PROLONGED ACTIVATION OF JUN AND COLLAGENASE GENES BY TUMOR NECROSIS FACTOR-ALPHA
PROLONGED ACTIVATION OF JUN AND COLLAGENASE GENES BY TUMOR NECROSIS FACTOR-ALPHA
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DOI：
10.1038/337661a0
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发表时间：
1989-02-16
期刊：
影响因子：
64.8
通讯作者：
KARIN, M
中科院分区：
文献类型：
--
作者：
BRENNER, DA;OHARA, M;KARIN, M
Tumour necrosis factor-α(TNF-α) is secreted by macrophages in response to inflammation, infection and cancer1. Sublethal doses of recombinant TNF-αto rats causes cachexia, anaemia and inflammation2. TNF-αplays a major part in tissue inflammation3and remodelling4by stimulating production of collagenase. Cellular responses to TNF-a are initiated by binding to high-affinity cell surface receptors5,6. TNF-αthen profoundly affects gene regulation, stimulating thefos, myc, interleukin-1 and interleukin-6 genes7-9and inhibiting the type I collagen gene10. Here we demonstrate that TNF-αalso stimulates collagenase gene transcription; this stimulation is mediated by an element of the gene that is responsive to the transcription factor AP-1, the major component of which (jun/AP-1) is encoded by thejungene; and that TNF-αstimulates prolonged activation ofjungene expression. This prolonged induction ofjuncontrasts with its transient activation by the phorbol ester TPA and provides a physiological example of the ability of jun/AP-1 to stimulate its own transcription11. This may be a key mechanism for mediating at least some of the biological effects of TNF-α.
