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A sub-set of immediate early mRNAs induced by tumor necrosis factor-α during cellular cytotoxic and non-cytotoxic responses

✍ Scribed by Juha Klefstrom; Eero Saksela; Kari Alitalo; Päivi J. Koskinen; Marja Jäättelä; Rodrigo Bravo


Publisher
John Wiley and Sons
Year
1993
Tongue
French
Weight
740 KB
Volume
55
Category
Article
ISSN
0020-7136

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✦ Synopsis


TNF-cu is a multifunctional cytokine which is cytotoxic for some cell lines. In order to characterize the early genomic response to TNF-a, 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-a, and in the 3T3-LI pre-adipocytic cell line, which is resistant to TNF-cu cytotoxicity. Among 77 immediate early mRNAs screened by dot blot and/or Northern blot analyses, the expression of 23 rnRNAs was found to be induced by TNF-a. Ten of these rnRNAs 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-a inversely correlated with cell-type-specific cytotoxicity. Rapid and transient mRNA responses were observed in the TNF-a-resistant cells, whereas a slower and more persistent response was characteristic for TNF-a-sensitive cells. The prolonged induction of immediate early mRNAs may contribute to TNF-a-induced cellular cytotoxic responses.