THE ROLE OF TNF-α IN THE GROWTH AND DIFFERENTIATION OF U 937 CELLS INDUCED BY PMA AND IFN-γ
Wu Jiong Wang Ming-lun Xu Zhen Qiu Shao-lu Zhu Jian-qing Zhu De-xu (National Key Laboratory of Pharmaceutic Biotechnology, Department of Biochemistry, Nanjing University, Nanjing 210008; Department of Microbiology & Immunology, Nanjing Medical College, Nanjing 210029)
The effects of PMA and IFN-γ on regulation of growth and differentiation of human monoblastic leukemic cell U937 were examined. U 937 cells were stimulated by different concentrations of PMA and IFN-γ respectivelty and NBT reduction assay was used to detect the differentiation of the cells. The results showed that both PMA and IFN-γ dose-dependently induced differentiation of U 937 cells into mature macrophage-like cells. The data also revealed a time-course response in the differentiation induction. Moreover, the U 937 cell growth was significantly inhibited by the treatment of PMA and IFN-γ.These results suggested that PMA and IFN-γ coupled the regulation of U 937 cell growth and differentiation. It was found that tumor necrosis factor-α (TNF-α) was expressed by the stimulated U 937 cells. The specific monoclonal antibody against TNF-α diminised the effects of PMA and IFN-γ on the growth and differentiation of U 937 cells. Thus the endogenous TNF-α may involved in the mechanism of the effects of PMA and IFN-γ on the differentiation of U 937 cells. The regulatory action of the endogenous TNF-α on U 937 cells was not due to its cytotoxic effect.