Immunoregulation of bone marrow stromal cells transfected interleukin 18 on intracranial glioma rats / 中国免疫学杂志

ABSTRACT

Objective:To clarify the mechanism of immunoregulation of bone marrow stromal cells(BMSCs) transfected interleukin 18(IL-18) after their transplantation into glioma bearing rats.Methods:Cultured BMSCs from SD rats were transfected with rmIL-18(BMSCs/IL-18).Untransfected BMSCs were used as control.Culture supernatant medium was collected for IL-18 examination at different time point by ELISA kit.After establishment of glioma bearing rats followed by BMSCs/IL-18 transplantation,serum concentration of IFN-?,IL-2 and IL-10 were examined by means of ELISA kit.And their splenocytes were cultured with C6 cells and BMSCs/IL-18 for in vitro cytotoxicity assay,and subsets of splenocyte were detected by flow cytometry.TUNEL was used to clarify apoptosis cells inside glioma and anti-CD34 staining was performed to observe microvessel density(MVD).Results:BMSCs/IL-18 could secret IL-18 long term and stably.After being transplanted with BMSCs/IL-18,serum concentration of IL-2,IFN-? in glioma bearing rats' increased obviously and serum concentration of IL-10 decreased.Flow cytometry results showed that CD4+ and CD8+ T lymphocytes increased in the splenocytes.And rechallenge with C6 cells induced a rapid immuno-reaction.In vitro cytotoxicity assays.It was showed that BMSCs/IL-18 could stimulate splenocytes to kill C6 cells obviously.TUNEL assay showed that there were 15.74?6.23 apoptosis cells inside glioma in each view in Group 2,which was much more when compared with other groups.Microvessel density inside glioma in group 2(6.51?2.71) was lower than in group 1(13.52?3.06),group 3(12.67?2.61) and control group(14.84?1.47).Conclusion:By means of inducing Th1 cytokine and suppressing Th2 cytokine and activating cytotoxic T lymphocyte,BMSCs/IL-18 induces obviously anti-tumor activity.