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PLoS One ; 12(8): e0182308, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28767696

RESUMO

BACKGROUND: SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn's disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients. METHODS: SHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880. RESULTS: SHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort. CONCLUSIONS: Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Doença de Crohn/genética , Regulação para Baixo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Polimorfismo de Nucleotídeo Único , Adulto , Linhagem Celular , Estudos de Coortes , Doença de Crohn/metabolismo , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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