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A sub‐set of immediate early mRNAs induced by tumor necrosis factor‐α during cellular cytotoxic and non‐cytotoxic responses
Author(s) -
Klefstrom Juha,
Saksela Eero,
Alitalo Kari,
Koskinen Päivi J.,
Jäättelä Marja,
Bravo Rodrigo
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910550424
Subject(s) - cytotoxic t cell , tumor necrosis factor alpha , biology , northern blot , cytotoxicity , cytokine , microbiology and biotechnology , cell culture , gene expression , fibrosarcoma , immunology , gene , in vitro , biochemistry , genetics
TNF‐α is a multifunctional cytokine which is cytotoxic for some cell lines. In order to characterize the early genomic response to TNF‐α, 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‐α, and in the 3T3‐L1 pre‐adipocytic cell line, which is resistant to TNF‐α 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‐α. 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‐α inversely correlated with cell‐type‐specific cytotoxicity. Rapid and transient mRNA responses were observed in the TNF‐α‐resistant cells, whereas a slower and more persistent response was characteristic for TNF‐α‐sensitive cells. The prolonged induction of immediate early mRNAs may contribute to TNF‐α‐induced cellular cytotoxic responses.