在p70瘤坏死因子受体中介细胞毒性
1Institute of Cancer and Developmental Biology, Syntex Research, Palo Alto, California 94303.
Cell
|July 10, 1992
概括
瘤坏死因子 (TNF) 杀死瘤细胞是由p55和p70受体介导的. p70受体特别调解瘤细胞死亡,为TNF向癌症治疗提供了新的见解.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 瘤亡因子α (TNF) 呈现选择性瘤细胞细胞毒性,尽管潜在的机制尚不清楚.
- TNF的作用由两个不同的细胞表面受体介导:p55和p70.
- 瘤细胞对TNF的不同敏感性表明受体特异性作用.
研究的目的:
- 研究p70受体在TNF诱导的细胞毒性中的特定作用.
- 阐明p55和p70受体在各种细胞类型中调解TNF效应中的差异性功能.
主要方法:
- 使用小鼠TA1细胞,人类HeLa细胞和NIH 3T3小鼠纤维细胞.
- 使用的人类 (h) 和小鼠 (m) TNF治疗.
- 用人类p70受体 (TNFR) 感染的HeLa细胞进行功能分析.
- 评估了TNF治疗后的细胞活力和c-fos和超氧化物脱酶 (MnSOD) 的诱导.
主要成果:
- 鼠标TA1细胞对mTNF敏感,但不对hTNF敏感,p70受体 (被mTNF识别) 参与了它们的杀死.
- 主要表达p55的HeLa细胞对hTNF有抗性,但在与人体p70受体转染后发生细胞死亡.
- 表达p70受体的HeLa细胞显示TNF降低了c-fos和MnSOD诱导.
- 对mTNF敏感的NIH 3T3纤维细胞对hTNF变得敏感,并且在过度表达人类p70受体时显示出mTNF敏感度增加.
结论:
- p70受体在TNF诱导的细胞毒性中发挥着直接和关键的作用.
- p70受体的不同表达或功能有助于各种细胞类型的TNF敏感性.
- 这些发现为TNF的选择性作用提供了机制基础,并建议对p70受体进行治疗向.
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