Abstract:
Objective To examine the immunoregulation of Celastrus orbiculatus extracts (COE), a traditional Chinese medicine, on maturation and function of dendritic cells (DCs) in vitro and in vivo. Methods In vitro, after treated with COE in different nontoxic concentrations (0, 10, 20, 40, 80, and 160 μg/mL) for 5 d, the surface immunological molecules and cytokine secretion of mice bone marrow-derived DCs in response to COE were analyzed by flow cytometric analysis (FACS) and enzyme linked immunosorbent assay (ELISA), respectively. In vivo, mouse hepatoma cells (Hepa1-6, 1 × 106) were injected sc and were treated with different dosages of COE (10, 20 or 40 mg/kg/d). Effects on tumor growth were determined by tumor volume and histology analysis after 28 d administration of COE. The relative proportions of mature DCs and CD8+ T cells were measured in mononuclear cells that had been isolated from spleen by FACS. Results COE stimulated IL-2 and IFN-γ secretion of DCs, simultaneously enhanced the maturation of DCs by enhancing immunological molecule (CD40, CD80, CD86, H-2Kb, and I-Ab) expression in a dose-dependent manner. Furthermore, the chemotactic responses of DCs were significantly higher in COE-treated than untreated DCs, in association with higher chemokine receptor 7 expression. Furthermore, COE increased DCs produce IFN-γ and IL-2 in a dose-dependent manner when the concentration of COE less than 40 μg/mL, decreased DCs produce IL-10 and IL-4 also in a dose-dependent manner. In in vivo studies, COE can not only suppress growth of malignant hepatocellular carcinomas but also stimulate maturation of DCs, associated with strongly enhanced CD8+ CTL responses. Conclusion These data provide new insight into the mechanism of action of COE and indicate that the stimulation of maturation and function of DCs by COE contributes to its immunoregulatory effects.
