of Non-Small Cell Lung Cancer (NSCLC) in Rats Using ‘Cracked’ Adenoproducer Cells
    Gene Therapy (1998) 5, 778–788 1998 Stockton Press All rights reserved 0969-7128/98 $12.00 http://www.stockton-press.co.uk/gt IL-1/IL-3 gene therapy of non-small cell lung cancer (NSCLC) in rats using ‘cracked’ adenoproducer cells MC Esandi1,2, GD van Someren1, A Bout3, AH Mulder4, DW van Bekkum3, D Valerio1,3 and JL Noteboom1,5 1Section Gene Therapy, Department of Molecular Cell Biology, Leiden University; 3IntroGene BV, Leiden; and 4Pathologisch Laboratorium, Dordrecht, The Netherlands Cytokine gene therapy was studied in established L42 tumour responses. These were due to local release of cyto- tumours in syngeneic rats. L42 is a transplantable non- kines, not to systemic effects. Growth retardation also immunogenic non-small cell lung cancer (NSCLC). Genes occurred in contralateral tumours which were not injected. coding for human interleukin-1␣ and for rat interleukin-3␤ When rats carrying established tumours were vaccinated were transferred by injecting producer cells of recombinant with lysates of tumours collected during treatment with adenovirus vectors into the tumour in attempts to achieve ‘cracked’ producer cells, significant tumour growth retar- high concentrations of the cytokines inside the tumor with- dation was obtained. We speculate that both cytokines, if out systemic toxicity. Limited tumour growth delay was produced at sufficiently high concentrations in tumours, obtained with viable producer cells. For logistic reasons induce inflammation which in turn initiates an immune stocks of pooled frozen producer cells allowed intensive response against tumours growing at a distant site. These treatment of groups of tumour bearing rats. The cells were findings seem to justify further exploration of IL-1 and IL-3 lysed by thawing before administration.
    [Show full text]
  • Human Cytokine Response Profiles
    Comprehensive Understanding of the Human Cytokine Response Profiles A. Background The current project aims to collect datasets profiling gene expression patterns of human cytokine treatment response from the NCBI GEO and EBI ArrayExpress databases. The Framework for Data Curation already hosted a list of candidate datasets. You will read the study design and sample annotations to select the relevant datasets and label the sample conditions to enable automatic analysis. If you want to build a new data collection project for your topic of interest instead of working on our existing cytokine project, please read section D. We will explain the cytokine project’s configurations to give you an example on creating your curation task. A.1. Cytokine Cytokines are a broad category of small proteins mediating cell signaling. Many cell types can release cytokines and receive cytokines from other producers through receptors on the cell surface. Despite some overlap in the literature terminology, we exclude chemokines, hormones, or growth factors, which are also essential cell signaling molecules. Meanwhile, we count two cytokines in the same family as the same if they share the same receptors. In this project, we will focus on the following families and use the member symbols as standard names (Table 1). Family Members (use these symbols as standard cytokine names) Colony-stimulating factor GCSF, GMCSF, MCSF Interferon IFNA, IFNB, IFNG Interleukin IL1, IL1RA, IL2, IL3, IL4, IL5, IL6, IL7, IL9, IL10, IL11, IL12, IL13, IL15, IL16, IL17, IL18, IL19, IL20, IL21, IL22, IL23, IL24, IL25, IL26, IL27, IL28, IL29, IL30, IL31, IL32, IL33, IL34, IL35, IL36, IL36RA, IL37, TSLP, LIF, OSM Tumor necrosis factor TNFA, LTA, LTB, CD40L, FASL, CD27L, CD30L, 41BBL, TRAIL, OPGL, APRIL, LIGHT, TWEAK, BAFF Unassigned TGFB, MIF Table 1.
    [Show full text]
  • RT² Profiler PCR Array (384-Well Format) Human Inflammatory Response & Autoimmunity
    RT² Profiler PCR Array (384-Well Format) Human Inflammatory Response & Autoimmunity Cat. no. 330231 PAHS-3803ZE For pathway expression analysis Format For use with the following real-time cyclers RT² Profiler PCR Array, Applied Biosystems® models 7900HT (384-well block), Format E ViiA™ 7 (384-well block); Bio-Rad CFX384™ RT² Profiler PCR Array, Roche® LightCycler® 480 (384-well block) Format G Description The Human Inflammatory Response & Autoimmunity RT² Profiler PCR Array profiles the expression of 370 key genes involved in immune response during autoimmunity and inflammation. It represents the expression of inflammatory cytokines, chemokines, and their receptors. It also contains genes related to the production and metabolism of cytokines. Genes involved in cytokine-cytokine receptor interactions are as well as thoroughly researched panels of genes involved in the acute-phase, inflammatory, and humoral immune responses. Using real-time PCR, you can easily and reliably analyze the expression of a focused panel of genes related to autoimmunity and inflammation with this array. For further details, consult the RT² Profiler PCR Array Handbook. Sample & Assay Technologies Shipping and storage RT² Profiler PCR Arrays in formats E and G are shipped at ambient temperature, on dry ice, or blue ice packs depending on destination and accompanying products. For long term storage, keep plates at –20°C. Note: Ensure that you have the correct RT² Profiler PCR Array format for your real-time cycler (see table above). Note: Open the package and store
    [Show full text]
  • Leukocyte Adhesion Molecule 1 Gene Activation of Human Endothelial Cells
    Interleukin 3 stimulates proliferation and triggers endothelial- leukocyte adhesion molecule 1 gene activation of human endothelial cells. M F Brizzi, … , G C Avanzi, L Pegoraro J Clin Invest. 1993;91(6):2887-2892. https://doi.org/10.1172/JCI116534. Research Article Proliferation and functional activation of endothelial cells within a tissue site of inflammation are regulated by humoral factors released by cells, such as T lymphocytes and monocytes, infiltrating the perivascular space. In the present study we investigated the effects of interleukin 3 (IL-3), an activated T lymphocyte-derived cytokine, on cultured human umbilical vein endothelial cells (HUVEC). Proliferative activity, evaluated both by estimation of the fraction of cells in the S phase and by direct cell count demonstrated that IL-3, at the dose of 25 ng/ml, enhances more than threefold both DNA synthesis and cell proliferation above baseline control conditions. Binding studies with radioiodinated ligand demonstrated that HUVEC constitutively express a smaller number of IL-3 binding sites (approximately 99 binding sites per cell, with an apparent Kd of 149 pM). Accordingly, molecular analysis showed the presence of transcripts for both alpha and beta subunits of the IL-3 receptor. Functional activation of endothelial cells was evaluated by the expression of the endothelial- leukocyte adhesion molecule 1 (ELAM-1) transcript and by leukocyte adhesion. The ELAM-1 gene transcript was clearly detectable 4 h after IL-3 addition and started to decrease after 12 h. Moreover, IL-3-induced
    [Show full text]
  • Bhlhe40 Controls Cytokine Production by T Cells and Is Essential for Pathogenicity in Autoimmune Neuroinflammation
    ARTICLE Received 31 Jul 2013 | Accepted 4 Mar 2014 | Published 3 Apr 2014 DOI: 10.1038/ncomms4551 Bhlhe40 controls cytokine production by Tcells and is essential for pathogenicity in autoimmune neuroinflammation Chih-Chung Lin1, Tara R. Bradstreet1, Elizabeth A. Schwarzkopf1, Julia Sim2, Javier A. Carrero1, Chun Chou1, Lindsey E. Cook1, Takeshi Egawa1, Reshma Taneja3, Theresa L. Murphy1, John H. Russell2 & Brian T. Edelson1 TH1 and TH17 cells mediate neuroinflammation in experimental autoimmune encephalo- myelitis (EAE), a mouse model of multiple sclerosis. Pathogenic TH cells in EAE must produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). TH cell pathogenicity in EAE is also regulated by cell-intrinsic production of the immuno- suppressive cytokine interleukin 10 (IL-10). Here we demonstrate that mice deficient for the basic helix–loop–helix (bHLH) transcription factor Bhlhe40 (Bhlhe40 À / À ) are resistant to the induction of EAE. Bhlhe40 is required in vivo in a T cell-intrinsic manner, where it posi- tively regulates the production of GM-CSF and negatively regulates the production of IL-10. À / À In vitro, GM-CSF secretion is selectively abrogated in polarized Bhlhe40 TH1 and TH17 cells, and these cells show increased production of IL-10. Blockade of IL-10 receptor in Bhlhe40 À / À mice renders them susceptible to EAE. These findings identify Bhlhe40 as a critical regulator of autoreactive T-cell pathogenicity. 1 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA. 2 Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
    [Show full text]
  • Supplemental Table S10. Differentially Expressed Interleukins Comparing SARS-Cov-2 Versus Medium
    Supplemental Table S10. Differentially expressed interleukins comparing SARS-CoV-2 versus medium ProbeName p ([SARS-CoV-2]Regulation Vs [Medium])FC ([SARS-CoV-2] ([SARS-CoV-2]GeneSymbol Vs Vs [Medium]) [Medium])Description A_33_P3211608 3,97E-02 up 2,974933 IL1RL1 Homo sapiens interleukin 1 receptor-like 1 (IL1RL1), transcript variant 4, non-coding RNA [NR_104167] A_23_P17053 6,39262E-05 up 6,132556 IL36G Homo sapiens interleukin 36, gamma (IL36G), transcript variant 1, mRNA [NM_019618] A_33_P3339625 1,17303E-05 up 16,473091 IL17C Homo sapiens interleukin 17C (IL17C), mRNA [NM_013278] A_33_P3243230 1,76904E-07 up 16,647413 HSINTLK8M interleukin 8 {Homo sapiens} (exp=-1; wgp=0; cg=0), partial (97%) [THC2544321] A_32_P223777 0,00139653 up 1,9878159 IL6ST Homo sapiens interleukin 6 signal transducer (IL6ST), transcript variant 1, mRNA [NM_002184] A_23_P76078 0,045698304 up 1,8592229 IL23A Homo sapiens interleukin 23, alpha subunit p19 (IL23A), mRNA [NM_016584] A_23_P336554 0,00221631 up 1,7976834 IL1RAP Homo sapiens interleukin 1 receptor accessory protein (IL1RAP), transcript variant 2, mRNA [NM_134470] A_33_P3251876 0,03411692 up 1,5917065 IL18R1 Homo sapiens interleukin 18 receptor 1 (IL18R1), transcript variant 1, mRNA [NM_003855] A_33_P3211666 0,026903022 up 1,5705488 IL18R1 Homo sapiens interleukin 18 receptor 1 (IL18R1), transcript variant 1, mRNA [NM_003855] A_23_P90925 0,004416244 up 2,695789 IL36B Homo sapiens interleukin 36, beta (IL36B), transcript variant 2, mRNA [NM_173178] A_24_P68783 0,000239245 up 2,834167 IL36RN Homo sapiens
    [Show full text]
  • IL-23 Drives Pathogenic IL-17-Producing CD8 T Cells
    The Journal of Immunology IL-23 Drives Pathogenic IL-17-Producing CD8؉ T Cells1 Bogoljub Ciric,2,3* Mohamed El-behi,3* Rosalyn Cabrera,† Guang-Xian Zhang,* and Abdolmohamad Rostami* ,IL-17-producing CD8؉ T cells (Tc17) appear to play a role in a range of conditions, such as autoimmunity and cancer. Thus far Tc17 cells have been only marginally studied, resulting in a paucity of data on their biology and function. We demonstrate that Tc17 and Th17 cells share similar developmental characteristics, including the previously unknown promoting effect of IL-21 on Tc17 cell differentiation and IL-23-dependent expression of IL-22. Both STAT1 and STAT4 are required for optimal devel- opment of Tc17 cells and maximal secretion of cytokines. Tc17 cells are cytotoxic, and they can be either pathogenic or non- pathogenic upon adoptive transfer in the model of autoimmune diabetes. Tc17 cells treated with TGF-␤1 plus IL-6 are not diabetogenic, whereas IL-23-treated cells potently induce the disease. IL-17A and IL-17F are necessary but not sufficient for diabetes induction by Tc17 cells. Tc17 cells treated with TGF-␤1 plus IL-6 or IL-23 likely differ in pathogenicity due to their disparate capacity to attract other immune cells and initiate inflammation. The Journal of Immunology, 2009, 182: 5296–5305. he involvement of IL-17-producing CD8ϩ T cells (Tc17) that tumors, by secreting large quantities of TGF-␤1, induce de- in various conditions, such as infection, cancer, and au- velopment of IL-17Aϩ T cells, which in turn promote tumor sur- T toimmune inflammation, has been documented in both vival in an IL-17A-dependent manner (12).
    [Show full text]
  • Development of Non-Overlapping Multiplex ELISA Arrays for the Quantitative Measurement of 400 Human and 200 Mouse Proteins in Parallel
    Development of non-overlapping multiplex ELISA arrays for the quantitative measurement of 400 human and 200 mouse proteins in parallel Yingqing Mao1, Zhiqiang Lv1, Haw-Han Yen1, Yanni Sun1 and Ruo-Pan Huang1,2,3 1RayBiotech, Inc., 3607 Parkway Lane, Suite 100, Norcross, GA 30092, USA; 2RayBiotech Inc., Guangzhou, 510600 China; 3South China Biochip Research Center, Guangzhou, China 510630 Web: www.raybiotech.com Email: [email protected] Phone: 770-729-2992 Abstract Platform & Principal Sensitivity & X-reactivity Highlights Accurate detection of multiple cytokines in complex biological samples is essential to progress in immunological research. However, development of Human receptor array • Proven sandwich ELISA detection high-density multiplex sandwich-based ELISA panels is hampered by 60,000 50,000 Control Array sensitivity test nonspecific cross-reactivity between and among target-specific reagents 40,000 Std7 (Left): One set of 3x • High throughput multiplex array format (i.e., capture antibodies, detection antibodies, and/or antigens); this is 30,000 Std6 Std5 diluted standards were 20,000 particularly challenging for bead-based assays, in which all three are free to Std4 run on human receptor 10,000 • Quadruplicate data for each target per run interact in solution. To overcome this bottleneck, we tested for nonspecific Std3 0 Std2 array. 2 1 1 3 1 1 2 1 1 - - - - - - - - - 3L b1 Fas - Dtk - 1 RI 1 17R 21R 1BB DR6 2 Rg 2 1 R4 1 - B7 GITR - - - - Std1 - uPAR CD14 CD30 MICB MICA RAGE 10 Rb 10 Flt cross-reactivity among reagents used on our quantitative antibody arrays (in TIM 4 ErbB3 IL BCMA HVEM LIMPII - IL IL IL XEDAR IL LYVE CD40L ALCAM ICAM Selectin Selectin Fluor dye (cy3 equivalent) IL VCAM - PDGF Rb Endoglin - TRAIL R3 TRAIL NRG1 • ELISA sensitivity with wider dynamic range PECAM L Trappin E CEACAM which capture antibodies are affixed to a glass slide).
    [Show full text]
  • IL-3 Receptor Expression on Activated Human Th Cells Is Regulated by IL
    IL-3 Receptor Expression on Activated Human Th Cells Is Regulated by IL-4, and IL-3 Synergizes with IL-4 to Enhance Th2 Cell Differentiation This information is current as of October 1, 2021. Anil Kumar, Lekha Rani, Suhas T. Mhaske, Satish T. Pote, Shubhanath Behera, Gyan C. Mishra and Mohan R. Wani J Immunol published online 3 January 2020 http://www.jimmunol.org/content/early/2020/01/02/jimmun ol.1801629 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2020/01/02/jimmunol.180162 Material 9.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 1, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2020 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published January 3, 2020, doi:10.4049/jimmunol.1801629 The Journal of Immunology IL-3 Receptor Expression on Activated Human Th Cells Is Regulated by IL-4, and IL-3 Synergizes with IL-4 to Enhance Th2 Cell Differentiation Anil Kumar, Lekha Rani, Suhas T.
    [Show full text]
  • The Functional Biology of IL-25
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2011 The Functional Biology of IL-25 Steven A. Saenz [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Allergy and Immunology Commons, and the Immunology and Infectious Disease Commons Recommended Citation Saenz, Steven A., "The Functional Biology of IL-25" (2011). Publicly Accessible Penn Dissertations. 962. https://repository.upenn.edu/edissertations/962 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/962 For more information, please contact [email protected]. The Functional Biology of IL-25 Abstract CD4+ T helper (Th) 2 cells secrete interleukin (IL)-4, IL-5 and IL-13 and promote immunity to gastrointestinal helminth infections and chronic inflammation associated with asthma and allergic disorders. However, the innate immune pathways that promote Th2 cell responses remain poorly characterized. The non-hematopoietic cell-derived cytokines thymic stromal lymphopoietin (TSLP), IL-33 and IL-25 (IL-17E) have been implicated in promoting Th2 cell-dependent inflammation at mucosal sites [1-4], but how these cytokines influence innate immune responses are less well defined. Studies in Chapter 2 and 3 examined the cellular mechanisms through which IL-25 promotes Th2 cell responses and demonstrated that IL-25 promotes the accumulation of a previously unrecognized non-B/non-T cell (NBNT) c-kit+ cell population in the gut-associated lymphoid tissue (GALT). Adoptive transfer of IL-25-elicited c-kit+ cells promoted Th2 cytokine responses and conferred protective immunity to helminth infection in normally susceptible Il17e-/- mice. In Chapter 3, characterization of the IL-25-elicited c-kit+ cells revealed these cells to be a lineage negative (Linneg) multi-potent progenitor (MPP) cell population.
    [Show full text]
  • Interleukin-3, Mouse (I4144 and I5286)
    Interleukin-3, mouse recombinant, expressed in Escherichia coli Catalog Number I4144, with BSA as carrier Catalog Number I5286, carrier free Storage Temperature –20 °C Synonyms: IL-3, mIL-3, Mast cell growth factor, The products are sterile filtered through a 0.2 mm filter Multipotential colony-stimulating factor, MULTI-CSF, and lyophilized either with 500 mg BSA (Catalog Hematopoietic growth factor Number I4144) or without a carrier (Catalog Number I5286). Product Description Interleukin-3 (IL-3) is a species-specific, variably Recombinant mouse IL-3 contains 135 amino acid glycosylated, multifunctional protein produced by residues (Predicted molecular mass: 15,233 Da). activated T lymphocytes.1,2 IL-3 appears to support the formation of multilineage colonies in the early Purity: ³98% (SDS-PAGE) development of multipotent hematopoietic progenitor cells. It has been shown to induce colony formation of Endotoxin: £1 EU/mg-P macrophages, neutrophils, mast cells, and megakaroyctes from agar-suspended bone marrow ED : £0.05 ng/ml cells.3 IL-3 interacts with IL-2 to simulate growth of T 50 lymphocytes4 and induce IgG secretion from activated 5 The biological activity is measured by the dose- B cells. Other synonyms or activities attributed to IL-3 dependent stimulation of the proliferation of mouse include multicolony stimulating factor, mast cell growth 9 M-NFS-60 cells. The ED50 is defined as the effective factor, burst promoting activity, histamine-producing cell 6 concentration of growth factor that elicits a 50% stimulating factor, and WEHI-II-3 factor. increase in cell growth in a cell based bioassay. Recently it has been shown IL-3 in conjunction with Precautions and Disclaimer FGF-2, SDF-1a, and SCF promote human EC tube This product is for R&D use only, not for drug, morphogenesis in 3D collagen matrices under serum- 7 household, or other uses.
    [Show full text]