TNF-induced Mechanisms for IL6 Gene Induction
Tumor Necrosis Factor (TNF) is a pleiotropic cytokine, originally detected and at present still mostly important because of its cytostatic/cytotoxic potential towards several transformed cell lines (Fiers, 1993). One of the prototypic cell lines for studying the cell killing effects of TNF is the mouse fibrosarcoma line L929. TNF treatment of L929 cells not only leads to cellular toxicity, but also results in the induction of several genes, among which the gene coding for Interleukin-6 (IL6). However, the mechanism of both TNF effects, i.e. gene induction and cell killing, is not yet fully understood, nor are the corresponding signaling intermediates at present known in great detail. In an effort to elucidate the cellular processes, which take place following TNF induction, numerous studies are being pursued regarding different levels of the signaling path way (s), i.e. from intracellular interactions with the membrane bound receptor, down to the actual site of action. In this paper, we will briefly review and mainly focus oil the molecular mechanisms for activation of the IL6 gene promoter in response to TNF.
KeywordsL929 Cell NFKB Activation Transcription Factor NFKB Cell Killing Effect Tumor Necrosis Factor Treatment
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