title: Continuous presence of phorbol ester is required for its IL-1 beta mRNA stabilizing effect.
abstract: The protein kinase C (PKC) activating phorbol esters are known to prevent the decay of mRNA of several cytokines and proto-oncogenes. To examine whether the phorbol ester signal is continuously required for this stabilizing effect, THP-1 monocytic cells were stimulated either with phorbol 12,13-dibutyrate (PDBu), which can be removed from the cells by washings, or with the more hydrophobic phorbol 12-myristate 13-acetate (PMA). Both of these stimuli induced high levels of interleukin-1 beta (IL-1 beta) mRNA. When the cells were washed at the peak of the IL-1 beta mRNA expression, this mRNA decayed rapidly in the PDBu stimulated cells while in PMA stimulated cells the mRNA levels were not affected. Moreover, this mRNA degradation induced by the removal of PDBu could be inhibited by readdition of the phorbol ester. This restabilization could be prevented by pharmacologic inhibitors of PKC, but not by inhibiting protein or RNA synthesis. Thus these data suggest that the phorbol ester must be continuously present to exert its mRNA stabilizing effect and that its effect is PKC-mediated but does not require active protein or RNA synthesis.
authors.affiliation: Department of Bacteriology and Immunology, University of Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Siljander
authors.forename: M
authors.initials: M
authors.lastname: Hurme
mesh_terms: D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics*; D010703:Phorbol Esters / Q000008:administration & dosage*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors
chemical_list: D007375:Interleukin-1; D010703:Phorbol Esters; D012333:RNA, Messenger; D011493:Protein Kinase C