Regulation of interleukin (IL)-11 gene expression in IL-1 induced primate bone marrow stromal cells.

Interleukin (IL)-1 alpha treatment of a primate bone marrow stromal cell line, PU-34, transiently increased the steady state level of IL-11 mRNA. Nuclear run-on experiments showed that the transcription rate of the IL-11 gene was not affected appreciably by IL-1 alpha induction, but changes in the half-life of the IL-11 mRNA corresponded well with the changes in the steady state level of the IL-11 mRNA during the induction. Although transient transfection of PU-34 cells with IL-11 promoter constructs failed to respond to IL-1 alpha, a 10-base pair promoter region and JunD.AP-1 complex were found to be responsible for the basal level transcription of the IL-11 gene. The tyrosine kinase inhibitor genistein accelerated the degradation of the IL-11 mRNA without affecting the transcription rate of the IL-11 gene in IL-1 alpha stimulated cells. The insertion of DNA sequences corresponding to the 3'-untranslated region of the IL-11 gene into a rabbit beta-globin gene resulted in destabilization of the chimeric mRNA which failed to be induced by IL-1 alpha. Exogenous IL-11 expression generated from transient transfection with plasmid pCMV-IL-11, however, can be stabilized by IL-1 alpha. In contrast to the hypothesis that AUUUA motifs in the 3'-untranslated region are sufficient to regulate cytokine mRNA stability, our results suggest that IL-1 alpha induced stabilization of the IL-11 mRNA requires participation of RNA sequences from different regions of the IL-11 message.