Interleukin-1-mediated stabilization of mouse KC mRNA depends on sequencesin both 5 '- and 3 '-untranslated regions

mRNA transcribed from the mouse KC chemokine gene accumulated to significan tly higher levels in multiple cell types after treatment with interleukin 1 alpha (IL-1 alpha) as compared with tumor necrosis factor-alpha (TNF alpha ). Although TNF alpha and IL-1 alpha both signaled the activation of nuclea r factor kappa B and enhanced transcription of the KC gene with equal poten cy, only IL-1 alpha treatment resulted in stabilization of KC mnNA. Nucleot ide sequences that confer sensitivity for IL-1 alpha-mediated mRNA stabiliz ation were identified within the 5'- and 3'-untranslated regions (UTRs) of KC mRNA using transient transfection of chimeric plasmids containing specif ic portions of KC mRNA linked to the chloramphenicol acetyltransferase (CAT ) gene. When plasmids containing either the 3'- or 5'-UTR of KC mRNA were u sed, the half-life of CAT mRNA was unaltered either in untreated or IL-1 al pha-stimulated cells. In contrast, CAT mRNA transcribed from plasmids that contained both the 5'- and 3'-UTRs of the KC mRNA decayed more rapidly than control CAT mRNA, and this enhanced decay was prevented in cells treated w ith IL-1 alpha. A cluster of four overlapping AUUUA motifs within the 3'-UT R was required, whereas the 5'-UTR region exhibited orientation dependence. These findings indicate that cooperative function of the two nucleotide se quences involves a distinct signaling pathway used by IL-1 alpha but not TN F alpha.