A sub-set of immediate early mRNAs induced by tumor necrosis factor-alpha during cellular cytotoxic and non-cytotoxic responses.
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.
Klefstrom
J
J
Department of Pathology, University of Helsinki, Finland.
Koskinen
P J
PJ
Saksela
E
E
Jäättelä
M
M
Bravo
R
R
Alitalo
K
K
D000818:Animals; D015152:Blotting, Northern; D016923:Cell Death; D003720:Densitometry; D005354:Fibrosarcoma; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha