Gene expression in chronic granulomatous disease and interferon-gamma receptor-deficient cells treated in vitro with interferon-gamma

Autor(es):Mostrar menos -

Frazao, Josias B. ^{[1, 2, 3, 4]} ; Colombo, Martino ^[5] ; Simillion, Cedric ^{[5, 6]} ; Bilican, Adem ^[5] ; Keller, Irene ^{[5, 6]} ; Wuethrich, Daniel ^[5] ; Zhu, Zhiqing ^{[3, 4]} ; Okoniewski, Michal J. ^[7] ; Bruggmann, Remy ^[5] ; Condino-Neto, Antonio ^{[1, 2]} ; Newburger, Peter E. ^{[3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Trop Med, Dept Immunol, Sao Paulo - Brazil

^[3] Univ Massachusetts, Sch Med, Dept Pediat, 55 Lake Ave North, Worcester, MA 01655 - USA

^[4] Univ Massachusetts, Sch Med, Dept Mol Cell & Canc Biol, Worcester, MA - USA

^[5] Univ Bern, Swiss Inst Bioinformat, Interfac Bioinformat Unit, Bern - Switzerland

^[6] Univ Bern, Dept Clin Res, Bern - Switzerland

^[7] Swiss Fed Inst Technol, Sci IT Serv, Zurich - Switzerland

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Biochemistry; v. 120, n. 3, p. 4321-4332, MAR 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 08/58840-6 - Efeito do IFN-y E TFN-a sobre a expressão gênica de CYBB e processamento de seus transcritos
• Beneficiário: Josias Soares de Brito
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/15920-0 - Efeito do interferon-gama na expressão gênica e splicing de leucócitos de pacientes com doença granulomatosa crônica
• Beneficiário: Josias Soares de Brito
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 12/51094-2 - Efeito do interferon-gama sobre defeitos de splicing em doença granulomatosa crônica e em pacientes com deficiência de IFNGR
• Beneficiário: Antonio Condino Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/50460-8 - Caracterização do perfil de splicing e transcriptômico de leucócitos de pacientes com doença granulomatosa crônica estimulados com IFN-gama
• Beneficiário: Josias Soares de Brito
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado