Analysis of tumor necrosis factor promoter responses to ultraviolet light

Details

Serval ID
serval:BIB_CA3FBB9BA76E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Analysis of tumor necrosis factor promoter responses to ultraviolet light
Journal
Journal of Clinical Investigation
Author(s)
Bazzoni  F., Kruys  V., Shakhov  A., Jongeneel  C. V., Beutler  B.
ISSN
0021-9738 (Print)
Publication state
Published
Issued date
01/1994
Volume
93
Number
1
Pages
56-62
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan
Abstract
Ultraviolet (UV) light induces the biosynthesis of chloramphenicol acetyltransferase (CAT) in the skin of mice bearing the CATTNF reporter transgene. Moreover, nuclear run-on assays indicate that UV light induces transcription of the TNF gene in RAW 264.7 macrophages. These observations suggest that the TNF gene (and/or its mRNA product) responds to signals elicited by UV light. To identify transcriptional UV response elements within the TNF promoter, and to determine whether a posttranscriptional response might also exist, a series of reporter constructs using a CAT coding sequence attached to various portions of the TNF promoter and 3' untranslated region were devised and transfected into several cultured cell lines. All cells tested were found to be UV responsive, and in NIH 3T3 cells, induction was found to depend upon two general regions of the promoter. The more distal region encompassed nucleotides (nt) -1059 through -451 with respect to the cap site, while the more proximal region spanned nt -403 through -261. A negative element, blocking the UV response, was interposed (nt -451 through -403). As with the response to LPS, the response to UV irradiation appears to involve translational activation in macrophages. However, the UV and LPS signaling pathways have little in common with one another, as indicated by three observations. First, no difference in responsiveness was observed on comparison of TNF gene induction in macrophages derived from C3H/HeN as opposed to C3H/HeJ mice. Second, cell fusion studies showed that while the LPS signaling pathway is extinguished by fusion of RAW 264.7 cells with NIH 3T3 cells, the UV signaling pathway remained intact. Finally, induction did not depend upon the NF-kappa B binding sites that are known to be required for LPS response in macrophages, since mutation of these sites did not impair the UV response.
Keywords
3T3 Cells Animals Blotting, Northern Cell Line Cell Nucleus/drug effects/metabolism/radiation effects Cells, Cultured Chloramphenicol O-Acetyltransferase/biosynthesis/metabolism Fibrosarcoma Hela Cells Humans Lipopolysaccharides/pharmacology Macrophages Macrophages, Peritoneal/drug effects/metabolism/*radiation effects Mice Mice, Inbred C3H Mice, Transgenic Promoter Regions (Genetics)/*drug effects RNA Probes RNA, Messenger/biosynthesis Transcription, Genetic/*radiation effects Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha/*biosynthesis/*genetics *Ultraviolet Rays
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:39
Last modification date
20/08/2019 15:45
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