RESUMO
Fibroblast growth factor 21 (FGF-21) is a major paracrine and endocrine regulator of metabolic homeostasis. Here we demonstrate that FGF-21 is also a potent mediator of innate immunity. Double-staining flow cytometry identified neutrophils and monocytes as the main sources of FGF-21 among circulating leukocytes. Functional assays showed that FGF-21 stimulates phagocytosis and production of reactive oxygen species in neutrophil-like HL-60 cells and monocytic THP-1 cells. The mechanism of action of FGF-21 was observed to involve FGF receptor activation, signal transduction through the PI3K/Akt pathway, and stimulation of NADPH oxidase activity. This study indicates that FGF-21 could be an attractive target for the management of inflammatory disorders.
Assuntos
Fatores de Crescimento de Fibroblastos/fisiologia , Imunidade Inata/fisiologia , NADPH Oxidases/metabolismo , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Monócitos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Adulto JovemRESUMO
The clearance of host cell DNA is a critical indicator for Vero-cell culture-derived rabies vaccine. In this study, we evaluated the clearance of DNA in Vero-cell culture-derived rabies vaccine by purification process utilizing ultrafiltration, nuclease digestion, and gel filtration chromatography. The results showed that the bioprocess of using nuclease decreased residual DNA. Dot-blot hybridization analysis showed that the residual host cell DNA was <100 pg/ml in the final product. The residual nuclease in rabies vaccine was less than 0.1 ng/ml protein. The residual nuclease could not paly the biologically active role of digestion of DNA. Experiments of stability showed that the freeze-drying rabies virus vaccine was stable and titers were >5.0 IU/ml. Immunogenicity test and protection experiments indicated mice were greatly induced generation of neutralizing antibodies and invoked protective effects immunized with intraperitoneal injections of the rabies vaccine. These results demonstrated that the residual DNA was removed from virus particles and nuclease was removed by gel filtration chromatography. The date indicated that technology was an efficient method to produce rabies vaccine for human use by using nuclease.