IL-1 beta, a pro-inflammatory cytokine, has sequences in its 3' untran
slated region (UTR) that may play a role in the post-transcriptional r
egulation of IL-1 beta production. To test this hypothesis, a series o
f chimeric reporter genes were developed consisting of a chloramphenic
ol acetyltransferase (CAT) gene the native 3'-UTR of which was replace
d by the full-length IL-1 beta 3'-UTR or various 3'-UTR deletion mutan
ts. Expression of these constructs under the SV40 late promoter in THP
-1 cells showed that the full-length 3'-UTR repressed constitutive CAT
activity to 28% of control CAT activity. Further analysis of the 3'-U
TR localized the repressor signal to an adenosine-thymidine (AdT)-rich
region. Upon exposure to LPS, the full-length IL-1 beta 3'-UTR mediat
ed almost a fivefold increase in CAT activity. The LPS response was no
t simply loss of AdT-mediated repression; when this sequence was teste
d alone, it did not respond to LPS. The LPS response effect was locali
zed to the terminal 177 base pairs of the IL-1 beta 3'-UTR. The increa
se in CAT activity following LPS stimulation was associated with an in
creased CAT.IL-1 beta 3'-UTR mRNA half-life, indicating at least one e
ffect of the 3'-UTR on a post-transcriptional process. These studies d
emonstrate that the IL-1 beta 3'-UTR is involved in the regulation of
IL-1 beta protein production, and a LPS response element may be in the
IL-1 beta 3'-UTR.