Wolchok J D, Goodman A R, Vilcek J
Department of Microbiology, New York University Medical Center, New York 10016.
J Leukoc Biol. 1994 Jan;55(1):7-12. doi: 10.1002/jlb.55.1.7.
We have investigated the role of the transcription factor NF-kappa B in the induction of H-2 antigens by tumor necrosis factor (TNF) in murine J558L myeloma cells. An earlier report suggested that J558L cells may have a defect in NF-kappa B activation in response to some stimuli. Treatment of J558L cells with either TNF or lipopolysaccharide (LPS) resulted in nuclear translocation of NF-kappa B, as demonstrated by electrophoretic mobility shift assay. Both TNF and LPS activated the same NF-kappa B nuclear complexes, composed of the p50 and p65 subunits. LPS mediated a stronger and more sustained activation of NF-kappa B than TNF. In contrast, TNF induced higher levels of H-2 antigen surface expression than did LPS, suggesting that activation of NF-kappa B is not sufficient for optimal enhancement of H-2 expression. An inhibitor of NF-kappa B activation, pyrrolidinedithiocarbamate (PDTC), dramatically reduced the induction of H-2 antigen by TNF, supporting the view that NF-kappa B is required for TNF-induced H-2 antigen expression. Constitutive levels of H-2 antigen expression on the cell surface and of nuclear NF-kappa B also decreased after PDTC treatment. However, PDTC had a smaller inhibitory effect on LPS-induced NF-kappa B activation and H-2 antigen expression, suggesting that TNF and LPS activate NF-kappa B by somewhat different pathways.
我们研究了转录因子NF-κB在肿瘤坏死因子（TNF）诱导小鼠J558L骨髓瘤细胞H-2抗原表达中的作用。较早的一份报告表明，J558L细胞在对某些刺激的NF-κB激活方面可能存在缺陷。用电泳迁移率变动分析证明，用TNF或脂多糖（LPS）处理J558L细胞会导致NF-κB的核转位。TNF和LPS均激活了由p50和p65亚基组成的相同NF-κB核复合物。LPS介导的NF-κB激活比TNF更强且更持久。相比之下，TNF诱导的H-2抗原表面表达水平高于LPS，这表明NF-κB的激活不足以最佳地增强H-2表达。NF-κB激活抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）显著降低了TNF诱导的H-2抗原表达，支持了NF-κB是TNF诱导的H-2抗原表达所必需的观点。PDTC处理后，细胞表面H-2抗原表达的组成水平和核NF-κB水平也降低。然而，PDTC对LPS诱导的NF-κB激活和H-2抗原表达的抑制作用较小，表明TNF和LPS通过 somewhat 不同的途径激活NF-κB。
