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J. Biol. Chem., Vol. 269, Issue 16, 11769-11775, Apr, 1994
A Ristimaki, S Garfinkel, J Wessendorf, T Maciag and T Hla
Prostanoids, produced by diverse cell types, modulate a variety of
pathophysiological processes. The rate of prostanoid synthesis is
determined, in part, by the levels of prostanoid-synthetic enzymes, such as
cyclooxygenase (Cox), a rate-limiting enzyme in the conversion of
arachidonic acid to prostanoids. While two Cox genes have been identified,
Cox-2 is unique because it is highly induced in response to cell activation
processes including inflammation. We have studied the effect of
interleukin-1 alpha (IL-1 alpha), a proinflammatory cytokine that
facilitates its actions in part by inducing the synthesis of prostanoids,
on the expression of Cox-2 in a human cell line (ECV304) and demonstrated
that IL-1 alpha induces a sustained increase in the expression of the Cox-2
mRNA as well as the functional enzyme. Three mechanistically distinct
inhibitors of translation stimulated the expression of the Cox-2 mRNA and
potentiated the effect of IL-1 alpha. Furthermore, IL-1 alpha induced rapid
but transient activation of Cox-2 transcription and, in the absence of
transcription, prolonged the half- life of the Cox-2 mRNA. Together, these
data suggest that post- transcriptional mechanisms are important in the
sustained induction of the Cox-2 mRNA and that IL-1 alpha may increase the
stability of the Cox-2 transcript.
Induction of cyclooxygenase-2 by interleukin-1 alpha. Evidence for post- transcriptional regulation
Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855.
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