Post-transcriptional regulation of groα, β, γ, and IL-8 mRNAs by IL-1β

Abstract

Expression of the cytokine gene gro, also known as melanoma growth stimulatory activity, is induced by inflammatory stimuli, including IL-1. To determine whether gro expression is regulated at a post-transcriptional level, the effect of IL-1 on gro mRNA stability was examined. Treatment of fibroblasts with IL-1 beta caused a dose-dependent induction of gro mRNA. When IL-1 was withdrawn, gro mRNA decayed rapidly with a half life of 1 hour. This decay occurred whether or not actinomycin D was added to block new transcription. In contrast, when IL-1 was present in the medium, the level of gro mRNA was stable over 8 hours following addition of actinomycin D. In addition, the stability of a related mRNA, IL-8, was found to be regulated by IL-1. To examine whether Northern results reflected expression of gro alpha, or of the closely related genes, gro beta and gro gamma, RNA samples were analyzed by PCR. All three genes were found to be induced by IL-1 and all mRNAs were stabilized in the presence of IL-1. Northern analysis revealed a minor species of gro mRNA which lacked poly(A). The pattern of expression of this RNA suggested that it was a decay intermediate of one or more of the gro mRNAs. The findings indicate that mRNA stabilization is an important component of IL-1 induced gene expression.