Cachectin/TNF kills or inhibits the differentiation of 3T3-L1 cells according to developmental stage.
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.
Clinical Research Institute, National Medical Center Hospital, Tokyo, Japan.
M
M
Kawakami
N
N
Watanabe
H
H
Ogawa
A
A
Kato
H
H
Sando
N
N
Yamada
T
T
Murase
F
F
Takaku
S
S
Shibata
T
T
Oda
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha