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Front Immunol ; 12: 796744, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35095873

RESUMEN

Mesenchymal stem cells (MSCs) are capable of homing injury sites to exert anti-inflammatory as well as anti-damage effects and can be used as a vehicle for gene therapy. Angiotensin-converting enzyme 2 (ACE2) plays an important role in numerous inflammatory diseases, but fewer studies have been reported in animal mastitis. We hypothesized that MSCs overexpressing ACE2 is more effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory injury in mammary epithelial cells compared to MSCs alone. The results showed that MSC-ACE2 inhibited the LPS induction by upregulation of TNF-α, IL-Iß, IL-6, and iNOS mRNA expression levels in EpH4-Ev cells compared with MSCs. Furthermore, results showed that both MSC and MSC-ACE2 were significantly activated IL-10/STAT3/SOCS3 signaling pathway as well as inhibited TLR4/NF-κB and MAPK signaling pathways, but MSC-ACE2 had more significant effects. Meanwhile, MSC-ACE2 promoted the expression of proliferation-associated proteins and inhibited the expression of the apoptosis-associated proteins in EpH4-Ev cells. In addition, MSC and MSC-ACE2 reversed the LPS-induced downregulation expression levels of the tight junction proteins in mammary epithelial cells, indicating that both MSC as well as MSC-ACE2 could promote blood-milk barrier repair, and MSC-ACE2 was more effective. These results suggested that MSCs overexpressing ACE2 were more anti-inflammatory as well as anti-injurious action into LPS-induced inflammatory injury in the EpH4-Ev cells. Thus, MSCs overexpressing ACE2 is expected to serve as a potential strategy for mastitis treatment.


Asunto(s)
Enzima Convertidora de Angiotensina 2/genética , Células Epiteliales/metabolismo , Expresión Génica , Mastitis/etiología , Mastitis/metabolismo , Células Madre Mesenquimatosas/metabolismo , Angiotensina II/metabolismo , Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Biomarcadores , Células Cultivadas , Susceptibilidad a Enfermedades , Células Epiteliales/patología , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-10/metabolismo , Lipopolisacáridos/efectos adversos , Mastitis/patología , FN-kappa B/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Receptor Toll-Like 4/metabolismo , Transducción Genética
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