Kawakami M, Watanabe N, Ogawa H, Kato A, Sando H, Yamada N, Murase T, Takaku F, Shibata S, Oda T
Clinical Research Institute, National Medical Center Hospital, Tokyo, Japan.
J Cell Physiol. 1989 Jan;138(1):1-7. doi: 10.1002/jcp.1041380102.
The effects of cachectin/tumor necrosis factor (TNF) on growth and differentiation of 3T3-L1 cells were examined. This fibroblastic cell line can be induced to differentiate into a mature cell type having the biochemical and morphological characteristics of normal adipocytes. At various stages of growth and differentiation, 3T3-L1 cells were exposed to 2.5 x 10(-16) to 2.5 x 10(-8) M (4.2 fg/ml to 420 ng/ml = ca. 1.2 x 10(-14) to 1.2 x 10(-16) U/ml) recombinant human cachectin/TNF for 24 hr, after which cytotoxicity or differentiation was evaluated. During log-phase cell growth, cachectin/TNF had no significant effect on cell viability, and the preadipocytic cells were also resistant to the cytotoxic effect of cachectin/TNF at the contact-inhibited confluent stage. However, when cachectin/TNF was added to the cells during induced differentiation, only 20% of the cells survived. After differentiation into adipocytes, cells regained their resistance to cachectin/TNF-induced cytotoxicity. Cachectin/TNF also markedly affected the differentiation of 3T3-L1 cells into adipocytes. When cells in the confluent phase of growth were exposed to cachectin/TNF for 24 hr, their subsequent hormone-induced differentiation to adipocytes was inhibited. Like cachectin/TNF, IL-1 also induces suppression of lipoprotein lipase and enhances lipolysis in differentiated 3T3-L1 adipocytes; however, in contrast to cachectin/TNF, IL-1 had no effect on the viability or differentiation of pre-adipocyte 3T3-L1 cells. These results indicate that the cytotoxic action of cachectin/TNF varies in the same cell type depending on the stage of growth or differentiation. The results also imply that cachectin/TNF may play a normal role in controlling the differentiation of certain types of cells in vivo including adipocyte lineages.
研究了恶病质素/肿瘤坏死因子（TNF）对3T3-L1细胞生长和分化的影响。这种成纤维细胞系可被诱导分化为具有正常脂肪细胞生化和形态特征的成熟细胞类型。在生长和分化的各个阶段，将3T3-L1细胞暴露于2.5×10⁻¹⁶至2.5×10⁻⁸M（4.2飞克/毫升至420纳克/毫升 = 约1.2×10⁻¹⁴至1.2×10⁻¹⁶单位/毫升）的重组人恶病质素/TNF中24小时，之后评估细胞毒性或分化情况。在对数期细胞生长期间，恶病质素/TNF对细胞活力无显著影响，并且前脂肪细胞在接触抑制汇合阶段也对恶病质素/TNF的细胞毒性作用具有抗性。然而，当在诱导分化期间将恶病质素/TNF添加到细胞中时，只有20%的细胞存活。分化为脂肪细胞后，细胞恢复了对恶病质素/TNF诱导的细胞毒性的抗性。恶病质素/TNF也显著影响3T3-L1细胞向脂肪细胞的分化。当处于生长汇合期的细胞暴露于恶病质素/TNF 24小时时，其随后由激素诱导的向脂肪细胞的分化受到抑制。与恶病质素/TNF一样，IL-1也诱导分化的3T3-L1脂肪细胞中脂蛋白脂肪酶的抑制并增强脂解作用；然而，与恶病质素/TNF相反，IL-1对前脂肪细胞3T3-L1细胞的活力或分化没有影响。这些结果表明，恶病质素/TNF在同一细胞类型中的细胞毒性作用因生长或分化阶段而异。结果还暗示，恶病质素/TNF可能在体内控制包括脂肪细胞谱系在内的某些类型细胞的分化中发挥正常作用。
