The effects of butyrate on the modulation of urokinase plasminogen activator (uPA) and its receptor (uPAR) mRNAs were studied. While both mRNA levels were increased after stimulation by tumor necrosis factor alpha (TNFα), phorbol ester (PMA) and cycloheximide, they were inhibited by butyrate at 2.5 to 25 mM. Nuclear run-on transcription assays indicated that uPA mRNA was modulated by butyrate at the transcriptional level but the uPAR gene was regulated at both transcriptional and post-transcriptional levels in the presence or absence of TNFα. In the presence of PMA, however, butyrate acts at the post-transcriptional level on both genes.
