Hori M, Kamijo R, Takeda K, Nagumo M
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan.
J Interferon Res. 1994 Apr;14(2):49-55. doi: 10.1089/jir.1994.14.49.
The modulation of cell growth by tumor necrosis factor-alpha (TNF-alpha), or TNF-alpha in combination with transforming growth factor-beta (TGF-beta) or interferon-gamma (IFN-gamma) was investigated. TNF-alpha inhibited the proliferation of U937 cells, a monocytic leukemic cell line, and of NA cells that were established from oral squamous cell carcinoma. TNF-alpha showed a cytolytic effect on NA cells in the presence of actinomycin D. TNF-alpha in combination with TGF-beta and TNF-alpha combined with INF-gamma synergistically inhibited the cell proliferation of U937 and NA cells, respectively. TNF-alpha dose-dependently reduced c-myc mRNA expression of U937 and NA cells within 1 h. The combination of TNF-alpha and TGF-beta in U937 cells and that of TNF-alpha and IFN-gamma in NA cells cooperatively reduced the expression of c-myc mRNA. TNF-alpha had little or no effect on the half-life of c-myc mRNA, indicating that c-myc mRNA expression was reduced at transcriptional level. Cycloheximide did not mediate the inhibition of c-myc gene expression, suggesting that the TNF-alpha action was independent of de novo protein synthesis. These data suggest that the reduction of c-myc gene at transcriptional level by TNF-alpha or TNF-alpha in combination with TGF-beta or IFN-gamma plays a primary role in the inhibition of cell growth at an early stage.
研究了肿瘤坏死因子-α（TNF-α）或TNF-α与转化生长因子-β（TGF-β）或干扰素-γ（IFN-γ）联合对细胞生长的调节作用。TNF-α抑制了单核细胞白血病细胞系U937细胞以及从口腔鳞状细胞癌建立的NA细胞的增殖。在放线菌素D存在的情况下，TNF-α对NA细胞显示出细胞溶解作用。TNF-α与TGF-β联合以及TNF-α与INF-γ联合分别协同抑制了U937和NA细胞的增殖。TNF-α在1小时内剂量依赖性地降低了U937和NA细胞的c-myc mRNA表达。U937细胞中TNF-α与TGF-β的联合以及NA细胞中TNF-α与IFN-γ的联合协同降低了c-myc mRNA的表达。TNF-α对c-myc mRNA的半衰期几乎没有影响，表明c-myc mRNA表达在转录水平降低。环己酰亚胺不介导c-myc基因表达的抑制，提示TNF-α的作用独立于从头合成蛋白质。这些数据表明，TNF-α或TNF-α与TGF-β或IFN-γ联合在转录水平降低c-myc基因在早期细胞生长抑制中起主要作用。
