TITLE

IFN-γ alters the expression of diverse immunity related genes in a cell culture model designed to represent maturing neutrophils

AUTHOR(S)
Ellison, Michael A.; Gearheart, Christy M.; Porter, Christopher C.; Ambruso, Daniel R.
PUB. DATE
October 2017
SOURCE
PLoS ONE;10/05/2017, Vol. 12 Issue 10, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The cytokine interferon-γ (IFN-γ) is approved as a drug to treat chronic granulomatous disease (CGD) and osteopetrosis and is also used in hyperimmunoglobulin E syndromes. Patients with CGD have defects in proteins of the NOX2 NADPH oxidase system. This leads to reduced production of microbicidal ROS by PMNs and recurrent life threatening infections. The goal of this study was to better understand how IFN-γ might support phagocyte function in these diseases, and to obtain information that might expand potential uses for IFN-γ. Neutrophils mature in the bone marrow and then enter the blood where they quickly undergo apoptotic cell death with a half-life of only 5–10 hours. Therefore we reasoned that IFN-γ might exert its effects on neutrophils via prolonged exposure to cells undergoing maturation in the marrow rather than by its brief exposure to short-lived circulating cells. To explore this possibility we made use of PLB-985 cells, a myeloblast-like myeloid cell line that can be differentiated into a mature, neutrophil-like state by treatment with various agents including DMSO. In initial studies we investigated transcription and protein expression in PLB-985 cells undergoing maturation in the presence or absence of IFN-γ. We observed IFN-γ induced differences in expression of genes known to be involved in classical aspects of neutrophil function (transmigration, chemotaxis, phagocytosis, killing and pattern recognition) as well as genes involved in apoptosis and other mechanisms that regulating neutrophil number. We also observed differences for genes involved in the major histocompatibility complex I (MHCI) and MHCII systems whose involvement in neutrophil function is controversial and not well defined. Finally, we observed significant changes in expression of genes encoding guanylate binding proteins (Gbps) that are known to have roles in immunity but which have not as yet been linked to neutrophil function. We propose that changes in the expression within these classes of genes could help explain the immune supportive effects of IFN-γ. Next we explored if the effect of IFN-γ on expression of these genes is dependent on whether the cells are undergoing maturation; to do this we compared the effects of IFN-γ on cells cultured with and without DMSO. For a subset of genes the expression level changes caused by IFN-γ were much greater in maturing cells than non-maturing cells. These findings indicate that developmental changes associated with cell maturation can modulate the effects of IFN-γ but that this is gene specific. Since the effects of IFN-γ depend on whether cells are maturing, the gene expression changes observed in this study must be due to more than just prolonged application of IFN-γ and are instead the result of interplay between cell maturation and changes caused by the chemokine. This supports our hypothesis that the effects of IFN-γ on developing neutrophils in the bone marrow may be very different from its effects on mature cells in the blood. Collectively the findings in this study enhance our understanding of the effects of IFN-γ on maturing myeloid cells and indicate possible mechanisms by which this cytokine could support immune function.
ACCESSION #
125495850

 

Related Articles

  • Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68. Gentschev, Ivaylo; Müller, Meike; Adelfinger, Marion; Weibel, Stephanie; Grummt, Friedrich; Zimmermann, Martina; Bitzer, Michael; Heisig, Martin; Qian Zhang; Yu, Yong A.; Chen, Nanhai G.; Stritzker, Jochen; Lauer, Ulrich M.; Szalay, Aladar A. // PLoS ONE;2011, Vol. 6 Issue 7, p1 

    Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5...

  • Yet Another Immune System Role in Brain Development. Breindl, Anette // BioWorld Today;3/7/2011, Vol. 22 Issue 44, p1 

    The article discusses research study being done on the role of major histocompatibility complex (MHC) in brain development . It references a study by Kimberley McAllister and colleagues in the February 27, 2011 issue of the journal "Nature Neuroscience." Researchers examined isolated neurons in...

  • Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503. Thammavongsa, Vilasack; Schaefer, Malinda; Filzen, Tracey; Collins, Kathleen L.; Carrington, Mary; Bangia, Naveen; Raghavan, Malini // Immunogenetics;Dec2009, Vol. 61 Issue 11/12, p703 

    Residue 116 of major histocompatibility complex (MHC) class I heavy chains is an important determinant of assembly, that can influence rates of ER-Golgi trafficking, binding to the transporter associated with antigen processing (TAP), tapasin dependence of assembly, and the efficiency and...

  • Effects of Repeated Lipopolysaccharide Stimulation on the Development of Antigen-presenting Cells and T Cells Pool in Hen Vagina. Nii, Takahiro; Isobe, Naoki; Yoshimura, Yukinori // Journal of Poultry Science;2013, Vol. 50 Issue 1, p83 

    The aim of this study was to determine how the mucosal immunity mediated by T cells is developed in the vagina. Antigen-presenting cells and T cells play important roles in the early process of host defense. Mature T cells and immature dendritic cells expressing CC chemokine receptor (CCR) 6. In...

  • Expansion of genetically corrected neutrophils in chronic granulomatous disease mice by cotransferring a therapeutic gene and a selective amplifier gene. Hara, T.; Kume, A.; Hanazono, Y.; Mizukami, H.; Okada, T.; Tsurumi, H.; Moriwaki, H.; Ueda, Y.; Hasegawa, M.; Ozawa, K. // Gene Therapy;Sep2004, Vol. 11 Issue 18, p1370 

    Hematopoietic stem cell gene therapy has not provided clinical success in disorders such as chronic granulomatous disease (CGD), where genetically corrected cells do not show a selective advantage in vivo. To facilitate selective expansion of transduced cells, we have developed a fusion receptor...

  • Progress in rheumatology: Understanding autoimmune disease. Bennett, Robert M. // Geriatrics;Jan96, Vol. 51 Issue 1, p44 

    Takes a look at Wegener's granulomatosis a uniformly fatal condition. How it is diagnosed; How patients survive; Classifications of vasculitides; Therapy; Resolution. INSETS: Laboratory findings in workup of case patient by Robert M..;ACR criteria for diagnosis of Wegener's...

  • Enfermedad granulomatosa crónica. Álvarez-Cardona, Aristóteles; Yamazaki-Nakashimada, Marco Antonio; Espinosa-Padilla, Sara Elva // Revista Alergia de Mexico;sep/oct2009, Vol. 56 Issue 5, p165 

    Chronic granulomatous disease (CGD) is a primary immunodeficiency, a phagocyte defect that appears in 1:200,000 live births and is produced by mutations in the genes that codify for the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). The inheritance form is X linked...

  • T-cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: the molecular basis of negative selection. Clayton, Linda K.; Ghendler, Yoseph; Mizoguchi, Emiko; Patch, Raymond J.; Ocain, Timothy D.; Orth, Kim; Bhan, Atul K.; Dixit, Vishva M.; Reinherz, Ellis L. // EMBO Journal;5/1/1997, Vol. 16 Issue 9, p2282 

    T-cell receptors (TCRs) are created by a stochastic gene rearrangement process during thymocyte development, generating thymocytes bearing useful, as well as unwanted, specificities. Within the latter group, autoreactive thymocytes arise which are subsequently eliminated via a thymocyte-specific...

  • The Association Between HLA-A Alleles and Young Alu Dimorphisms Near the HLA-J, -H, and -F Genes in Workshop Cell Lines and Japanese and Australian Populations. Dunn, David S.; Naruse, Taeko; Inoko, Hidetoshi; Kulski, Jerzy K. // Journal of Molecular Evolution;Dec2002, Vol. 55 Issue 6, p718 

    At least two polymorphic Alu insertions have been previously identified and characterized within the class I region of the major histocompatibility complex (MHC). We have identified another two new polymorphic Alu insertions, AluyHJ and AluyHF, located near HLA-J and HLA-F, respectively, within...

  • The ganglioside antigen GD2 is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting. Kailayangiri, S; Altvater, B; Meltzer, J; Pscherer, S; Luecke, A; Dierkes, C; Titze, U; Leuchte, K; Landmeier, S; Hotfilder, M; Dirksen, U; Hardes, J; Gosheger, G; Juergens, H; Rossig, C // British Journal of Cancer;3/13/2012, Vol. 106 Issue 6, p1123 

    Background:Novel treatment strategies are needed to cure disseminated Ewing sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin are both compatible with aberrant expression of the ganglioside antigen GD2 and led us to explore GD2 immune targeting in this...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics