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Biomed Pharmacother ; 118: 109031, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545219

RESUMO

BACKGROUND: This study was conducted to investigate the protective effect of Fms-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L)-dependent CD103+ dendritic cells (DCs) on hepatic ischemia-reperfusion injury (IRI). METHODS: A mouse model of hepatic IRI and cellular model following hypoxia-reperfusion (H/R) treatment were established. Peripheral blood and liver tissues were obtained and analyzed by flow cytometer in terms of percentage of CD103+DCs and regulatory T (Treg) cells. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were determined to assess liver function. Moreover, pro-inflammatory cytokines levels including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). The histological morphology of liver tissues was examined with hematoxylin and eosin (HE) staining. The apoptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP Nick End Labeling (TUNEL) assay. Treg-associated cytokines transforming growth factor (TGF)-ß and IL-10 expressions were measured using quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: CD103+ DCs were significantly decreased in peripheral blood and liver tissues of mouse model of hepatic IRI. In vivo experiments indicated that CD103+ DCs infusion ameliorated IRI-induced liver damage and Treg inhibition. Further investigations demonstrated that FLT3/FLT3L-dependent CD103+ DCs suppressed hepatocyte apoptosis via activation of Treg cells in vitro. CONCLUSION: FLT3/FLT3L-induced CD103+ DCs alleviated hepatic IRI through activating Treg cells.


Assuntos
Antígenos CD/metabolismo , Células Dendríticas/transplante , Cadeias alfa de Integrinas/metabolismo , Fígado/irrigação sanguínea , Proteínas de Membrana/metabolismo , Traumatismo por Reperfusão/terapia , Linfócitos T Reguladores/imunologia , Tirosina Quinase 3 Semelhante a fms/metabolismo , Animais , Transplante de Células , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Fígado/imunologia , Testes de Função Hepática , Ativação Linfocitária , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/imunologia
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