Journal of hepatology · 2015
Allo-transplantation of mesenchymal stem cells attenuates hepatic injury through IL1Ra dependent macrophage switch in a mouse model of liver disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lee Kuei-Chuan, Lin Han-Chieh, Huang Yi-Hsiang, Hung Shih-Chieh
Аннотация
BACKGROUND & AIMS: Autologous transplantation of mesenchymal stem cells (MSCs) reduces concanavalin A (Con A)-induced hepatic injury in mice. However, the mechanism is unclear and the therapeutic effect of allo-transplantation remains unknown. Our aim was to investigate the effects and mechanisms related to allo-transplantation of MSCs when used to treat Con A hepatic injury.
METHODS: After Con A-induced liver injury was created in C57BL/6J mice, MSCs derived from BALB/c mice or a vehicle control was administered.
RESULTS: Allo-transplantation of MSCs derived from BALB/c mice attenuated hepatic apoptosis in C57BL/6J mice that had undergone Con A-induced liver injury. MSCs increased the level of serum interleukin (IL)-10 and the phosphorylation of hepatic STAT3, but decreased the level of hepatic IFN-γ and phospho-STAT1. Notably, the administered MSCs were trapped mostly in the lungs and promoted the macrophage M2 switch, which contributed to the increased IL10 levels in the lungs and serum. Loss of the therapeutic effect was observed after knock-down of the expression of interleukin 1 receptor antagonist (IL1Ra) in the MSCs. In vitro investigation supported the hypothesis that MSCs are able to switch Con A-stimulated macrophages to the M2 phenotype, which results in an increase in IL10 production.
CONCLUSIONS: Allo-transplantation of MSCs reduces Con A liver injury by increasing IL10 production through an IL1Ra dependent macrophage switch.
METHODS: After Con A-induced liver injury was created in C57BL/6J mice, MSCs derived from BALB/c mice or a vehicle control was administered.
RESULTS: Allo-transplantation of MSCs derived from BALB/c mice attenuated hepatic apoptosis in C57BL/6J mice that had undergone Con A-induced liver injury. MSCs increased the level of serum interleukin (IL)-10 and the phosphorylation of hepatic STAT3, but decreased the level of hepatic IFN-γ and phospho-STAT1. Notably, the administered MSCs were trapped mostly in the lungs and promoted the macrophage M2 switch, which contributed to the increased IL10 levels in the lungs and serum. Loss of the therapeutic effect was observed after knock-down of the expression of interleukin 1 receptor antagonist (IL1Ra) in the MSCs. In vitro investigation supported the hypothesis that MSCs are able to switch Con A-stimulated macrophages to the M2 phenotype, which results in an increase in IL10 production.
CONCLUSIONS: Allo-transplantation of MSCs reduces Con A liver injury by increasing IL10 production through an IL1Ra dependent macrophage switch.
Предметные рубрики MeSH
AllograftsAnimalsApoptosisChemical and Drug Induced Liver InjuryConcanavalin ADisease Models, AnimalGene Knockdown TechniquesInterferon-gammaInterleukin 1 Receptor Antagonist ProteinInterleukin-10LiverLungMacrophagesMacrophages, AlveolarMaleMesenchymal Stem Cell TransplantationMiceMice, Inbred BALB CMice, Inbred C57BLPhenotypeSTAT1 Transcription FactorSTAT3 Transcription Factor