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Gene expression in chronic granulomatous disease and interferon-γ receptor-deficient cells treated in vitro with interferon-γ.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2019 Mar; Vol. 120 (3), pp. 4321-4332. Date of Electronic Publication: 2018 Sep 27. - Publication Year :
- 2019
-
Abstract
- Interferon-γ (IFN-γ) plays an important role in innate and adaptive immunity against intracellular infections and is used clinically for the prevention and control of infections in chronic granulomatous disease (CGD) and inborn defects in the IFN-γ/interleukin (IL)-12 axis. Using transcriptome profiling (RNA-seq), we sought to identify differentially expressed genes, transcripts and exons in Epstein-Barr virus-transformed B lymphocytes (B-EBV) cells from CGD patients, IFN-γ receptor deficiency patients, and normal controls, treated in vitro with IFN-γ for 48 hours. Our results show that IFN-γ increased the expression of a diverse array of genes related to different cellular programs. In cells from normal controls and CGD patients, IFN-γ-induced expression of genes relevant to oxidative killing, nitric oxide synthase pathway, proteasome-mediated degradation, antigen presentation, chemoattraction, and cell adhesion. IFN-γ also upregulated genes involved in diverse stages of messenger RNA (mRNA) processing including pre-mRNA splicing, as well as others implicated in the folding, transport, and assembly of proteins. In particular, differential exon expression of WARS (encoding tryptophanyl-transfer RNA synthetase, which has an essential function in protein synthesis) induced by IFN-γ in normal and CGD cells suggests that this gene may have an important contribution to the benefits of IFN-γ treatment for CGD. Upregulation of mRNA and protein processing related genes in CGD and IFNRD cells could mediate some of the effects of IFN-γ treatment. These data support the concept that IFN-γ treatment may contribute to increased immune responses against pathogens through regulation of genes important for mRNA and protein processing.<br /> (© 2018 Wiley Periodicals, Inc.)
- Subjects :
- B-Lymphocytes virology
Cell Line
Exons genetics
Granulomatous Disease, Chronic pathology
Herpesvirus 4, Human
Humans
RNA Splicing genetics
RNA, Messenger genetics
RNA-Seq
Signal Transduction drug effects
Tryptophan-tRNA Ligase genetics
Interferon gamma Receptor
B-Lymphocytes metabolism
Gene Expression drug effects
Granulomatous Disease, Chronic blood
Granulomatous Disease, Chronic genetics
Interferon-gamma pharmacology
Receptors, Interferon deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4644
- Volume :
- 120
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 30260027
- Full Text :
- https://doi.org/10.1002/jcb.27718