RESUMEN
Hepatic stellate cell (HSC) activation is closely associated with the progression of liver fibrosis.As an important component of the innate immune system,natural killer (NK) cells are enriched in the liver and play a key role in host defense against viral infection and tumor,and their anti-fibrotic effect has also been confirmed.NK cells can reduce liver fibrosis by killing early-activated or senescent HSCs or secreting interferon-γ.This article summarizes related research advances in recent years,and introduces the molecular immunological mechanism of NK cells in regulating HSCs and their potential anti-fibrotic effect based on the function and phenotype of NK cells and HSCs.
RESUMEN
Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a key component of the endosomal sorting complexes required for transport and has been demonstrated to play a regulatory role in endocytosis/exocytosis and the accumulation of internal vesicles in multivesicular bodies. Citron kinase is a Ser/The kinase that we previously reported to enhance human immunodeficiency virus type 1 (HIV-1) virion production. However, the relationship between Hrs and citron kinase in HIV-1 production remains elusive. Here, we report that Hrs interacts with citron kinase via its FYVE domain. Overexpression of Hrs or the FYVE domain resulted in a significant decrease in HIV-1 virion production. Depletion of Hrs by RNA interference in HEK293T cells increased HIV-1 virion production and enhanced the activity of citron kinase. These data suggest that Hrs inhibits HIV-1 production by inhibiting citron kinase-mediated exocytosis.
Asunto(s)
Humanos , Regulación hacia Abajo , Complejos de Clasificación Endosomal Requeridos para el Transporte , Genética , Metabolismo , Endosomas , Metabolismo , Exocitosis , Expresión Génica , Silenciador del Gen , Células HEK293 , Infecciones por VIH , Genética , Metabolismo , Virología , VIH-1 , Genética , Inmunoprecipitación , Péptidos y Proteínas de Señalización Intracelular , Genética , Metabolismo , Microscopía Fluorescente , Fosfoproteínas , Genética , Metabolismo , Plásmidos , Unión Proteica , Genética , Dominios y Motivos de Interacción de Proteínas , Estructura Terciaria de Proteína , Transporte de Proteínas , Proteínas Serina-Treonina Quinasas , Genética , Metabolismo , ARN Interferente Pequeño , Farmacología , Transfección , Virión , Genética , Liberación del Virus , Replicación ViralRESUMEN
AIDS caused by HIV-1, is a major threat to human being. An anti-HIV formulation from Chinese herbs, so called "Qu Du Zeng Ning", have been recently developed. In this work, the pharmacodynamics of the formulation in vitro was studied. The results showed that Qu Du Zeng Ning inhibit the replication of HIV-1 efficiently in all cell-based assay, with IC50 at 105.2, 70.7, 77.4 microg mL(-1), separately. A significant synergy between the formulation and zidovudine (AZT) was observed, and it also showed a potent activity against HIV-1 drug-resistant mutant.