A Sub-Set of Immediate Early mRNAs Induced by Tumor Necrosis Factor-Alpha During Cellular Cytotoxic and Non-Cytotoxic Responses

Int J Cancer. 1993 Oct 21;55(4):655-9. doi: 10.1002/ijc.2910550424.


TNF-alpha is a multifunctional cytokine which is cytotoxic for some cell lines. In order to characterize the early genomic response to TNF-alpha, we have analyzed the induction of a sub-set of serum-inducible immediate early genes in WEHI-S and L929 fibrosarcoma cell lines, which are sensitive to TNF-alpha, and in the 3T3-LI pre-adipocytic cell line, which is resistant to TNF-alpha cytotoxicity. Among 77 immediate early mRNAs screened by dot blot and/or Northern blot analyses, the expression of 23 mRNAs was found to be induced by TNF-alpha. Ten of these mRNAs encode proteins known to function as pro-inflammatory cytokines or transcription factors, while 13 others have as yet uncharacterized activities. The magnitude of c-fos induction by TNF-alpha inversely correlated with cell-type-specific cytotoxicity. Rapid and transient mRNA responses were observed in the TNF-alpha-resistant cells, whereas a slower and more persistent response was characteristic for TNF-alpha-sensitive cells. The prolonged induction of immediate early mRNAs may contribute to TNF-alpha-induced cellular cytotoxic responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Death
  • Densitometry
  • Fibrosarcoma
  • Gene Expression Regulation*
  • Genes, Immediate-Early*
  • Mice
  • RNA, Messenger / biosynthesis*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*


  • RNA, Messenger
  • Tumor Necrosis Factor-alpha