Interactive effects of the tumor necrosis factor promoter and 3′-untranslated regions

J. Han, G. Huez, B. Beutler

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

The tumor necrosis factor (TNF) promoter and 3′-untranslated region (3′-UTR) each contain sequence elements that mediate a response to bacterial endotoxin. Although the promoter contains sequences that permit augmented TNF gene transcription in response to LPS, the 3′-UTR contains sequences that normally confer translational repression, but which allow "derepression" to occur after cell contact with endotoxin. We now show that both genetic elements act in concert during activation of TNF gene expression in macrophages. In order to do so, we have made use of chloramphenicol acetyltransferase reporter constructs in which the TNF promoter and 3′-UTR are represented either independently or in combination with one another. Suppression of chloramphenicol acetyltransferase and TNF mRNA synthesis, observed after treatment of the macrophages with dexamethasone, 2-aminopurine, pentoxifylline, or dibutyryl cAMP, has also been studied in detail. Each class of inhibitor suppresses TNF biosynthesis through a separate mechanism. Interestingly, suppression by pentoxifylline is manifested partly (but not entirely) at the level of transcription, and depends upon the presence of both the TNF promoter and 3′-UTR. The data suggest that other sequences within the TNF gene could also be required for the full effect of pentoxifylline, which may act to prevent processing of the primary transcript. The suppressive effect of dexamethasone is manifested both at the level of transcription and at the level of translation, and is mediated both by sequences present in the TNF promoter and by sequences present in the 3′-UTR. Suppression by 2-aminopurine is solely dependent upon promoter sequences.

Original languageEnglish (US)
Pages (from-to)1843-1848
Number of pages6
JournalJournal of Immunology
Volume146
Issue number6
StatePublished - Mar 15 1991

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3' Untranslated Regions
Tumor Necrosis Factor-alpha
Pentoxifylline
2-Aminopurine
Chloramphenicol O-Acetyltransferase
Endotoxins
Dexamethasone
Macrophages
Genes
Gene Expression
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Interactive effects of the tumor necrosis factor promoter and 3′-untranslated regions. / Han, J.; Huez, G.; Beutler, B.

In: Journal of Immunology, Vol. 146, No. 6, 15.03.1991, p. 1843-1848.

Research output: Contribution to journalArticle

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