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dc.contributor.authorFrazao, Josias B.
dc.contributor.authorColombo, Martino
dc.contributor.authorSimillion, Cedric
dc.contributor.authorBilican, Adem
dc.contributor.authorKeller, Irene
dc.contributor.authorWuthrich, Daniel
dc.contributor.authorZhu, Zhiqing
dc.contributor.authorOkoniewski, Michal J.
dc.contributor.authorBruggmann, Remy
dc.contributor.authorCondino-Neto, Antonio
dc.contributor.authorNewburger, Peter E.
dc.date2022-08-11T08:10:13.000
dc.date.accessioned2022-08-23T16:59:45Z
dc.date.available2022-08-23T16:59:45Z
dc.date.issued2018-09-27
dc.date.submitted2018-12-21
dc.identifier.citation<p>J Cell Biochem. 2018 Sep 27. doi: 10.1002/jcb.27718. [Epub ahead of print] <a href="https://doi.org/10.1002/jcb.27718">Link to article on publisher's site</a></p>
dc.identifier.issn0730-2312 (Linking)
dc.identifier.doi10.1002/jcb.27718
dc.identifier.pmid30260027
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43660
dc.description.abstractInterferon-gamma (IFN-gamma) 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-gamma/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-gamma receptor deficiency patients, and normal controls, treated in vitro with IFN-gamma for 48 hours. Our results show that IFN-gamma increased the expression of a diverse array of genes related to different cellular programs. In cells from normal controls and CGD patients, IFN-gamma-induced expression of genes relevant to oxidative killing, nitric oxide synthase pathway, proteasome-mediated degradation, antigen presentation, chemoattraction, and cell adhesion. IFN-gamma 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-gamma in normal and CGD cells suggests that this gene may have an important contribution to the benefits of IFN-gamma treatment for CGD. Upregulation of mRNA and protein processing related genes in CGD and IFNRD cells could mediate some of the effects of IFN-gamma treatment. These data support the concept that IFN-gamma treatment may contribute to increased immune responses against pathogens through regulation of genes important for mRNA and protein processing.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30260027&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1002/jcb.27718
dc.subjectchronic granulomatous disease
dc.subjectinterferon-γ
dc.subjectinterferon-γ receptor deficiency
dc.subjectphagocyte
dc.subjecttranscriptome
dc.subjectBiochemistry
dc.subjectCongenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subjectGenetic Phenomena
dc.subjectHemic and Lymphatic Diseases
dc.subjectImmune System Diseases
dc.subjectImmunology and Infectious Disease
dc.titleGene expression in chronic granulomatous disease and interferon-gamma receptor-deficient cells treated in vitro with interferon-gamma
dc.typeJournal Article
dc.source.journaltitleJournal of cellular biochemistry
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_pp/235
dc.identifier.contextkey13525448
html.description.abstract<p>Interferon-gamma (IFN-gamma) 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-gamma/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-gamma receptor deficiency patients, and normal controls, treated in vitro with IFN-gamma for 48 hours. Our results show that IFN-gamma increased the expression of a diverse array of genes related to different cellular programs. In cells from normal controls and CGD patients, IFN-gamma-induced expression of genes relevant to oxidative killing, nitric oxide synthase pathway, proteasome-mediated degradation, antigen presentation, chemoattraction, and cell adhesion. IFN-gamma 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-gamma in normal and CGD cells suggests that this gene may have an important contribution to the benefits of IFN-gamma treatment for CGD. Upregulation of mRNA and protein processing related genes in CGD and IFNRD cells could mediate some of the effects of IFN-gamma treatment. These data support the concept that IFN-gamma treatment may contribute to increased immune responses against pathogens through regulation of genes important for mRNA and protein processing.</p>
dc.identifier.submissionpathpeds_pp/235
dc.contributor.departmentDepartment of Pediatrics, Division of Hematology Oncology


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