RESUMO
Accumulated evidence indicates that the activating transcription factor 4 (atf4) is a developmentally relevant gene. Here, we report on the characterization of atf4 in Xenopus embryos, which is differentially expressed in the central nervous system, eyes, blood, and the pronephros, as well as in developing endodermal organs such as the stomach, duodenum, liver, and pancreas. Ectopic expression of atf4 in the animal hemisphere of Xenopus embryos had no obvious effects on the induction of neural progenitors, but suppressed neurogenesis and eye formation without promoting apoptosis. Our data suggest that tightly controlled atf4 activities may be crucial for normal neurogenesis and early eye patterning.
Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Proteínas de Anfíbios/metabolismo , Olho/embriologia , Neurogênese , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Xenopus laevis/genética , Fator 4 Ativador da Transcrição/genética , Proteínas de Anfíbios/genética , Animais , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/metabolismo , Olho/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Xenopus/genética , Xenopus laevis/metabolismoRESUMO
Immunosuppression in tumor-bearing hosts may be a major obstacle in eradicating tumors. This study investigated whether hepatocellular carcinoma suppressed the functions of dendritic cells to escape tumor surveillance. Dendritic cells (DC), propagated from C57BL/10J mice, were cocultured with or without murine hepatoma Hepa1-6 cells to examine the influence of hepatocellular carcinoma on dendritic cells. The results revealed that dendritic cells cocultured with hepatoma cells expressed low levels of costimulatory molecules, and the stimulatory capacity was decreased. The antigen-specific cytotoxic effects of T cells activated by the DC cocultured with hepatoma cells were also decreased. In ex vivo studies, the maturation and function of dendritic cells propagated from tumor-bearing mice were suppressed. The suppressive effect of Hepa1-6 cells on dendritic cells could be partially reversed by neutralizing IL-10. In conclusion, the maturation and stimulatory function of DC are suppressed by hepatocellular carcinoma. IL-10 release may be one of the mechanisms employed by hepatocellular carcinoma to suppress dendritic cells.